U.S. patent application number 14/108016 was filed with the patent office on 2014-05-22 for organoactinide-, organolanthanide-, and organogroup-4-mediated hydrothiolation of terminal alkynes with aliphatic, aromatic and benzylic thiols.
This patent application is currently assigned to Northwestern University. The applicant listed for this patent is Tobin J. Marks, Charles J. Weiss, Stephen D. Wobser. Invention is credited to Tobin J. Marks, Charles J. Weiss, Stephen D. Wobser.
Application Number | 20140142319 14/108016 |
Document ID | / |
Family ID | 43588973 |
Filed Date | 2014-05-22 |
United States Patent
Application |
20140142319 |
Kind Code |
A1 |
Marks; Tobin J. ; et
al. |
May 22, 2014 |
ORGANOACTINIDE-, ORGANOLANTHANIDE-, AND ORGANOGROUP-4-MEDIATED
HYDROTHIOLATION OF TERMINAL ALKYNES WITH ALIPHATIC, AROMATIC AND
BENZYLIC THIOLS
Abstract
An efficient and highly Markovnikov selective organoactinide-,
organolanthanide-, and organozirconium-catalyzed addition of aryl,
benzyl, and aliphatic thiols to terminal alkynes is described. The
corresponding vinyl sulfides are produced with little or no
side-products.
Inventors: |
Marks; Tobin J.; (Evanston,
IL) ; Weiss; Charles J.; (Richland, WA) ;
Wobser; Stephen D.; (Evanston, IL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Marks; Tobin J.
Weiss; Charles J.
Wobser; Stephen D. |
Evanston
Richland
Evanston |
IL
WA
IL |
US
US
US |
|
|
Assignee: |
Northwestern University
Evanston
IL
|
Family ID: |
43588973 |
Appl. No.: |
14/108016 |
Filed: |
December 16, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
12856154 |
Aug 13, 2010 |
8609902 |
|
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14108016 |
|
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|
|
61233541 |
Aug 13, 2009 |
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Current U.S.
Class: |
546/339 ; 568/18;
568/74; 568/77 |
Current CPC
Class: |
C07C 319/18 20130101;
C07C 319/18 20130101; C07C 319/18 20130101; C07C 2601/14 20170501;
C07C 323/27 20130101; C07C 323/03 20130101; C07C 319/18 20130101;
C07C 319/18 20130101; C07C 2601/16 20170501; C07C 321/20 20130101;
C07D 213/32 20130101; C07C 321/18 20130101; C07C 321/28 20130101;
C07C 321/22 20130101; C07B 45/06 20130101 |
Class at
Publication: |
546/339 ; 568/18;
568/77; 568/74 |
International
Class: |
C07B 45/06 20060101
C07B045/06; C07D 213/32 20060101 C07D213/32; C07C 319/18 20060101
C07C319/18 |
Goverment Interests
[0002] This invention was made with government support under Grant
No. CHE0809589 awarded by the National Science Foundation. The
government has certain rights in the invention.
Claims
1. A vinyl sulfide of formula ##STR00069## prepared by the steps
comprising 1) reacting a thiol of formula R''--SH with a terminal
alkyne of formula II .ident.--' in the presence of a catalyst
selected from the group consisting of; a) CGCM.sup.1R.sup.1.sub.2,
wherein M.sup.1 is selected from an actinide metal and Zr(IV), and
R.sup.1 is selected from NMe.sub.2, NEt.sub.2 and Me; b)
CGCM.sup.2R.sup.2, wherein M.sup.2 is lanthanide metal and R.sup.2
is N(TMS).sub.2; c) Cp*.sub.2 M.sup.1R.sup.3.sub.2, wherein R.sup.3
is selected from NMe.sub.2, NEt.sub.2, Me and CH.sub.2TMS; d)
Cp*.sub.2M.sup.2R.sup.4, wherein R.sup.4 is selected from
N(TMS).sub.2 and CH(TMS).sub.2; e)
Me.sub.2SiCp''M.sup.3R.sup.5.sub.2, wherein M.sup.3 is an actinide
metal, and R.sup.5 is selected from CH.sub.2TMS and Bn;
M.sup.1[R.sup.4].sub.3; g) Cp* M.sup.4R.sup.6, wherein M.sup.4 is a
Group 4 metal and R.sup.6 is selected from Bn and
Cl.sub.2NMe.sub.2; and M.sup.4(R.sup.3).sub.4; and h)
M.sup.4(R.sup.3).sub.4, wherein R' and R'' are independently
selected from the group consisting of alkyl, aryl, heteroaryl,
cycloalkyl, arylalkyl, heteroarylalkyl and cycloalkylalkyl; and 2)
isolating the vinyl sulfide.
2. A vinyl sulfide of claim 1 wherein the catalyst is selected from
Cp.sup.*.sub.2SmN(TMS).sub.2,
Me.sub.2SiCp''.sub.2Th[CH.sub.2(TMS)].sub.2. CGCZrMe.sub.2,
Cp.sup.*.sub.2YCH(TMS).sub.2, Me.sub.2SiCp''.sub.2UBn.sub.2,
Cp.sup.*.sub.2ZrMe.sub.2, CGCSmN(TMS).sub.2, CGCU(NMe.sub.2).sub.2,
Cp*ZrBn.sub.3, La[N(TMS).sub.2].sub.3, CGCTh(NMe.sub.2).sub.2,
Zr[NMe.sub.2].sub.4, Nd[N(TMS).sub.2].sub.3, U(NEt.sub.2).sub.4,
Cp*ZrCl.sub.2NMe.sub.2, Lu[CH(TMS).sub.2].sub.3,
Cp.sup.*.sub.2U(NMe.sub.2).sub.2, Y[N(TMS).sub.2].sub.3,
Cp.sup.*.sub.2Th(CH.sub.2TMS).sub.2, Cp.sup.*.sub.2LaCH(TMS).sub.2,
Cp.sup.*.sub.2U(CH.sub.2TMS).sub.2, Cp.sup.*.sub.2SmCH(TMS).sub.2,
and Cp.sup.*.sub.2LuCH(TMS).sub.2.
3. A vinyl sulfide according to claim 1 selected from the group
consisting of a) hex-1-en-2-yl(pentyl)sulfane; b)
cyclohexyl(hex-1-en-2-yl)sulfane; c)
hex-1-en-2-yl(4-methylbenzyl)sulfane; d)
pentyl(1-phenylvinyl)sulfane; e)
(1-(cyclohex-1-en-1-yl)vinyl)(pentyl)sulfane f)
(1-cyclohexylvinyl)(pentyl)sulfane; g)
(1-cyclohexylvinyl)(4-methylbenzyl)sulfane; h)
ethyl(hex-1-en-2-yl)sulfane; i) hex-
1-en-2-yl(2,2,2-trifluoroethyl)sulfane; j)
benzyl(hex-1-en-2-yl)sulfane; k)
(3-cyclohexylprop-1-en-2-yl)(pentyl)sulfane; l)
pentyl(3-phenylprop-1-en-2-yl)sulfane; m)
3-(1-(pentylthio)vinyl)pyridine; and n)
2-(pentylthio)prop-2-en-1-amine.
Description
[0001] This application is a divisional of and claims priority to
U.S. application Ser. No. 12/856,154 filed Aug. 13, 2010, which
claimed priority to U.S. provisional application Ser. 61/233,541
filed Aug. 13, 2009-each of which is incorporated herein by
reference in its entirety.
FIELD OF THE INVENTION
[0003] The present invention relates generally to atom-efficient
organoactinide-, organolanthanide-, and organoGroup-4-catalyzed
intermolecular hydrothiolation of terminal alkynes or allenes. The
methods of the invention can be used to incorporate sulfur into
organic frameworks, to synthesize carbon-carbon bond forming
reagents, and to synthesize vinyl cross-coupling reagents.
BACKGROUND OF THE INVENTION
[0004] Sulfur is a constituent of many important polymeric
materials, natural products, and synthetic reagents, providing
impetus to devise efficient catalytic methodologies for
sulfur-carbon bond formation. The addition of S--H bonds across
alkynes is an atom-economical route to a variety of vinyl sulfides
that can be achieved by several pathways, including radical
(Capella, L. et al., J. Org. Chem. 1996, 61, 6783-6789; Benati, L.
et al., J. Chem. Soc., Perkin Trans. 1995, 1035-1038; Benati, L. et
al., J. Chem. Soc., Perkin Trans. 1991, 2103-2109; Ichinose, Y. et
al., Chem. Lett. 1987, 16, 1647-1650; Griesbaum, K., Angew. Chem.
Int. Ed. Engl. 1970, 9, 273-287) and catalytic processes (Sabarre,
A.; Love, J., Org. Lett. 2008, 10, 3941-3944; Corma, A. et al.,
Appl. Catal., A 2010, 375, 49-54; Ananikov, Valentine P. et al.,
Chem. Eur. 12010, 16, 2063-2071; Shoai, S. et al., Organometallics
2007, 26, 5778-5781; Kondoh, A. et al., Org. Lett. 2007, 9,
1383-1385; Fraser, L. R. et al., Organometallics 2007, 26,
5602-5611; Delp, S. A. et al., Inorg. Chem. 2007, 46, 2365-2367;
Beletskaya, I. P. et al., Pure Appl. Chem. 2007, 79, 1041-1056;
Beletskaya, I. P. et al., Eur. J Org. Chem. 2007, 3431-3444;
Ananikov, V. P. et al., J. Am. Chem. Soc. 2007, 129, 7252-7253;
Malyshev, D. A. et al., Organometallics 2006, 25, 4462-4470;
Ananikov, V. P. et al., Russ. Chem. Bull. 2006, 55, 2109-2113;
Ananikov, V. P. et al., Organometallics 2006, 25, 1970-1977; Cao,
C. et al., J. Am. Chem. Soc. 2005, 127, 17614-17615; Ananikov, V.
P. et al., Adv. Synth. Catal. 2005, 347, 1993-2001; Kondo, T. et
al., Chem. Rev. 2000, 100, 3205-3220). Radical hydrothiolation
yields unselective mixtures of E and Z vinyl sulfides, while
organometallic catalysts offer access to Markovnikov vinyl sulfides
or E anti-Markovnikov vinyl sulfides with varying degrees of
turnover and selectivity (Misumi, Y. et al., J. Organomet. Chem.
