U.S. patent application number 17/332394 was filed with the patent office on 2021-10-21 for stable silylating reagents.
The applicant listed for this patent is California Institute Of Technology. Invention is credited to Robert H. Grubbs, Wenbo Liu, David P. Schuman, Brian M. Stoltz, Anton Toutov.
Application Number | 20210323983 17/332394 |
Document ID | / |
Family ID | 1000005692711 |
Filed Date | 2021-10-21 |
United States Patent
Application |
20210323983 |
Kind Code |
A1 |
Toutov; Anton ; et
al. |
October 21, 2021 |
STABLE SILYLATING REAGENTS
Abstract
The present disclosure is directed to methods of silylating
organic substrates containing C--H or O--H bonds. In some
embodiments, the methods use compositions that are derived from the
preconditioning of mixtures of hydrosilanes or organodisilanes with
bases, including metal hydroxide, metal alkoxide, metal silanoates,
potassium amides, and/or graphitic potassium bases.
Inventors: |
Toutov; Anton; (Magnolia,
TX) ; Liu; Wenbo; (Wuhan, CN) ; Schuman; David
P.; (Pasadena, CA) ; Stoltz; Brian M.; (San
Marino, CA) ; Grubbs; Robert H.; (South Pasadena,
CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
California Institute Of Technology |
Pasadena |
CA |
US |
|
|
Family ID: |
1000005692711 |
Appl. No.: |
17/332394 |
Filed: |
May 27, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15438929 |
Feb 22, 2017 |
11028107 |
|
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17332394 |
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62298337 |
Feb 22, 2016 |
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62361929 |
Jul 13, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
C07F 7/0814 20130101;
C07F 7/1804 20130101; C07F 7/0896 20130101 |
International
Class: |
C07F 7/08 20060101
C07F007/08; C07F 7/18 20060101 C07F007/18 |
Goverment Interests
GOVERNMENT RIGHTS
[0002] This invention was made with government support under Grant
No. CHE1212767 and Grant No. CHE1205646 awarded by the National
Science Foundation. The government has certain rights in the
invention.
Claims
1. A method of silylating an organic substrate having a C--H bond
or an O--H bond, the method comprising contacting the organic
substrate with a mixture of: (a) a precursor hydrosilane or
organodisilane; and (b) a base comprising a potassium silanolate, a
potassium amide, rubidium hydroxide, a rubidium alkoxide, a
rubidium silanolate, cesium hydroxide, a cesium alkoxide, a cesium
silanolate, a graphitic potassium (KC.sub.8), or a combination
thereof; wherein the contacting results in the formation of a C--Si
bond in the position previously occupied by the C--H bond or an
O--Si bond in the position previously occupied by the O--H bond,
respectively; and wherein the C--H bond is: (a) located on a
heteroaromatic moiety; (b) located on an alkyl, alkoxy, or alkylene
moiety positioned alpha to an aryl or heteroaryl moiety; (c) an
alkynyl C--H bond; or (d) a terminal olefinic C--H bond.
2. The method of claim 1 wherein the mixture is preconditioned
before contacting with the organic substrate, the preconditioning
comprising holding the mixture comprising the precursor hydrosilane
and the base at one or more temperatures in a range of from about
25.degree. C. to about 125.degree. C. for a time in a range of from
about 30 minutes to about 24 hours.
3. The method of claim 1, wherein the mixture further comprises a
solvent.
4. The method of claim 3, wherein the solvent is tetrahydrofuran or
2-methyltetrahydrofuran.
5. The method of claim 1, wherein the base comprises rubidium
hydroxide, or cesium hydroxide.
6. The method of claim 1, wherein the base comprises a potassium
amide.
7. The method of claim 1, wherein the base comprises a rubidium
alkoxide, or a cesium alkoxide.
8. The method of claim 1, wherein the base comprises a potassium
silanoate, a rubidium silanolate, or a cesium silanolate.
9. The method of claim 1, wherein the base comprises a graphitic
potassium (KC.sub.8).
10. The method of claim 1, wherein the precursor hydrosilane is of
the Formula (I) or Formula (II) or the precursor organodisilane is
of the Formula (III): (R).sub.3-mSi(H).sub.m+1 (I)
(R).sub.3-m(H).sub.mSi--Si(R).sub.2-m(H).sub.m+1 (II)
(R').sub.3Si--Si(R').sub.3 (III) where: m is independently 0, 1, or
2; and each R and R' are independently optionally substituted
C.sub.1-24 alkyl or heteroalkyl, optionally substituted C.sub.2-24
alkenyl, optionally substituted C.sub.2-24 alkynyl, optionally
substituted C.sub.6-12 aryl, C.sub.3-12 heteroaryl, optionally
substituted C.sub.7-13 alkaryl, optionally substituted C.sub.4-12
heteroalkaryl, optionally substituted C.sub.7-13 aralkyl,
optionally substituted C.sub.4-12 heteroaralkyl, and, if
substituted, the substituents may be phosphonato, phosphoryl,
phosphanyl, phosphino, sulfonato, C.sub.1-C.sub.20 alkylsulfanyl,
C.sub.5-C.sub.20 arylsulfanyl, C.sub.1-C.sub.20 alkylsulfonyl,
C.sub.5-C.sub.20 arylsulfonyl, C.sub.1-C.sub.20 alkylsulfinyl, 5 to
12 ring-membered arylsulfinyl, sulfonamido, amino, imino, nitro,
nitroso, hydroxyl, C.sub.1-C.sub.20 alkoxy, C.sub.5-C.sub.20
aryloxy, C.sub.2-C.sub.20 alkoxycarbonyl, C.sub.5-C.sub.20
aryloxycarbonyl, carboxyl, carboxylato, mercapto, formyl,
C.sub.1-C.sub.20 thioester, cyano, cyanato, thiocyanato,
isocyanate, thioisocyanate, carbamoyl, epoxy, styrenyl, silyl,
silyloxy, silanyl, siloxazanyl, boronato, boryl, or halogen, or a
metal-containing or metalloid-containing group, where the metalloid
is Sn or Ge, where the substituents may optionally provide a tether
to an insoluble or sparingly soluble support media comprising
alumina, silica, or carbon.
11. The method of claim 1, wherein the at least one hydrosilane is
(R).sub.3SiH or (R).sub.2SiH.sub.2, where R is independently at
each occurrence C.sub.1-6 alkyl, phenyl, tolyl, or pyridinyl.
12. The method of claim 1, wherein the organic substrate contains
an --OH bond and the contacting results in the formation of an
O--Si bond in the position previously occupied by the O--H
bond.
13. The method of claim 1, wherein the organic substrate contains a
C--H bond, wherein the C--H bond is: (a) located on the
heteroaromatic moiety; or (b) located on an alkyl, alkoxy, or
alkylene moiety positioned alpha to an aryl or heteroaryl moiety;
and the contacting results in the formation of a C--Si bond in the
position previously occupied by the C--H bond.
14. The method of claim 1, wherein the organic substrate contains a
C--H bond, wherein the C--H bond is an alkynyl C--H bond and the
contacting results in the formation of a C--Si bond in the position
previously occupied by the C--H bond.
15. The method of claim 1, wherein the organic substrate contains a
C--H bond, wherein the C--H bond is a terminal olefinic C--H bond
and the contacting results in the formation of a C--Si bond in the
position previously occupied by the C--H bond.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application
Ser. No. 15/438,929 filed Feb. 22, 2017 which claims the benefit of
priority to U.S. Patent Application Nos. 62/298,337, filed Feb. 22,
2016, and 62/361,929, filed Jul. 13, 2016, the contents of which
are incorporated by reference herein for all purposes.
TECHNICAL FIELD
[0003] This invention is directed to reagents for silylating
organic substrates.
BACKGROUND
[0004] The ability to silylate organic moieties has attracted
significant attention in recent years, owing to the utility of the
silylated materials in their own rights and as intermediates for
other important materials used, for example, in agrichemical,
pharmaceutical, and electronic material applications.
[0005] Over the past several decades, considerable effort has been
allocated to the development of powerful catalyst architectures to
accomplish a variety of C--H functionalization reactions,
revolutionizing the logic of chemical synthesis and consequently
streamlining synthetic chemistry. Accomplishing such challenging
transformations can often necessitate the use of stoichiometric
additives, demanding reaction conditions, complex ligands, and most
notably precious metal catalysts. The need to use precious metal
catalysts for these transformations remains a fundamental and
longstanding limitation.
[0006] Recently, systems involving the use of various hydroxides,
alkoxides, and other bases have been reported for the silylation of
heteroaromatic, alkynyl, alkenyl, and exocyclic C--H bonds and
hydroxy O--H bonds using organosilanes (a.k.a. hydrosilanes) and
organodisilanes. Not reported, however, is the varying induction
times which are seen in these transformations. Nor has it ever been
reported or suggested that stable, storable compositions derived
from these bases and silanes can be prepared in advance of
contacting the organic substrates and that these preconditioned
solutions are also operable on these substrates.
[0007] The present invention takes advantage of the discoveries
cited herein to avoid at least some of the problems associated with
previously known methods.
SUMMARY
[0008] Herein disclosed are chemical compositions and methods
employing these compositions which eliminate the previously
unreported induction times. These compositions, which are
stable/storable for up to 6 months or longer at low temperatures,
are prepared by the preconditioning of mixtures comprising
hydrosilanes/organodisilanes and various alkali metal hydroxides
and alkoxides and other bases. Reaction of organic substrates,
previously shown to be susceptible to silylation with these
compositions, results in their immediate silylation, i.e., absent
any induction periods. At least one of the many advantage of these
compositions is the ability to prepare and store these silylating
agents, without the need to mix and combine all of the ingredients
in small batches, each time they are needed. The catalytic
cross-dehydrogenative method avoids the limitations of previous
strategies and successfully couples the appropriate substrates and
hydrosilanes.
[0009] Various embodiments includes compositions prepared by or
preparable by preconditioning a mixture of: [0010] (a) a precursor
hydrosilane or organodisilane; and [0011] (b) a base comprising or
consisting essentially of potassium hydroxide, a potassium
alkoxide, a potassium silanolate (e.g., KOTMS), rubidium hydroxide,
a rubidium alkoxide, a rubidium silanolate, cesium hydroxide, a
cesium alkoxide, a cesium silanolate, a potassium amide (e.g.,
potassium bis(trimethylsilyl) amide), a graphitic potassium (e.g.,
KC.sub.8), or a combination thereof; [0012] in the substantial
absence of a heteroaromatic, olefinic, or acetylenic substrate
capable of C--H silylation,
[0013] the preconditioning comprising holding the mixture of the
combined hydrosilane or organodisilane and the base for a time and
temperature sufficient to produce the composition capable of
initiating measurable silylation of 1-methyl indole
(N-methylindole) at a temperature of 45.degree. C. (or less) with
an induction period of less than 30, 25, 20, 15, 10, 5, or 1
minutes. The presence or absence of an induction period may be
determined using any of the methods described herein for this
purpose, for example time-dependent gas chromatography (GC). One
exemplary temperature range to produce such compositions include
from about 25.degree. C. to about 125.degree. C. Higher or lower
temperatures may also be employed. One exemplary temporal range to
produce such compositions include from about 30 minutes to about 48
hours. Greater or less times may also be employed, and may be
affected by the presence of trace amounts of oxygen or water. That
is, while exemplary ranges, it should be appreciated that times and
temperatures outside these exemplary ranges may also result in the
formation of these compositions.
[0014] While the compositions are described in terms of their
reactivity with respect to 1-methyl indole (N-methylindole) (also
known as N-methyl indole or 1-methyl-1H-indole), the compositions
are useful for silylating a range of other C--H bonds and --OH
bonds. The use of 1-methyl indole (N-methylindole) is used simply
as one standard gauge against which activity is to be measured. It
is not meant to be seen as limiting the composition to applications
of this substrate.
[0015] Further, these compositions are stable once prepared and may
be stored for up to weeks or months without loss of activity.
Exhaustive studies have been conducted to elucidate the specific
nature of the stable ingredients of the preconditioned compositions
and the mechanisms of their action. IR data support the existence
of such a hypercoordinated silicon species formed, at least, by the
hydrosilane and alkoxide, hydroxide or silanolate, and the
postulated mechanisms involving such hypercoordinated silicon
hydride anions explain all known observations made with respect to
these silylating systems.
[0016] Other embodiments includes compositions comprising
Si--H-based species derivable from a preconditioning reaction
between: [0017] (a) a precursor hydrosilane; and [0018] (b) a base
comprising or consisting essentially of potassium hydroxide, a
potassium alkoxide, a potassium silanolate (e.g., KOTMS), rubidium
hydroxide, a rubidium alkoxide, a rubidium silanolate, cesium
hydroxide, a cesium alkoxide, a cesium silanolate, a potassium
amide (e.g., potassium bis(trimethylsilyl) amide, or a combination
thereof; again in the substantial absence of a heteroaromatic,
olefinic, or acetylenic substrate capable of C--H silylation; and
wherein the precursor hydrosilane exhibits an absorption peak in
the Si--H stretching region of infrared spectrum and the
Si--H-based species exhibits an absorption peak in the Si--H
stretching region of an infrared spectrum that is of lower energy
than the absorption peak of the precursor hydrosilane, when
evaluated under comparable conditions.
[0019] In some embodiments, Si--H-based species is present in
sufficient amounts in the compositions to be characterized by the
IR absorbance attributable to a Si--H stretching frequency, either
in solution--e.g., using ReactI --or as an isolable/isolated solid.
While the relative intensities of these absorption peak
attributable to the Si--H stretching depend on concentration of
these Si--H-based species, and the various embodiments may be
defined in terms of the concentrations of these species (including
detectable vs. non-detectable). That is, in some embodiments, the
Si--H-based species are present in the compositions at
concentrations sufficient for the IR absorbance attributable to a
Si--H stretching frequency to be present or observed using ReactIR
methods.
[0020] In various embodiments, compositions are isolable or
isolated solids. In other embodiments, the compositions consist of
the precursor hydrosilane (or organodisilane) and an appropriate
base (i.e., neat, or without extraneous solvent). In still other
embodiments, the compositions are solutions comprising an added
solvent--e.g., the reaction solvent used in the preconditioning.
Preferably, the solvent is not measurably reactive with the
Si--H-based species or to the silylation reaction over times
corresponding to storage of use. These solvents may be hydrocarbon-
or ether-based, preferably an oxygen donor containing solvent,
preferably an ether-type solvent. Ether solvents, such as
tetrahydrofurans (including 2-methyl-tetrahydrofuran), diethyl and
dimethyl ether, methyl-t-butyl ether, dioxane, and alkyl terminated
glycols, such as 1,2-dimethoxyethane, have been shown to work well.
Polar aprotic solvents including HMPA are also believed to be
acceptable. Optionally substituted tetrahydrofuran, for example THF
or 2 Me-THF (2-methyl tetrahydrofuran) are especially preferred for
this purpose.
[0021] In some cases, the compositions and methods can be derived
from precursor hydrosilanes of the Formula (I) or Formula (II) or
organosilanes of Formula (III):
(R).sub.3-m Si(H).sub.m+1 (I)
(R).sub.3-m(H).sub.mSi--Si(R).sub.2-m(H).sub.m+.sub.1 (II),
(R').sub.3Si--Si(R').sub.3 (III)
where m is independently 0, 1, or 2; and each R and R' are
independently an optionally substituted alkyl, alkenyl, alkynyl,
aryl, and/or heteroaryl moiety, the specifics of which are further
described elsewhere. R' may also independently comprise optionally
substituted alkoxy, aryloxy, or trimethylsiloxy moieties. In
preferred embodiments, the at least one hydrosilane is (R).sub.3SiH
or (R).sub.2SiH.sub.2, where R is independently at each occurrence
C.sub.1-6 alkyl, phenyl, tolyl, or pyridinyl. In some preferred
embodiments, the organodisilane is hexamethyldisilane.
[0022] In certain preferred embodiments, the base comprises a
potassium cation and a hydroxide or a C.sub.1-6 alkoxide.
Compositions comprising potassium tert-butoxide are especially
preferred.
