U.S. patent application number 10/880951 was filed with the patent office on 2004-12-02 for catalyst ligands, catalytic metal complexes and processes using same.
This patent application is currently assigned to Symyx Technologies, Inc.. Invention is credited to Guram, Anil, Lund, Cheryl, Turner, Howard W., Uno, Tetsuo.
Application Number | 20040242881 10/880951 |
Document ID | / |
Family ID | 25214927 |
Filed Date | 2004-12-02 |
United States Patent
Application |
20040242881 |
Kind Code |
A1 |
Guram, Anil ; et
al. |
December 2, 2004 |
Catalyst ligands, catalytic metal complexes and processes using
same
Abstract
A new ligands that include a benzene ring in the backbone can be
combined with a metal or metal precursor compound or formed into a
metal-ligand complex catalyze a number of different chemical
transformations, including olefin polymerization reactions. The
ligands, complexes formed with the ligands and compositions
including the ligands are useful catalysts, depending on the
reaction.
Inventors: |
Guram, Anil; (San Jose,
CA) ; Lund, Cheryl; (Pleasanton, CA) ; Turner,
Howard W.; (Campbell, CA) ; Uno, Tetsuo; (San
Diego, CA) |
Correspondence
Address: |
SYMYX TECHNOLOGIES INC
LEGAL DEPARTMENT
3100 CENTRAL EXPRESS
SANTA CLARA
CA
95051
|
Assignee: |
Symyx Technologies, Inc.
|
Family ID: |
25214927 |
Appl. No.: |
10/880951 |
Filed: |
June 29, 2004 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10880951 |
Jun 29, 2004 |
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09956157 |
Sep 18, 2001 |
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09956157 |
Sep 18, 2001 |
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09814393 |
Mar 21, 2001 |
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6316663 |
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09814393 |
Mar 21, 2001 |
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09146206 |
Sep 2, 1998 |
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Current U.S.
Class: |
546/2 ; 548/402;
556/13 |
Current CPC
Class: |
C07C 211/49 20130101;
C08F 10/00 20130101; C07C 251/24 20130101; C08F 10/00 20130101;
C08F 10/00 20130101; C08F 4/7006 20130101; C07C 223/06 20130101;
C08F 4/60013 20130101 |
Class at
Publication: |
546/002 ;
548/402; 556/013 |
International
Class: |
C07F 015/00 |
Claims
1-55. Canceled.
56. A transition metal-catalyzed reaction employing a complex
characterized by one of the following general formulas: 15wherein
each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 is
independently selected from the group consisting of hydrogen, alkyl
substituted alkyl, cycloalkyl, substituted cycloalky, heteroalkyl,
heterocycloalkyl substituted heterocycloalkyl, aryl, substituted
aryl, substituted heteroaryl, alkoxy, aryloxy, silyl, boryl
phosphino, amino, thio, seleno, and combinations thereof,
optionally, R.sup.1 and R.sup.2 are joined together in a ring
structure and/or R.sup.4 and R.sup.5 are joined together in a ring
structure; G is either nitrogen or oxygen and a is 0 or 1 depending
on G: b is 0, 1, 2, 3 or 4; M is a transition metal selected from
the group consisting of Groups 3, 4, 5, 6, 7, 8, 9 and 10 of the
Periodic Table of Elements; L is independently each occurrence, a
ligand; n is a number 0, 1, 2, 3, 4, and 5; and m is 1, 2, 3 or
4.
57. The reaction of claim 56, wherein the reaction involves C--H,
C--C, C--N, C--O, C--S, C--P, C-B and C-Si bond formation.
58. The reaction of claim 57, wherein C--H, C--C, C--N, C--O, C--S,
C--P, C--B, and C--Si bond formation involves a sp.sup.2-hybridized
C atom.
59. The reaction of claim 56, wherein the reactions involves
carbonylation, hydroformylation, hydroxycarbonylation,
hydrocarbonylation, hydroesterification, hydrogenation,
hydrosilylation, hydroboration, hydroamination, epoxidation,
aziridation, reductive amination, C--H activation, insertion, C--H
activation-insertion, C--H activation-substitution, C-halogen
activation, C-halogen activation-substitution, C-halogen
activation-insertion, alkene metathesis, polymerization, alkene
oligomerization, alkene polymerization, alkyne oligomerization,
alkyne polymerization, co-polymerization, CO-alkene
co-oligomerization, CO-alkene co-polymerization, CO-alkyne
co-oligomerization, or CO-alkyne co-polymerization.
60-190. canceled.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to new organic compounds
(e.g., ligands), their metal complexes and compositions using those
compounds; the invention also relates to the field of catalysis. In
particular, this invention relates to new compounds which when
combined with suitable metals or metal precursor compounds provide
useful catalysts for various bond-forming reactions, including
polymerizations and small molecule transformations. The invention
also relates to combinatorial chemistry in that combinatorial
techniques were used in connection with creating the ligands and
testing compositions containing the ligands.
BACKGROUND OF THE INVENTION
[0002] Ancillary (or spectator) ligand-metal coordination complexes
(e.g., organometallic complexes) and compositions are useful as
catalysts, additives, stoichiometric reagents, monomers, solid
state precursors, therapeutic reagents and drugs. Ancillary
ligand-metal coordination complexes of this type can be prepared by
combining an ancillary ligand with a suitable metal compound or
metal precursor in a suitable solvent at a suitable temperature.
The ancillary ligand contains functional groups that bind to the
metal center(s), remain associated with the metal center(s), and
therefore provide an opportunity to modify the steric, electronic
and chemical properties of the active metal center(s) of the
complex.
[0003] Certain known ancillary ligand-metal complexes and
compositions are catalysts for reactions such as oxidation,
reduction, hydrogenation, hydrosilylation, hydrocyanation,
hydroformylation, polymerization, carbonylation, isomerization,
metathesis, carbon-hydrogen activation, carbon-halogen activation,
cross-coupling, Friedel-Crafts acylation and alkylation, hydration,
dimerization, trimerization, oligomerization, Diels-Alder reactions
and other transformations. See, e.g., U.S. Pat. Nos. 5,576,460 and
5,550,236, both of which are incorporated herein by reference.
[0004] One example of the use of these types of ancillary
ligand-metal complexes and compositions is in the field of
polymerization catalysis. In connection with single site catalysis,
the ancillary ligand offers opportunities to modify the electronic
and/or steric environment surrounding an active metal center. This
allows the ancillary ligand to create possibly different polymers.
Ancillary ligands and ancillary metal complexes that are similar to
those disclosed herein have been discussed in WO 98/30609,
incorporated herein by reference for all purposes. However, that
application does not specifically disclose any of the ligands,
complexes or compositions disclosed herein and does not disclose
any method of making the ligands (i.e., the ancillary ligands) of
this invention.
[0005] It is always a desire to discover new ancillary ligands,
which upon coordination to a metal center or addition of a metal
compound or precursor will catalyze or assist in catalysis of
reactions differently from known ligand systems. This invention
provides new ancillary ligands that may be used for coordination to
a metal center or included in a composition with a metal or metal
precursor compound. Upon coordination to the metal center or
inclusion in the composition, such ligands influence the electronic
and steric environment of the resulting coordination complex and
may catalyze reactions differently, including more efficiently and
selectively than known systems.