2006, 691, 3157-3164). While diverse variants of organometallic
complex-mediated hydroelementation have been extensively explored,
including hydroamination, hydrophosphination and hydroalkoxylation,
only recently has hydrothiolation been investigated in detail due
to the historic reputation of sulfur as a catalyst poison (Hegedus,
L. L.; McCabe, R. W., Chemical Industries Series, Vol. 17: Catalyst
Poisoning. 1984), reflecting its high affinity for "soft"
transition metal centers (Stephan, D. W. et al., Coord. Chem. Rev.
1996, 147, 147-208; Krebs, B. et al., Angew. Chem. Int. Ed. Engl.
1991, 30, 769-788).
[0005] Interest in homogeneous, catalytic alkyne hydrothiolation
over the past few years has yielded a number of metal complexes
competent to effect this transformation using late transition metal
catalysts (Field, L. D. et al., Dalton Trans. 2009, 3599-3614;
Ogawa, A. et al., J. Am. Chem. Soc. 1999, 121, 5108-5114; Kuniyasu,
H. et al., J. Am. Chem. Soc. 1992, 114, 5902-5903). For example,
Rh, Ir, Ni, Pd, Pt and Au complexes have been previously reported.
While some late transition metal catalysts exhibit high activity,
achieving high Markovnikov selectivity still presents a challenge,
with the exception of Pd, as does competing isomerization of the
alkene product, double-thiolation products and product insertion
into a second alkyne. Furthermore, while some late transition metal
complexes effect efficient alkyne hydrothiolation with benzyl and
aryl thiols, few mediate hydrothiolation with the less reactive
aliphatic thiols. Previous work with rhodium catalysts demonstrates
the ability to utilize both terminal and internal alkynes with
selectivity typically favoring the linear E anti-Markovnikov
products with the exception of Tp*Rh(PPh.sub.3).sub.2, where
Markovnikov vinyl sulfides are selectively produced. Studies on
group 10 metals find that nickel and palladium catalysts favor the
Markovnikov product.
[0006] Available mechanistic data for late transition
metal-mediated hydrothiolation complexes are consistent with
pathways in which the alkyne undergoes insertion into either a
metal-hydride or metal-thiolate bond. The accepted hydride pathway
for most Rh complexes is initiated by .pi.-coordination/activation
of the acetylene to/by the metal-hydride complex, followed by
alkyne insertion into the Rh--H bond. Finally, regeneration of the
catalyst occurs through reductive elimination of product followed
by RS--H oxidative addition to the metal center. Rhodium complexes
selectively yield E anti-Markovnikov products as a result of the
hydride insertion regiochemistry. In contrast, Pd complexes are
proposed to effect hydrothiolation via acetylene insertion into the
metal-thiolate bond followed by thiol-mediated displacement of
product from the metal center, resulting in Markovnikov
selectivity.
[0007] The efficacy of inexpensive organozirconium complexes for
formally analogous hydroamination processes has been reported
(Leitch, D. C. et al., J. Am. Chem. Soc. 2009, 131, 18246-18247;
Smolensky, E. et al., Organometallics 2007, 26, 4510-4527;
Ackermann, L. et al., J. Am. Chem. Soc. 2003, 125, 11956-11963;
Arredondo, V. M. et al., Organometallics 1999, 18, 1949-1960;
Majumder, S. et al., Organometallics 2008, 27, 1174-1177; Stubbert,
B. D. et al., J. Am. Chem. Soc. 2007, 129, 6149-6167). Likewise,
lanthanide complexes have also been used in hydroamination (Andrea,
T. et al., Chem. Soc. Rev. 2008, 37, 550-567; Muller, T. E. et al.,
Chem. Rev. 2008, 108, 3795-3892; Hartwig, J. F., Nature 2008, 455,
314-322; Motta, A. et al., Organometallics 2006, 25, 5533-5539;
Alonso, F. et al., Chem. Rev. 2004, 104, 3079-3160; Motta, A. et
al., Organometallics 2004, 23, 4097-4104; Hong, S. et al., Acc.
Chem. Res. 2004, 37, 673-686; Ackermann, L. et al., J. Am. Chem.
Soc. 2003, 125, 11956-11963; Arredondo, V. M. et al.,
Organometallics 1999, 18, 1949-1960; Arredondo, V. M. et al., J.
Am. Chem. Soc. 1999, 121, 3633-3639; Arredondo, V. M. et al., J.
Am. Chem. Soc. 1998, 120, 4871-4872; Haskel, A. et al.,
Organometallics 1996, 15, 3773-3775; Giardello, M. A. et al., J.
Am. Chem. Soc. 1994, 116, 10241-10254; Gagne, M. R. et al., J. Am.
Chem. Soc. 1992, 114, 275-294), hydrophosphination (Perrier, A. et
al., Chem. Eur. 12009, 16, 64-67; Douglass, M. R. et al., J. Am.
Chem. Soc. 2000, 122, 1824-1825; Douglass, M. R. et al., J. Am.
Chem. Soc. 2001, 123, 10221-10238; Kawaoka, A. M. et al.,
Organometallics 2003, 22, 4630-4632; Motta, A. et al.,
Organometallics 2005, 24, 4995-5003; Nagata, S. et al., Tetrahedron
Lett. 2007, 48, 6637-6640; Sadow, A. D. et al., J. Am. Chem. Soc.
2004, 126, 14704-14705; Takaki, K. et al., J. Org. Chem. 2003, 68,
6554-6565; Wicht, D. K. et al., J. Am. Chem. Soc. 1997, 119,
5039-5040), and hydroalkoxylation processes (Motta, A. et al.,
Organometallics 2010, 29, 2004-2012;. Dzudza, A. et al., Chem.-Eur.
12010, 16, 3403-3422; Seo, S. et al., Chem.-Eur. 12010, 16,
5148-5162; Cui, D.-M. et al., Synlett 2009, 7, 1103-1106; Dzudza,
A. et al., Org. Lett. 2009, 11, 1523-1526; Janini, T. E. et al.,
Dalton Trans. 2009, 10601-10608; Nishina, N. et al., Tetrahedron
2009, 65, 1799-1808; Seo, S. et al., J. Am. Chem. Soc. 2009, 131,
263-276; Zhang, Z. et al., Org. Lett. 2008, 10, 2079-2081; Nishina,
N. et al., Tetrahedron Lett. 2008, 49, 4908-4911; Harkat, H. et
al., Tetrahedron Lett. 2007, 48, 1439-1442; Yu, X. et al., J. Am.
Chem. Soc. 2007, 129, 7244-7245; Zhang, Z. et al., J. Am. Chem.
Soc. 2006, 128, 9066-9073; Yang, C. G. et al., Org. Lett. 2005, 7,
4553-4556; Qian, H. et al., J. Am. Chem. Soc. 2004, 126,
9536-9537). However, the use of these complexes in the
hydrothiolation of alkynes has yet to be reported.
[0008] Accordingly, an efficient catalytic system is desired for
the hydrothiolation of terminal alkynes by aromatic, benzylic, and
less reactive aliphatic thiols. This system should proceed with a
high degree of Markovnikov selectivity and reduce 1) the formation
of double-thiolated side product, 2) the competing isomerization of
the alkene product, and 3) the product insertion into a second
alkyne.
SUMMARY OF THE INVENTION
[0009] In light of the foregoing, it is an object of the present
invention to provide an organolanthanide, organoactinide, or
organoGroup-4 catalyst for the intermolecular hydrothiolation of
terminal alkynes using a variety of aryl, benzyl and aliphatic
thiols, thereby overcoming various deficiencies and shortcomings of
the prior art, including those outlined above. It will be
understood by those skilled in the art that one or more aspects of
this invention can meet certain objectives, while one or more other
aspects can meet certain other objectives. Each objective may not
apply equally, in all its respects, to every aspect of this
invention. As such, the following objects can be viewed in the
alternative with respect to any one aspect of this invention.
[0010] It can also be an object of the present invention to provide
an efficient method for a catalyzed addition of aryl, benzyl and
aliphatic thiols to terminal alkynes to yield vinyl sulfides. In an
aspect of the invention, the method is Markovnikov-selective, and
the vinyl sulfides produced by the method can also be free, or
substantially free, of a double-thiolated side product. Thus, the
method comprises treating a thiol with a terminal alkyne in the
presence of a catalyst selected from the group consisting of an
organolanthanide, organoactinide and organoGroup-4 catalyst to
afford a vinyl sulfide.
[0011] It is another object of the present invention to provide a
vinyl sulfide prepared by treating a thiol with a terminal alkyne
in the presence of a catalyst selected from the group consisting of
an organolanthanide, organoactinide and organoGroup-4 catalyst.
[0012] Other objects, features, benefits and advantages of this
invention would be apparent from the summary, in conjunction with
the following descriptions of certain embodiments, and will be
readily apparent to those skilled in the art. Such objects,
features, benefits and advantages will be apparent from the above
as to taken into conjunction with the accompanying examples, data,
figures and all reasonable inferences to be drawn therefrom, alone
or with consideration of the references incorporated herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a representative plot of product formation rate
against time for CGCZrMe.sub.2 (Zr-i)-mediated hydrothiolation
1A+2B.fwdarw.3AB. (A) Plot of product formation rate of
1A+2A.fwdarw.3AA versus Zr-i; (B), [2A] and (C) [1A] at (D) [1A]
and [2A]=0.2 M.