[0023] Some embodiments include a compound, or compositions,
comprising the compound, having an optionally solvated silicon
hydride structure of Formula (IV):
##STR00001##
[0024] wherein [0025] M.sup.+ is or comprises a cation comprising
potassium, rubidium, cesium, or a combination thereof; [0026]
--OR.sup.B is or comprises hydroxide, an alkoxide, an alkyl
silanolate; or a combination thereof; and [0027] --R.sup.S is or
comprises H, --R, or --Si(R).sub.3-mH.sub.m, or a combination
thereof [0028] where m is and R is as described elsewhere herein;
or an isomer thereof.
[0029] Additional embodiments of the present invention involve the
use of these compositions in silylating an organic substrate having
an C--H bond or --OH bond, the method comprising contacting the
organic substrate with a preconditioned mixture described elsewhere
herein wherein the contacting results in the formation of a C--Si
bond or O--Si bond in the position previously occupied by the C--H
bond or --OH bond, respectively; and
[0030] wherein the C--H bond of the organic substrate is:
[0031] (a) located on a heteroaromatic moiety;
[0032] (b) located on an alkyl, alkoxy, or alkylene moiety
positioned alpha to an aryl or heteroaryl moiety;
[0033] (c) an alkynyl C--H bond; or
[0034] (d) a terminal olefinic C--H bond;
[0035] and wherein the preconditioned mixture is able to initiate
[measurable] silylation of 1-methyl indole at a temperature of
45.degree. C. (or less) with an induction period of less than 30,
25, 20, 15, 10, 5, or 1 minutes (each induction period representing
an independent embodiment).
[0036] Still other embodiments include methods comprising
silylating at least one organic substrate containing a C--H bond or
--OH bond, the method comprising contacting the organic substrate
with:
[0037] (a) a precursor hydrosilane; and
[0038] (b) a base comprising or consisting essentially of cesium
hydroxide, rubidium hydroxide, KC.sub.8, or a combination
thereof;
[0039] wherein the C--H bond of the organic substrate is:
[0040] (a) located on a heteroaromatic moiety;
[0041] (b) located on an alkyl, alkoxy, or alkylene moiety
positioned alpha to an aryl or heteroaryl moiety;
[0042] (c) an alkynyl C--H bond; or
[0043] (d) a terminal olefinic C--H bond; and
[0044] wherein the contacting results in the formation of a C--Si
bond in the position previously occupied by the C--H bond. These
bases have not previously been recognized as competent for
silylating these organic substrates.
[0045] In related embodiments, the precursor hydrosilane and the
base comprising or consisting essentially of cesium hydroxide,
rubidium hydroxide, KC.sub.8, or a combination thereof are
preconditioned, as described above, before contacting with the
organic substrate.
BRIEF DESCRIPTION OF THE DRAWINGS
[0046] The file of this patent or application contains at least one
drawing/photograph executed in color. Copies of this patent or
patent application publication with color drawing(s)/photograph(s)
will be provided by the Office upon request and payment of the
necessary fee. The present application is further understood when
read in conjunction with the appended drawings. For the purpose of
illustrating the subject matter, there are shown in the drawings
exemplary embodiments of the subject matter; however, the presently
disclosed subject matter is not limited to the specific methods,
devices, and systems disclosed. In addition, the drawings are not
necessarily drawn to scale. In the drawings:
[0047] FIG. 1 illustrates a representative time course of the
silylation of 1-methylindole (1), monitored by in situ .sup.1H
NMR.
[0048] FIG. 2 illustrates the induction period when ingredients
mixed simultaneously and the stability of the preconditioned
mixtures for the silylation of 1-methylindole when applied 2 hours,
24 hours, and 6 weeks after formation of the preconditioned
mixtures
[0049] FIG. 3 shows an EPR spectrum taken in THF at 77K at 9.377
GHz, 2.036 mW power.
[0050] FIG. 4 provides a comparison of the kinetic profiles of
multiple base catalysts. Data was acquired via GC analysis of
aliquots of crude reaction mixture.
[0051] FIG. 5 shows a ReactIR plot of KOt-Bu and Et3SiH in THF. New
peak adjacent to Si--H signal of Et.sub.3SiH clearly visible.
[0052] FIG. 6 is a representative ReactIR spectrum showing the
growth of the new Si--H peak assigned to the hypercoordinated
species, followed by injection of substrate and immediate product
formation.
[0053] FIG. 7(A) illustrates the FTIR spectra of Si--H stretching
region of select metal alkoxides with hydrosilane. Spectra were
acquired under an atmosphere of N.sub.2 and are normalized and
stacked for clarity. (a) Neat Et.sub.3SiH. (b) Neat KOt-Bu. (c),
(d), (e), and (f) Prepared as indicated with MOR=KOt-Bu, KOEt,
CsOH, and NaOt-Bu, respectively.
[0054] FIG. 7(B) is an IR spectrum of pure Et.sub.3SiH.
[0055] FIG. 7(C) is an IR spectrum of pure KOt-Bu.
[0056] FIG. 7(D) is an IR spectrum of the product of the reaction
of KOt-Bu with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for 2
hours, followed by removal of volatiles (including Et.sub.3SiH and
THF).
[0057] FIG. 7(E) is an IR spectrum of the product of the reaction
of KOEt with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for 2
hours, followed by removal of volatiles (including Et.sub.3SiH and
THF).
[0058] FIG. 7(F) is an IR is an IR spectrum of the product of the
reaction of KOMe with Et.sub.3SiH (5 equiv) in THF at 45.degree. C.
for 2 hours, followed by removal of volatiles (including
Et.sub.3SiH and THF).
[0059] FIG. 7(G) is an IR spectrum of the product of the reaction
of KOTMS with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for 2
hours, followed by removal of volatiles (including Et.sub.3SiH and
THF).
[0060] FIG. 7(H) is an IR spectrum of the product of the reaction
of KOH with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for 2
hours, followed by removal of volatiles (including Et.sub.3SiH and
THF).
[0061] FIG. 7(I) is an IR spectrum of the product of the reaction
of RbOH.xH2O with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for
2 hours, followed by removal of volatiles (including Et.sub.3SiH
and THF).
[0062] FIG. 7(J) is an IR spectrum of the product of the reaction
of CsOH.xH2O with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for
2 hours, followed by removal of volatiles (including Et.sub.3SiH
and THF).
[0063] FIG. 7(K) is an IR spectrum of the product of the reaction
of KOt-Bu with Et.sub.3SiD (5 equiv) in THF-D.sub.8 at 45.degree.
C. for 2 hours, followed by removal of volatiles (including
Et.sub.3SiH and THF).
[0064] FIG. 7(L) is an IR spectrum of the product of the reaction
of KOt-Bu with Et.sub.3SiD (2.5 equiv) and Et.sub.3SiH (2.5 equiv)
in THF-D.sub.8 at 45.degree. C. for 2 hours, followed by removal of
volatiles (including Et.sub.3SiH and THF).
[0065] FIG. 7(M) is an IR spectrum of the product of the reaction
of LiOt-Bu with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for 2
hours, followed by removal of volatiles (including Et.sub.3SiH and
THF).
[0066] FIG. 7(N) is an IR spectrum of the product of the reaction
of NaOt-Bu with Et.sub.3SiH (5 equiv) in THF at 45.degree. C. for 2
hours, followed by removal of volatiles (including Et.sub.3SiH and
THF).
[0067] FIG. 7(O) is an IR spectrum of the product of the reaction
of Mg(Ot-Bu).sub.2 with Et.sub.3SiH (5 equiv) in THF at 45.degree.
C. for 2 hours, followed by removal of volatiles (including
Et.sub.3SiH and THF).
[0068] The file of this patent or application contains at least one
drawing/photograph executed in color. Copies of this patent or
patent application publication with color drawing(s)/photograph(s)
will be provided by the Office upon request and payment of the
necessary fee.
DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
[0069] The present invention is directed to stable silylation
compositions and methods of using the same. The compositions do not
require the presence of transition metal catalysts, and their
ability to silylate heteroaryl and other unsaturated substrates
does not require their presence or the presence of UV radiation or
electrical (including plasma) discharges.
[0070] Methodology for the direct dehydrogenative C--H silylation
of heteroaryl C--H bonds, acetylenic C--H bonds, and terminal
olefinic C--H bonds have previously been reported, but these
previous methods have been described only in terms of the
simultaneous or near-simultaneous mixing of the ingredients before
subjecting them to the reaction conditions. See, e.g., U.S. patent
application Ser. No. 14/043,929, filed Oct. 2, 2013
(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167; Ser.
No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics with
hydroxides); Ser. No. 14/841,964 filed Sep. 1, 2015 (alkynes), now
U.S. Pat. No. 9,556,206; Ser. No. 14/972,653, filed Dec. 17, 2015
(disilanes), now U.S. Pat. No. 9,556,08; and Ser. No. 15/166,405
(terminal olefins), filed May 27, 2016, each of which is
incorporated by reference herein in its entirety for all purposes,
but especially for their methods of use, substrate range, and
experimental conditions.
[0071] While these systems and methods described the use of
hydrosilanes or organodisilanes and bases such as hydroxides,
alkoxides, and anionic amides, their underlying mechanisms were
undefined. In studies aimed at identifying the mechanistic bases
for these reactions, the present inventors have identified a series
of solution-stable compositions capable of silylating the same
substrates as previously reported. These solution-stable
compositions allow for the bulk preparation and storage of the
silylating agents, avoiding the need to handle small quantities of
reactive hydrosilanes on an individual batch basis, and thereby
simplifying their use. These compositions may also incorporate
highly volatile liquid or even gaseous hydrosilanes or
organodisilanes into less volatile solvents, again simplifying
handling of these silane reagents. Thirdly, the use of these
preconditioned solutions also provides a reactivity that avoids the
previously observed induction periods associated with the
silylation reactions.
[0072] The present invention may be understood more readily by
reference to the following description taken in connection with the
accompanying Figures and Examples, all of which form a part of this
disclosure. It is to be understood that this invention is not
limited to the specific products, methods, conditions or parameters
described or shown herein, and that the terminology used herein is
for the purpose of describing particular embodiments by way of
example only and is not intended to be limiting of any claimed
invention. Similarly, unless specifically otherwise stated, any
description as to a possible mechanism or mode of action or reason
for improvement is meant to be illustrative only, and the invention
herein is not to be constrained by the correctness or incorrectness
of any such suggested mechanism or mode of action or reason for
improvement. Throughout this text, it is recognized that the
descriptions refer to both the compositions and methods of making
and using said compositions. That is, where the disclosure
describes or claims a feature or embodiment associated with a
composition or a method of making or using a composition, it is
appreciated that such a description or claim is intended to extend
these features or embodiment to embodiments in each of these
contexts (i.e., compositions, methods of making, and methods of
using).
[0073] Silylating Compositions
[0074] Certain embodiments of the present invention include those
compositions prepared by preconditioning a mixture of: (a) a
precursor hydrosilane or organodisilane; and (b) a base comprising
or consisting essentially of potassium hydroxide, a potassium
alkoxide, a potassium silanolate (e.g., potassium
trimethylsilanolate, KOTMS), rubidium hydroxide, a rubidium
alkoxide, a rubidium silanolate, cesium hydroxide, a cesium
alkoxide, a cesium silanolate, a potassium amide (e.g., potassium
bis(trimethylsilyl) amide), a potassium graphite (e.g., KC.sub.8),
or a combination thereof; the preconditioning comprising holding
the mixture of combined hydrosilane and the base under conditions
sufficient to produce the composition capable of initiating
measurable silylation of a suitable substrate on contacting the
mixture and the substrate after at least 30 minutes of
preconditioning the mixture. The preconditioning may also comprise
holding the mixture of combined hydrosilane and the base under
conditions sufficient to silylate 1-methyl indole at a temperature
of 45.degree. C. (or less) with an induction period of less than
30, 25, 20, 15, 10, 5, or 1 minutes. The presence or absence of an
induction period may be determined using any of the methods
described herein for this purpose, for example time-dependent gas
chromatography (GC). One exemplary temperature range to produce
such compositions include from about 25.degree. C. to about
125.degree. C. One exemplary temporal range to produce such
compositions include from about 30 minutes to about 24 hours. While
exemplary ranges, it should be appreciated that times and
temperatures outside these exemplary ranges may also result in the
formation of these compositions.
[0075] Given the effectiveness of graphitic potassium (e.g.,
KC.sub.8) in these applications, it is also reasonable to expect
that potassium deposited on other surfaces (e.g., allotropes of
carbons such as graphene, graphene oxide, charcoal, or activated
carbon, alumina, or silica) are also operable, and considered
within the scope of the present disclosure.
[0076] Again, while the compositions are described in terms of
their reactivity with respect to 1-methyl indole (N-methyl indole),
the compositions are useful for silylating a range of other C--H or
--OH bond. The use of 1-methyl indole (N-methyl indole) is used
simply as one standard gauge against which activity is to be
measured. It is not meant to be seen as limiting the composition to
applications of this substrate.
[0077] While other embodiments may describe these preconditioned
compositions in terms of silicon hydrides, as described elsewhere
herein, this preconditioning reaction may or may not result in the
observable presence of a Si--H-based species. Rather, another
measure of the presence of a persistent, stable silylation reaction
is the ability of the material to silylate suitable substrates
(i.e., previously shown to be susceptible to silylation when mixed
simultaneously with the hydrosilane/base combinations, such as
previously reported and described elsewhere herein), even after
cold storage of the Si--H-based species in solution for periods of
time in excess of 1 hour, 6 hours, 12 hours, 24 hours, a week, two
weeks, a month, six months, up to a year or more. See FIGS. 1 and
2. At least in this regard, the term "stable" may be also refer to
"storable." Even more interesting, these preconditioned
compositions are capable of silylating suitable organic substrates,
including heteroaromatic substrates, on immediate or practically
immediate contact with these substrates, or shortly thereafter.
[0078] While not previously reported, but as described in the
present Examples, silylations of heteroaromatic substrates using
hydrosilanes and base catalysts in which the ingredients are
simultaneously or near-simultaneously mixed, such as described in
U.S. patent application Ser. No. 14/043,929, filed Oct. 2, 2013
(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167; Ser.
No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics with
hydroxides); Ser. No. 14/841,964 filed Sep. 1, 2015 (alkynes), now
U.S. Pat. No. 9,556,206; and Ser. No. 15/166,405 (terminal
olefins), filed May 27, 2016, each of which is incorporated by
reference herein, undergo the silylation reactions with a
measurable induction period. This feature has not been previously
reported. Yet, when the hydrosilanes and the bases are
preconditioned as described herein, the preconditioned mixtures are
stable and the reaction proceeds without any such induction
period.
[0079] In other embodiments, the preconditioned compositions may be
characterized or described in terms of Si--H-based species, as
described herein. That is, certain other embodiments of the present
invention include those compositions comprising a Si--H-based
species derivable from the preconditioning reaction between: (a) a
precursor hydrosilane; and (b) a base comprising or consisting
essentially of potassium hydroxide, a potassium alkoxide, a
potassium silanolate (e.g., KOTMS), rubidium hydroxide, a rubidium
alkoxide, a rubidium silanolate, cesium hydroxide, a cesium
alkoxide, a cesium silanolate, a potassium amide (e.g., potassium
bis(trimethylsilyl) amide), or a combination thereof. In some
aspects of these embodiments, the Si--H-based species derived or
derivable from the preconditioning reaction may be identified by a
characteristic shift of its infrared Si--H stretching frequency.
That is, the precursor hydrosilane exhibits an absorption peak in
the Si--H stretching region of infrared spectrum which depends on
the nature of the precursor hydrosilane, and the Si--H-based
species exhibits an absorption peak in the Si--H stretching region
of an infrared spectrum that is of lower energy (lower wavenumbers)
than the absorption peak of the precursor hydrosilane, when
evaluated under comparable conditions. Such Si--H-based species can
be present and detected in solution, or as solid compositions (see
Examples).
[0080] In solution, the presence of the product/intermediate
Si--H-based species can be and has been observed in solution using
in situ Fourier Transform Infrared (FTIR) methods. For example,
Mettler Toledo makes ReactIR equipment for just such analyses.
Suitable for a wide range of chemistries, ReactIR provides
real-time monitoring of key reaction species, and how these species
change during the course of the reaction. Designed to follow
reaction progression, ReactIR Attenuated Total Reflection (ATR)
provides specific information about reaction initiation,
conversion, intermediates and endpoint. As shown in the Examples,
reactions of the exemplar silane Et.sub.3SiH has been shown to
react with the alkoxides and hydroxides cited herein to provide
spectroscopically structures consistent with hypercoordinated
silicon hydrides.