SUMMARY OF THE INVENTION
[0006] In a first aspect, the invention disclosed herein is a new
ligand (i.e., an ancillary ligand), which can be characterized by
the general formula: 1
[0007] wherein each R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.6
is independently selected from the group consisting of hydrogen,
alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl,
heteroalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,
substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, silyl, boryl, phosphino, amino, thio, seleno, and
combinations thereof; optionally, R.sup.1 and R.sup.2 are joined
together in a ring structure and/or R.sup.3 and R.sup.4 are joined
together in a ring structure and/or R.sup.1 and R.sup.6 are joined
together in a ring structure; and b is 0, 1, 2, 3 or 4. Where b is
at least 2, two R.sup.6 groups may be joined in a fused ring
structure with the benzene ring in the backbone of the ligand. G is
either oxygen or nitrogen. When G is oxygen, a is 0. When G is
nitrogen, a is 1.
[0008] In a second aspect, this invention is a compound
characterized by the general formula: 2
[0009] wherein each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and
R.sup.6 is independently selected from the group consisting of
hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, boryl, phosphino, amino, thio,
seleno, and combinations thereof; optionally, R.sup.1 and R.sup.2
are joined together in a ring structure and/or R.sup.3 and R.sup.4
are joined together in a ring structure and/or R.sup.4 and R.sup.5
are joined together in a ring structure and/or R.sup.1 and R.sup.6
are joined together in a ring structure; G is either oxygen or
nitrogen and a is either 1 or 2 depending on G; and b is 0, 1, 2, 3
or 4. When G is nitrogen and a is 2, the two R.sup.3 groups may
also join to form a ring structure.
[0010] This invention also relates to a novel method of making
these new ligands. The general method of making these ligands is to
start with a compound characterized by the general formula: 3
[0011] wherein R.sup.4 and R.sup.6 are as defined above and X is
selected from the group consisting of chloro, bromo, iodo,
triflate, tosylate and nonaflate; and R.sup.8 and R.sup.9 are
independently selected from the group consisting of hydrogen,
alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl,
heteroalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,
substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, silyl, boryl, phosphino, amino, thio, seleno, and
combinations thereof. This compound is reacted with an amine
characterized by the general formula HNR.sup.1R.sup.2, where
R.sup.1 and R.sup.2 are as defined above. This provides ligands
within the second aspect. Optionally, an acetyl or ketal
functionality of the product is then hydroylzed, providing ligands
within the first aspect. Thereafter, the product can be reacted
with a primary or secondary amine to transform the ligand.
Hydrogenation is thereafter an optional step. All steps may or may
not be performed using parallel or high throughput or combinatorial
methods.
[0012] In yet another aspect, this invention provides new
metal-ligand complexes or compositions comprising the new ligands
and a metal precursor. For catalysis, the ligands can be included
in a composition including a suitable metal or metal precursor
compound that can be of the form ML.sub.n, where the composition
has catalytic properties. Also, the ligands can be coordinated with
a metal precursor to form metal-ligand complexes, which may be
catalysts. Depending on the groups chosen for R.sup.1, R.sup.2 and
R.sup.3 in the ligand (i.e., prior to reaction with the metal
precursor), the metal-ligand complexes can be characterized by one
of many different general formulas depending on how the ligand
attaches to or associates with the metal.
[0013] A further aspect of this invention provides for the novel
ligands, compositions or complexes to be created and tested in a
combinatorial manner. Thus, the ligands, compositions or complexes
may be in an array with each ligand, composition or complex in a
different region of a substrate. The number of ligands,
compositions or complexes on a single substrate will vary according
to the desired density, but will typically have at least 10
ligands, compositions or complexes on a single substrate.
[0014] These metal-ligand complexes or compositions catalyze
polymerization and copolymerization reactions, particularly with
monomers that are olefins, diolefins or otherwise acetylenically
unsaturated. Other reactions that can be catalyzed include
activation of and/or formation of H--Si, H--H, H--N, H--O, H--P,
H--S, C--H, C--C, C.dbd.C, C.ident.C, C-halogen, C--N, C--O, C--S,
C--P, and C--Si bonds. Specifically, such reactions include
carbonylation, hydroformylation, hydroxycarbonylation,
hydrocarbonylation, hydroesterification, hydrogenation, transfer
hydrogenation, hydrosilylation, hydroboration, hydroamination,
epoxidation, aziridation, reductive amination, C--H activation,
insertion, C--H activation-insertion, C--H activation-substitution,
C-halogen activation, C-halogen activation-substitution, C-halogen
activation-insertion, cyclopropanation, alkene metathesis, alkene
oligomerization, alkene polymerization, alkyne oligomerization,
alkyne polymerization, CO-alkene co-oligomerization, CO-alkene
co-polymerization, CO-alkyne co-oligomerization and CO-alkyne
co-polymerization.
[0015] Thus, in another aspect of the invention, a polymerization
process is disclosed for olefins, diolefins and other
acetylenically unsaturated compounds. The polymerization process
involves contacting monomers to the catalyst compositions or to the
coordination complexes of this invention under polymerization
conditions. The catalyst compositions or the coordination complexes
may be active catalysts themselves or make be activated with a
known activating technique or compound. The polymerization process
can be continuous, batch or semi-batch and can be homogeneous or
heterogeneous, as discussed further below.
[0016] Further aspects of this invention will be evident to those
of skill in the art upon review of this specification.
DETAILED DESCRIPTION OF THE INVENTION
[0017] The inventions disclosed herein are new ligands that may be
combined with metals or metal precursor compounds to form
coordination complexes or compositions of matter, which are useful
as catalysts for chemical reactions. The invention also is for
processes for making the ligand, processes for making the metal
complexes and processes for using the resultant composition or
coordination complex as a catalyst. Finally, the invention provides
these new compounds and compositions and complexes in an array
format.
[0018] As used herein, the phrase "characterized by the formula" is
not intended to be limiting and is used in the same way that
"comprising" is commonly used. The term "independently selected" is
used herein to indicate that the R groups, e.g., R.sup.1, R.sup.2,
R.sup.3, R.sup.4, and R.sup.5 can be identical or different (e.g.
R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 may all be
substituted alkyls or R.sup.1 and R.sup.2 may be a substituted
alkyl and R.sup.3 may be an aryl, etc.). A named R group will
generally have the structure that is recognized in the art as
corresponding to R groups having that name. For the purposes of
illustration, representative R groups as enumerated above are
defined herein. These definitions are intended to supplement and
illustrate, not preclude, the definitions known to those of skill
in the art.
[0019] The term "alkyl" is used herein to refer to a branched or
unbranched, saturated or unsaturated acyclic hydrocarbon radical.
Suitable alkyl radicals include, for example, methyl, ethyl,
n-propyl, i-propyl, 2-propenyl (or allyl), vinyl, n-butyl, t-butyl,
i-butyl (or 2-methylpropyl), etc. In particular embodiments, alkyls
have between 1 and 200 carbon atoms, between 1 and 50 carbon atoms
or between 1 and 20 carbon atoms.
[0020] "Substituted alkyl" refers to an alkyl as just described in
which one or more hydrogen atom to any carbon of the alkyl is
replaced by another group such as a halogen, aryl, substituted
aryl, cycloalkyl, substituted cycloalkyl, and combinations thereof.