[0014] FIG. 2 is a plot of product formation rate for the reaction
1A+2B.fwdarw.3AB as a function of [Cp*.sub.2SmCH(TMS).sub.2
(Ln-ix)] (A) and [2B] (B) with [1A] and [2B]=0.2 M; (C) plot of
hydrothiolation conversion (%) versus time with 17.times. molar
excess 2A over 1A exhibits a linear trend indicating a
pseudo-zero-order reaction, demonstrating rate independence with
respect to [1A] except at the highest concentrations where catalyst
precipitation becomes extensive.
DETAILED DESCRIPTION OF THE INVENTION
[0015] In part, the present invention can be directed to a method
of preparing a vinyl sulfide comprising treating a thiol with a
terminal alkyne in the presence of a catalyst selected from the
group consisting of CGCM.sup.1R.sup.1.sub.2, wherein M.sup.1 is
selected from an actinide metal and a Group 4 metal, and R.sup.1 is
selected from NMe.sub.2, NEt.sub.2 and Me; CGCM.sup.2R.sup.2,
wherein M.sup.2 is lanthanide metal and R.sup.2 is N(TMS).sub.2;
Cp*.sub.2 M.sup.1R.sup.3.sub.2, wherein R.sup.3 is selected from
NMe.sub.2, NEt.sub.2, Me and CH.sub.2TMS; Cp*.sub.2M.sup.2R.sup.4,
wherein R.sup.4 is selected from N(TMS).sub.2 and CH(TMS).sub.2;
Me.sub.2SiCp''.sub.2M.sup.3R.sup.5.sub.2, wherein M.sup.3 is an
actinide metal, and R.sup.5 is selected from CH.sub.2TMS and Bn;
M.sup.2[R.sup.4].sub.3; Cp*M.sup.4R.sup.6, wherein M.sup.4 is a
Group 4 metal and R.sup.6 is selected from Bn.sub.3 and
Cl.sub.2NMe.sub.2; and M.sup.3(R.sup.3).sub.4. In an aspect of the
invention, the thiol is selected from aryl, benzyl and aliphatic
thiols.
[0016] The present invention can also be directed to a method of
preparing a vinyl sulfide comprising treating a thiol of the
formula I
R''--SH I
with an alkyne of formula II
.ident.--R' II
to afford a corresponding vinyl sulfide of formula III
##STR00001##
in the presence of a catalyst selected from the group consisting of
CGCM.sup.1R.sup.1.sub.2, wherein M.sup.1 is selected from an
actinide metal and a Group IV metal, and R.sup.1 is selected from
NMe.sub.2, NEt.sub.2 and Me; CGCM.sup.2R.sup.2, wherein M.sup.2 is
lanthanide metal and R.sup.2 is N(TMS).sub.2; Cp*.sub.2
M.sup.1R.sup.3.sub.2, wherein R.sup.3 is selected from NMe.sub.2,
NEt.sub.2, Me and CH.sub.2TMS;
Me.sub.2SiCp''.sub.2M.sup.3R.sup.5.sub.2, wherein M.sup.3 is an
actinide metal, and R.sup.5 is selected from CH.sub.2TMS and Bn;
M.sup.2[R.sup.4].sub.3; Cp*M.sup.4R.sup.6, wherein M.sup.4 is a
Group 4 metal and R.sup.6 is selected from Bn.sub.3 and
Cl.sub.2NMe.sub.2; and M.sup.3(R.sup.3).sub.4; and wherein R' and
R'' are independently selected from the group consisting of alkyl,
aryl, heteroaryl, cycloalkyl, arylalkyl, heteroarylalkyl and
cycloalkylalkyl.
[0017] The general scheme for the hydrothiolation reaction of the
invention is depicted in Scheme 1.
##STR00002##
[0018] By "alkyl" in the present invention is meant a straight or
branched chain alkyl radical having 1-20, and preferably from 1-12,
carbon atoms. Examples include but are not limited to methyl,
ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl,
2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl, and
3-methylpentyl. Each alkyl group may be optionally substituted with
one, two or three substituents such as, for example, a halo,
cycloalkyl, aryl, alkenyl, hydroxy or alkoxy group and the
like.
[0019] By "aromatic" is meant an "aryl" or "heteroaryl" group.
[0020] By "aryl" is meant an aromatic carbocylic radical having a
single ring (e.g. phenyl), multiple rings (e.g. biphenyl) or
multiple fused rings in which at least one is aromatic (e.g.
1,2,3,4-tetrahydronaphthyl). The aryl group can also be optionally
mono-, di-, or trisubstituted with, for example, halo, alkyl,
alkenyl, cycloalkyl, hydroxy or alkoxy and the like.
[0021] By "heteroaryl" is meant one or multiple fused aromatic ring
systems of 5-, 6- or 7-membered rings containing at least one and
up to four heteroatoms selected from nitrogen, oxygen or sulfur.
Examples include but are not limited to furanyl, thienyl,
pyridinyl, pyrimidinyl, benzimidazolyl and benzoxazolyl. The
heteroaryl group can also be optionally mono-, di-, or
trisubstituted with, for example, halo, alkyl, alkenyl, cycloalkyl,
hydroxy or alkoxy and the like.
[0022] By "cycloalkyl" is meant a carbocylic radical having a
single ring (e.g. cyclohexyl), multiple rings (e.g. bicyclohexyl)
or multiple fused rings (e.g. naphthlene). The cycloalkyl group can
optionally contain from 1 to 4 heteroatoms. In addition, the
cycloalkyl group may have one or more double bonds. The cycloalkyl
group can also be optionally mono-, di-, or trisubstituted with,
for example, halo, alkyl, alkenyl, aryl, hydroxy or alkoxy and the
like.
[0023] By "alkoxy" is meant an oxy-containing radical having an
alkyl portion. Examples include, but are not limited to, methoxy,
ethoxy, propoxy, butoxy and tert-butoxy. The alkoxy group can also
be optionally mono-, di-, or trisubstituted with, for example,
halo, aryl, cycloalkyl or hydroxy and the like.
[0024] By "alkenyl" is meant a straight or branched hydrocarbon
radical having from 2 to 20, and preferably from 2-6, carbon atoms
and from one to three double bonds and includes, for example,
ethenyl, propenyl, 1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl. The
alkenyl group can also be optionally mono-, di-, or trisubstituted
with, for example, halo, aryl, cycloalkyl or alkoxy and the
like.
[0025] By "alkynyl" is meant a straight or branched hydrocarbon
radical having from 2 to 20, and preferably from 3-12, carbon atoms
and from one to three double bonds and includes, for example,
propenyl, 1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl. The alkenyl
group can also be optionally mono-, di-, or trisubstituted with,
for example, halo, aryl, cycloalkyl or alkoxy and the like.
[0026] "Halo" is a halogen radical of fluorine, chlorine, bromine
or iodine.
[0027] By "Group 4 metal" is meant Ti(IV), Zr(IV) and Hf(IV).
[0028] The following abbreviations/structures can be used
interchangeably herein:
[0029] CGC--Me.sub.2SiCp''NCMe.sub.3
[0030] Me--Methyl
[0031] Et--Ethyl
[0032] Bn--Benzyl
[0033] TMS--Trimethylsilyl
##STR00003##
[0034] The present invention can also be directed to a vinyl
sulfide of formula III
##STR00004##
prepared by the steps comprising the step of reacting a thiol of
formula I
R''--SH I
with a terminal alkyne of formula II
.ident.--R' II
wherein R' and R'' are independently selected from the group
consisting of alkyl, aryl, heteroaryl, cycloalkyl, arylalkyl,
heteroarylalkyl and cycloalkylalkyl, in the presence of a catalyst
selected from the group consisting of CGCM.sup.1R.sup.1.sub.2,
wherein M.sup.1 is selected from an actinide metal and a Group 4
metal, and R.sup.1 is selected from NMe.sub.2, NEt.sub.2 and Me;
CGCM.sup.2R.sup.2, wherein M.sup.2 is lanthanide metal and R.sup.2
is N(TMS).sub.2; Cp*.sub.2 M.sup.1R.sup.3.sub.2, wherein R.sup.3 is
selected from NMe.sub.2, NEt.sub.2, Me and CH.sub.2TMS;
Me.sub.2SiCp''.sub.2M.sup.3R.sup.5.sub.2, wherein M.sup.3 is an
actinide metal, and R.sup.5 is selected from CH.sub.2TMS and Bn;
M.sup.2[R.sup.4].sub.3; Cp*M.sup.4R.sup.6, wherein M.sup.4 is a
Group 4 metal and R.sup.6 is selected from Bn.sub.3 and
Cl.sub.2NMe.sub.2; and M.sup.3(R.sup.3).sub.4; and isolating the
vinyl sulfide.
[0035] Preferably, R' is C.sub.1-C.sub.6-alkyl, aryl, heteroaryl,
C.sub.3-C.sub.7-cyloalkyl, aryl-C.sub.1-C.sub.6-alkyl,
heteroaryl-C.sub.1-C.sub.6-alkyl or
C.sub.3-C.sub.7-cyloalkyl-C.sub.1-C.sub.6-alkyl. Non-limiting
examples of alkynes include 1-hexyne, ethynylcyclohexane,
prop-2-ynylcyclohexane, 1-ethynylcyclohex-1-ene, 3-ethynylpyridine,
prop-2-yn-1-amine or ethynylbenzene.
[0036] Preferably, R'' is C.sub.1-C.sub.12-alkyl, aryl, heteroaryl,
C.sub.3-C.sub.7-cyloalkyl or aryl-C.sub.1-C.sub.6-alkyl.
Non-limiting examples of thiols include 1-pentanethiol,
1-pentanethiol-d, 1-dodecanethiol, cyclohexanethiol,
2-methyl-2-butanethiol, benzyl mercaptan, 4-methylbenzyl mercaptan,
prop-2-yn-1-amine or thiophenol.
[0037] Representative examples of suitable catalysts are those
depicted in Table 1 below.