[0081] These Si--H-based species resulting from the preconditioning
exhibit IR absorption shifts, depending on both the hydrosilanes
and especially with the nature of the alkoxide or hydroxide bases,
consistent with the relative reactivities of these hydrosilane/base
pairs with organic substrates.
[0082] It is noted here that, while consistent with such structures
and the observation of such infrared absorptions correlate with
silylation reactivities, the claims are not necessarily bound to
the correctness or incorrectness of such an interpretation. Stated
otherwise, these preconditioned compositions may be described or
characterized as exhibiting an infrared absorbance peak in a range
consistent with, but not necessarily attributable to, a Si--H
stretching frequency; e.g., in a range of from about 2000 to 2100
cm'. And again, these absorbances are of lower energy (at lower
wavenumbers) than the precursor silane. In some embodiments, the
absorbance peaks may be shifted to lower wavenumbers in a range of
from 10 to 100 cm-1, or as shown in FIG. 7A. It should be apparent
to the skilled artisan, that compositions preconditioned with
deuterosilanes do not exhibit absorbances in this range, but do
exhibit the reactivities described above.
[0083] In various embodiments, the Si--H-based species are present
in the preconditioned composition in amounts sufficient to detect
this absorption peak attributed to the Si--H stretching region of
an infrared spectrum.
[0084] In some embodiments, these preconditioned compositions exist
as solutions. In other embodiments, they are present solvent-free
or as isolated solids or semi-solids. In the former case, then,
these preconditioned compositions may be described as comprising a
solvent, typically an organic solvent, preferably an anhydrous
solvent. Preferably such compositions are substantially free of
other oxidizing species, including air, oxygen, or transition metal
compounds or species. Also, the solvent is preferably not
measurably reactive with the preconditioned compositions, including
the Si--H-based species, or to the silylation reaction. Suitable
solvents include hydrocarbons, such as aromatic hydrocarbons, for
example benzene or toluene Other suitable and preferred solvents
include those comprising so-called oxygen donor solvents,
preferably ether-type solvents. Tetrahydrofurans (including
2-methyl-tetrahydrofuran), diethyl and dimethyl ether,
methyl-t-butyl ether, dioxane, and alkyl terminated glycols, such
as 1,2-dimethoxyethane have been shown to work well. Other polar
aprotic solvents including hexamethylphosphoramide (HMPA) are also
believed to be acceptable. Tetrahydrofurans, including
2-methyl-tetrahydrofuran), are preferred.
[0085] As described above, in some embodiments, the base used in
the precondition reaction comprises potassium hydroxide, rubidium
hydroxide, cesium hydroxide, potassium alkoxide, a rubidium
alkoxide, or a cesium alkoxide, or a mixture thereof. Other bases,
such as those described elsewhere herein may also be used. Suitable
alkoxides include C.sub.1-6 alkoxides, such as methoxide, ethoxide,
n-propoxide, isopropoxide, n-butoxide, sec-butoxide, tert-butoxide,
n-pentoxide, 2-pentoxide 3-pentoxide, or iso-pentoxide, preferably
tert-butyl butoxide. Of the bases tested thus far, potassium
alkoxide, and especially potassium tert-butoxide is preferred.
[0086] Suitable silanolates include those structures of formulae
(C.sub.1-6 alkyl).sub.3Si--O--, where the C.sub.1-6 alkyls are
independently placed. KOTMS, potassium trimethylsilanolate, is an
attractive silanolate in this application.
[0087] In some embodiments, the precursor hydrosilane used in the
preconditioned composition is of the Formula (I) or Formula
(II):
(R).sub.3-mSi(H).sub.m+1 (I)
(R).sub.3-m(H).sub.mSi--Si(R).sub.2-m(H).sub.m+1 (II)
where: m is independently 0, 1, or 2; and each R is independently
optionally substituted C.sub.1-24 alkyl or heteroalkyl, optionally
substituted C.sub.2-24 alkenyl, optionally substituted C.sub.2-24
alkynyl, optionally substituted C.sub.6-12 aryl, C.sub.3-12
heteroaryl, optionally substituted C.sub.7-13 alkaryl, optionally
substituted C.sub.4-12 heteroalkaryl, optionally substituted
C.sub.7-13 aralkyl, or optionally substituted C.sub.4-12
heteroaralkyl, and, if substituted, the substituents may be
phosphonato, phosphoryl, phosphonyl, phosphino, sulfonato,
C.sub.1-C.sub.20 alkylsulfanyl, C.sub.5-C.sub.20 arylsulfanyl,
C.sub.1-C.sub.20 alkylsulfonyl, C.sub.5-C.sub.20 arylsulfonyl,
C.sub.1-C.sub.20 alkylsulfinyl, 5 to 12 ring-membered arylsulfinyl,
sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl,
C.sub.1-C.sub.20 alkoxy, C.sub.5-C.sub.20 aryloxy, C.sub.2-C.sub.20
alkoxycarbonyl, C.sub.5-C.sub.20 aryloxycarbonyl, carboxyl,
carboxylato, mercapto, formyl, C.sub.1-C.sub.20 thioester, cyano,
cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy,
styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl,
or halogen, or a metal-containing or metalloid-containing group,
where the metalloid is Sn or Ge, where the substituents may
optionally provide a tether to an insoluble or sparingly soluble
support media comprising alumina, silica, or carbon.
[0088] In certain preferred embodiments, the precursor hydrosilane
used in the preconditioned composition is or comprises a compound
of formula (R).sub.3SiH or (R).sub.2SiH.sub.2, where R is
independently at each occurrence C.sub.1-6 alkyl, phenyl, tolyl, or
pyridinyl. Exemplary precursor hydrosilane include those were R is
independently at each occurrence methyl, ethyl, propyl, butyl,
propyl, phenyl, biphenyl, benzyl, or pyridinyl, or substituted
derivatives thereof.
[0089] In some embodiments, the precursor organodisilane used in
the preconditioned composition is of the Formula (III):
(R').sub.3Si--Si(R').sub.3 (III),
where R' is described above. R' may additionally independently
comprise an optionally substituted C.sub.1-24 alkoxy, an optionally
substituted C.sub.6-12 aryloxy, optionally substituted C.sub.3-12
heteroaryloxy, optionally substituted C.sub.7-13 alkaryloxy,
optionally substituted C.sub.4-12 heteroalkaryloxy, optionally
substituted C.sub.6-12 aralkoxy, C.sub.4-12 heteroaralkoxy or a
trimethylsiloxy moiety. In preferred embodiments, R' is
independently C.sub.1-3 alkyl or aryl; in other preferred
embodiments, the organodisilane is hexamethyldisilane,
tetramethyldiphenyldisilane, hexaethoxydisilane, or
hexamethoxydisilane.
[0090] Accordingly, certain embodiments of the present invention
include a compound having an optionally solvated silicon hydride
structure of Formula (IV):
##STR00002##
[0091] wherein [0092] M.sup.+ is or comprises a cation comprising
potassium, rubidium, cesium, or a combination thereof; [0093]
--OR.sup.B is or comprises hydroxide, an alkoxide, an alkyl
silanolate; or a combination thereof; and [0094] --R.sup.S is or
comprises H, --R, or --Si(R).sub.3-mH.sub.m, or a combination
thereof where m is and R is as described elsewhere herein; or an
isomer thereof.
[0095] Alternatively stated, this compound may be described or
characterized as the addition product of (a) potassium hydroxide, a
potassium alkoxide, a potassium silanolate, rubidium hydroxide, a
rubidium alkoxide, a rubidium silanolate, cesium hydroxide, a
cesium alkoxide, a cesium silanolate, or a combination thereof with
(b) a precursor hydrosilane of Formula (I) or (II), or any of the
individual precursor hydrosilanes as described elsewhere
herein.
[0096] The structure of Formula (IV) is analogous to structures
previously observed in other systems, though the present structures
exhibit dramatically different and totally unexpected activity. For
example, the addition of strong silicophilic Lewis bases (e.g.
fluoride, alkoxide) are known to be able to increase the reactivity
of hydrosilanes in the hydrosilylation of C.dbd.O bonds. It has
been speculated that strongly reducing hypercoordinate silicate
complexes are formed by coordination of nucleophilic anions during
such processes, which typically weakens the Si--H bond and
increases the hydridic character of this bond. Studies by Corriu et
al. revealed that the direct reaction of (RO).sub.3SiH with the
corresponding KOR (R=alkyl or aryl) in THF at room temperature
affords the anionic, five-coordinate hydridosilicate
[HSi(OR).sub.4]K in good yield. See, e.g., Becker, B., et al., J.
Organometallic Chem., 359 (2), January 1989, pp. C33-C35; Corriu,
R., et al., J. C. Chem. Rev. 1993, 93, 1371-1448; Corriu, R. J., et
al., Tetrahedron 1983, 39, 999-1009; Boyer, J.; et al., Tetrahedron
1981, 37, 2165-2171; Corriu, R., et al., Organometallics 2002, 10,
2297-2303; and Corriu, R., et al., Wang, Q. J. Organomet. Chem.
1989, 365, C7-C10.
[0097] As is described elsewhere herein, the compounds having an
optionally solvated structure of Formula (IV) have been
characterized spectroscopically and by their reactivity (in terms
of substrate and regioselectivity) and kinetic profiles. The Si--H
bond of the compound having an optionally solvated structure of
Formula (IV) appears exhibit Bronsted-Lowry basicity. Silicon is
less electronegative than hydrogen, and the Si--H bond in (IV)
possesses some hydridic character. Upon nucleophilic (tBuO-)
attack, the Si--H bond in the hypercoordinated silicon intermediate
(IV) can, in some circumstances, serve as a hydride donor. Indeed,
cleavage of the Si--H bond in hydrosilanes by strong nucleophiles
to form alkylated or arylated silanes with loss of hydride is
precedented in the literature. Therefore, the silane hydrogen in
(IV) is expected to be sufficiently basic to abstract a proton from
heteroaromatic substrates leading to formation of H2. This
proposition is further supported by an isotope labelling
experiment: when C.sub.2-deuterated 1-methyl indole substrate was
used as a substrate, the evolution of HD gas was observed.
[0098] Likewise, when different alkoxide bases were used as
catalysts in stoichiometric reactions, the reaction efficiencies
followed roughly the basicities (i.e., KOtBu>KOEt>KOMe).
(alkoxide application). This behavior is consistent with the
proposed addition of the alkoxide anion to the silane precursor
silane to form the reactive hypercoordinated silicon
intermediate.
[0099] The nature of the cation has previously been
described--i.e., the silylations, at least of heteroarenes, fail to
operate with sodium or lithium cations by themselves or when the
added potassium ions are sequestered (for example, by crown
ethers), but operate with facility when potassium, rubidium, or
cesium are used. Interestingly, the silylation of alkynes or
alcohols operate when the bases comprise sodium cations, and, while
hydrides comprising these cations have not been observed, the
stable preconditioned mixtures may be derived from such bases.
Clearly, the cations play a non-innocent role in the activity of
these reagents. Without intending to be bound by the correctness of
any particular theory, perhaps this role involves either the
(de)stabilization of the catalytic intermediate or the activation
the substrate. As such, where the bases are characterized herein as
comprising potassium, rubidium, or cesium hydroxides, alkoxides, or
silanolates are to be used in the absence of crown ethers or other
cation sequestering agents. Further, these bases can also be
described as including sources of these unsequestered cations
(K.sup.+, Cs.sup.+, Rb.sup.+) with sources the operative hydroxide,
alkoxide, or silanolate anions. For example, the use LiOH, NaOH, or
alkaline earth metal hydroxides in the presence of added potassium
salts, such as potassium chloride, nitrate, sulfate, or of a
potassium salt comprising another similar non-reactive anion, may
be considered a functional equivalent to KOH itself.
[0100] Under certain conditions, the preconditioned compositions
exhibit character consistent with the homolytic scission of the
Si--H bond, and the corresponding formation of a radical species.
This may suggest the potential utility of these compounds or
compositions as one-electron reductants, for example of transition
metal complexes such as those comprising iron or cobalt.
[0101] Methods of Use
[0102] To this point, the invention has been describe in terms of
compositions, but it should be appreciated that the compositions
are also useful in silylation methods, and certain embodiments are
directed toward their use in this capacity.
[0103] Some embodiments of the present invention include those
where the preconditioned compositions, and/or the compositions of
Formula (IV) are contacted with an organic substrate having an
appropriate C--H bond or an O--H bond to silylate that carbon or
oxygen. For example, some embodiments include method comprising
contacting the organic substrate with any of the preconditioned
mixtures described herein, wherein the contacting results in the
formation of a C--Si bond in the position previously occupied by
the C--H bond or in the formation of a O--Si bond in the position
previously occupied by the O--H bond;
[0104] wherein the C--H bond of the unsaturated substrate is:
[0105] (a) located on a heteroaromatic moiety;
[0106] (b) located on an alkyl, alkoxy, or alkylene moiety
positioned alpha to an aryl or heteroaryl moiety;
[0107] (c) an alkynyl C--H bond; or
[0108] (d) a terminal olefinic C--H bond.
[0109] Each of the permutations of preconditioning conditions,
bases, hydrosilanes, and substrates is deemed an independent
embodiment of this disclosure as if each had been individually
cited. In specific independent embodiments, the preconditioned
mixtures and organic substrates are placed into contact for times
of at least 30 minutes, 1 hour, 4 hours, 8 hours, 12 hours, 24
hours, 2 days, 4 days, 7 days, 14 days, or 28 days after the
preconditioning reaction is done. Typically, especially for the
extended periods, the preconditioned mixtures are refrigerated to
favor the stability. Contacting the preconditioning conditions,
bases, hydrosilanes, and substrates generally includes holding the
resulting mixtures at one or more temperatures in a range of from
about 25.degree. C. to about 75.degree. C. for a time in a range of
from about 1 hour to about 48 hours, or as described in the various
applications cited herein with respect to the specific organic
substrates.
[0110] It is further recognized that the use of cesium hydroxide,
rubidium hydroxide, or KC.sub.8 has not been previously recognized
or disclosed as a competent base for silylation reactions in
combinations with hydrosilanes and, at least, heteroaromatic
substrates. As such, methods describing their use in this capacity
are considered independent embodiments of this disclosure. Certain
embodiments, then, include those methods silylating at least one
organic substrate containing a C--H bond or --OH bond, the method
comprising contacting the organic substrate with: [0111] (a) a
precursor hydrosilane; and [0112] (b) a base comprising or
consisting essentially of cesium hydroxide, rubidium hydroxide,
KC.sub.8, or a combination thereof; [0113] wherein the C--H bond of
the unsaturated substrate is: [0114] (a) located on a
heteroaromatic moiety; [0115] (b) located on an alkyl, alkoxy, or
alkylene moiety positioned alpha to an aryl or heteroaryl moiety;
[0116] (c) an alkynyl C--H bond; or [0117] (d) a terminal olefinic
C--H bond; and
[0118] wherein the contacting results in the formation of a C--Si
bond in the position previously occupied by the C--H bond.
[0119] Still further embodiments include those methods wherein the
precursor hydrosilane and the base are preconditioned before
contacting with the organic substrate, the preconditioning
comprising holding a mixture comprising the precursor hydrosilane
and the base under conditions sufficient to produce the composition
capable of initiating measurable silylation of a suitable substrate
on contacting the mixture and the substrate after at least 30
minutes of preconditioning the mixture. The preconditioning may
also comprise holding the mixture of combined hydrosilane and the
base under conditions sufficient to initiate measurable silylation
of 1-methyl indole at a temperature of 45.degree. C. (or less) with
an induction period of less than 30, 25, 20, 15, 10, 5, or 1
minutes.
[0120] Substrates Susceptible to Silylations
[0121] Previous applications by some of the same inventors have
described the use of base and hydrosilanes to silylate organic
substrates having C--H bonds or --OH bonds, wherein the silylation
is defined in terms of replacing a C--H bond with C--Si bond or an
O--H bond with an O--Si bond. See, for example, U.S. patent
application Ser. No. 14/043,929, filed Oct. 2, 2013
(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167; Ser.