Suitable substituted alkyls include, for example, benzyl,
trifluoromethyl and the like.
[0021] The term "heteroalkyl" refers to an alkyl as described above
in which one or more hydrogen atoms to any carbon of the alkyl is
replaced by a heteroatom selected from the group consisting of N,
O, P, B, S, Si, Se and Ge. The bond between the carbon atom and the
heteroatom may be saturated or unsaturated. Thus, an alkyl
substituted with a heterocycloalkyl, substituted heterocycloalkyl,
heteroaryl, substituted heteroaryl, alkoxy, aryloxy, boryl,
phosphino, amino, silyl, thio, or seleno is within the scope of the
term heteroalkyl. Suitable heteroalkyls include cyano, benzoyl,
2-pyridyl, 2-furyl and the like.
[0022] The term "cycloalkyl" is used herein to refer to a saturated
or unsaturated cyclic non-aromatic hydrocarbon radical having a
single ring or multiple condensed rings. Suitable cycloalkyl
radicals include, for example, cyclopentyl, cyclohexyl,
cyclooctenyl, bicyclooctyl, etc. In particular embodiments,
cycloalkyls have between 3 and 200 carbon atoms, between 3 and 50
carbon atoms or between 3 and 20 carbon atoms.
[0023] "Substituted cycloalkyl" refers to cycloalkyl as just
described including in which one or more hydrogen atom to any
carbon of the cycloalkyl is replaced by another group such as a
halogen, alkyl, substituted alkyl, aryl, substituted aryl,
cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted
heterocycloalkyl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, boryl, phosphino, amino, silyl, thio, seleno and
combinations thereof. Suitable substituted cycloalkyl radicals
include, for example, 4-dimethylaminocyclohexyl,
4,5-dibromocyclohept-4-enyl, and the like.
[0024] The term "heterocycloalkyl" is used herein to refer to a
cycloalkyl radical as described, but in which one or more or all
carbon atoms of the saturated or unsaturated cyclic radical are
replaced by a heteroatom such as nitrogen, phosphorous, oxygen,
sulfur, silicon, germanium, selenium, or boron. Suitable
heterocycloalkyls include, for example, piperazinyl, morpholinyl,
tetrahydropyranyl, tetrahydrofuranyl, piperidinyl, pyrrolidinyl,
oxazolinyl and the like.
[0025] "Substituted heterocycloalkyl" refers to heterocycloalkyl as
just described including in which one or more hydrogen atom to any
atom of the heterocycloalkyl is replaced by another group such as a
halogen, alkyl, substituted alkyl, aryl, substituted aryl,
heteroaryl, substituted heteroaryl, alkoxy, aryloxy, boryl,
phosphino, amino, silyl, thio, seleno and combinations thereof.
Suitable substituted heterocycloalkyl radicals include, for
example, N-methylpiperazinyl, 3-dimethylaminomorpholinyl and the
like.
[0026] The term "aryl" is used herein to refer to an aromatic
substituent which may be a single aromatic ring or multiple
aromatic rings which are fused together, linked covalently, or
linked to a common group such as a methylene or ethylene moiety.
The common linking group may also be a carbonyl as in benzophenone
or oxygen as in diphenylether or nitrogen in diphenylamine. The
aromatic ring(s) may include phenyl, naphthyl, biphenyl,
diphenylether, diphenylamine and benzophenone among others. In
particular embodiments, aryls have between 1 and 200 carbon atoms,
between 1 and 50 carbon atoms or between 1 and 20 carbon atoms.
[0027] "Substituted aryl" refers to aryl as just described in which
one or more hydrogen atom to any carbon is replaced by one or more
functional groups such as alkyl, substituted alkyl, cycloalkyl,
substituted cycloalkyl, heterocycloalkyl, substituted
heterocycloalkyl, halogen, alkylhalos (e.g., CF.sub.3), hydroxy,
amino, phosphido, alkoxy, amino, thio and both saturated and
unsaturated cyclic hydrocarbons which are fused to the aromatic
ring(s), linked covalently or linked to a common group such as a
methylene or ethylene moiety. The linking group may also be a
carbonyl such as in cyclohexyl phenyl ketone.
[0028] The term "heteroaryl" as used herein refers to aromatic
rings in which one or more carbon atoms of the aromatic ring(s) are
replaced by a heteroatom(s) such as nitrogen, oxygen, boron,
selenium, phosphorus, silicon or sulfur. Heteroaryl refers to
structures that may be a single aromatic ring, multiple aromatic
ring(s), or one or more aromatic rings coupled to one or more
non-aromatic ring(s). In structures having multiple rings, the
rings can be fused together, linked covalently, or linked to a
common group such as a methylene or ethylene moiety. The common
linking group may also be a carbonyl as in phenyl pyridyl ketone.
As used herein, rings such as thiophene, pyridine, isoxazole,
phthalimide, pyrazole, indole, furan, etc. or benzo-fused analogues
of these rings are defined by the term "heteroaryl."
[0029] "Substituted heteroaryl" refers to heteroaryl as just
described including in which one or more hydrogen atoms to any atom
of the heteroaryl moiety is replaced by another group such as a
halogen, alkyl, substituted alkyl, aryl, substituted aryl,
heteroaryl, substituted heteroaryl, alkoxy, aryloxy, boryl,
phosphino, amino, silyl, thio, seleno and combinations thereof.
Suitable substituted heteroaryl radicals include, for example,
4-N,N-dimethylaminopyridine.
[0030] The term "alkoxy" is used herein to refer to the --OZ.sup.1
radical, where Z.sup.1 is selected from the group consisting of
alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl,
heterocylcoalkyl, substituted heterocycloalkyl, silyl groups and
combinations thereof as described herein. Suitable alkoxy radicals
include, for example, methoxy, ethoxy, benzyloxy, t-butoxy, etc. A
related term is "aryloxy" where Z.sup.1 is selected from the group
consisting of aryl, substituted aryl, heteroaryl, substituted
heteroaryl, and combinations thereof. Examples of suitable aryloxy
radicals include phenoxy, substituted phenoxy, 2-pyridinoxy,
8-quinalinoxy and the like.
[0031] As used herein the term "silyl" refers to the
--SiZ.sup.1Z.sup.2Z.sup.3 radical, where each of Z.sup.1, Z.sup.2,
and Z.sup.3 is independently selected from the group consisting of
alkyl, substituted alkyl, cycloalkyl, heterocycloalkyl,
heterocyclic, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, amino, silyl and combinations
thereof.
[0032] As used herein the term "boryl" refers to the
--BZ.sup.1Z.sup.2 group, where each of Z.sup.1 and Z.sup.2 is
independently selected from the group consisting of alkyl,
substituted alkyl, cycloalkyl, heterocycloalkyl, heterocyclic,
aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, amino, silyl and combinations thereof.
[0033] As used herein, the term "phosphino" refers to the group
--PZ.sup.1Z.sup.2, where each of Z.sup.1 and Z.sup.2 is
independently selected from the group consisting of hydrogen,
substituted or unsubstituted alkyl, cycloalkyl, heterocycloalkyl,
heterocyclic, aryl, heteroaryl, silyl, alkoxy, aryloxy, amino and
combinations thereof.