TABLE-US-00001 TABLE 1 Lanthanide Actinide Group 4 ##STR00005##
Cp*.sub.2SmN(TMS).sub.2 (Ln-i) ##STR00006##
Me.sub.2SiCp''.sub.2Th[CH.sub.2(TMS)].sub.2 (An-i) ##STR00007##
CGCZrMe.sub.2 (Zr-i) ##STR00008## Cp*.sub.2YN(TMS).sub.2 (Ln-ii)
##STR00009## Me.sub.2SiCp''.sub.2UBn.sub.2 (An-ii) ##STR00010##
Cp*.sub.2ZrMe.sub.2 (Zr-ii) ##STR00011## CGCSmN(TMS).sub.2 (Ln-iii)
##STR00012## CGCU(NMe.sub.2).sub.2 (An-iii) ##STR00013##
Cp*ZrBn.sub.3 (Zr-iii) La[N(TMS).sub.2].sub.3 (Ln-iv) ##STR00014##
CGCTh(NMe.sub.2).sub.2 (An-iv) Zr[NMe.sub.2].sub.4 (Zr-iv)
Nd[N(TMS).sub.2].sub.3 U(NEt.sub.2).sub.4 Cp*ZrCl.sub.2NMe.sub.2
(Ln-v) (An-v) (Zr-v) Lu[CH(TMS).sub.2].sub.3 (Ln-vi) ##STR00015##
Cp*.sub.2U(NMe.sub.2).sub.2 (An-vi) Y[N(TMS).sub.2].sub.3
Cp*.sub.2Th(CH.sub.2TMS).sub.2 (Ln-vii) (An-vii)
Cp*.sub.2LaCH(TMS).sub.2 Cp*.sub.2U(CH.sub.2TMS).sub.2 (Ln-viii)
(An-viii) Cp*.sub.2SmCH(TMS).sub.2 (Ln-ix) Cp*.sub.2LuCH(TMS).sub.2
(Ln-x) Cp*.sub.2YCH(TMS).sub.2 (Ln-xi)
[0038] The present hydrothiolation process exhibits a high level of
Markovnikov selectivity. This presumably reflects a four-membered
transition state, with the alkyne insertion regiochemistry dictated
by transition state sterics and bond polarity orientation Marks, T.
J. et al., J. Am. Chem. Soc. 2009, 131, 2062-2063, incorporated in
its entirety herein by reference. Additional competing,
non-catalytic, anti-Markovnikov products are occasionally detected
under the present reaction conditions. These products are, for the
most part, formed in negligible quantities. Anti-Markovnikov
side-products can be further suppressed with the addition of a
radical inhibitor, as, for example, .gamma.-terpinene, into the
reaction mixture. Despite formal similarities to the proposed
insertion/protonolysis mechanisms of several Pd and Ni catalysts
(Malyshev, D. A. et al., Organometallics 2006, 25, 4462-4470),
double-thiolated side-products are surprisingly not observed in the
instant invention.
[0039] Hydrothiolation rates appear to be dependent on the type of
thiol used. Changing from primary to secondary aliphatic thiols
results in significant rate depression, suggesting steric
impediments in the turnover-limiting alkyne insertion. As much as
50.times. rate reduction is observed in transitioning from a
primary to a secondary thiol (Table 2). Aromatic thiol
functionality also influences hydrothiolation rates. For example,
use of a benzyl mercaptan (1G) or thiophenol increases the turnover
frequency (N.sub.t) greatly. The enhanced reactivity of aryl- and
benzyl-thiols likely reflects electronic factors. However, for
benzenethiol, any electronic gain is offset by increased sterics
when compared to 1-pentanethiol. The 4-methylbenzyl mercaptan
yields the largest thiol substrate N.sub.t, likely reflecting a
combination of favorable electronics and sterics.
[0040] Alkyne structure also affects the rate of hydrothiolation,
however steric encumberance exhibits a less pronounced influence
than electronic characteristics. Switching from an
.alpha.-monosubstituted to an .alpha.-disubstituted alkyne results
in a moderate decrease in rate (Table 2). Similar to the
aforementioned trend with thiols, alkyne electronic characteristics
also play a prominent role in influencing hydrothiolation rates,
with conjugated alkynes exhibiting significantly enhanced rates. In
particular, introduction of unsaturation .alpha. to the CC bond
results in a 5.times. rate increase versus the unconjugated alkyne,
while phenylacetylene (2B) increases the activity versus the
cyclohexylacetylene (2D). Rate enhancement is also observed with a
3-ethynylpyridine, although not as pronounced as that for phenyl
substitution.
TABLE-US-00002 TABLE 2 N.sub.t Thiol Alkyne Product
(h.sup.-1,.degree. C.) ##STR00016## 1A ##STR00017## 2A ##STR00018##
3AA 5(90) 0.7(120) ##STR00019## 1A-d 2A ##STR00020## 3AA --
##STR00021## 3A-dA ##STR00022## 1B 2A ##STR00023## 3BA 1(110)
##STR00024## 1C 2A ##STR00025## 3CA 14(90) 27(110) ##STR00026## 1D
2A ##STR00027## 3DA 4(110) 1A ##STR00028## 2B ##STR00029## 3AB
5(90) 1D 2B ##STR00030## 3DB 8(110) 0.2(120) 1A ##STR00031## 2C
##STR00032## 3AC 6(110) 1A ##STR00033## 2D ##STR00034## 3AD 4(110)
1C 2D ##STR00035## 3CD 16(90) ##STR00036## 1E 2A ##STR00037## 3EA
0.6(120) ##STR00038## 1F 2A ##STR00039## 3FA 0.6(120) ##STR00040##
1G 2A ##STR00041## 3GA 3(120) 1A ##STR00042## 2E ##STR00043## 3AE
0.3(120) 1A ##STR00044## 2F ##STR00045## 3AF 1.5(120) 1A
##STR00046## 2G ##STR00047## 3AG 1.2(120) 1A ##STR00048## 2H
##STR00049## 3AH 4.8(120) 4.7(120)
[0041] In spite of some variations in conversion, good to excellent
selectivities are observed for all thiols examined with 1-hexyne.
Most of the hydrothiolation reactions proceed with >90%
Markovnikov selectivity (Table 3). Likewise, selectivity remains
high when varying the alkyne, sometimes requiring the presence of a
radical inhibitor such as .gamma.-terpinene.
TABLE-US-00003 TABLE 3 Selectivity Conversion Thiol Alkyne Catalyst
(%) (%) 1E 2A Ln-ix >99 .gtoreq.95 1A 2A Ln-ix >99 55 1B 2A
Ln-ix 90 11 1G 2A Ln-ix >99 92 1D 2A Ln-ix 91 48 1E 2A Zr-i 96
95 1A 2A Zr-i 94 95 1B 2A Zr-i 59 55 1G 2A Zr-i 95 95 1D 2A Zr-i 94
94 1A 2D Ln-ix 88 26 1A 2E Ln-ix 95 20 1A 2F Ln-ix 72 55 1A 2C
Ln-ix 77 (with .gamma.- 56 terpinene) 1A 2B Ln-ix 95 (with .gamma.-
39 terpinene) 1A 2D Zr-i 92 92 1A 2E Zr-i 96 98 1A 2F Zr-i 91 100
1A 2C Zr-i 97 (with .gamma.- 100 terpinene) 1A 2B Zr-i 66 100 1A 2D
An-vii 94 32 1G 2A An-vii 90 43 1D 2B An-vii 83 (with .gamma.- 61
terpinene) 1A 2H Zr-i 75 1A 2H Zr-iii 98
[0042] Ancillary ligand selection has consequences for the
stability of organolanthanide-, organoactinide- and
organozirconium-complexes in hydrothiolation catalysis. While the
addition of excess thiol to Ln-iv, for example, results in
immediate precipitation, Cp-based ligation delays precipitation.
The non-bonded repulsions of the Cp-based ligands likely suppress
the formation of insoluble, highly aggregated metal complexes.
Also, metal ionic radius exerts an influence on catalyst thiolytic
stability, with the smaller ions exhibiting greater resistance to
precipitation.
[0043] Kinetic studies are performed to define the hydrothiolation
reaction pathway and to better understand the influence of
[catalyst], [thiol], and [alkyne] on the sequence of reaction
events. Experiments are conducted on the CGCZrMe.sub.2
(Zr-i)-mediated hydrothiolation of 1-hexyne (2A) by 1-pentanethiol
(1A), and kinetic results are plotted in FIG. 1. The empirical rate
law is derived by systematically varying concentration of Zr-1,1A,
and 2A at 120.degree. C. Experiments carried out by varying [Zr-i]
over the range 1.9-21 mM exhibit a clear, linear trend when plotted
against the measured rate (FIG. 1B) indicating a first-order
dependence of rate on catalyst concentration. By varying [2A] over
the range 0.10-1.5 M, a first-order trend is also observed in the
plot of [2A] versus product formation rate (FIG. 1C). The varying
of 1A concentration reveals a more complex trend, with an
approximate first-order behavior for [1A]<0.3 M, followed by
saturation in the rate at concentrations >0.3 M (FIG. 1D). As a
result, the empirical rate law for the reaction 1A+2A.fwdarw.3AA is
described by Equation 1a with [Zr-i] and [2A] both first-order, and
[1A] x-order with x=1 for [1A]<0.3 M and x=0 for [1A]>0.3 M.
Additional catalyst- and alkyne-dependance studies performed under
high [thiol] conditions (i.e. [thiol]=1.2 M) show that [alkyne] and
[catalyst] remain first-order even at elevated [thiol].
Rate=k.sub.obs[Zr-i].sup.1[2A].sup.1[1A].sup.X (Equation 1a)
[0044] To derive activation parameters, the rate of the conversion
1A+2A .fwdarw.3AA mediated by Zr-i is analyzed from 50 to
80.degree. C., and the data are plotted with respect to the Eyring
equation. Variable temperature studies at 0.2 M [alkyne] and
[thiol] result in an Eyring plot yielding
.DELTA.H.sup..dagger-dbl.=+18.1(1.2) kcal/mol and
.DELTA.S.sup..dagger-dbl.=-20.9(2.5) e.u. Repeating the temperature
studies with [thiol]=1.2 M from 40 to 80.degree. C. yields similar
reactions parameters of .DELTA.H.sup..dagger-dbl.=+17.8(1.5)
kcal/mol and .DELTA.S.sup..dagger-dbl.=-24.4(4.8) e.u.