No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics with
hydroxides); Ser. No. 14/841,964 filed Sep. 1, 2015 (alkynes), now
U.S. Pat. No. 9,556,206; Ser. No. 15/166,405 (terminal olefins),
filed May 27, 2016; and Ser. No. 15/219,710, filed Jul. 26, 2016
(alcohols with hydroxides), each of which is incorporated by
reference, at least for their teaching of methods and reaction
conditions, including substrates and reactants relating to
silylating their respective substrates.
[0122] The methods described herein are appropriately applied to
any of the substrates described in these patent applications,
including those wherein the organic substrate is or comprises:
[0123] (1) a heteroaromatic moiety, for example comprising an
optionally substituted furan, pyrrole, thiophene, pyrazole,
imidazole, triazole, isoxazole, oxazole, thiazole, isothiazole,
oxadiazole, pyridine, pyridazine, pyrimidine, pyrazine, triazone,
benzofuran, benzothiophene, isobenzofuran, isobenzothiophene,
indole, isoindole, indolizine, indazole, azaindole, benzisoxazole,
benzoxazole, quinoline, isoquinoline, cinnoline, quinazoline,
naphthyridine, 2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,
2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, or
dibenzothiophene moiety. More specific example of these substrates
are described in U.S. patent application Ser. No. 14/043,929, filed
Oct. 2, 2013 (heteroaromatics with alkoxides), now U.S. Pat. No.
9,000,167 or Ser. No. 14/818,417, filed Aug. 5, 2015
(heteroaromatics with hydroxides), each of which is incorporated by
reference herein at least for these teachings.
[0124] (2) a substrate comprising an alkyl, alkoxy, or alkylene
moiety positioned alpha to an aryl or heteroaryl moiety, for
example a benzylic C--H bond or a C--H bond which exists alpha to a
heteroaryl group, such as 1,2 dimethylindole or
2,5-dimethylthiophene, or an exocyclic methoxy group. More specific
example of these substrates are described in U.S. patent
application Ser. No. 14/043,929, filed Oct. 2, 2013
(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167 or
Ser. No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics with
hydroxides).
[0125] (3) an alkynyl C--H bond having a formula:
R.sup.3--C.ident.C--H,
where R.sup.3 comprises an optionally substituted C.sub.1-18 alkyl,
optionally substituted C.sub.2-18 alkenyl, optionally substituted
C.sub.2-18 alkynyl, optionally substituted C.sub.6-18 aryl,
optionally substituted C.sub.6-18 aryloxy, optionally substituted
C.sub.7-18 aralkyl, optionally substituted C.sub.7-18 aralkyloxy,
optionally substituted C.sub.3-18 heteroaryl, optionally
substituted C.sub.3-18 heteroaryloxy, optionally substituted
C.sub.4-18 heteroarylalkyl, optionally substituted C.sub.4-18
heteroaralkyloxy, or optionally substituted metallocene. More
specific example of these substrates are described in U.S. patent
application Ser. No. 14/841,964 filed Sep. 1, 2015 (alkynes), now
U.S. Pat. No. 9,556,206, which is incorporated by reference herein
at least for these teachings.
[0126] (4) a terminal olefin has a Formula (V):
##STR00003##
[0127] where p is 0 or 1; R.sup.1 and R.sup.2 independently
comprises H, an optionally substituted C.sub.1-18 alkyl, optionally
substituted C.sub.2-18 alkenyl, optionally substituted C.sub.2-18
alkynyl, optionally substituted C.sub.6-18 aryl, optionally
substituted C.sub.1-18 heteroalkyl, optionally substituted 5-6 ring
membered heteroaryl, optionally substituted 5-6 ring membered
aralkyl, optionally substituted 5-6 ring membered heteroaralkyl, or
optionally substituted metallocene, provided that R.sup.1 and
R.sup.2 are not both H. More specific example of these substrates
are described in U.S. patent application Ser. No. 15/166,405
(terminal olefins), filed May 27, 2016, which is incorporated by
reference herein at least for these teachings.
[0128] (5) an organic alcohol, having a structure of Formula (VIA)
or (VIB).
R.sup.4--OH (VIA)
HO--R.sup.5--OH (VIB),
where R.sup.4 comprises an optionally substituted C.sub.1-24 alkyl,
optionally substituted C.sub.2-24 alkenyl, optionally substituted
C.sub.2-24 alkynyl, optionally substituted C.sub.6-24 aryl,
optionally substituted C.sub.1-24 heteroalkyl, optionally
substituted 5- or 6-ring membered heteroaryl, optionally
substituted C.sub.7-24 aralkyl, optionally substituted
heteroaralkyl, or optionally substituted metallocene; and where
R.sup.5 comprises an optionally substituted C.sub.2-12 alkylene,
optionally substituted C.sub.2-12 alkenylene, optionally
substituted C.sub.6-24 arylene, optionally substituted C.sub.1-12
heteroalkylene, or an optionally substituted 5- or 6-ring membered
heteroarylene. In some Aspect of this Embodiments, the organic
substrate having at least one organic alcohol moiety is or
comprises an optionally substituted catechol moiety or has a
Formula (IV):
##STR00004##
[0129] wherein n is from 0 to 6, preferably 0 or 1;
[0130] R.sup.M and R.sup.N are independently H or methyl
[0131] R.sup.D, R.sup.E, R.sup.F, and R.sup.G are independently H,
C.sub.1-6 alkyl, C.sub.1-6 alkenyl, optionally substituted phenyl,
optionally substituted benzyl, or an optionally substituted 5- or
6-ring membered heteroaryl, wherein the optional substituents are
C.sub.1-3 alkyl, C.sub.1-3 alkoxy, or halo. Within this genus, the
organic substrate includes substituted 1,2-diols, 1,3-diols,
1,4-diols, these being substituted with one or more alkyl and/or
optionally substituted aryl or heteroaryl substituents. The organic
substrate is any one having a terminal olefin as described in U.S.
patent application Ser. No. 15/219,710 (alcohols), filed Jul. 26,
2016, which is incorporated by reference herein at least for these
teachings.
[0132] As shown in the Examples, the present compositions/compounds
also appear to be suitable reagents for the deprotection/cleavage
of amide groups or other acyl protected functional groups (e.g.,
esters). While Example 2.7 shows the exemplary deprotection of
N-benzoylindole, other carbonyl protected amines or alcohols, for
example by acetyl (Ac) as well as benzoyl (Bz) functional groups
may be expected to react similarly.
Terms
[0133] In the present disclosure the singular forms "a," "an," and
"the" include the plural reference, and reference to a particular
numerical value includes at least that particular value, unless the
context clearly indicates otherwise. Thus, for example, a reference
to "a material" is a reference to at least one of such materials
and equivalents thereof known to those skilled in the art.
[0134] When a value is expressed as an approximation by use of the
descriptor "about," it will be understood that the particular value
forms another embodiment. In general, use of the term "about"
indicates approximations that can vary depending on the desired
properties sought to be obtained by the disclosed subject matter
and is to be interpreted in the specific context in which it is
used, based on its function. The person skilled in the art will be
able to interpret this as a matter of routine. In some cases, the
number of significant figures used for a particular value may be
one non-limiting method of determining the extent of the word
"about." In other cases, the gradations used in a series of values
may be used to determine the intended range available to the term
"about" for each value. Where present, all ranges are inclusive and
combinable. That is, references to values stated in ranges include
every value within that range.
[0135] It is to be appreciated that certain features of the
invention which are, for clarity, described herein in the context
of separate embodiments, may also be provided in combination in a
single embodiment. That is, unless obviously incompatible or
specifically excluded, each individual embodiment is deemed to be
combinable with any other embodiment(s) and such a combination is
considered to be another embodiment. Conversely, various features
of the invention that are, for brevity, described in the context of
a single embodiment, may also be provided separately or in any
sub-combination. Finally, while an embodiment may be described as
part of a series of steps or part of a more general structure, each
said step may also be considered an independent embodiment in
itself, combinable with others.
[0136] The transitional terms "comprising," "consisting essentially
of," and "consisting" are intended to connote their generally in
accepted meanings in the patent vernacular; that is, (i)
"comprising," which is synonymous with "including," "containing,"
or "characterized by," is inclusive or open-ended and does not
exclude additional, unrecited elements or method steps; (ii)
"consisting of" excludes any element, step, or ingredient not
specified in the claim; and (iii) "consisting essentially of"
limits the scope of a claim to the specified materials or steps and
those that do not materially affect the basic and novel
characteristic(s) of the claimed invention. Embodiments described
in terms of the phrase "comprising" (or its equivalents), also
provide, as embodiments, those which are independently described in
terms of "consisting of" and "consisting essentially of." For those
embodiments provided in terms of "consisting essentially of," the
basic and novel characteristic(s) is the facile operability of the
methods to provide silylated products at meaningful yields (or the
ability of the systems used in such methods to provide the product
compositions at meaningful yields or the compositions derived
therefrom) using only those active ingredients listed. In those
embodiments that provide a composition consisting essentially of
hydrosilane or organodisilane and strong base, the term refers to
the fact that this composition is present in the absence of
silylatable aromatic, olefinic, or acetylenic substrates.
[0137] The term "meaningful product yields" is intended to reflect
product yields of greater than 20%, but when specified, this term
may also refer to yields of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%,
or 90% or more, relative to the amount of original substrate.
[0138] When a list is presented, unless stated otherwise, it is to
be understood that each individual element of that list, and every
combination of that list, is a separate embodiment. For example, a
list of embodiments presented as "A, B, or C" is to be interpreted
as including the embodiments, "A," "B," "C," "A or B," "A or C," "B
or C," or "A, B, or C." Similarly, a designation such as C.sub.1-3
includes not only C.sub.1-3, but also C.sub.1, C.sub.2, C.sub.3,
C.sub.1-2, C.sub.2-3, and C.sub.1,3, as separate embodiments.
[0139] Throughout this specification, words are to be afforded
their normal meaning, as would be understood by those skilled in
the relevant art. However, so as to avoid misunderstanding, the
meanings of certain terms will be specifically defined or
clarified.
[0140] The term "alkyl" as used herein refers to a linear,
branched, or cyclic saturated hydrocarbon group typically although
not necessarily containing 1 to about 24 carbon atoms, preferably 1
to about 12 carbon atoms, such as methyl, ethyl, n-propyl,
isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, octyl, decyl,
and the like, as well as cycloalkyl groups such as cyclopentyl,
cyclohexyl and the like. Generally, although again not necessarily,
alkyl groups herein contain 1 to about 12 carbon atoms. The term
also includes "lower alkyl" as separate embodiments, which refers
to an alkyl group of 1 to 6 carbon atoms, and the specific term
"cycloalkyl" intends a cyclic alkyl group, typically having 4 to 8,
preferably 5 to 7, carbon atoms. The term "substituted alkyl"
refers to alkyl groups substituted with one or more substituent
groups, and the terms "heteroatom-containing alkyl" and
"heteroalkyl" refer to alkyl groups in which at least one carbon
atom is replaced with a heteroatom. If not otherwise indicated, the
terms "alkyl" and "lower alkyl" include linear, branched, cyclic,
unsubstituted, substituted, and/or heteroatom-containing alkyl and
lower alkyl groups, respectively.
[0141] The term "alkylene" as used herein refers to a difunctional
linear, branched, or cyclic alkyl group, where "alkyl" is as
defined above.
[0142] The term "alkenyl" as used herein refers to a linear,
branched, or cyclic hydrocarbon group of 2 to about 24 carbon atoms
containing at least one double bond, such as ethenyl, n-propenyl,
isopropenyl, n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl,
hexadecenyl, eicosenyl, tetracosenyl, and the like. Preferred
alkenyl groups herein contain 2 to about 12 carbon atoms. The term
also includes "lower alkenyl" as separate embodiments, which refers
to an alkenyl group of 2 to 6 carbon atoms, and the specific term
"cycloalkenyl" intends a cyclic alkenyl group, preferably having 5
to 8 carbon atoms. The term "substituted alkenyl" refers to alkenyl
groups substituted with one or more substituent groups, and the
terms "heteroatom-containing alkenyl" and "heteroalkenyl" refer to
alkenyl groups in which at least one carbon atom is replaced with a
heteroatom. If not otherwise indicated, the terms "alkenyl" and
"lower alkenyl" include linear, branched, cyclic, unsubstituted,
substituted, and/or heteroatom-containing alkenyl and lower alkenyl
groups, respectively.
[0143] The term "alkenylene" as used herein refers to a
difunctional linear, branched, or cyclic alkenyl group, where
"alkenyl" is as defined above.
[0144] The term "alkynyl" as used herein refers to a linear or
branched hydrocarbon group of 2 to about 24 carbon atoms containing
at least one triple bond, such as ethynyl, n-propynyl, and the
like. Preferred alkynyl groups herein contain 2 to about 12 carbon
atoms. The term "lower alkynyl" intends an alkynyl group of 2 to 6
carbon atoms. The term also includes "lower alkynyl" as separate
embodiments, which refers to an alkynyl group substituted with one
or more substituent groups, and the terms "heteroatom-containing
alkynyl" and "heteroalkynyl" refer to alkynyl in which at least one
carbon atom is replaced with a heteroatom. If not otherwise
indicated, the terms "alkynyl" and "lower alkynyl" include a
linear, branched, unsubstituted, substituted, and/or
heteroatom-containing alkynyl and lower alkynyl group,
respectively.
[0145] The term "alkoxy" as used herein intends an alkyl group
bound through a single, terminal ether linkage; that is, an
"alkoxy" group may be represented as --O-alkyl where alkyl is as
defined above. The term also includes "lower alkoxy" as separate
embodiments, which refers to an alkoxy group containing 1 to 6
carbon atoms. Analogously, "alkenyloxy" and "lower alkenyloxy"
respectively refer to an alkenyl and lower alkenyl group bound
through a single, terminal ether linkage, and "alkynyloxy" and
"lower alkynyloxy" respectively refer to an alkynyl and lower
alkynyl group bound through a single, terminal ether linkage.
[0146] The term "aromatic" refers to the ring moieties which
satisfy the Huckel 4n+2 rule for aromaticity, and includes both
aryl (i.e., carbocyclic) and heteroaryl (also called
heteroaromatic) structures, including aryl, aralkyl, alkaryl,
heteroaryl, heteroaralkyl, or alk-heteroaryl moieties, or
pre-polymeric (e.g., monomeric, dimeric), oligomeric or polymeric
analogs thereof.
[0147] The term "aryl" as used herein, and unless otherwise
specified, refers to a carbocyclic aromatic substituent or
structure containing a single aromatic ring or multiple aromatic
rings that are fused together, directly linked, or indirectly
linked (such that the different aromatic rings are bound to a
common group such as a methylene or ethylene moiety). Preferred
aryl groups contain 6 to 24 carbon atoms, and particularly
preferred aryl groups contain 6 to 14 carbon atoms. Exemplary aryl
groups contain one aromatic ring or two fused or linked aromatic
rings, e.g., phenyl, naphthyl, biphenyl, diphenylether,
diphenylamine, benzophenone, and the like. "Substituted aryl"
refers to an aryl moiety substituted with one or more substituent
groups, and the terms "heteroatom-containing aryl" and "heteroaryl"
refer to aryl substituents in which at least one carbon atom is
replaced with a heteroatom, as will be described in further detail
infra.
[0148] Unless otherwise specified, as used herein in the context of
silylation reactions, the term "C--H bond" refers to an acetylenic
or alkynyl C--H bond, a terminal olefinic C--H bond, an aromatic
(aryl or heteroaryl)C--H bond, or C--H bond of an alkyl, alkoxy, or
alkylene group positioned alpha to an aromatic/heteroaromatic ring
system (e.g., benzylic, or 2, 5-dimethylthiophene substrates), such
as previously described in any of the references cited herein
showing the propensity to be silylated using simultaneous mixing of
the precursor substrate, hydrosilane/organosilane, and strong
bases, including hydroxides.
[0149] The term "aryloxy" as used herein refers to an aryl group
bound through a single, terminal ether linkage, wherein "aryl" is
as defined above. An "aryloxy" group may be represented as --O-aryl
where aryl is as defined above. Preferred aryloxy groups contain 6
to 24 carbon atoms, and particularly preferred aryloxy groups
contain 6 to 14 carbon atoms. Examples of aryloxy groups include,
without limitation, phenoxy, o-halo-phenoxy, m-halo-phenoxy,
p-halo-phenoxy, o-methoxy-phenoxy, m-methoxy-phenoxy,
p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy, 3,4,5-trimethoxy-phenoxy,
and the like.