[0034] The term "amino" is used herein to refer to the group
--NZ.sup.1Z.sup.2, where each of Z.sup.1 and Z.sup.2 is
independently selected from the group consisting of hydrogen;
alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl,
heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl, alkoxy, aryloxy, silyl
and combinations thereof.
[0035] The term "thio" is used herein to refer to the group
--SZ.sup.1, where Z.sup.1 is selected from the group consisting of
hydrogen; alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,
substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, silyl and combinations thereof.
[0036] The term "seleno" is used herein to refer to the group
--SeZ.sup.1, where Z.sup.1 is selected from the group consisting of
hydrogen; alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,
substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, silyl and combinations thereof.
[0037] The term "saturated" refers to lack of double and triple
bonds between atoms of a radical group such as ethyl, cyclohexyl,
pyrrolidinyl, and the like.
[0038] The term "unsaturated" refers to the presence one or more
double and triple bonds between atoms of a radical group such as
vinyl, acetylenyl, oxazolinyl, cyclohexenyl, acetyl and the
like.
[0039] The new ligands of this invention can be characterized by
either of the general formulas: 4
[0040] wherein each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and
R.sup.6 is independently selected from the group consisting of
hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, boryl, phosphino, amino, thio,
seleno, and combinations thereof; optionally, R.sup.1 and R.sup.2
are joined together in a ring structure and/or R.sup.3 and R.sup.4
are joined together in a ring structure and/or R.sup.4 and R.sup.5
are joined together in a ring structure; and b is 0, 1, 2, 3 or 4.
G is an element selected from the group consisting of oxygen and
nitrogen. In connection with structure I, a is 0 when G is oxygen
and a is 1 when G is nitrogen. In connection with structure II, a
is 1 when G is oxygen and a is 2 when G is nitrogen. Also in
connection with structure II, when a is 2, the two R.sup.3 groups
may be the same or different and optionally may be joined together
in a ring structure.
[0041] In more specific embodiments, R.sup.1 and R.sup.2 are
independently selected from a group consisting of hydrogen, alkyl,
substituted alkyl, cycloalkyl, substituted cycloalkyl,
heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl and silyl. Specific
examples of R.sup.1 and R.sup.2 are hydrogen, methyl, ethyl,
propyl, butyl, cyclopentyl, cylcohexyl, cyclooctyl, phenyl,
naphthyl, benzyl, trimethylsilyl, and the like. In those
embodiments where R.sup.1 and R.sup.2 are joined together in a ring
structure, the ring (including R.sup.1, R.sup.2 and N) has from 3
to 15 non-hydrogen atoms as part of the backbone of the ring.
Specific examples of R.sup.1 and R.sup.2 together are ethylene
(giving a 3-member ring), propylene (giving a 4-membered ring),
butylene (giving a 5-membered ring), 3-oxopentylene (giving a
6-membered ring) and the like.
[0042] In a preferred embodiment, R.sup.1 is a substituted or
unsubstituted phenyl and R.sup.2 is hydrogen. If R.sup.1 is a
substituted phenyl, there may be 1, 2, 3, 4 or 5 substituents
attached to carbon atoms in the phenyl ring. Each of these
substituents may be independently selected from the group
consisting of alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, boryl, phosphino, amino, thio,
seleno, and combinations thereof. More preferably, there are 1, 2
or 3 substituents on the substituted phenyl and the substituents
are selected from the group consisting of chloro, fluoro, iodo,
bromo, methyl, ethyl, propyl, butyl, cyclopentyl, cylcohexyl,
cyclooctyl, phenyl, naphthyl, benzyl, trimethylsilyl and isomers
thereof.
[0043] More specifically, R.sup.3 is selected from a group
consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl,
substituted cycloalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkyloxy, aryloxy, amino, silyl, boryl and phosphino.
Specific examples of R.sup.3 are methyl, ethyl, propyl, butyl,
cyclohexyl, cyclopropyl, cycloheptyl, t-butyl, phenyl, biphenyl,
naphthyl, benzyl, pyridyl, furyl, quinolyl, morpholinyl, cyano,
methoxy, ethoxy, t-butoxy, phenoxy, benzyloxy, dimethylamino,
diethylamino, diphenylamino, phenylmethylamino, benzylmethylamino,
trimethylsilyl, dimethyl-t-butylsilyl, triphenylsilyl,
triethoxysilyl, dimethylboryl, diphenylboryl, diphenoxyboryl,
1,2-dioxyphenylboryl, 2,2'-biphenoxyboryl, 2,2'-dinaphthoxyboryl,
diphenylphosphino, dibutylphosphino, dimethylphosphino,
dicyclohexylphosphino, dicylcyclopentylphosphino, nitro, and
methylphenylphosphino.
[0044] Most preferably, R.sup.3 is benzyl or a substituted or
unsubstituted phenyl. Where R.sup.3 is a substituted phenyl and
there are 1, 2, 3, 4 or 5 substituents on the phenyl ring, with
each of said substituents independently selected from the group
consisting of alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, hydroxy, halogens, alkoxy, aryloxy, silyl, boryl,
phosphino, amino, thio, seleno, and combinations thereof.
Preferably in those embodiments there are 1, 2 or 3 substituents on
the substituted phenyl and the substituents are selected from the
group consisting of chloro, fluoro, iodo, bromo, methyl, ethyl,
propyl, butyl, cyclopentyl, cylcohexyl, cyclooctyl, phenyl,
naphthyl, benzyl, trimethylsilyl and isomers thereof. Also in more
specific embodiments, R.sup.4 is selected from the group consisting
of hydrogen, alkyl, substituted alkyl, heteroalkyl, cycloalkyl,
substituted cycloalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkyloxy, aryloxy, boryl, amino and silyl. In yet other
embodiments, R.sup.4 may be selected from the group consisting of
hydrogen, alkyl, aryl and cycloalkyl. Specific examples of R.sup.4
are hydrogen, methyl, ethyl, propyl, butyl, cyclopentyl,
cylcohexyl, cyclooctyl, phenyl, naphthyl, benzyl, pyridyl, furyl,
morpholino, methoxy, ethoxy, butoxy, phenoxy, benzyloxy,
dimethylboryl, diphenylboryl, methylphenylboryl, dimethylamino,
diethylamino, diphenylamino, dibenzylamino, trimethylsilyl,
triethoxysilyl, triphenylsilyl, triphenoxysilyl,
dimethyl-t-butylsilyl, and the like.
[0045] In some embodiments where R.sup.3 and R.sup.4 are joined
together in a ring structure, the ring (including R.sup.3, R.sup.4,
G and C) has from 4 to 15 non-hydrogen atoms as part of the
backbone of the ring. In connection with structure I, G is nitrogen
and a is 1 and R.sup.3 is selected from the group consisting of
hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, boryl, phosphino, amino and
combinations thereof. Specific examples of R.sup.3 and R.sup.4
together are ethylene (giving a 4-membered ring), butylene (giving
a 6-membered ring), bicyclooctyl, bicyclohexyl, 2,2'-biphenyl
(giving a dibenzo fused 6-membered ring), 2,2'-binaphthyl (giving a
dinaphtho fused 6-membered ring), 2,2'-biphenoxy (giving a
8-membered ring), 2,2'-dinaphthoxy (giving a 8-membered ring) and
diethoxy (giving a 6-membered ring).