[0045] To trace the fate of the D-CC.ident.R' hydrogens in the
present catalytic transformations, deuterium-labeling experiments
are performed using deuterated phenylacetylene (2B-d). Upon
addition of 1A and 2B-d to Zr-i at room temperature, a single
methane (CH.sub.4) resonance is immediately observed in the .sup.1H
NMR spectrum. The absence of CH.sub.3-D suggests exclusive
activation of the catalyst by thiol protonolysis despite known
alkyne protonolysis activity. To further rule out alkyne-mediated
protonolysis as a kinetically signifigant route for the cleavage of
Zr-alkyl bonds, relative rates of alkyne- and thiol-mediated
protonolysis are examined in the activation of Cp*.sub.2ZrMe.sub.2
(Zr-ii). By addition of either 2A or 1A to Zr-ii, thiol
protonolysis of the Zr--Me bonds is measured to be 150.times. more
rapid than the analogous alkyne protonolysis.
[0046] An apparent ME of k.sub.H/k.sub.D=1.3(0.1) is measured for
the reaction 1A +2B-d catalyzed by complex Zr-i, consistent with a
secondary kinetic isotope effect. At early reaction times, a single
olefinic resonance appears in the .sup.1H NMR at .delta. 5.13 ppm
assigned to a product 3AB-d.sub.E by 1D NOESY NMR. In addition,
.sup.2H NMR shows a single product deuterium resonance at .delta.
5.4 ppm. Upon further heating, additional product olefinic
resonances appear in the .sup.1H NMR spectra at .delta. 5.41, 5.40,
and 5.14 ppm with a second olefinic resonance in the .sup.2H NMR at
.delta. 5.1 ppm indicating the formation of products 3AB,
3AB-d.sub.z, and possibly 3AB-d.sub.2 (Scheme 2). Interestingly, a
deuterium resonance is also observed growing in at .delta. 1.07 ppm
indicating deuteration of the thiol (i.e., RSD).
[0047] To further examine the deuterium exchange from alkyne-d to
thiol, phenylacetylene-d (2B-d), t-butylmercaptan, and Zr-i were
dissolved in benzene-d.sub.6 and heated at 120.degree. C. for 9
hours. Despite no evidence of zirconium-mediated hydrothiolation,
deuterium/proton exchange is observed by 1H and .sup.2H NMR
spectroscopy, indicating that the exchange is independent of the
zirconium-mediated hydrothiolation pathway. A similar combination
of 2B-d and 1A without catalyst evidences no deuterium exchange
showing that zirconium is involved in the isotopic exchange
process.
##STR00050##
[0048] Kinetic experiments are also conducted on the Ln-ix-mediated
hydrothiolation of 2A by 1A in benzene-d.sub.6 at 120.degree. C.
The empirical rate law is derived by examining the
turnover-frequency (N.sub.t) while systematically varying
[catalyst], [alkyne], and [thiol]. By examining Ln-ix from 0.4-8.6
mM, a linear trend is observed for concentrations of 0.4-5.2 mM
(FIG. 2A), indicating a first-order dependence on [catalyst] at
lower concentrations, while a fall in activity is observed at
higher concentrations. Attempts to explore the reaction at even
higher Ln-ix values, 9-17 mM, results in reduced activity and rapid
catalyst precipitation from solution. An investigation of the
effects of increasing [1-hexyne] from 0.1-3.5 M reveals a linear
correlation with activity over the [1-hexyne] range, 0.1-0.9 M
(FIG. 2B), indicating initial first-order dependence on [alkyne].
On increasing the alkyne concentration further, a slight reduction
in activity is observed which may be the result of partial alkyne
saturation of the metal center and/or alkyne acting as a
hydrothiolation inhibitor. Finally, the dependence of N.sub.t on
[1-penthanethiol] from 0.01-0.2 M at 1-hexyne concentrations (i.e.,
3.5 M) to force the reaction to pseudo zero-order shows the
reaction to be zero-order with respect to [thiol] (FIG. 2C). The
fall in rate near the end of the reaction corresponds to the onset
of observable catalyst precipitation. Therefore, the empirical rate
law, under standard catalytic conditions with minimal catalyst
precipitation, is given by Equation 1b.
Rate=k.sub.obs[Sm].sup.1[Alkyne].sup.1[Thiol].sup.0 (Equation
1b)
[0049] To trace the fate of D-CC.ident.R' during Ln-ix- and
An-1-mediated hydrothiolation, deuterium-labeling studies are
performed using deuterated 2B-d and 1A. Exclusive observation of
H.sub.2C(TMS).sub.2 in the .sup.1H and .sup.2H NMR evidences
thiol-mediated protonolytic activation of the catalyst. By
comparing the activity with that of non-deuterated phenylacetylene,
apparent KIEs of k.sub.H/k.sub.D=1.40(0.1) and 1.35(0.1) are
observed for catalysts Ln-ix and An-i, respectively. This is
consistent with a secondary kinetic isotope effect in a
turnover-limiting insertion mechanism. At early reaction times, a
single product isotopomer is primarily observed. However, upon
further heating, other known isotopomer products are observed,
along with substantial loss of the phenylacetylene deuterium label.
The observation of 3AB-dE product early in the reaction is
consistent with thiol-mediated protonolysis. As the reaction
progresses, increasing quantities of other product isotopomers
form, corresponding to redistribution of the alkyne .sup.2H label.
Based on .sup.1H and .sup.2H NMR spectroscopy, deuterium is
observed to migrate from the alkyne terminus to the thiol
functionality, as evidenced by a prominent RSD resonance in the 2H
NMR. To determine if the migration is the result of the catalytic
cycle, t-butylmercaptan, phenylacetylene-d, and either complex
Ln-ix or An-i are heated in benzene-d.sub.6 at 120.degree. C. for
0.75 hours. Proton NMR integration indicates that 15-30% of the
deuterium migrates from the alkyne during this time period despite
the fact that no measurable hydrothiolation product is observed. A
control experiment without the addition of catalyst results in no
detectable deuterium scrambling. The observed .sup.2H exchange
between phenylacetylene-d and t-BuSH, prior to significant
catalytic turnover, as well as negligible .sup.2H migration in the
absence of catalyst, strongly supports a metal complex pathway
independent of the hydrothiolation catalytic cycle. The known
protonolytic reactivity of terminal alkynes, with lanthanide- and
actinide-heteroelement bonds suggests a pathway such as shown in
Scheme 3.
##STR00051##
[0050] Interestingly, the more rapid formation of the product
isotopomers in lanthanide- and actinide-mediated hydrothiolation
than in zirconium-mediated hydrothiolation is consistent with the
more polar bonding and larger ionic radii of lanthanide and
actinide complexes and lanthanide and actinide complexes exhibiting
a lower protonolytic/deuterolytic barrier. Bond enthalpy estimates
indicate that the protonolytic detachment of alkyne from organo-Th
or Sm complexes is ca. -24 kcal/mol and -22 kcal/mol, respectively
(Equation 2).
R''SH+M-C.ident.CR'.fwdarw.M-SR''+H--C.ident.CR' (Equation 2)
[0051] Due to the Markonikov selectivity and exothermicity of
thiol-mediated protonolysis of metal-alkynyl bonds, the
metal-alkynylmetal-thiolate equilibrium should strongly favor the
corresponding thiolates. In the Ln-ix- and An-1-mediated
hydrothiolation of phenylacetylene-d by 1A, the formation of
primarily 3AB-d.sub.2 further supports the insertion/thiol-mediated
protonolysis mechanism (Scheme 4). The observation of small
quantities of 3AB early in the reaction demonstrates the rapid
nature of deuterium/proton scrambling between the alkyne and thiol
positions.
##STR00052##
[0052] While alkyne deuterolysis of M-vinyl product from the
lanthanide or actinide center could result in .sup.2H delivery to
the Z product position, it seems more likely to originate from
thiol-mediated deuterolysis of products bound to the metal center
(Scheme 5), because of the RSD detected in situ by .sup.2H NMR, and
REH (E=O and S) protonolysis pathways in analogous
organozirconium-mediated hydrothiolation and lanthanide-mediated
hydroalkoyxlation processes.
##STR00053##
[0053] The disclosures in this application of all articles and
references, including patents, are incorporated herein by
reference.
[0054] The invention is illustrated further by the following
examples which are not to be construed as limiting the invention in
scope or spirit to the specific procedures described herein. The
starting materials and various intermediates may be obtained from
commercial sources, prepared from commercially available compounds,
or prepared using well known synthetic methods. Representative
examples of methods for preparing intermediates of the invention
are set forth below. All thiols, alkynes and vinyl sulfide products
of the examples below are named by ChemBioDraw Ultra, version
12.0.
EXAMPLES
Materials and Methods
[0055] Due to the air and moisture sensitivity of the
organoactinide complexes in this study, all manipulations are
carried out in oven-dried, Schlenk-type glassware interfaced to
either a dual-manifold Schlenk line, high-vacuum line (10.sup.-6
Torr), or in a nitrogen-filled glove box (<2 ppm O.sub.2). Argon
(Airgas) is further purified by passing it through columns of MnO
and activated 4 A Davison molecular sieves immediately before use.
Toluene-d.sub.8 and benzene-d.sub.6 (all 99+atom % D) for NMR
reactions and kinetic measurements are stored over Na/K alloy in
vacuo and vacuum transferred immediately prior to use or are stored
in a nitrogen-filled glovebox until use. Diethylether for synthesis
is distilled from Na/benzophenone immediately prior to use.
D.sub.2O (99+ atom % D) is used as received. Tetraglyme is
vacuumed-pumped to remove volatiles. Ethanethiol-d (98 atom % D) is
prepared according to literature methods (Marks et al., J. Am.