[0150] The term "alkaryl" refers to an aryl group with an alkyl
substituent, and the term "aralkyl" refers to an alkyl group with
an aryl substituent, wherein "aryl" and "alkyl" are as defined
above. Preferred alkaryl and aralkyl groups contain 7 to 24 carbon
atoms, and particularly preferred alkaryl and aralkyl groups
contain 7 to 16 carbon atoms. Alkaryl groups include, for example,
p-methylphenyl, 2,4-dimethylphenyl, p-cyclohexylphenyl, 2,
7-dimethylnaphthyl, 7-cyclooctylnaphthyl,
3-ethyl-cyclopenta-1,4-diene, and the like. Examples of aralkyl
groups include, without limitation, benzyl, 2-phenyl-ethyl,
3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl,
4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl,
4-benzylcyclohexylmethyl, and the like. The terms "alkaryloxy" and
"aralkyloxy" refer to substituents of the formula --OR wherein R is
alkaryl or aralkyl, respectively, as just defined.
[0151] The term "acyl" refers to substituents having the formula
--(CO)-alkyl, --(CO)-aryl, or --(CO)-aralkyl, and the term
"acyloxy" refers to substituents having the formula --O(CO)-alkyl,
--O(CO)-aryl, or --O(CO)-aralkyl, wherein "alkyl," "aryl, and
"aralkyl" are as defined above.
[0152] The terms "cyclic" and "ring" refer to alicyclic or aromatic
groups that may or may not be substituted and/or
heteroatom-containing, and that may be monocyclic, bicyclic, or
polycyclic. The term "alicyclic" is used in the conventional sense
to refer to an aliphatic cyclic moiety, as opposed to an aromatic
cyclic moiety, and may be monocyclic, bicyclic, or polycyclic. The
term "acyclic" refers to a structure in which the double bond is
not contained within a ring structure.
[0153] The terms "halo," "halide," and "halogen" are used in the
conventional sense to refer to a chloro, bromo, fluoro, or iodo
substituent.
[0154] "Hydrocarbyl" refers to univalent hydrocarbyl radicals
containing 1 to about 30 carbon atoms, preferably 1 to about 24
carbon atoms, most preferably 1 to about 12 carbon atoms, including
linear, branched, cyclic, saturated, and unsaturated species, such
as alkyl groups, alkenyl groups, aryl groups, and the like. The
term "lower hydrocarbyl" intends a hydrocarbyl group of 1 to 6
carbon atoms, preferably 1 to 4 carbon atoms, and the term
"hydrocarbylene" intends a divalent hydrocarbyl moiety containing 1
to about 30 carbon atoms, preferably 1 to about 24 carbon atoms,
most preferably 1 to about 12 carbon atoms, including linear,
branched, cyclic, saturated and unsaturated species. The term
"lower hydrocarbylene" intends a hydrocarbylene group of 1 to 6
carbon atoms. "Substituted hydrocarbyl" refers to hydrocarbyl
substituted with one or more substituent groups, and the terms
"heteroatom-containing hydrocarbyl" and "heterohydrocarbyl" refer
to hydrocarbyl in which at least one carbon atom is replaced with a
heteroatom. Similarly, "substituted hydrocarbylene" refers to
hydrocarbylene substituted with one or more substituent groups, and
the terms "heteroatom-containing hydrocarbylene" and
heterohydrocarbylene" refer to hydrocarbylene in which at least one
carbon atom is replaced with a heteroatom. Unless otherwise
indicated, the term "hydrocarbyl" and "hydrocarbylene" are to be
interpreted as including substituted and/or heteroatom-containing
hydrocarbyl and hydrocarbylene moieties, respectively.
[0155] The term "heteroatom-containing" as in a
"heteroatom-containing hydrocarbyl group" refers to a hydrocarbon
molecule or a hydrocarbyl molecular fragment in which one or more
carbon atoms is replaced with an atom other than carbon, e.g.,
nitrogen, oxygen, sulfur, phosphorus or silicon, typically
nitrogen, oxygen or sulfur. Similarly, the term "heteroalkyl"
refers to an alkyl substituent that is heteroatom-containing, the
term "heterocyclic" refers to a cyclic substituent that is
heteroatom-containing, the terms "heteroaryl" and heteroaromatic"
respectively refer to "aryl" and "aromatic" substituents that are
heteroatom-containing, and the like. It should be noted that a
"heterocyclic" group or compound may or may not be aromatic, and
further that "heterocycles" may be monocyclic, bicyclic, or
polycyclic as described above with respect to the term "aryl."
Examples of heteroalkyl groups include alkoxyaryl,
alkylsulfanyl-substituted alkyl, N-alkylated amino alkyl, and the
like. Non-limiting examples of heteroaryl substituents include
pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl,
pyrimidinyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, etc., and
examples of heteroatom-containing alicyclic groups are pyrrolidino,
morpholino, piperazino, piperidino, etc.
[0156] As used herein, the terms "substrate" or "organic substrate"
are intended to connote both discrete small molecules (sometimes
described as "organic compounds") and oligomers and polymers
containing a C--H group capable of silylation under the described
reaction conditions. The term "aromatic moieties" is intended to
refer to those portions of the compounds, pre-polymers (i.e.,
monomeric compounds capable of polymerizing), oligomers, or
polymers having at least one of the indicated aromatic structures.
Where shown as structures, the moieties contain at least that which
is shown, as well as containing further functionalization,
substituents, or both, including but not limited to the
functionalization described as "Fn" herein.
[0157] By "substituted" as in "substituted hydrocarbyl,"
"substituted alkyl," "substituted aryl," and the like, as alluded
to in some of the aforementioned definitions, is meant that in the
hydrocarbyl, alkyl, aryl, heteroaryl, or other moiety, at least one
hydrogen atom bound to a carbon (or other) atom is replaced with
one or more non-hydrogen substituents. Examples of such
substituents include, without limitation: functional groups
referred to herein as "Fn," such as halo (e.g., F, Cl, Br, I),
hydroxyl, sulfhydryl, C.sub.1-C.sub.24 alkoxy, C.sub.2-C.sub.24
alkenyloxy, C.sub.2-C.sub.24 alkynyloxy, C.sub.5-C.sub.24 aryloxy,
C.sub.6-C.sub.24 aralkyloxy, C.sub.6-C.sub.24 alkaryloxy, acyl
(including C.sub.1-C.sub.24 alkylcarbonyl (--CO-alkyl) and
C.sub.6-C.sub.24 arylcarbonyl (--CO-aryl)), acyloxy (--O-acyl,
including C.sub.2-C.sub.24 alkylcarbonyloxy (--O--CO-- alkyl) and
C.sub.6-C.sub.24 arylcarbonyloxy (--O--CO-aryl)), C.sub.2-C.sub.24
alkoxycarbonyl ((CO)--O-alkyl), C.sub.6-C.sub.24 aryloxycarbonyl
(--(CO)--O-aryl), halocarbonyl (--CO)--X where X is halo),
C.sub.2-C.sub.24 alkylcarbonato (--O--(C.sub.0)--O-alkyl),
C.sub.6-C.sub.24 arylcarbonato (--O--(CO)--O-aryl), carboxy
(--COOH), carboxylato (--COO--), carbamoyl (--(CO)--NH.sub.2),
mono-(C.sub.1-C.sub.24 alkyl)-substituted carbamoyl
(--(CO)NH(C.sub.1-C.sub.24 alkyl)), di-(C.sub.1-C.sub.24
alkyl)-substituted carbamoyl (--(CO)--N(C.sub.1-C.sub.24
alkyl).sub.2), mono-(C.sub.1-C.sub.24 haloalkyl)-substituted
carbamoyl (--(CO)--NH(C.sub.1-C.sub.24 alkyl)),
di-(C.sub.1-C.sub.24 haloalkyl)-substituted carbamoyl
(--(CO)--N(C.sub.1-C.sub.24 alkyl).sub.2), mono-(C.sub.5-C.sub.24
aryl)-substituted carbamoyl (--(CO)--NH-aryl), di-(C.sub.5-C.sub.24
aryl)substituted carbamoyl (--(CO)--N(C.sub.5-C.sub.24
aryl).sub.2), di-N--(C.sub.1-C.sub.24 alkyl), N--(C.sub.5-C.sub.24
aryl)-substituted carbamoyl, thiocarbamoyl (--(CS)--NH.sub.2),
mono-(C.sub.1-C.sub.24 alkyl)-substituted thiocarbamoyl
(--(CO)--NH(C.sub.1-C.sub.24 alkyl)), di-(C.sub.1-C.sub.24
alkyl)-substituted thiocarbamoyl (--(CO)--N(C.sub.1-C.sub.24
alkyl).sub.2), mono-(C.sub.5-C.sub.24 aryl)substituted
thiocarbamoyl (--(CO)--NH-aryl), di-(C.sub.5-C.sub.24
aryl)-substituted thiocarbamoyl (--(CO)--N(C.sub.5-C.sub.24
aryl).sub.2), di-N--(C.sub.1-C.sub.24 alkyl), N--(C.sub.5-C.sub.24
aryl)-substituted thiocarbamoyl, carbamido (--NH--(CO)--NH.sub.2),
cyano (--C.ident.N), cyanato (--O--C.dbd.N), thiocyanato
(--S--C.dbd.N), formyl (--(CO)--H), thioformyl (--(CS)--H), amino
(--NH.sub.2), mono-(C.sub.1-C.sub.24 alkyl)-substituted amino,
di-(C.sub.1-C.sub.24 alkyl)-substituted amino,
mono-(C.sub.5-C.sub.24 aryl)substituted amino, di-(C.sub.5-C.sub.24
aryl)-substituted amino, C.sub.1-C.sub.24 alkylamido
(--NH--(CO)-alkyl), C.sub.6-C.sub.24 arylamido (--NH--(CO)-aryl),
imino (--CR.dbd.NH where R=hydrogen, C.sub.1-C.sub.24 alkyl, C5-C24
aryl, C.sub.6-C.sub.24 alkaryl, C.sub.6-C.sub.24 aralkyl, etc.),
C.sub.2-C.sub.20 alkylimino (--CR.dbd.N(alkyl), where R=hydrogen,
C.sub.1-C.sub.24 alkyl, C.sub.5-C.sub.24 aryl, C.sub.6-C.sub.24
alkaryl, C.sub.6-C.sub.24 aralkyl, etc.), arylimino
(--CR.dbd.N(aryl), where R=hydrogen, C.sub.1-C.sub.20 alkyl,
C.sub.5-C.sub.24 aryl, C.sub.6-C.sub.24 alkaryl, C.sub.6-C.sub.24
aralkyl, etc.), nitro (--NO.sub.2), nitroso (--NO), sulfo
(--SO.sub.2OH), sulfonate (SO.sub.2O--), C.sub.1-C.sub.24
alkylsulfanyl (--S-alkyl; also termed "alkylthio"),
C.sub.5-C.sub.24 arylsulfanyl (--S-aryl; also termed "arylthio"),
C.sub.1-C.sub.24 alkylsulfinyl (--(SO)-alkyl), C.sub.5-C.sub.24
arylsulfinyl (--(SO)-aryl), C.sub.1-C.sub.24 alkylsulfonyl
(--SO.sub.2-alkyl), C.sub.1-C.sub.24
monoalkylaminosulfonyl-SO.sub.2--N(H) alkyl), C.sub.1-C.sub.24
dialkylaminosulfonyl-SO.sub.2--N(alkyl).sub.2, C.sub.5-C.sub.24
arylsulfonyl (--SO.sub.2-aryl), boryl (--BH.sub.2), borono
(--B(OH).sub.2), boronato (--B(OR).sub.2 where R is alkyl or other
hydrocarbyl), phosphono (--P(O)(OH).sub.2), phosphonato
(--P(O)(O).sub.2), phosphinato (P(O)(O--)), phospho (--PO.sub.2),
and phosphine (--PH2); and the hydrocarbyl moieties
C.sub.1-C.sub.24 alkyl (preferably C.sub.1-C.sub.12, alkyl, more
preferably C.sub.1-C.sub.6 alkyl), C.sub.2-C.sub.24 alkenyl
(preferably C.sub.2-C.sub.12 alkenyl, more preferably
C.sub.2-C.sub.6 alkenyl), C.sub.2-C.sub.24 alkynyl (preferably
C.sub.2-C.sub.12 alkynyl, more preferably C.sub.2-C.sub.6 alkynyl),
C.sub.5-C.sub.24 aryl (preferably C.sub.5-C.sub.24 aryl),
C.sub.6-C.sub.24 alkaryl (preferably C.sub.6-C.sub.16 alkaryl), and
C.sub.6-C.sub.24 aralkyl (preferably C.sub.6-C.sub.16 aralkyl).
Within these substituent structures, the "alkyl," "alkylene,"
"alkenyl," "alkenylene," "alkynyl," "alkynylene," "alkoxy,"
"aromatic," "aryl," "aryloxy," "alkaryl," and "aralkyl" moieties
may be optionally fluorinated or perfluorinated. Additionally,
reference to alcohols, aldehydes, amines, carboxylic acids,
ketones, or other similarly reactive functional groups also
includes their protected analogs. For example, reference to hydroxy
or alcohol also includes those substituents wherein the hydroxy is
protected by acetyl (Ac), benzoyl (Bz), benzyl (Bn),
.beta.-Methoxyethoxymethyl ether (MEM), dimethoxytrityl,
[bis-(4-methoxyphenyl)phenylmethyl] (DMT), methoxymethyl ether
(MOM), methoxytrityl [(4-methoxyphenyl)diphenylmethyl, MMT),
p-methoxybenzyl ether (PMB), methylthiomethyl ether, pivaloyl
(Piv), tetrahydropyranyl (THP), tetrahydrofuran (THF), trityl
(triphenylmethyl, Tr), silyl ether (most popular ones include
trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS),
tri-iso-propylsilyloxymethyl (TOM), and triisopropylsilyl (TIPS)
ethers), ethoxyethyl ethers (EE). Reference to amines also includes
those substituents wherein the amine is protected by a BOC glycine,
carbobenzyloxy (Cbz), p-methoxybenzyl carbonyl (Moz or MeOZ),
tert-butyloxycarbonyl (BOC), 9-fluorenylmethyloxycarbonyl (FMOC),
acetyl (Ac), benzoyl (Bz), benzyl (Bn), carbamate, p-methoxybenzyl
(PMB), 3,4-dimethoxybenzyl (DMPM), p-methoxyphenyl (PMP), tosyl
(Ts) group, or sulfonamide (Nosyl & Nps) group. Reference to
substituent containing a carbonyl group also includes those
substituents wherein the carbonyl is protected by an acetal or
ketal, acylal, or diathane group. Reference to substituent
containing a carboxylic acid or carboxylate group also includes
those substituents wherein the carboxylic acid or carboxylate group
is protected by its methyl ester, benzyl ester, tert-butyl ester,
an ester of 2,6-disubstituted phenol (e.g. 2,6-dimethylphenol,
2,6-diisopropylphenol, 2,6-di-tert-butylphenol), a silyl ester, an
orthoester, or an oxazoline. Preferred substituents are those
identified herein as not or less affecting the silylation
chemistries, for example, including those substituents comprising
alkyls; alkoxides, aryloxides, aralkylalkoxides, protected carbonyl
groups; aryls optionally substituted with F, Cl, --CF.sub.3;
epoxides; N-alkyl aziridines; cis- and trans-olefins; acetylenes;
pyridines, primary, secondary and tertiary amines; phosphines; and
hydroxides.
[0158] By "functionalized" as in "functionalized hydrocarbyl,"
"functionalized alkyl," "functionalized olefin," "functionalized
cyclic olefin," and the like, is meant that in the hydrocarbyl,
alkyl, aryl, heteroaryl, olefin, cyclic olefin, or other moiety, at
least one hydrogen atom bound to a carbon (or other) atom is
replaced with one or more functional groups such as those described
herein and above. The term "functional group" is meant to include
any of the substituents described herein with the ambit of
"Fn.".