[0046] Also in more specific embodiments, R.sup.6 is selected from
the group consisting of electron withdrawing and electron donating
groups and b is 0, 1, 2, 3 or 4. R.sup.6 can take any open position
on the benzene ring that helps form the backbone of the ligand.
More specifically, R.sup.6 may be chosen from the group consisting
of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl,
heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl, silyl, amino, alkoxy,
aryloxy, phosphino, boryl, transition metals, halogens and
combinations thereof. Specific examples of R.sup.6 include methyl,
ethyl, propyl, t-butyl, phenyl, cyano, acetyl, benzyl, nitro,
dimethylamino, diethylamino, methylphenylamino, benzylmethylamino,
trimethylsilyl, dimethylboryl, diphenylboryl, methylphenylboryl,
dimethoxyboryl, chromium tricarbonyl, ruthenium tricarbonyl, and
cyclopentadienyl iron. Optionally, two or more R.sup.5 groups
combine to form a fused ring structure with the aromatic group that
forms a part of the ligand backbone. The additional fused ring may
or may not contain a heteroatom. Examples of the aromatic group
that is part of the backbone as combined with two or more R.sup.6
groups that have formed a fused ring are naphthalene, quinoline,
indole and the like.
[0047] In connection with structure II, R.sup.5 is present. R.sup.5
may be selected from the group consisting of hydrogen, alkyl,
substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl,
aryl, substitute aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, amino and silyl. In more specific embodiments, R.sup.5 is
selected from the group consisting of hydrogen, methyl, ethyl,
propyl, butyl, cyclopentyl, cylcohexyl, cyclooctyl, phenyl,
naphthyl, benzyl, pyridyl, furyl, morpholino, methoxy, ethoxy,
butoxy, phenoxy, benzyloxy, dimethylboryl, diphenylboryl,
methylphenylboryl, dimethylamino, diethylamino, diphenylamino,
dibenzylamino, trimethylsilyl, triethoxysilyl, triphenylsilyl,
triphenoxysilyl, dimethyl-t-butylsilyl, and the like. Also in
connection with structure II, R.sup.5 may be joined in a ring
structure with G and R.sup.3 in the backbone of the ring. Such a
ring will have at least four atoms in the backbone of the ring. In
the case of a ring, G can be oxygen or nitrogen and R.sup.3 forms a
methylene bridge to R.sup.5. In this case, R.sup.5 is alkoxy, so
that the ring has at least five atoms in the backbone of the ring,
as follows: C--O--(CH.sub.2).sub.n--CH.sub.2--O, with the last 0
being bonded to the first C and x denoting the length of the alkyl
portion of R.sup.5. In yet other embodiments, R.sup.4 and R.sup.5
are joined in a ring structure, having at least three atoms in the
backbone. Where R.sup.4 and R.sup.5 are joined together in a ring
structure, the ring (including R.sup.4, R.sup.5 and C) has from 3
to 15 non-hydrogen atoms as part of the backbone of the ring.
Specific examples of R.sup.4 and R.sup.5 together are ethylene
(giving a 3-member ring), propylene (giving a 4-membered ring),
butylene (giving a 5-membered ring), 3-oxopentylene (giving a
6-membered ring) and the like.
[0048] The ligands of this invention may be synthesized using an
aryl amination reaction. The synthesis can be carried out in
solution phase or solid phase (using organic or inorganic
supports). For solid-phase synthesis, the ligands may be left on
the support and used with metal added metal complexes as
heterogeneous catalysts. Alternatively, the ligands can be cleaved
either before or after reaction with a metal precursor and then
used as a homogeneous catalyst. One the general route for synthesis
of the ligands of this invention is shown below in scheme 1: 5
[0049] As shown in scheme 1, compounds 3 and 4 are within general
structure I above, and compounds 2 and 5 are within general
structure II above. Generally, the synthesis employs an aryl
amination reaction to attach the nitrogen group to the benzene ring
at the appropriate location. Following scheme 1, above, step 1 is
an aryl amination reaction starting with a compound characterized
by the general formula: 6
[0050] wherein R.sup.4 and R.sup.6 are as defined above and X is
selected from the group consisting of chloro, bromo, iodo,
triflate, nonaflate, alkyl sulfonates, aryl sulfonates and
tosylate; and R.sup.8 and R.sup.9 are independently selected from
the group consisting of alkyl, substituted alkyl, cycloalkyl,
substituted cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, boryl, phosphino, amino, thio,
seleno, and combinations thereof. Compounds of this type can be
purchased from Aldrich Chemical or prepared using known techniques.
See, e.g., Greene, Theodra W. and Wuts, Peter G. M., Protecting
Groups in Organic Synthesis, 2.sup.nd Edition (John Wiley &
Sons, New York, N.Y. 1991).
[0051] The aryl amination reaction could also start with other
compounds, such as those characterized by the following general
formulas in the following Schemes 2 and 3: 7
[0052] In these schemes, the variable groups have the previously
indicated meanings.
[0053] Step 1 is any scheme is the aryl amination reaction. This
reaction uses an amine that can be characterized by the general
formula HNR.sup.1R.sup.2, where R.sup.1 and R.sup.2 are as defined
above. This aryl amination reaction is typically performed using a
catalyst that comprises known or possibly new metal and ligand
catalyst compositions. For example, the catalyst may be
characterized by the general formula M'/L', where M' is a complex
that contains a metal selected from the group consisting of late
transition metals, preferably a Group 10 metal such as Pd, Ni or
Pt. M' is any homogeneous or heterogeneous metal precursor catalyst
or catalyst, L' is a ligand that may be selected from the group
consisting of phosphine or nitrogen ligands. L' may be monodentate,
bidentate, tridentate, hemi-labile, unsubstituted or substituted,
supported or unsupported, water-soluble or insoluble, soluble or
insoluble in organic solvents including fluorinated solvents. The
reaction can take place at known conditions, such as a temperature
of from room temperature to about 150.degree. C. Aryl amination
reactions are described in U.S. Pat. No. 5,576,460 herein
incorporated by reference.
[0054] Referring now to scheme 1, the second step of the reaction
converts compound 2 to compound 3 by hydrolysis of an acetal or
ketal functionality. This reaction can be performed by one of skill
in the art. See, e.g., Greene, Theodra W. and Wuts, Peter G. M.,
Protecting Groups in Organic Synthesis, 2.sup.nd Edition (John
Wiley & Sons, New York, N.Y. 1991), herein incorporated by
reference.
[0055] Thereafter in scheme 1, compound 3 can be reacted with a
primary or secondary amine for transform the ligand. The primary or
secondary amine in step 3 or 3' can be characterized by the general
formula H.sub.3-aNR.sup.3.sub.a, where R.sup.3 is as defined above
and a is 1 for a primary amine and a is 2 for a secondary amine. A
primary amine provides compound 4 in above scheme 1 following step
3. A secondary amine in the presence of a hydride source provides a
compound within above general ligand structure II in above scheme 1
following step 3'. If a primary amine is employed, hydrogenation is
thereafter an optional fourth step in scheme 1.