Chem. Soc. 2009, 131, 2062-2063). Thiols and alkynes are
transferred from multiple beds of activated Davison 4 A molecular
sieves as solutions in benzene-d.sub.6 or neat, followed by
degassing (10.sup.-6 Torr) via freeze-pump-thaw methods. Conjugated
alkynes and thiols are stored at -10.degree. C. until use. All
substrates are stored under argon until use, and phenylacetylene
and 1-ethynylcyclohexene are distilled just prior to use. The
catalysts are prepared as reported in the literature (see Stubbert;
B. D., Marks, T. J. J. Am. Chem. Soc. 2007, 129, 6149-6167;
Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129,
4253-4271; and Stubbert, B. D.; Stern, C. L.; Marks, T. J.
Organometallics 2003, 22, 4836-4838, all of which are incorporated
herein by reference). The methyltriphenylsilane .sup.1H NMR
internal integration standard for kinetics is sublimed under
high-vacuum and stored in a glove box until use.
[0056] Physical and Analytical Measurements.
[0057] NMR spectra are recorded on Mercury 400 (400 MHz, .sup.1H;
100 MHz, .sup.13C; 61 MHz, .sup.2H) and Avance III 500 (500 MHz,
.sup.1H; 125 MHz, .sup.13C) NMR spectrometers. Chemical shifts
(.delta.) are referenced relative to internal solvent or
integration standard resonances and reported relative to
Me.sub.4Si. Spectra of air-sensitive reactions and materials are
taken in airtight, Teflon-valved J. Young NMR tubes. Samples are
heated in silicon oil baths with the temperature controlled by an
Ika ETS-D4 probe. GC data for selectivity measurements are
collected on a HP6890 GC-MS equipped with a HP5972 detector and an
HP-5MS (5% phenyl methyl siloxane, 30m.times.250 .mu.m.times.0.25
.mu.m) capillary column while high-resolution mass spectra are
collected on an Agilent 6210 LC-TOP (ESI, APPI) and Thermo Finnegan
MAT900 (EI).
[0058] Typical NMR Scale Catalytic Reaction.
[0059] a) In a glove box, Zr-i (3.7 mg, 10 .mu.mol) and
methyltriphenylsilane (8.0 mg, 29.5 .mu.mol are dissolved in 0.6 ml
of C.sub.6D.sub.6 and added to a J. Young NMR tube. The tube is
sealed, removed from the glove box, and attached to a high-vacuum
line where 0.2 ml of thiol and 0.2 ml of alkyne solutions (both 1.0
M in benzene-d.sub.6; 0 2 mmol; 20-molar excess) are syringed in
under an argon flush. The reaction mixture is then sealed, shaken
well, degassed by a single freeze-pump-thaw cycle, and placed in a
pre-heated, temperature controlled oil bath covered with aluminum
foil.
[0060] b) In a glove box, Ln-ix (3.0 mg, 5.2 .mu.mol) and
methyltriphenylsilane (8.0 mg, 29.5 .mu.mol) are dissolved in 0.6
ml benzene-d.sub.6 and added to a J. Young NMR tube. The tube is
sealed, removed from the glove box, and attached to a high-vacuum
line where 0.2 ml of thiol and 0.2 ml of alkyne solutions (both 1.0
M in benzene-d.sub.6; 0.2 mmol; 38-molar excess) are syringed in
under an argon flush. The reaction mixture is then sealed, shaken
well, degassed by a single freeze-pump-thaw cycle, and placed in a
pre-heated, temperature controlled oil bath covered with aluminum
foil.
[0061] Typical NMR Scale Kinetic Experiment. The same procedure as
described above is followed except that the sample is periodically
cooled to room temperature to collect .sup.1H NMR spectra. Turnover
frequency (N.sub.t) is determined by the method of initial rate
where data points are collected early in the reaction before the
substrates are appreciably consumed. As a result, the reaction
during this period of time is approximated as pseudo-zero-order
with respect to the substrate concentrations, resulting in a linear
trend. The resulting linear plots are fit by a linear-regression
analysis using R.sup.2.gtoreq.0.99 according to Equation 3, and
N.sub.t is calculated according to Equation 4 where
[catalyst].sub.o=initial concentration of catalyst and t=time in
hours. Kinetic experiments in this study are performed at 0.2 M
[thiol] and [alkyne] unless otherwise indicated. Linear corrections
for slight variations in initial [thiol] and [alkyne] are applied
as needed.
[ product ] = mt Equation 3 N t ( h - 1 ) = m [ catalyst ] 0
Equation 4 ##EQU00001##
[0062] Yield and Selectivity Measurements.
[0063] a) In the glovebox, Zr-iv (5.0 mg, 10 .mu.mol is dissolved
in 0.4 ml of C.sub.6D.sub.6 and the resulting solution is
transferred to a J. Young NMR tube. The tube is then sealed,
removed from the glovebox, and attached to a high-vacuum line where
0.2 ml of thiol and 0.6 ml of alkyne solutions (both 1.0 M in
benzene-d.sub.6; 0.2 mmol; 20-molar excess in thiol) are syringed
in under an argon flush. The reaction mixture is then sealed,
shaken, degassed by a single freeze-pump-thaw cycle, and placed in
a temperature-controlled, 120.degree. C. oil bath for 24.0 hours.
The product conversion and selectivity are determined by .sup.1H
NMR and GC/MS.
[0064] b) In a glove box, Ln-ix (5.0 mg, 10 .mu.mol is dissolved in
0.4 ml benzene-d.sub.6 and the resulting solution transferred to a
J. Young NMR tube. The tube is then sealed and attached to a
high-vacuum line where 0.2 ml thiol and 0.6 mL alkyne solutions
(both 1.0 M in benzene-d.sub.6; 0.2 mmol; 20-molar excess in thiol)
are syringed in under an argon flush. The reaction mixture is then
sealed, shaken, and placed in temperature-controlled, 120.degree.
C. oil bath for 16.0 hours. The product selectivity is determined
by GC/MS while conversion is determined by .sup.1H NMR integrations
against internal standards or quantitatively liberated catalyst
ligands.
[0065] General Procedure for Purification of Products.
[0066] The reaction mixture is cooled to room temperature and the
contents are eluted through a silica gel plug with .about.10 ml of
hexanes to remove the catalyst. The filtrate is pumped with a
Schlenk line to remove volatiles. Further purification by flash
chromatography (ether:hexanes eluent) is performed when necessary.
To avoid degradation, some products are purified by precipitating
the catalyst from exposure to air, centrifuging the precipitated
catalyst, and decanting the solution. Volatiles are pumped off on a
Schlenk line to yield pure product.
[0067] General Preparative Scale Procedure.
[0068] a) In a glovebox, Zr-iv (220 mg, 0.44 mmol) is added to an
oven-dried, 20 ml J. Young-valved glass storage tube with a stir
bar and dissolved in 10 ml of toluene. The tube is then sealed and
placed on a high-vacuum line where 1A (1.0 ml, 8.1 mmol) and 2A
(2.5 ml, 22 mmol) are syringed into the tube under an argon flush.
The vessel is next sealed and placed in a preheated 100.degree. C.
oil bath for 24 hours. After cooling, the vessel is opened to
ambient and the catalyst is removed by filtering through silica
gel, eluting with .about.20 ml of hexanes. The volatiles are then
removed under vacuum to yield pure 3AA as a yellow oil (1.08 g, 5.8
mmol, 72% yield) which is determined to be 99% Markovnikov pure by
GC/MS.
[0069] b) In a glove box, Ln-ix (75 mg, 0.13 mmol) is added to an
oven dried, 20 ml Teflon-valved, glass storage tube dissolved in 1
ml benzene. On a high-vacuum line, an additional 9 ml of benzene
are added by vacuum transfer. The tube is cooled to -78.degree. C.
and 2A (7,0.90 ml, 7.8 mmol) and 1F (0.30 ml, 2.6 mmol) are
syringed into the tube under an argon flush. The vessel is sealed,
thawed, and placed in a pre-heated 120.degree. C. oil bath for 36.0
hours with no stirring. Under ambient conditions, the catalyst is
removed by filtering through silica gel and eluting with 20 ml
hexanes. The volatiles are then removed under vacuum (10.sup.-6
mTorr) to yield 97% Markovnikov-pure 3FA as a yellow oil (0.22 g,
1.1 mmol, 41% yield).
Example 1
a) pentane-1-thiol-d
##STR00054##
[0071] An oven-dried, 200 ml Schlenk flask is charged with LiH
(0.72 g, 91 mmol) and a magnetic stir bar. While under nitrogen, 50
ml of dry tetraglyme is cannulated into the flask and stirred
vigorously to form a slurry. The flask is cooled to 0.degree. C.
before dropwise addition of dry 1A (8.4 g, 80.6 mmol). The reaction
is allowed to warm to room temperature and then stirred for 1 hour
followed by recooling to 0.degree. C. and dropwise quenching with
D.sub.2O (2.5 ml, 140 mmol). The product 1A-d is vacuum-transferred
from the tetraglyme and dried over 4 A molecular sieves before use
(.about.2.5 g, 30% yield). .sup.1H NMR (benzene-d.sub.6, 400 MHz,
6): .delta. 2.17 (q, J=7.2 Hz, 2H); 1.34 (m, 2H); 1.12 (m, 4H);
0.79 (t, J=5.6 Hz, 3H). .sup.2H NMR (benzene-d.sub.6, 76.7 MHz,
.delta.): .delta. 1.09 (s). .sup.13C NMR (benzene-d.sub.6, 100 MHz,
.delta.): .delta. 33.9; 30.8; 24.9; 22.3; 14.2.
[0072] b) Ethanethiol-d (1E-d)- .sup.1H NMR (benzene-d.sub.6, 500
MHz, .delta.): .delta. 2.16 (m, 2H); 0.97 (t, 7.0 Hz, 1H). .sup.13C
NMR (benzene-d.sub.6, 125 MHz, .delta.): .delta. 20.1; 19.3. 2H
(benzene-d.sub.6, 61 MHz, .delta.): .delta. 1.07 (s).