[0159] In addition, the aforementioned functional groups may, if a
particular group permits, be further substituted with one or more
additional functional groups or with one or more hydrocarbyl
moieties such as those specifically enumerated above. Analogously,
the above-mentioned hydrocarbyl moieties may be further substituted
with one or more functional groups or additional hydrocarbyl
moieties such as those specifically enumerated.
[0160] "Optional" or "optionally" means that the subsequently
described circumstance may or may not occur, so that the
description includes instances where the circumstance occurs and
instances where it does not. For example, the phrase "optionally
substituted" means that a non-hydrogen substituent may or may not
be present on a given atom or organic moiety, and, thus, the
description includes structures wherein a non-hydrogen substituent
is present and structures wherein a non-hydrogen substituent is not
present.
[0161] As used herein, the terms "organosilane" or "hydrosilane"
may be used interchangeably and refer to a compound or reagent
having at least one silicon-hydrogen (Si--H) bond and preferably at
least one carbon-containing moiety. The hydrosilane may further
contain a silicon-carbon, a silicon-oxygen (i.e., encompassing the
term "organosiloxane"), a silicon-nitrogen bond, or a combination
thereof, and may be monomeric, or contained within an oligomeric or
polymeric framework, including being tethered to a heterogeneous or
homogeneous support structure. The term "hydrosilane" also include
deuterosilanes, in which the corresponding S--H bond is enriched in
Si-D cogeners.
[0162] As used herein, the terms "organodisilane" and "disilane"
are used interchangeably and refer to a compound or reagent having
at least one Si--Si bond. These terms include those embodiments
where the disilane contains at least one Si--H bond and those
embodiments wherein the disilane no silicon-hydrogen (Si--H) bonds.
While the present disclosure refers to the reaction of compounds
having Si--Si bonds, the optional presence of Si--H bonds may allow
the reaction to proceed through reaction manifolds also described
for silylations using organosilane reagents. Such a Si--H pathway
is not required for silylation to proceed in the disilane systems,
but where the silylating reagent contains both a Si--Si and Si--H
bond, the reactions may operate in parallel with one another. The
organodisilane may further contain a silicon-carbon, a
silicon-oxygen, a silicon-nitrogen bond, or a combination thereof,
and may be monomeric, or contained within an oligomeric or
polymeric framework, including being tethered to a heterogeneous or
homogeneous support structure.
[0163] As used herein, unless explicitly stated to the contrary,
the organosilanes or organodisilanes are intended to refer to
materials that contain no Si-halogen bonds. However, in some
embodiments, the organosilanes or organodisilanes may contain a
Si-halogen bond.
[0164] As used herein, the terms "silylating" or "silylation" refer
to the forming of carbon-silicon bonds, in a position previously
occupied by a carbon-hydrogen bond. Silylating may be seen as
dehydrogenative coupling of a C--H and Si--H bond or a C--H and
Si--Si bond to form a C--Si bond.
[0165] As used herein, the term "substantially free of a
transition-metal compound" is intended to reflect that the system
is stable (in the context of the preconditioned compositions) and
effective for its intended purpose of silylating the C--H bonds
under the relatively mild conditions described herein(in the case
of the methods), even in the absence of any exogenous (i.e.,
deliberately added or otherwise) transition-metal catalyst(s).
While certain embodiments provide that transition metals, including
those capable of catalyzing silylation reactions, may be present
within the systems or methods described herein at levels normally
associated with such catalytic activity (for example, in the case
where the substrates comprise metallocenes), the presence of such
metals (either as catalysts or spectator compounds) is not required
and in many cases is not desirable. As such, in many preferred
embodiments, the system and methods are "substantially free of
transition-metal compounds." Unless otherwise stated, then, the
term "substantially free of a transition-metal compound" is defined
to reflect that the total level of transition metal within the
silylating system, independently or in the presence of organic
substrate, is less than about 5 ppm, as measured by ICP-MS. When
expressly stated as such, additional embodiments also provide that
the concentration of transition metals is less than about 10 wt %,
5 wt %, 1 wt %, 100 ppm, 50 ppm, 30 ppm, 25 ppm, 20 ppm, 15 ppm, 10
ppm, or 5 ppm to about 1 ppm or 0 ppm. As used herein, the term
"transition metal" is defined to include d-block elements, for
example Ag, Au, Co, Cr, Rh, Ir, Fe, Ru, Os, Ni, Pd, Pt, Cu, Zn, or
combinations thereof. In further specific independent embodiments,
the concentration of Ni, as measured by ICP-MS, is less than 25
ppm, less than 10 ppm, less than 5 ppm, or less than 1 ppm.
[0166] Likewise, the term "substantial absence of a heteroaromatic,
olefinic, or acetylenic substrate capable of C--H silylation" is
intended to reflect that the compounds or preconditioned
compositions contain substoichiometric amounts of these materials
relative to the amount of precursor hydrosilane, or the absence of
added substrate materials, and preferably no added substrates
capable of being otherwise silylated at a C--H position, under the
stated conditions. Such unsaturated organic substrate especially
refer to the heteraromatic substrate, but also the terminal
olefinic or acetylylinic substrates described in the patent
applications cited elsewhere herein.
[0167] While it may not be necessary to limit the system's exposure
to water and oxygen, the presence of these materials may materially
affect the stability of the preconditioned mixtures, the hydride
compounds, or the rate of the subsequent silylation reactions, for
example by the formation of free radical intermediates. In some
embodiments, the chemical systems and the methods are substantially
free of water, oxygen, or both water and oxygen. In other
embodiments, air and/or water are present. Unless otherwise
specified, the term "substantially free of water" refers to levels
of water less than about 500 ppm and "substantially free of oxygen"
refers to oxygen levels corresponding to partial pressures less
than 1 torr. Where stated, additional independent embodiments may
provide that "substantially free of water" refers to levels of
water less than 1.5 wt %, 1 wt %, 0.5 wt %, 1000 ppm, 500 ppm, 250
ppm, 100 ppm, 50 ppm, 10 ppm, or 1 ppm and "substantially free of
oxygen" refers to oxygen levels corresponding to partial pressures
less than 50 torr, 10 torr, 5 torr, 1 torr, 500 millitorr, 250
millitorr, 100 millitorr, 50 millitorr, or 10 millitorr. In the
General Procedure described herein, deliberate efforts were made to
exclude both water and oxygen, unless otherwise specified.
[0168] The term "terminally silylated olefinic product" refers to
an olefinic product of the reactions as described herein, and
includes terminally substituted vinyl silanes or allylic silanes.
The term "terminally silylated olefinic moiety" refers to the silyl
moiety of the terminally silylated olefinic product, whether the
product is an allylic or vinyl silyl compound. The term "terminally
hydrosilylated product" refers to a product in wherein the silyl
group is positioned at a terminal position of an ethylene linkage,
typically the result of an anti-Markovnikov hydrosilylation
addition to a vinyl aromatic substrate.
[0169] The following listing of Embodiments is intended to
complement, rather than displace or supersede, the previous
descriptions.
[0170] Embodiment 1. A composition prepared by preconditioning a
mixture of: [0171] (a) a precursor hydrosilane or organodisilane;
and [0172] (b) a base comprising or consisting essentially of
potassium hydroxide, a potassium alkoxide, a potassium silanolate
(e.g., KOTMS), rubidium hydroxide, a rubidium alkoxide, a rubidium
silanolate, cesium hydroxide, a cesium alkoxide, a cesium
silanolate, a potassium amide (e.g., potassium bis(trimethylsilyl)
amide), a potassium graphite (e.g., KC.sub.8), or a combination
thereof;
[0173] the preconditioning comprising or consisting essentially of
holding the mixture of combined hydrosilane and the base at
conditions sufficient to produce the composition capable of
initiating measurable silylation of 1-methyl indole at a
temperature of 45.degree. C. (or less) with an induction period of
less than 30, 25, 20, 15, 10, 5, or 1 minutes. In certain Aspects
of this Embodiment, the composition is free of added
heteroaromatic, olefinic, or acetylenic substrates.
[0174] Embodiment 2. A composition comprising a Si--H-based species
derived or derivable from the preconditioning reaction as described
in Embodiment 1 between: [0175] (a) a precursor hydrosilane; and
[0176] (b) a base comprising or consisting essentially of potassium
hydroxide, a potassium alkoxide, a potassium silanolate (e.g.,
KOTMS), rubidium hydroxide, a rubidium alkoxide, a rubidium
silanolate, cesium hydroxide, a cesium alkoxide, a cesium
silanolate, a potassium amide (e.g., potassium bis(trimethylsilyl)
amide), or a combination thereof; and
[0177] wherein the precursor hydrosilane exhibits an absorption
peak in the Si--H stretching region of infrared spectrum and the
Si--H-based species exhibits an absorption peak in the Si--H
stretching region of an infrared spectrum that is of lower energy
than the absorption peak of the precursor hydrosilane, when
evaluated under comparable conditions. In some Aspects of this
Embodiment, the Si--H-based species is or comprises an
hypercoordinated silicon species containing a Si--H bond. In
certain Aspects of this Embodiment, the composition is free of
added heteroaromatic, olefinic, or acetylenic substrates. The term
"derivable" connotes that the composition may be derived, but is
not necessarily derived, from the reaction between the precursor
hydrosilane and the base.
[0178] Embodiment 3. The composition of Embodiment 1 or 2, wherein
the composition further comprises a solvent. In other Aspects of
this Embodiment, the composition is solvent-free (i.e., the
hydrosilane or organodisilane and the base are present as a neat
mixture). In some Aspects of this Embodiment, the composition is a
solution comprising a hydrocarbon solvent. In some preferred
Aspects of this Embodiment, the composition is a solution
comprising an oxygen donor-containing solvent, such as described
elsewhere herein, preferably an ether-type solvent, more preferably
an optionally substituted tetrahydrofuran, for example 2-methyl
tetrahydrofuran.
[0179] Embodiment 4. The composition of any one of Embodiment 1 to
3, wherein the base comprises potassium hydroxide, rubidium
hydroxide, or cesium hydroxide.
[0180] Embodiment 5. The composition of any one of Embodiments 1 to
3, wherein the base comprises potassium hydroxide.
[0181] Embodiment 6. The composition of any one of Embodiment 1 to
3, wherein the base comprises a potassium alkoxide, a rubidium
alkoxide, or a cesium alkoxide.
[0182] Embodiment 7. The composition of any one of Embodiments 1 to
3, wherein the base comprises a potassium alkoxide.
[0183] Embodiment 8. The composition of any one of Embodiments 1,
6, or 7, wherein the alkoxide comprises a C.sub.1-6 alkoxide, such
as methoxide, ethoxide, propoxide, or butoxide, preferably
tert-butyl butoxide.
[0184] Embodiment 9. The composition of any one of Embodiments 1 to
8, wherein the precursor hydrosilane is of the Formula (I) or
Formula (II):
(R).sub.3-mSi(H).sub.m+1 (I)
(R).sub.3-m(H).sub.mSi--Si(R).sub.2-m(H).sub.m+1 (II)
where: m is independently 0, 1, or 2; and each R is independently
optionally substituted C.sub.1-24 alkyl or heteroalkyl, optionally
substituted C.sub.2-24 alkenyl, optionally substituted C.sub.2-24
alkynyl, optionally substituted C.sub.6-12 aryl, C.sub.3-12
heteroaryl, optionally substituted C.sub.7-13 alkaryl, optionally
substituted C.sub.4-12 heteroalkaryl, optionally substituted
C.sub.7-13 aralkyl, optionally substituted C.sub.4-12
heteroaralkyl, optionally substituted --O--C.sub.1-24 alkyl,
optionally substituted C.sub.6-12 aryloxy, optionally substituted
C.sub.3-12 heteroaryloxy, optionally substituted C.sub.7-13
alkaryloxy, optionally substituted C.sub.4-12 heteroalkaryloxy,
optionally substituted C.sub.6-12 aralkoxy, or C.sub.4-12
heteroaralkoxy, and, if substituted, the substituents may be
phosphonato, phosphoryl, phosphanyl, phosphino, sulfonato,
C.sub.1-C.sub.20 alkylsulfanyl, C.sub.5-C.sub.20 arylsulfanyl,
C.sub.1-C.sub.20 alkylsulfonyl, C.sub.5-C.sub.20 arylsulfonyl,
C.sub.1-C.sub.20 alkylsulfinyl, 5 to 12 ring-membered arylsulfinyl,
sulfonamido, amino, amido, imino, nitro, nitroso, hydroxyl,
C.sub.1-C.sub.20 alkoxy, C.sub.5-C.sub.20 aryloxy, C.sub.2-C.sub.20
alkoxycarbonyl, C.sub.5-C.sub.20 aryloxycarbonyl, carboxyl,
carboxylato, mercapto, formyl, C.sub.1-C.sub.20 thioester, cyano,
cyanato, thiocyanato, isocyanate, thioisocyanate, carbamoyl, epoxy,
styrenyl, silyl, silyloxy, silanyl, siloxazanyl, boronato, boryl,
or halogen, or a metal-containing or metalloid-containing group,
where the metalloid is Sn or Ge, where the substituents may
optionally provide a tether to an insoluble or sparingly soluble
support media comprising alumina, silica, or carbon. In certain
Aspects of this Embodiment, the precursor organodisilane is of the
Formula (III)
(R').sub.3Si--Si(R').sub.3 (III)
where R' is R, as defined above, or may additionally comprise
optionally substituted alkoxy or aryloxy moieties or
trimethylsiloxy. In other Aspects of this Embodiment, R or R' is
independently an optionally substituted alkyl, alkenyl, alkynyl,
aryl, and/or heteroaryl moiety, the specifics of which are further
described elsewhere. R' may also independently comprise optionally
substituted alkoxy or aryloxy moieties or trimethylsiloxy.
[0185] Embodiment 10. The composition of any one of Embodiments 1
to 9, wherein the at least one hydrosilane is (R).sub.3SiH or
(R).sub.2SiH.sub.2, where R is independently at each occurrence
C.sub.1-6 alkyl, phenyl, tolyl, or pyridinyl. In certain Aspects of
this Embodiment, R is independently at each occurrence methyl,
ethyl, propyl, butyl, propyl, phenyl, biphenyl, benzyl, or
pyridinyl, for example EtMe.sub.2SiH, PhMe.sub.2SiH, BnMe.sub.2SiH,
(n-Bu).sub.3SiH, Et.sub.2SiH.sub.2, Me.sub.3SiH, Et.sub.3SiH,
n-Pr.sub.3SiH, i-Pr.sub.3SiH, n-Bu.sub.3SiH, sec-Bu.sub.3SiH,
tert-Bu.sub.3SiH, Me.sub.2(pyridinyl)SiH, or
Me.sub.3Si--SiMe.sub.2H. In certain Aspects of this Embodiment,
these substituents are optionally substituted.
[0186] Embodiment 11. The composition of Embodiment 10, that is a
solution, wherein the base comprises potassium tert-butoxide.
[0187] Embodiment 12. The composition of any one of Embodiments 1
to 11, wherein the composition contains no added transition metal
or transition metal species. In certain Aspects of this Embodiment,
transition metals or transition metal species are present at less
than 1%, 1000 ppm, 100 ppm, 50 ppm, or 10 ppm, based on the total
weight of the composition.
[0188] Embodiment 13. The composition of any one of Embodiments 1
to 11, wherein the composition is an ether-based solution, most
preferably tetrahydrofuran or 2-methyl-tetrahydrofuran.
[0189] Embodiment 14. The composition of Embodiment 13, which in
tetrahydrofuran further exhibits an electron paramagnetic resonance
(EPR) signal in THF centered at g=2.0007 substantially as shown in
FIG. 3.
[0190] Embodiment 15. A compound, or a composition comprising the
compound itself, having an optionally solvated silicon hydride
structure of Formula (IV):
##STR00005##
[0191] or a geometric isomer thereof, wherein [0192] M.sup.+ is or
comprises a cation comprising potassium, rubidium, cesium, or a
combination thereof; [0193] --OR.sup.B is or comprises hydroxide,
an alkoxide, an alkyl silanolate; or a combination thereof; and
[0194] --R.sup.S is or comprises H, --R, or --Si(R).sub.3-mH.sub.m,
or a combination thereof [0195] where m is and R is as described
elsewhere herein; or an isomer thereof.