[0056] Once the desired ligand is formed, it may be combined with a
metal atom, ion, compound or other metal precursor compound. In
many applications, the ligands of this invention will be combined
with such a metal compound or precursor and the product of such
combination is not determined, if a product forms. For example, the
ligand may be added to a reaction vessel at the same time as the
metal or metal precursor compound along with the reactants. The
metal precursor compounds may be characterized by the general
formula M(L).sub.n where M is a metal selected from the group
consisting of Groups 3, 4, 5, 6, 7, 8, 9 and 10 of the Periodic
Table of Elements. In more specific embodiments, M is selected from
the group consisting of Ti, Zr, Hf, V, Ta, Cr, W, Mo, Ru, Co, Ni,
Pd, Fe, Mn, and Pt. L is a ligand chosen from the group consisting
of halide, alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,
substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, hydroxy, boryl, silyl, hydrido, thio, seleno, phosphino,
amino, and combinations thereof. When L is a charged ligand, L is
selected from the group consisting of hydrogen, halogens, alkyl,
substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl,
heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl, alkoxy, aryloxy, acetoxy,
silyl, boryl, phosphino, amino, thio, seleno, and combinations
thereof. When L is a neutral ligand, L is selected from the group
consisting of carbon monoxide, isocyanide, dibenzylideneacetone,
nitrous oxide, PA.sub.3, NA.sub.3, OA.sub.2, SA.sub.2, SeA.sub.2,
and combinations thereof, wherein each A is independently selected
from a group consisting of alkyl, substituted alkyl, heteroalkyl,
cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, and amino. Specific examples of
suitable metal precursor compounds include Pd(dba).sub.2
(dba=dibenzylideneacteone), Pd(OAc).sub.2 (Ac=acetate) and the
like. In this context, the ligand to metal precursor compound ratio
is in the range of about 0.01:1 to about 100:1, more preferably in
the range of about 0.5:1 to about 20:1.
[0057] In other applications, the ligand will be mixed with a
suitable metal precursor compound prior to or simultaneous with
allowing the mixture to be contacted to the reactants. When the
ligand is mixed with the metal precursor compound, a metal-ligand
complex may be formed, which may be a catalyst.
[0058] Depending on the substituents chosen for the ligand prior to
reaction with the metal precursor compound, the metal complexes may
be characterized by any of the following general formulas. For
general ligand structure I, the possible metal complexes formed
include: 8
[0059] For general ligand structure II, the possible metal
complexes formed include: 9
[0060] In each of these formulas, each R.sup.1, R.sup.2, R.sup.3,
R.sup.4, R.sup.5, R.sup.6, G, a and b are as defined above; and
[0061] M is a transition metal selected from the group consisting
of Groups 3, 4, 5, 6, 7, 8, 9 and 10 of the Periodic Table of
Elements. Selection of the metal is most preferably dependent on
whether the ligand is monoanionic or dianionic. In more specific
embodiments, M is selected from the group consisting of V, Ta, Cr,
W, Mo, Ru, Co, Ni, Pd, Fe, Mn and Pt.
[0062] L is independently each occurrence, a neutral and/or charged
ligand. Generally, L is a ligand chosen from the group consisting
of halide, alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,
substituted aryl, heteroaryl, substituted heteroaryl, alkoxy,
aryloxy, hydroxy, boryl, silyl, hydrido, thio, seleno, phosphino,
amino, and combinations thereof. When L is a charged ligand, L is
selected from the group consisting of hydrogen, halogens, alkyl,
substituted alkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl,
heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl, alkoxy, aryloxy, silyl,
boryl, phosphino, amino, thio, seleno, and combinations thereof.
When L is a neutral ligand, L is selected from the group consisting
of carbon monoxide, isocyanide, nitrous oxide, PA.sub.3, NA.sub.3,
OA.sub.2, SA.sub.2, SeA.sub.2, and combinations thereof, wherein
each A is independently selected from a group consisting of alkyl,
substituted alkyl, heteroalkyl, cycloalkyl, substituted cycloalkyl,
heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted
aryl, heteroaryl, substituted heteroaryl, alkoxy, aryloxy, silyl,
and amino.
[0063] N is the number 0, 1, 2, 3, 4, and 5. Additionally, m is 1,
2, 3, or 4. M can be neutral, cationic or anionic. In this form,
the ligands of this invention that bind to a metal via the N atoms
with dative bonds are shown with arrows and covalent binding is
shown with a line. Coordination modes described above may or may
not depend on the nature of ligands L on the metal M, and for a
given ligand L, the coordination modes may switch from one to
another at different stages of a catalytic cycle.
[0064] These transition metal-ligand complexes or metal/ligand
compositions of matter catalyze reactions involving activation of
and formation of bonds between H--Si, H--H, H--N, H--O, H--P, H--S,
C--H, C--C, C.dbd.C, C--C, C-halogen, C--N, C--O, C--S, C--P, and
C-Si. Specifically, such reactions include carbonylation,
hydroformylation, hydroxycarbonylation, hydrocarbonylation,
hydroesterification, hydrogenation, hydrosilylation, hydroboration,
hydroamination, epoxidation, aziridation, reductive amination, C--H
activation, insertion, C--H activation-insertion, C--H
activation-substitution, C-halogen activation, C-halogen
activation-substitution, C-halogen activation-insertion, alkene
metathesis, polymerization, alkene oligomerization, alkene
polymerization, alkyne oligomerization, alkyne polymerization,
co-polymerization, CO-alkene co-oligomerization, CO-alkene
co-polymerization, CO-alkyne co-oligomerization and CO-alkyne
co-polymerization. These reactions may occur at previously known
conditions (or possibly novel conditions). Moreover, these
reactions may be homogeneous or heterogeneous. In the case of
heterogeneous reactions, the ligands may be supported, with or
without the metal coordinated, on an organic or inorganic support.
Suitable supports include silicas, aluminas, zeolites,
polyethyleneglycols, polystyrenes, polyesters, polyamides, peptides
and the like.
[0065] Polymerization catalysis with the compositions and metal
complexes of this invention is a particularly effective process. In
particular, the complexes and compositions of this invention are
active catalysts also for the polymerization of olefins, possibly
in combination with an activator or activating technique. When an
activator or activating technique is used, those of skill in the
art may use alumoxanes, strong Lewis acids, compatible
noninterfering activators and combinations of the foregoing. The
foregoing activators have been taught for use with different metal
complexes in the following references, which are hereby
incorporated by reference in their entirety: U.S. Pat. Nos.
5,599,761, 5,616,664, 5,453,410, 5,153,157, 5,064,802, and
EP-A-277,004. Preferred activators include methylalumoxane,
trimethylaluminum, AgBF.sub.4, AgBPh4, NaBAr'.sub.4,
H(OEt.sub.2).sub.2BAr'.sub.4 and the like (where Ar' is a
substituted aromatic, like perfluorophenyl or
3,5-(CF.sub.3).sub.2(C.sub.6H.sub.3)).
[0066] Ratios of neutral complex to activator are on the order of 1
to 1000 to 1000 to 1. A scavenger can also be used with this
invention. Scavengers useful herein include metal complexes,
alumoxanes, aluminum alkyls and the like. Other additives that are
standard for polymerization reactions can be used.