Example 2
a) phenylacetylene-d
[0073] In an oven-dried, 200 ml Schlenk flask, phenylacetylene (7.0
ml, 64 mmol) is dissolved in 60 ml of anhydrous diethylether. The
flask is cooled to 0.degree. C. before the slow addition of 45 ml
of n-BuLi solution (1.6 M in hexanes, 72 mmol) and stirring for 15
minutes at 0.degree. C., followed by 30 minutes at room
temperature. The flask is recooled to 0.degree. C., and D.sub.2O
(2.5 ml, 125 mmol) is slowly added. The reaction is stirred
overnight at room temperature before the solvent is removed in
vacuo, and the product is distilled to afford a clear liquid in 57%
yield. The deuterium incorporation is determined to be 98% atom % D
by
[0074] .sup.1H NMR. .sup.1H NMR (benzene-d.sub.6, 500 MHz,
.delta.): .delta. 7.40 (m, 2H); 6.91 (m, 3H). .sup.13C NMR
(benzene-d.sub.6, 125 MHz, .delta.): .delta. 132.7; 129.1; 128.9;
123.1; 83.8 (t, 7.5 Hz); 78.0 (t, 38 Hz). 2H (benzene-d.sub.6, 61
MHz, .delta.): .delta. 2.68 (s).
Example 3
a) hex-1-en-2-yl(pentyl)sulfane
##STR00055##
[0076] In a glove box, An-iv (140 mg, 0.25 mmol) is added to an
oven-dried, J. Young-valved glass tube with stir bar. The tube is
sealed, placed on a high-vacuum line where toluene (30 ml) is
vacuum transferred from Na/K to dissolve the catalyst. Under an
argon flush, 1A (0.60 ml, 4.8 mmol) and 2A (0.65 m, 5.7 mmol) are
syringed into the tube, degassed by freeze-pump-thaw, sealed, and
placed in a pre-heated 120.degree. C. oil bath for 24 hours. Next,
the vessel is opened to ambient surroundings and catalyst is
removed by filtering through silica gel and eluting with hexanes.
The product is purified by flash chromatography (SiO.sub.2, eluted
with 5:1 hexanes/ethyl acetate) and pumped down on a Schlenk line
to yield pure 3AA as a yellow oil (0.62 g, 3.3 mmol, 69%
yield).
[0077] .sup.1H NMR (benzene-d.sub.6, 400 MHz, 6): .delta. 5.34 (s,
1H); 4.72 (s, 1H); 2.53 (t, J=7.2 Hz, 2H); 2.25 (t, J=8.0 Hz, 2H);
1.63-1.47 (m, 4H); 1.34-1.08 (m, 6H); 0.90-0.75 (m, 6H). .sup.13C
NMR (benzene-d.sub.6, 125 MHz, 6): .delta. 147.2; 105.1; 38.2;
31.9; 31.8; 31.7; 28.6; 22.9; 22.8; 14.5; 14.4. HRMS-EI (m/z):
M.sup.+ calcd for C.sub.11H.sub.22S, 186.144. found, 186.144.95%
yield; 94% Markovnikov-selective.
Example 4
[0078] The following compounds are prepared using essentially the
same procedure as that described in the schemes, with reaction
temperature as that found in Table 2, and the general and specific
examples of above.
a) cyclohexyl (hex-1-en-2-yl)sulfane
##STR00056##
[0079] (yellow oil) .sup.1H NMR (benzene-d.sub.6, 500 MHz, 6):
.delta. 5.07 (s, 1H); 4.85 (s, 1H); 2.94 (m, 1H); 2.22 (t, J=7.5
Hz, 2H); 1.98 (m, 2H); 1.57 (m, 4H); 1.38 (m, 3H); 1.27 (m, 2H);
1.11 (m, 3H); 0.85 (t, J=7.5 Hz, 3H). .sup.13C NMR
(benzene-d.sub.6, 125 MHz, .delta.): .delta. 145.8; 107.4; 50.42;
43.4; 38.4; 33.5; 31.7; 26.5; 22.8; 14.4. HRMS-EI (m/z): M.sup.+
calcd for C.sub.12H.sub.22S 198.144. found, 198.144. 55% yield; 59%
Markovnikov-selective.
b) hex-1-en-2-yl(4-methylbenzyl)sulfane
##STR00057##
[0080] (dark yellow oil) .sup.1H NMR (benzene-d.sub.6, 400 MHz,
.delta.): .delta. 7.20-7.14 (m, 2H); 6.94-6.90 (m, 2H); 5.00 (s,
1H); 4.76 (s, 1H); 3.72 (s, 2H); 2.21 (m, 3H); 2.06 (s, 3H); 1.53
(m, 2H); 1.22 (m, 2H); 0.81 (m, 3H). .sup.13C NMR (benzene-d.sub.6,
100 MHz, .delta.): .delta. 147.2; 137.1; 134.5; 129.8; 129.5;
106.2; 38.0; 36.6; 31.7; 22.7; 21.3; 14.4. HRMS-EI (m/z): M.sup.+
calcd for C.sub.14H.sub.20S, 220.129. found, 220.128.
c) pentyl(1-phenylvinyl)sulfane
##STR00058##
[0081] (dark yellow oil) .sup.1H NMR (benzene-d.sub.6, 500 MHz, 6):
.delta. 7.63 (d, J=7.5 Hz, 2H); 7.12 (dd, J=7.5 Hz, 2H); 7.07 (m,
1H); 5.41 (s, 1H); 5.14 (s, 1H); 2.48 (t, J=7.5 Hz, 2H); 1.48 (t,
J=7.5 Hz, 2H); 1.20-1.05 (m, 4H); 0.77 (t, J=7.0 Hz, 3H). .sup.13C
NMR (benzene-d.sub.6, 125 MHz, 6): .delta. 140.5; 129.0; 128.9;
127.9; 110.7; 32.6; 28.9; 22.9; 21.6; 14.4. HRMS-EI (m/z): M.sup.+
calcd for C.sub.13H.sub.i8S, 206.113. found, 206.113. 100% yield;
66% Markovnikov-selective.
d) (1-(cyclohex-1-en-1-yl)vinyl)(pentyl)sulfane
##STR00059##
[0082] (dark yellow oil) .sup.1H NMR (benzene-d.sub.6, 500 MHz, 6):
.delta. 6.43 (s, 1H); 5.29 (s, 1H); 4.97 (s, 1H); 2.54 (t, J=7.5,
2H); 2.23-2.18 (m, 2H); 1.99-1.94 (m, 2H); 1.58-1.50 (m, 2H);
1.52-1.47 (m, 2H); 1.42-1.36 (m, 2H), 1.27-1.19 (m, 2H); 1.20-1.12
(m, 2H); 0.80 (t, J=7.0, 3H). .sup.13C NMR (benzene-d.sub.6, 125
MHz, .delta.): .delta. 147.1; 136.4; 1277; 107.2; 32.5; 31.8; 29.0;
27.7; 26.3; 23.5; 23.0; 22.8; 14.5. HRMS-EI (m/z): M.sup.+ calcd
for C.sub.13H.sub.22S, 210.144. found 210.143. 100% yield; 75%
Markovnikov-selective.
e) (1-cyclohexylvinyl)(pentyl)sulfane
##STR00060##
[0083] (yellow oil) .sup.1H NMR (benzene-d.sub.6, 500 MHz, 6):
.delta. 5.07 (s, 1H); 4.67 (s, 1H); 2.53 (t, J=7.0 Hz, 2H); 2.14
(t, J=11.5 Hz, 1H); 1.98 (d, J=12.5 Hz, 2H); 1.68 (d, J=12.5 Hz,
2H); 1.54 (t, 7.5, 3H); 1.40 (m, 2H); 1.25-1.02 (m, 7H); 0.80 (t,
J=7.0 Hz, 3H). .sup.13C NMR (benzene-d.sub.6, 125 MHz, .delta.):
.delta. 153.1; 102.7; 47.1; 33.9; 31.9; 31.6; 28.5; 27.3; 26.8;
23.0; 14.5. HRMS-EI (m/z): M.sup.+ calcd for C.sub.13H.sub.24S,
212.160. found, 212.159.92% yield; 92% Markovnikov-selective.
f) (1-cyclohexylvinyl) (4-methylbenzyl)sulfane
##STR00061##
[0085] (dark yellow oil) .sup.1H NMR (benzene-d.sub.6, 400 MHz, 6):
.delta. 7.16 (d, J=8.0 Hz, 2H); 6.92 (d, J=8.0 Hz, 2H); 5.05 (s,
1H); 4.71 (s, 1H); 3.73 (s, 2H); 2.11 (m, 1H); 2.07 (s, 3H); 1.96
(m, 2H); 1.64 (m, 2H); 1.52 (m, 2H); 1.37 (m, 2H); 1.11 (m, 3H).
.sup.13C NMR (benzene-d.sub.6, 100 MHz, 6): .delta. 153.0; 137.0;
134.5; 129.7; 129.5; 103.8; 46.9; 36.6; 33.8; 27.2; 26.8; 21.4.
HRMS-EI (m/z): M.sup.+ calcd for C.sub.16H.sub.22S, 246.144. found,
246.144.
g) ethyl(hex-1-en-2-yl)sulfane
##STR00062##
[0087] .sup.1H NMR (benzene-d.sub.6, 500 MHz, .delta.): .delta.
5.01 (s, 1H); 4.66 (s, 1H); 2.43 (q, 7.5 Hz, 2H); 2.22 (t, 7.5 Hz,
2H); 1.55 (m, 2H); 1.24 (m, 2H); 1.06 (t, 7.5 Hz, 3H); 0.83 (t, 7.5
Hz, 3H). .sup.13C NMR (benzne-d.sub.6, 125 MHz, .delta.): .delta.