[0196] Embodiment 16. A compound that is the addition product of
(a) potassium hydroxide, a potassium alkoxide, a potassium
silanolate, rubidium hydroxide, a rubidium alkoxide, a rubidium
silanolate, cesium hydroxide, a cesium alkoxide, a cesium
silanolate, or a combination thereof with (b) a precursor
hydrosilane of Formula (I) or (II), or any of the individual
precursor hydrosilanes as described elsewhere herein.
[0197] Embodiment 17. A compound or composition of any one of
Embodiments 1 to 16 that is free of added heteroaromatic, olefinic,
or acetylenic substrates. In certain Aspects of this Embodiment,
the term "free" connotes free of added substrates.
[0198] Embodiment 18. A method comprising silylating an organic
substrate having a C--H bond or an alcoholic O--H bond, the method
comprising contacting the organic substrate with a composition or
compound of any one of Embodiments 1 to 17;
[0199] wherein the contacting results in the formation of a C--Si
bond in the position previously occupied by the C--H bond, or the
formation of an O--Si bond in the position previously occupied by
the O--H bond;
[0200] wherein the C--H bond is:
[0201] (a) located on a heteroaromatic moiety;
[0202] (b) located on an alkyl, alkoxy, or alkylene moiety
positioned alpha to an aryl or heteroaryl moiety;
[0203] (c) an alkynyl C--H bond; or
[0204] (d) a terminal olefinic C--H bond; and wherein the
preconditioned mixture is able to initiate measurable silylation of
1-methyl indole at a temperature of 45.degree. C. (or less) with an
induction period of less than 30, 25, 20, 15, 10, 5, or 1 minutes.
Each of the substrates or classes substrates is considered an
independent Embodiment. In certain individual Aspects of this
Embodiment, the precursor hydrosilane is a compound of Formula (I)
or (II), or any individual hydrosilane as described herein.
[0205] Embodiment 19. A method comprising silylating at least one
organic substrate containing a C--H bond or --OH bond, the method
comprising contacting the organic substrate with [0206] (a) a
precursor hydrosilane; and [0207] (b) a base comprising or
consisting essentially of cesium hydroxide, rubidium hydroxide,
KC.sub.8, or a combination thereof; [0208] wherein the C--H bond
is: [0209] (a) located on a heteroaromatic moiety; [0210] (b)
located on an alkyl, alkoxy, or alkylene moiety positioned alpha to
an aryl or heteroaryl moiety; [0211] (c) an alkynyl C--H bond; or
[0212] (d) a terminal olefinic C--H bond; and
[0213] wherein the contacting results in the formation of a C--Si
bond in the position previously occupied by the C--H bond or an
O--Si bond in the position previously occupied by the O--H bond.
Each of the substrates or classes of these substrates is considered
an independent Embodiment. In certain individual Aspects of this
Embodiment, the precursor hydrosilane is a compound of Formula (I)
or (II), or any individual hydrosilane as described herein. In
other individual Aspects of this Embodiment, the precursor
organodisilane is a compound of Formula (III), or any individual
hydrosilane as described herein
[0214] Embodiment 20. The method of Embodiment 19, wherein the
precursor hydrosilane or organodisilane and the base are
preconditioned before contacting with the organic substrate, the
preconditioning comprising holding a mixture comprising the
precursor hydrosilane and the base at one or more temperatures in a
range of from about 25.degree. C. to about 125.degree. C. for a
time in a range of from about 30 minutes to about 24 hours, the
combination of time and temperature being sufficient to produce the
composition capable of initiating measurable silylation of 1-methyl
indole at a temperature of 45.degree. C. (or less) with an
induction period of less than 30, 25, 20, 15, 10, 5, or 1
minutes.
[0215] Embodiment 21. The method of any one of Embodiments 18 to
20, wherein the organic substrate is a heteroaromatic moiety, for
example comprising an optionally substituted furan, pyrrole,
thiophene, pyrazole, imidazole, triazole, isoxazole, oxazole,
thiazole, isothiazole, oxadiazole, pyridine, pyridazine,
pyrimidine, pyrazine, triazone, benzofuran, benzothiophene,
isobenzofuran, isobenzothiophene, indole, isoindole, indolizine,
indazole, azaindole, benzisoxazole, benzoxazole, quinoline,
isoquinoline, cinnoline, quinazoline, naphthyridine,
2,3-dihydrobenzofuran, 2,3-dihydrobenzopyrrole,
2,3-dihydrobenzothiophene, dibenzofuran, xanthene, dibenzopyrol, or
dibenzothiophene moiety. In certain Aspects of this Embodiment, the
organic substrate is a heteroaryl substrate as described in U.S.
patent application Ser. No. 14/043,929, filed Oct. 2, 2013
(heteroaromatics with alkoxides), now U.S. Pat. No. 9,000,167 or
Ser. No. 14/818,417, filed Aug. 5, 2015 (heteroaromatics with
hydroxides), each of which is incorporated by reference herein at
least for these teachings.
[0216] Embodiment 22. The method of any one of Embodiments 18 to
20, wherein the organic substrate comprises as alkynyl C--H bond
having a formula:
R.sup.3--C.ident.C--H,
where R.sup.3 comprises an optionally substituted C.sub.1-18 alkyl,
optionally substituted C.sub.2-18 alkenyl, optionally substituted
C.sub.2-18 alkynyl, optionally substituted C.sub.6-18 aryl,
optionally substituted C.sub.6-18 aryloxy, optionally substituted
C.sub.7-18 aralkyl, optionally substituted C.sub.7-18 aralkyloxy,
optionally substituted C.sub.3-18 heteroaryl, optionally
substituted C.sub.3-18 heteroaryloxy, optionally substituted
C.sub.4-18 heteroarylalkyl, optionally substituted C.sub.4-18
heteroaralkyloxy, or optionally substituted metallocene. In certain
Aspects of this Embodiment, the organic substrate is an alkyne as
described in U.S. patent application Ser. No. 14/841,964 filed Sep.
1, 2015 (alkynes), now U.S. Pat. No. 9,556,206, which is
incorporated by reference herein at least for these teachings.
[0217] Embodiment 23. The method of any one of Embodiments 18 to
20, wherein the at least one organic substrate comprises a terminal
olefin has a Formula (V):
##STR00006##
[0218] where p is 0 or 1; R.sup.1 and R.sup.2 independently
comprises H, an optionally substituted C.sub.1-18 alkyl, optionally
substituted C.sub.2-18 alkenyl, optionally substituted C.sub.2-18
alkynyl, optionally substituted C.sub.6-18 aryl, optionally
substituted C.sub.1-18 heteroalkyl, optionally substituted 5-6 ring
membered heteroaryl, optionally substituted 5-6 ring membered
aralkyl, optionally substituted 5-6 ring membered heteroaralkyl, or
optionally substituted metallocene, provided that R.sup.1 and
R.sup.2 are not both H. In certain Aspects of this Embodiment, the
organic substrate is any one having a terminal olefin as described
in U.S. patent application Ser. No. 15/166,405 (terminal olefins),
filed May 27, 2016, which is incorporated by reference herein at
least for these teachings.
[0219] Embodiment 23. The method of any one of Embodiments 18 to
20, wherein the at least one organic substrate comprises an
alcoholic --OH group, having a structure of Formula (VIA) or
(VIB).
R.sup.4--OH (VIA)
HO--R.sup.5--OH (VIB),
where R.sup.4 comprises an optionally substituted C.sub.1-24 alkyl,
optionally substituted C.sub.2-24 alkenyl, optionally substituted
C.sub.2-24 alkynyl, optionally substituted C.sub.6-24 aryl,
optionally substituted C.sub.1-24 heteroalkyl, optionally
substituted 5- or 6-ring membered heteroaryl, optionally
substituted C.sub.7-24 aralkyl, optionally substituted
heteroaralkyl, or optionally substituted metallocene; and where
R.sup.5 comprises an optionally substituted C.sub.2-12 alkylene,
optionally substituted C.sub.2-12 alkenylene, optionally
substituted C.sub.6-24 arylene, optionally substituted C.sub.1-12
heteroalkylene, or an optionally substituted 5- or 6-ring membered
heteroarylene. In some Aspect of this Embodiments, the organic
substrate having at least one organic alcohol moiety is or
comprises an optionally substituted catechol moiety or has a
Formula (IV):
##STR00007##
[0220] wherein n is from 0 to 6, preferably 0 or 1;
[0221] R.sup.M and R.sup.N are independently H or methyl
[0222] R.sup.D, R.sup.E, R.sup.F, and R.sup.G are independently H,
C.sub.1-6 alkyl, C.sub.1-6 alkenyl, optionally substituted phenyl,
optionally substituted benzyl, or an optionally substituted 5- or
6-ring membered heteroaryl, wherein the optional substituents are
C.sub.1-3 alkyl, C.sub.1-3 alkoxy, or halo. Within this genus, the
organic substrate includes substituted 1,2-diols, 1,3-diols,
1,4-diols, these being substituted with one or more alkyl and/or
optionally substituted aryl or heteroaryl substituents. In certain
Aspects of this Embodiment, the organic substrate is any one having
a terminal olefin as described in U.S. patent application Ser. No.
15/219,710 (alcohols with hydroxides), filed Jul. 26, 2016, which
is incorporated by reference herein for all purposes, or at least
for these teachings.
EXAMPLES
[0223] The following Examples are provided to illustrate some of
the concepts described within this disclosure. While each Example
is considered to provide specific individual embodiments of
composition, methods of preparation and use, none of the Examples
should be considered to limit the more general embodiments
described herein.
[0224] In the following examples, efforts have been made to ensure
accuracy with respect to numbers used (e.g. amounts, temperature,
etc.) but some experimental error and deviation should be accounted
for. Unless indicated otherwise, temperature is in degrees C.,
pressure is at or near atmospheric.
Example 1: General Information
[0225] Unless otherwise stated, reactions were performed in a
nitrogen-filled glovebox or in flame-dried glassware under an argon
or nitrogen atmosphere using dry, deoxygenated solvents. Solvents
were dried by passage through an activated alumina column under
argon. Reaction progress was monitored by thin-layer chromatography
(TLC), GC or Agilent 1290 UHPLC-MS. TLC was performed using E.
Merck silica gel 60 F254 precoated glass plates (0.25 mm) and
visualized by UV fluorescence quenching, p-anisaldehyde, or
KMnO.sub.4 staining. Silicycle SiliaFlash.RTM. P60 Academic Silica
gel (particle size 40-63 nm) was used for flash chromatography.
.sup.1H NMR spectra were recorded on Varian Inova 500 MHz or Bruker
400 MHz spectrometers and are reported relative to residual
CHCl.sub.3 (.delta. 7.26 ppm), C.sub.6H.sub.6 (.delta. 7.16 ppm),
or THF (.delta. 3.58, 1.72 ppm). .sup.13C NMR spectra were recorded
on a Varian Inova 500 MHz spectrometer (125 MHz) or Bruker 400 MHz
spectrometers (100 MHz) and are reported relative to CHCl.sub.3
(.delta. 77.16 ppm). Data for .sup.13C NMR are reported in terms of
chemical shifts (.delta. ppm). IR spectra were obtained by use of a
Perkin Elmer Spectrum BXII spectrometer or Nicolet 6700 FTIR
spectrometer using thin films deposited on NaCl plates and reported
in frequency of absorption (cm.sup.-1). GC-FID analyses were
obtained on an Agilent 6850N gas chromatograph equipped with a
HP-1100% dimethylpolysiloxane capillary column (Agilent). GC-MS
analyses were obtained on an Agilent 6850 gas chromatograph
equipped with a HP-5 (5%-phenyl)-methylpolysiloxane capillary
column (Agilent). High resolution mass spectra (HRMS) were obtained
from Agilent 6200 Series TOF with an Agilent G1978A Multimode
source in electrospray ionization (ESI+), atmospheric pressure
chemical ionization (APCI+), or mixed ionization mode (MM:
ESI-APCI+), or obtained from Caltech mass spectrometry laboratory.
FT-ATR IR measurements were carried out on a Thermo Scientific
Nicolet iS 5 FT-IR spectrometer equipped with an iD5 ATR accessory.
ReactJR measurements were carried out on a Mettler-Toledo ReactJR
ic10 using a K4 conduit with a Sentinel high-pressure probe and
SIComp window. Electron paramagnetic resonance (EPR) spectra were
acquired on a X-band Bruker EMX spectrometer. An Omnical SuperCRC
or Insight CPR 220 reaction calorimeter were used to monitor heat
flow.
[0226] Triethyl silane (99%, Sure/Seal.TM.) and KOt-Bu (sublimed
grade, 99.99% trace metals basis) were purchased from Aldrich and
used directly. KOH was pulverized and dried in a desiccator over
P.sub.2O.sub.5 under vacuum for 24 h prior to use. Other reagents
were purchased from Sigma-Aldrich, Acros Organics, Strem, or Alfa
Aesar and used as received unless otherwise stated.
Example 2. Representative Conditions
Example 2.1. Reaction Conditions
[0227] General reaction procedure: In a nitrogen-filled glovebox,
catalyst (KOtBu, 0.5 equiv.) was measured into an oven-dried 2 mL
glass vial. The olefin substrate (1.0 equiv) was then added to the
vial. Solvent (DME, dimethoxyethane) to make a 1 M concentration of
olefin in DME) and silane (3.0 equiv) are then added, a Teflon
stir-bar is placed into the vial, and the reaction is sealed and
stirred for 24-96 h at temperatures ranging from 45-150.degree. C.
The reaction was quenched by diluting with diethyl ether; the
solution was filtered through a short plug of silica then
concentrated under reduced pressure. Purification by column
chromatography afforded the pure compounds detailed below. The
yield was determined by .sup.1H NMR or GC-FID analysis of the crude
mixture using an internal standard. Cis-/trans-ratios were
determined by NMR or GC-FID.
Example 2.2. General Method for the Screening of Base Catalysts and
Kinetic Profile
[0228] In a nitrogen-filled glove box, 1-methylindole (0.5 mmol, 1
equiv), triethylsilane (1.5 mmol, 3 equiv), the indicated base (0.1
mmol, 20 mol %), and THF (5 mL) were added to a 1 dram vial
equipped with a magnetic stirring bar. At the indicated time,
aliquots were removed using a glass capillary tube, diluted with
Et.sub.2O, and analyzed using GC-FID to determine regioselectivity
and yield. GC conversion is reported as product (C2- and
C3-silylation) divided by product and starting material. The
results are shown in Table 1.
TABLE-US-00001 TABLE 1 Results of Evaluating Base Catalysts
##STR00008## entry catalyst Time (h) conv (%) 2:3 1 KOt-Bu 10 88
11:1 2 KOEt 10 55 9:1 3 KOMe 20 35 9:1 4 KOTMS 20 53 12:1 5 KOAc 60
0 -- 6 KOH 20 52 11:1 7 KH 36 0 -- 8 KC.sub.8 10 73 8:1 9
CsOH.cndot.H.sub.2O 10 64 8:1 10 RbOH.cndot.xH.sub.2O 10 38 10:1 11
LiOt-Bu 36 0 -- 12 NaOt-Bu 36 0 -- 13 Mg(Ot-Bu).sub.2 36 0 -- 14
Ca(Oi-Pr).sub.2 36 0 -- 15 Ba(Ot-Bu).sub.2 36 0 -- 16
Al(Ot-Bu).sub.3 36 0 --
Example 2.3. Procedure for Time Course Reaction Monitoring by In
Situ .sup.1H NMR
[0229] In a nitrogen-filled glove box, a stock solution containing
KOt-Bu (60.5 mg, 0.539 mmol) and 1,2,5-trimethoxybenzene (if used,
45.4 mg, 0.267 mmol) is prepared in THF-D.sub.8 (2.7 ml).
Continuing in the glove box, a J-Young gas-tight NMR tube is then
charged with 1-methylindole (32.8 mg, 0.25 mmol, 1 equiv),
Et.sub.3SiH (0.75 mmol, 3 equiv), and 0.25 mL of stock solution.
The tube is tightly capped with the corresponding Teflon plug,
removed from the glove box, placed in the bore of the NMR, and
heated to 45.degree. C. .sup.1H NMR spectra were acquired in
"array" mode, with a spectrum taken approximately every 3 minutes
for the length of experiment. The data was processed using
MestReNova and peak integrations were normalized to
1,2,5-trimethoxybenzene (if used).