[0067] The catalysts herein may be used to polymerize ethylenically
or acetylenically unsaturated monomers having from 2 to 20 carbon
atoms either alone or in combination. Monomers include C.sub.2 to
C.sub.20 a-olefins such as ethylene, propylene, 1-butene, 1-hexene,
1-octene, 4-mtheyl-1-pentene, styrene and mixtures thereof.
[0068] The compounds and catalysts of this invention usefully
polymerize functionalized monomers, such as acetates and acrylates.
Novel polymers, copolymers or interpolymers may be formed having
unique physical and/or melt flow properties. Such novel polymers
can be employed alone or with other polymers in a blend to form
products that may be molded, cast, extruded or spun. End uses for
the polymers made with the catalysts of this invention include
films for packaging, trash bags, foams, coatings, insulating
devices and household items. Also, such functionalized polymers are
useful as solid supports for organometallic or chemical synthesis
processes.
[0069] Polymerization can be carried out in the Ziegler-Natta or
Kaminsky-Sinn methodology, including temperatures of from 0.degree.
C. to 400.degree. C. and pressures from atmospheric to 3000
atmospheres. Suspension, solution, slurry, gas phase or
high-pressure polymerization processes may be employed with the
catalysts and compounds of this invention. Such processes can be
run in a batch or continuous mode. Examples of such processes are
well known in the art. A support for the catalyst may be employed,
which may be alumina, silica or a polymers support. Methods for the
preparation of supported catalysts are known in the art. Slurry,
suspension, solution and high-pressure processes use a suitable
solvent as known to those skilled in the art.
[0070] The ligands, metal complexes and compositions of this
invention can be prepared and tested for catalytic activity in one
or more of the above reactions in a combinatorial fashion.
Combinatorial chemistry generally involves the parallel or rapid
serial synthesis and/or screening or characterization of compounds
and compositions of matter. U.S. Pat. No. 5,776,359 and WO
98/03521, both of which are incorporated herein by reference
generally disclose combinatorial methods. In this regard, the
ligands, complexes or compositions may be prepared and/or tested in
rapid serial and/or parallel fashion, e.g., in an array format.
When prepared in an array format, for example, the ligands may be
take the form of an array comprising a plurality of compounds
wherein each compound can be characterized by either of the general
formulas: 10
[0071] wherein each R.sup.1, R.sup.2, R.sup.3, R.sup.1 R.sup.1 and
R.sup.6 is independently selected from the group consisting of
hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted
cycloalkyl, heteroalkyl, heterocycloalkyl, substituted
heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted
heteroaryl, alkoxy, aryloxy, silyl, boryl, phosphino, amino, thio,
seleno, and combinations thereof, optionally, R.sup.1 and R.sup.2
are joined together in a ring structure and/or R.sup.3 and R.sup.4
are joined together in a ring structure; G is either oxygen or
nitrogen. In connection with structure I, a is 0 or 1 depending on
G. In connection with structure II, a is 1 or 2 depending on G.
Also, b is 0, 1, 2, 3 or 4.
[0072] In such a combinatorial array, typically each of the
plurality of compounds has a different composition and each
compound is at a selected region on a substrate such that each
compound is isolated from the other compounds. This isolation can
take many forms, typically depending on the substrate used. If a
flat substrate is used, there may simply be sufficient space
between regions so that there cannot be interdiffusion between
compounds. As another example, the substrate can be a microtiter or
similar plate having wells so that each compound is in a region
separated from other compounds in other regions by a physical
barrier.
[0073] The array typically comprises at least 10 compounds,
complexes or compositions each having a different chemical formula,
meaning that there must be at least one different atom or bond
differentiating the plurality in the array. In other embodiments,
there are at least 25 compounds, complexes or compositions on or in
the substrate each having a different chemical formula. In still
other embodiments, there are at least 50 or 96 or 124 compounds,
complexes or compositions on or in the substrate each having a
different chemical formula. Because of the manner of forming
combinatorial arrays, it may be that each compound, complex or
composition is not pure. Typically, plurality of compounds are at
least 50% pure within said regions.
[0074] The catalytic performance (activity and selectivity) of the
ligands of this invention in combination with a suitable metal
precursor or metal-ligand coordination complexes of this invention
can be tested in a combinatorial or high throughput fashion. For
any of the listed transformation, thin layer chromatography (TLC)
in combination with imaging technology may be employed. TLC is well
known in the art, see for example Vol. 1, Thin-Layer
Chromatography, Reagents & Detection Methods, Jork et al. (VCH
Publishers, New York, N.Y. 1990). Polymerizations can also be
performed in a combinatorial fashion, see, e.g., commonly owned
provisional U.S. Patent Application No. 60/096,603, filed Aug. 13,
1998 (having attorney docket no. 65304-010), herein incorporated by
reference. High throughput screening can also be performed
optically and in parallel, for example, as disclosed in commonly
owned U.S. patent application Ser. No. 09/067,448, filed Apr. 2,
1998, Ser. No. 08/947,085, filed Oct. 8, 1997, and Ser. No.
08/946,135, filed Oct. 7, 1997, each of which is incorporated by
reference.
EXAMPLES
[0075] General: All reactions were performed under argon atmosphere
in oven-dried glass Schlenk tubes using standard Schlenk
techniques. All aryl halides, all amines, sodium t-butoxide,
bis(dibenzylideneacetone)pal- ladium, and all solvents used were
purchased from commercial sources and used as such. All solvents
used were of the anhydrous, Sure-Seal.RTM. grade. Column
chromatography was performed using commercially available Silica
Gel 60 (particle size: 0.063-0.100 mm), hexanes and ethyl acetate.
GCMS analyses were conducted on a Hewlett-Packard 5890 instrument.
.sup.1H, and .sup.13C spectra were obtained using a Bruker 300 MHz
FT-NMR spectrometer. Chemical shifts in .sup.1H and .sup.13C NMR
spectra were calibrated with reference to the chemical shift of
residual protiated solvent. Elemental analyses were performed by E
& R Microanalytical Laboratory Inc., NJ. Ligand A was used for
the aryl amination reaction and is
2-(2'-dicyclohexylphosphinophenyl)-2-methyl-1,3-dioxolane having
the following structure: 11
[0076] Synthesis and use of ligand A Synthesis and use of ligand A
is disclosed in detail in commonly owned and copending U.S. patent
application Ser. No. 09/062,128 filed Apr. 17, 1998 and
incorporated herein by reference. Also U.S. provisional patent
application no. ______, filed Aug. 6, 1998 (Attorney Docket No.
98-22) and herein incorporated by reference discloses other ligands
that can be used in the aryl amination reaction.
[0077] The following ligands shown in structural form below are
referred to using the code given below each structure: 121314
Example 1
[0078] 2-Bromo-1-(dimethoxymethyl)benzene (1a). To a 500 mL round
bottom flask equipped with a reflux condenser were added
2-bromobenzaldehyde (102.5 g, 0.554 mol, Aldrich), trimethyl
orthoformate (64.9 mL, 0.594 mol, Aldrich), 10-camphor sulfonic
acid (1.25 g, 5.40 mmol, Aldrich), and methanol (100 mL). The
reaction was heated at reflux for 14 hrs and concentrated in vacuo.