146.8; 105.2; 38.1; 31.8; 25.6; 22.7; 14.4; 13.7. HRMS (EI) m/z
calcd for C.sub.8H.sub.16S: 144.0973. found: 144.0966.95% yield;
96% Markovnikov-selective.
h) hex-1-en-2-yl(2,2,2-trifluoroethyl)sulfane
##STR00063##
[0088] .sup.1H NMR (benzene-d.sub.6, 400 MHz, .delta.): .delta.
4.90 (s, 1H); 4.75 (s, .sup.1H); 2.69 (q, 10 Hz, 2H); 2.00 (t, 7.6
Hz, 2H); 1.34 (m, 2H); 1.40-1.30 (m, 2H); 1.17-1.07 (m, 2H); 0.78
(t, 7.2 Hz, 3H). .sup.13C NMR (benzene-d.sub.6, 100 MHz, .delta.):
.delta. 143.5; 129.0; 110.2; 36.9; 33.8 (q, J.sub.FC=10 Hz); 31.0;
22.5; 14.3. HRMS (EI) m/z calcd for C.sub.8H.sub.13F.sub.3S:
198.0690. found: 198.0684.79% yield; 84% Markovnikov-selective.
i) benzyl(hex-1-en-2-yl)sulfane
##STR00064##
[0089] .sup.1H NMR (benzene-d.sub.6, 500 MHz, .delta.): .delta.
7.22 (d, 7.5 Hz, 2H); 7.08 (t, 8.0 Hz, 2H); 7.01 (t, 7.5, 1H); 4.98
(s, 1H); 4.73 (s, 1H), 3.69 (s, 2H); 2.19 (t, 7.5 Hz, 2H); 1.51 (m,
2H); 1.22 (m, 2H); 0.81 (t, 7.5, 3H). .sup.BC NMR (benzene-d.sub.6,
125 MHz, .delta.): .delta. 147.0; 137.6; 129.5; 129.0; 127.6;
106.3; 37.9; 36.8; 31.7; 22.7; 14.4. HRMS (EI) m/z calcd for
C.sub.13H.sub.i8S: 206.1129. found: 206.1127.95% yield; 95%
Markovnikov-selective.
j) (3-cyclohexylprop-1-en-2-yl) (pentyl)sulfane
##STR00065##
[0090] .sup.1H NMR (benzene-d.sub.6, 500 MHz, .delta.): .delta.
5.02 (s, 1H); 4.74 (s, 1H); 2.53 (t, 7.0 Hz, 2H); 2.18 (d, 7.0 Hz,
2H); 1.83-1.78 (m, 2H); 1.78-1.70 (m, 1H); 1.70-1.63 (m, 2H);
1.63-1.56 (m, 1H); 1.56-1.48 (m, 2H); 1.26-1.04 (m, 7H); 0.87-0.78
(m, 5H). .sup.13C NMR (benzene-d.sub.6, 125 MHz, 6): .delta. 145.5;
106.0; 46.7; 37.3; 33.6; 31.9; 31.7; 28.6; 27.3; 27.0; 22.9; 14.5.
HRMS (EI) m/z calcd for C.sub.14H.sub.26.sub.S: 226.1755. found:
226.1748.98% yield; 96% Markovnikov-selective.
k) pentyl (3-phenylprop-1-en-2-yl)sulfane
##STR00066##
[0091] .sup.1H NMR (benzene-d.sub.6, 500 MHz, .delta.): .delta.
7.20-7.16 (m, 2H); 7.15-7.10 (m, 2H); 7.06-7.01 (m, 1H); 4.96 (s,
1H); 4.73 (s, 1H); 3.44 (s, 2H); 2.42 (t, 7.5 Hz, 2H); 1.44-1.36
(m, 2H); 1.13-1.01 (m, 4H); 0.72 (t, 7.0 Hz, 3H). .sup.BC NMR
(benzene-d.sub.6, 125 MHz, .delta.): .delta. 146.4; 139.5; 129.7;
128.9; 127.1; 107.1; 44.5; 31.9; 31.8; 28.5; 22.9; 14.4. HRMS (EI)
m/z calcd for C.sub.14H.sub.20S: 220.1286. found: 220.1287. 100%
yield; 91% Markovnikov-selective.
1) 3-(1-(pentylthio)vinyl)pyridine
##STR00067##
[0093] .sup.1H NMR (benzene-d.sub.6, 500 MHz, .delta.): .delta.
9.05 (s, 1H); 8.46 (dd, 5.0 Hz, 1H); 7.59 (dt, 8.0 Hz, 1H); 6.66
(dd, 8.0 Hz, 1H); 5.24 (s, 1H); 5.04 (s, 1H); 2.37 (t, 7.5 Hz, 2H);
1.40 (m, 2H); 1.15-1.05 (m, 4H); 0.77 (t, 7.0 Hz, 3H). .sup.13C NMR
(benzene-d.sub.6, 125 MHz, .delta.): .delta. 150.4; 149.2; 143.2;
136.1; 134.5; 123.4; 112.0; 32.5; 31.5; 28.7; 22.8; 14.4. HRMS
(APPI) m/z [M+H].sup.+ calcd for C.sub.12H.sub.17NS: 208.1161.
found: 208.1158. 100% yield; 90% Markovnikov-selective.
m) 2-(pentylthio)prop-2-en-1-amine
##STR00068##
[0095] .sup.1H NMR (benzene-d.sub.6, 500 MHz, 6): .delta. 5.16 (s,
1H); 4.74 (s, 1H); 3.26 (s, 2H); 2.49 (t, 7.5 Hz, 2H); 1.49 (m,
2H); 1.26-1.06 (m, 4H); 0.87-0.63 (bm, 5H). .sup.13C NMR
(benzene-d.sub.6, 125 MHz, 6): .delta. 149.5; 105.1; 48.8; 31.8;
31.5; 28.8; 22.9; 14.5. HRMS (ESI) m/z [M+H].sup.+ calcd for
C.sub.8H.sub.i8NS: 160.1154. found: 160.1155.
[0096] Table 4 shows representative examples of compounds made and
the catalyst and solvent employed. The reactions are performed at
temperatures ranging from 90-120.degree. C. While titanium is not
specifically listed in the table, the metal is employed in
complexes for methods of the invention. As with other Group 4
metals, optimization may vary with reaction conditions.
TABLE-US-00004 TABLE 4 Thiol Alkyne Catalyst Solvent 1H 2B Ln-i
Benzene-d.sub.6 (Dodecanethiol) 1H 2B Ln-i THF-d.sub.8 1H 2B Ln-ii
Benzene-d.sub.6 1H 2A Ln-i Benzene-d.sub.6 1C 2B Ln-i
Benzene-d.sub.6 1A 2A Ln-v THF-d.sub.8 1B 2A Ln-i Benzene-d.sub.6
1B 2A Ln-ix Benzene-d.sub.6 1A 2A Ln-iv THF-d.sub.8 1D 2A Ln-v
THF-d.sub.8 1D 2A Ln-ix Benzene-d.sub.6 1A 2A Ln-ii Benzene-d.sub.6
1A 2A Ln-vi Benzene-d.sub.6 1A 2A Ln-ix Benzene-d.sub.6 1G 2A Ln-ix
Benzene-d.sub.6 1A 2A Zr-ii Benzene-d.sub.6 1A 2A An-iii
Benzene-d.sub.6 1D 2B An-iv Benzene-d.sub.6 1D 2B An-ii
Benzene-d.sub.6 1C 2B An-ii Benzene-d.sub.6 1A 2B An-iii
Benzene-d.sub.6 1A 2A Zr-iii Benzene-d.sub.6 1A 2A Zr-ii
Benzene-d.sub.6 1A 2A Zr-i Benzene-d.sub.6 1G 2A Zr-i
Benzene-d.sub.6 1G 2A Zr-iii Benzene-d.sub.6 1G 2A Zr-iv
Benzene-d.sub.6 1G 2A Zr-v Benzene-d.sub.6 1D 2A Zr-iii
Benzene-d.sub.6 1A 2D Zr-i Benzene-d.sub.6 1A 2D An-vii
Benzene-d.sub.6 1G 2A An-vii Benzene-d.sub.6 1D 2B An-vii
Benzene-d.sub.6 1A 2C Zr-i Benzene-d.sub.6 1A 2B Zr-i
Benzene-d.sub.6 1A 2G Zr-i Benzene-d.sub.6 1A 2E Zr-i
Benzene-d.sub.6 1A 2H Zr-iii Benzene-d.sub.6 1A 2H Zr-i
Benzene-d.sub.6 1B 2A Zr-i Benzene-d.sub.6 1H 2A Zr-i
Benzene-d.sub.6 1H 2A Zr-iii Benzene-d.sub.6 1A 2A Zr-iv
Benzene-d.sub.6 1H 2A Zr-iv Benzene-d.sub.6 1E 2A Zr-i
Benzene-d.sub.6 1E 2A Ln-ix Benzene-d.sub.6 1F 2A Zr-i
Benzene-d.sub.6 1D 2A Zr-i Benzene-d.sub.6 1A 2F Zr-i
Benzene-d.sub.6
[0097] The catalytic organolanthanide-, organoactinide- and
organozirconium-mediated intermolecular hydrothiolathion of a wide
range of terminal alkynes by aliphatic, benzylic and aromatic
thiols is demonstrated by the methods disclosed herein. The
resulting vinyl sulfides are produced with high Markovnikov
selectivity. Based on kinetic experiments and deuterium labeling,
the reaction is proposed to proceed through an alkyne
insertion-thiol protonolysis sequence with turnover-limiting alkyne
insertion.
[0098] The invention and the manner and process of making and using
it are now described in such full, clear, concise and exact terms
as to enable any person skilled in the art to which it pertains, to
make and use the same. It is to be understood that the foregoing
describes preferred embodiments of the present invention and that
modifications may be made therein without departing from the spirit
or scope of the present invention as set forth in the claims.
* * * * *