[0230] A study was conducted following the procedure for time
course reaction monitoring by .sup.1H NMR (using internal standard)
while varying 1-methyl-indole [1], from 0.25-0.76 mmol (0.5-1.5
equiv). A burst phase of product formation followed an initial
induction phase, unfortunately due to the induction period it was
difficult to assign an initial rate for this phase but all trials
appear to have a similar rate during the burst phase. The length of
the burst phase (i.e. product formed) appears to be related to the
nature of the substrate. Interestingly, after the burst phase the
slope of all plots appear to be consistent, indicating the reaction
may not depend on the nature of the substrate. See FIGS. 2 and 4.
This work helped demonstrate that silylation reaction occurred in
the following 3 regimes; induction, burst, and sustained reaction
periods.
Example 2.4. Procedure for Time Course Reaction Monitoring by GC
Analysis of Reaction Aliquots
[0231] In a nitrogen-filled glove box, 1 dram vials with magnetic
stirring bars were charged with the indicated base (0.1 mmol, 20
mol %, RbOH supplied as unknown hydrate from Strem and used as
received), 1-methylindole (65.6 mg, 0.5 mmol, 1 equiv),
triethylsilane (174.4 mg, 1.5 mmol, 3 equiv) and THF (0.5 mL, 1M)
then sealed with a PTFE-lined screw-cap and heated to 45.degree. C.
while stirring. At the indicated time points, an aliquot was
removed with a clean, dry glass capillary tube, diluted with
Et.sub.2O, and analyzed by GC-FID. Conversion is reported as the
percent of both C2- and C3-silylation products divided by products
and starting material. Regioselectivity (i.e. C2- to C3-silylation
ratios, Table 2) were also obtained at each time point.
TABLE-US-00002 TABLE 2 Time C2:C3 ratio Base (h) Conversion (x:1)
KOt-Bu 1.0 0.0 -- 2.0 0.0 -- 3.0 25.8 27.3 4.0 44.2 24.1 5.0 57.4
23.2 6.0 66.5 12.8 8.0 81.4 16.9 10.0 88.0 15.0 20.0 89.2 15.0 36.0
91.0 9.3 KOTMS 1.0 0.0 -- 2.0 0.0 -- 3.0 0.0 -- 4.0 3.9 7.1 5.0
10.2 9.9 6.0 17.7 9.0 8.0 26.2 19.9 10.0 33.0 14.1 20.0 50.4 11.6
36.0 59.9 9.0 KHMDS 1.0 0.0 -- 2.0 0.0 -- 3.0 0.0 -- 4.0 1.2 >20
5.0 2.5 >20 6.0 4.7 9.7 8.0 8.3 15.0 10.0 10.3 11.0 20.0 21.6
21.5 36.0 34.9 7.3 KOEt 1.0 19.7 -- 2.0 24.8 26.8 3.0 30.6 22.3 4.0
35.7 19.4 5.0 38.5 19.2 6.0 40.9 11.4 8.0 51.1 14.0 10.0 54.9 12.5
20.0 67.1 8.2 36.0 75.6 6.2 KOMe 1.0 0.0 -- 2.0 0.0 -- 3.0 0.0 --
4.0 1.2 >20 5.0 2.5 >20 6.0 5.6 7.0 8.0 15.7 15.4 10.0 24.2
12.3 20.0 35.2 14.9 36.0 51.5 7.2 KOH 1.0 0.0 -- 2.0 0.0 -- 3.0 0.0
-- 4.0 0.0 -- 5.0 0.0 -- 6.0 0.0 -- 8.0 17.8 >20 10.0 34.3 18.4
20.0 49.9 11.3 36.0 63.2 7.0 CsOH 1.0 2.2 >20 2.0 14.9 21.4 3.0
27.6 23.0 4.0 35.6 20.5 5.0 42.8 19.5 6.0 51.2 12.1 8.0 57.7 15.2
10.0 64.0 11.6 20.0 73.2 7.7 36.0 74.0 5.8 RbOH 1.0 0.0 -- 2.0 0.0
-- 3.0 5.8 5.3 4.0 12.1 10.5 5.0 17.8 18.9 6.0 23.9 19.9 8.0 30.8
14.1 10.0 37.5 11.0 20.0 48.2 9.5 36.0 59.4 7.9 KC8 1.0 22.4 >20
2.0 28.0 33.1 3.0 30.6 23.1 4.0 41.4 21.2 5.0 43.7 22.8 6.0 52.5
14.6 8.0 63.0 14.9 10.0 72.6 8.5 20.0 82.2 7.7 36.0 84.7 5.0
Example 2.5. Procedure for Reaction Time Course Using ReactIR
[0232] The glass reaction vessel for use with the ReactIR Sentinel
high-pressure probe and a magnetic stirring bar were oven dried,
fitted with the PTFE adapter, and brought into a nitrogen-filled
glove box, or cooled under a flow of argon and standard air-free
technique is used for all additions. KOt-Bu (0.8 mmol, 20 mol %),
1-methylindole (1.05 g, 8 mmol, 1 equiv), triethylsilane (13.89 mL,
24 mmol, 3 equiv), additive, and THF (8 mL, 1M) were added to
reaction vessel, which was fitted to the ReactIR probe and heated
to 45.degree. C. while stirring under argon. The spectrum was
recorded over the course of the reaction and data was analyzed
using the ReactIR software. See FIGS. 5 and 6.
[0233] An analogous experiment was performed whereby the indole 1
is not added until the new peak attributed to the hypercoordinated
silicate is seen. Indole 1 is then added via syringe and the
reaction immediately proceeds with no induction period.
Example 2.6. General Procedure of ATR-FTIR Measurement
[0234] In a nitrogen-filled glove box, base (0.1 mmol), Et.sub.3SiH
(800.5 mmol, 5 equiv), and THF (0.5 mL) were added to a 1 dram
scintillation vial equipped with a magnetic stirring bar. The vial
was sealed and the mixture stirred at 45.degree. C. for the
indicated time as shown in Table 3. The vial was transferred to
another nitrogen-filled glove box with an ATR-FTIR and a few drops
of this mixture placed on the ATR crystal. After waiting for 5
minutes to evaporate all the volatiles (i.e. THF and silanes), the
IR spectrum of the residue was recorded. No new Si--H stretch was
observed with bases which did not catalyze the silylation reaction
(e.g. NaOt-Bu, Mg(Ot-Bu).sub.2, or LiOt-Bu) as these did not form
the requisite hypercoordinated complex. See Table 3 and FIGS.
7(A)-(O).
TABLE-US-00003 TABLE 3 Spectroscopic characterization of the
reaction of Et.sub.3Si--H with the bases evaluation in this study
##STR00009## .upsilon. [Si--H] Entry Base [Si]--X t (h).sup.a
(cm.sup.-1).sup.b .DELTA..upsilon.(cm.sup.-1).sup.c 1 --
Et.sub.3SiH -- 2099 -- 2 KOt-Bu Et.sub.3SiH 2 2028 71 3 KOEt
Et.sub.3SiH 2 2016 83 4 KOMe Et.sub.3SiH 7 2054 45 5 KOTMS
Et.sub.3SiH 7 2047 52 6 KOH Et.sub.3SiH 20 2045 54 7
RbOH.cndot.xH.sub.2O Et.sub.3SiH 7 2052 47 8 CsOH.cndot.xH.sub.2O
Et.sub.3SiH 7 2051 48 9 NaOt-Bu Et.sub.3SiH 36 -- -- 10 KOt-Bu
Et.sub.3SiD 12 -- -- 11 KOt-Bu Et.sub.3SiH (2.5 equiv) + 12 2029 70
Et.sub.3SiD(2.5 equiv) 12 Mg(Ot-Bu).sub.2 Et.sub.3SiH 36 -- -- 13
LiOt-Bu Et.sub.3SiH 36 -- -- .sup.aThe mixture was stirred for the
indicated time before IR spectrum was measured. .sup.bFrequency of
Si--H bond stretching. .sup.cFrequency shift of observed
hypercoordinated silicon species from Et.sub.3Si--H.
Example 2.7. Other Specific, Representative Examples
[0235] Trimethylsilane: In a related experiment, directed to
investigating the use of gaseous hydrosilanes, trimethylsilane
(Me.sub.3SiH, 15 mmol), KO-tBu (0.076 mmol), and THF (0.38 mL) were
added to a Schlenk flask, sealed with a Teflon stopper, and allowed
to sit at RT (.about.23.degree. C.) for approximately 3 weeks. In a
N.sub.2 filled glovebox, 1-methyl-indole (0.38 mmol) was added and
the reaction is heated to 45.degree. C. for 48 hours. .sup.1H-NMR
indicated a conversion to 1-methyl-2-trimethylsilyl indole of
approximately 73%.
[0236] Hexamethyldisilane: In another related experiment, directed
to investigating the use of organodisilanes, hexamethyldisilane (2
mmol), KO-tBu (0.2 mmol), and THF (1 mL) were combined in a sealed
vial in a nitrogen-filled glovebox and heated to 45.degree. C. for
24 hours. The solution was then allowed to cool and 241 mg of this
mixture is added to a vial containing 1-methyl-indole (0.2 mmol).
This vial is sealed and heated to 45.degree. C. for 24 hours.
.sup.1H-NMR indicated a conversion to 1-methyl-2-trimethylsilyl
indole of approximately 76%.
[0237] Benzyl alcohol: In a N.sub.2 filled glove box, benzyl
alcohol (0.2 mmol, 21.6 mg, dried by MgSO.sub.4 and 3 .ANG. MS) was
added to a vial. Premixed silylation solution (251 mg, containing
0.04 mmol KOtBu, 0.6 mmol Et.sub.3SiH, and 0.2 mL THF) was added
and the solution was heated to 45.degree. C. After 48 h the
reaction was removed from heat and a white precipitate was
observed. The mixture was quenched with Et.sub.2O when the
precipitate went into solution, transferred to a vial, and
concentrated in vacuo. The .sup.1H NMR spectrum showed full
conversion to the product benzyloxytriethylsilylether (along with
residual silane and a small amount of an unidentified product
<0.1 by integration).
[0238] Deprotecting N-benzoylindole: In a glovebox, a solution was
previously prepared which contained 3 mmol triethylsilane and 0.2
mmol KOtBu per 1 mL THF. This sol was heated to 45.degree. C. for
24 hours then allowed to cool and stored in a glovebox. To 0.2 mmol
N-benzoylindole was added 251 mg of the premix sol (containing 0.6
mmol silane, 0.04 mmol KOtBu, and 0.2 mL THF) The vial was sealed
and heated to 45.degree. C. for 24 hours. After dilution with
Et.sub.2O, a crude NMR was taken which appeared to show a 1:1 of
starting material: de-protected indole (i.e., free indole)
Example 3. Discussion
[0239] Example 3.1 Effect of Catalyst Identity. The combination of
a bulky basic anion and a potassium cation has previously been
reported as crucial for the C--H silylation of 1-methylindole and
other heteroaromatic substrates. A detailed study of the catalytic
competency of a variety of alkali, alkaline earth, and other metal
derived bases has been conducted. As shown in Table 1, alkoxides
and hydroxides of alkali metals with larger radius cations (i.e.
radius .gtoreq.K+), such as K.sup.+, Rb.sup.+, and Cs.sup.+ could
provide the silylation product in moderate to good yields (Table 1,
entries 1-4, 6, 9 and 10).
[0240] Among all the catalysts examined, KOt-Bu was proven to be
the ideal catalyst, affording the highest overall yield. However,
no product was detected when KOAc or KH was employed as the
catalyst (entries 5 and 7). Perhaps surprisingly, potassium on
graphite (KC8) afforded the desired product in good yield (entry
8). Alkali metal bases with small cations (e.g. LiOt-Bu and
NaOt-Bu) demonstrated a complete lack of reactivity and no product
was observed even after extended reaction time (entries 11 and 12).
Alkoxides of alkali earth metals or aluminum were also investigated
as catalysts and failed to afford any product (entries 13-16).
[0241] The kinetic behavior of the silylation reaction with KOt-Bu
catalyst was studied using in situ 41 NMR spectroscopy. While not
previously reported, as depicted in FIGS. 1 and 2, the silylation
reaction was found to take place in three stages: an induction
period (FIG. 1), an active period ("burst") with rapid formation of
product, and a final period with significantly reduced reaction
rate. The timeframes of these three stages varied with reaction
conditions and reaction components (including hydrosilanes, bases,
additives, oxygen, moisture, and solvent), but the induction period
was always observed when these ingredients were added
simultaneously, or near simultaneously.
[0242] Investigations were then expanded to include each active
catalyst presented in Table 1 (FIG. 4). The length of the induction
period was found to depend on the nature of both metal and counter
ion. For anions, the induction period increased in the order of KC8
(shortest)<KOEt <KOt-Bu<KOH (longest). An increase in
induction period was observed with decreasing radius of cations,
with CsOH (shortest)<RbOH <KOH (longest). It is worth noting
that the induction periods vary based on catalyst loading,
solvents, and reaction temperature. Additives, oxygen, and moisture
could also have a significant impact on the induction period,
generally prolonging the duration of such period. Nevertheless, the
induction period showed good reproducibility for identical
reactions setup at different times. Although the induction period
with KOt-Bu is not the shortest of all catalysts tested (see FIG.
4), this catalyst provides the highest post-initiation turnover
frequency and product yield.
Example 3.2. Investigation of Coordinated Silane Species by FTIR
Studies
[0243] By monitoring the silylation reaction using ReactIR,
evidence for the existence of a new, possibly hypercoordinated
silicate species was found. As shown in FIGS. 5 and 6, the in situ
IR spectrum, a new peak is visible at 2056 cm' adjacent to the
Si--H stretching band in Et.sub.3SiH (2100 cm.sup.-1). This lower
frequency peak is consistent with an elongated, weakened Si--H
axial bond in a five-coordinate silicate, as expected in such
hypercoordinated complexes. A similar shift has been reported
previously for the trans Si--H stretching in
N,N-dimethylaminopropylsilane [H.sub.3Si(CH.sub.2).sub.3NMe.sub.2]
from 2151 to 2107 cm.sup.-1. In this case, the observed redshift
was rationalized to occur because of an N--Si interaction to form a
hypercoordinate complex as confirmed by X-ray analysis. In the
instant case, a correlation between the newly formed IR peak (FIG.
5) and the onset of product formation (i.e. the induction period
ending) was observed. Once the new IR peak reached a steady state,
the consumption of 1-methylindole 1 and formation of silylation
product occurred immediately. Furthermore, the new IR peak was
visible throughout the reaction. This is consistent with the
observation that premixing Et.sub.3SiH and KOt-Bu in THF for 2 h at
45.degree. C. followed by the addition of 1-methylindole 1
eliminated the induction period. This is also consistent with the
fact that the formation of hypercoordinated silicate is responsible
for the observed induction period.
[0244] Further studies were undertaken with mixtures of Et.sub.3SiH
and metal alkoxides listed in Table 1 utilizing ATR-FTIR in a
nitrogen filled glove box after removal of the volatiles (i.e. THF,
Et.sub.3SiH). As shown in FIG. 7(A), any alkoxide base which was a
competent silylation catalyst developed a lower energy Si--H
feature (from 2016-2051 cm', corresponding to the Si--H bond of a
hypercoordinated silicon species. In sharp contrast, no such
species were detected with unreactive catalysts [i.e., LiOt-Bu,
NaOt-Bu (FIGS. 7(M) and 7(N)), alkali earth metals, or aluminum
alkoxides] demonstrating that this new optionally solvated
hypercoordinated complex appears to be crucial for the silylation
reaction. For the hypercoordinated silicates formed from KOt-Bu and
KOEt, the decrease in the frequencies of Si--H absorption
correlates to a shortening of induction period (FIGS. 7(D) and
7(E)). Finally, although there is a large variation in the
induction periods with KOH, RbOH and CsOH, no differentiating Si--H
frequencies of the hypercoordinated silicates derived from those
bases are observed. The hydroxides are converted to the
silanolates, and subsequently silicates, which serve as the active
catalysts.
[0245] As those skilled in the art will appreciate, numerous
modifications and variations of the present invention are possible
in light of these teachings, and all such are contemplated hereby.
All references cited within this specification are incorporated by
reference, at least for their teachings in the context of their
recitation.
* * * * *