The residue was taken up in 500 mL of ether, washed with 200 mL
each of sat. aqueous sodium bicarbonate, water, and sat. aqueous
NaCl, dryed over anhydrous sodium sulfate, filtered and
concentrated in vacuo. The crude product was distilled through a 27
cm Vigrew column (b.p. 78-82.degree. C./1.2 mmHg), affording a
clear colorless oil (120.8 g, 94%). .sup.1H-NMR (300 MHz,
CDCl.sub.3) .delta.3.37 (s, 6H), 5.54 (s, 1H), 7.18 (dt, 1H, J=1.7,
8.1 Hz), 7.31 (dt, 1H, J=1.2, 7.5 Hz), 7.54 (dd, 1H, J=1.2, 8.1
Hz), 7.59 (dd, 1H, J=1.7, 7.5 Hz). Mass spectrum (EI+) m/e 230, 232
(M+), 199, 201 (bp).
Example 2
[0079] 2-[2'-(2,6-Dimethylanilino)phenyl]-2-methyl-1,3-dioxolane
(2b-1): A mixture of 2-(2'-bromophenyl)-2-methyl-1,3-dioxolane (362
mg, 1.49 mmol), 2,6-dimethylaniline (189 mg, 1.56 mmol),
NaO.sup.tBu (172 mg, 1.79 mmol), Pd(dba).sub.2 (17 mg, 0.03 mmol),
ligand A (21 mg, 0.06 mmol) in toluene (4 mL) was heated to
105.degree. C. for 4.5 hours. The reaction was cooled to room
temperature, taken up in diethyl ether (125 mL), washed with water
(2.times.30 mL) and brine (30 mL), dried over MgSO.sub.4, filtered
and concentrated under vacuum. The crude product was purified by
column chromatography on silica gel using hexane (or hexanes:ethyl
acetate) as the eluent to afford compound 2b-1, after drying under
vacuum, as an off-white solid (yield: 391 mg, 93%). .sup.1H NMR
(CDCl.sub.3): .delta. 7.41 (dd, 1H, J=7.8, 1.8 Hz, ArH), 7.13-6.99
(m, 4H, ArH), 6.70 (dt, 1H, J=7.5, 1.2 Hz, ArH), 6.15 (dd, 1H,
J=7.8, 0.9, ArH), 4.12 (m, 2H, O--CH--CH--O), 3.93 (m, 2H,
O--CH--CH--O), 2.18 (s, 6H, Ar--CH.sub.3), 1.84 (s, 3H, CH.sub.3).
.sup.13C NMR (CDCl.sub.3): .delta. 143.5, 138.6, 135.2, 129.1,
128.5, 126.3, 125.6, 125.2, 117.3, 112.6, 109.8, 64.1, 24.1, 18.3.
Anal. for C.sub.18H.sub.21NO.sub.2; Calcd: C, 76.29; H, 7.47; N,
4.94; Found: C, 75.86; H, 7.46; N, 4.89.
Example 3
[0080] 2-2'(2-Chloro-6-methylanilinophenyl)]-2-methyl-1,3-dioxolane
(2b-2): Compound 2b-2 (381 mg, 96% yield) was obtained as a
colorless solid from the reaction of
2-(2'-bromophenyl)-2-methyl-1,3-dioxolane (318 mg, 1.31 mmol),
2-chloro-6-methylaniline (195 mg, 1.38 mmol), NaO.sup.tBu (152 mg,
1.58 mmol), Pd(dba).sub.2 (15 mg, 0.03 mmol), ligand A (18 mg, 0.05
mmol) in toluene (4 mL) at 105.degree. C. for 2 hours. The
experimental procedure described for the synthesis of compound 2a-1
was generally followed. .sup.1H NMR (CDCl.sub.3): .delta. 7.51 (m,
2H, ArH), 7.36 (d, 1H, J=7.9 Hz, ArH), 7.19 (d, 1H, J=7.3 Hz, ArH),
7.13-7.06 (m, 2H, ArH), 6.83 (t, 1H, J=7.3 Hz, ArH), 6.27 (d, 1H,
J=7.9 Hz, ArH), 4.17 (m, 2H, O--CH--CH--O), 3.97 (m, 2H,
O--CH--CH--O), 2.23 (s, 3H, Me), 1.89 (s, 3H, Me). .sup.13C NMR
(CDCl.sub.3): .delta. 142.4, 137.4, 136.8, 131.2, 129.3, 128.8,
127.5, 126.8, 126.4, 125.3, 118.5, 113.5, 109.6, 64.1, 24.1, 18.8.
Anal. for C.sub.17H.sub.18ClNO.sub.2; Calcd: C, 67.21; H, 5.97; N,
4.61; Found: C, 66.92; H, 5.83; N, 4.53.
Example 4
[0081] 2-[2'(2-Isopropylanilinophenyl)]-1,3-dioxolane (2b-3):
Compound 2b-3 (354 mg, 90% yield) was obtained as a yellow oil from
the reaction of 2-(2'-bromophenyl)-1,3-dioxolane (321 mg, 1.40
mmol), 2-isopropylaniline (199 mg, 1.47 mmol), NaO.sup.tBu (141 mg,
1.47 mmol), Pd(dba).sub.2 (16 mg, 0.03 mmol), ligand A (27 mg, 0.08
mmol) in toluene (4 mL) at 105.degree. C. for 75 minutes. The
experimental procedure described for the synthesis of compound 2a-1
was generally followed. .sup.1H NMR (CDCl.sub.3): .delta. 7.45 (d,
1H, J=7.6 Hz, ArH), 7.33-7.12 (m, 4H, ArH), 7.05 (t, 1H, J=7.4 Hz,
ArH), 6.85 (t, 1H, J=7.4 Hz, ArH), 6.68 (br.s, 1H, NH), 5.93 (s,
1H, O--CH--O), 4.10 (m, 4H, O--CH.sub.2--CH.sub.2--O), 3.13
(septet, 1H, J=6.8 Hz, CHMe.sub.2), 1.26 (d, 6H, J=6.8 Hz, 2 Me's).
.sup.13C NMR (CDCl.sub.3): .delta. 143.8, 140.0, 139.5, 129.7,
127.2, 126.3, 126.1, 123.7, 122.9, 121.6, 118.9, 115.5, 103.0,
64.9, 27.8, 22.8. Anal. for C.sub.18H.sub.21NO.sub.2; Calcd: C,
76.29; H, 7.47; N, 4.94; Found: C, 75.75; H, 7.96; N, 4.81.
Example 5
[0082] 2-[(2',4',6'-trimethylphenyl)amino]benzaldehyde (3a-1). In
an oven-dried 500 mL Schlenk flask were added sodium t-butoxide
(5.77 g, 60.0 mmol, Aldrich), Pd(dba).sub.2 (0.144 g, 0.250 mmol,
ACROS), ligand A (0.174 g, 0.500 mmol) and 1a (14.45 g, 62.6 mmol).
Toluene (130 mL, anhydrous, Aldrich) and 2,4,6-trimethylaniline
(8.71 g, 64.4 mmol, Aldrich) were added and the reaction was heated
to 105 C for 6 hrs. An additional 1.44 g of sodium t-butoxide was
added to the reaction and the reaction was heated at the same
temperature for an additional 1 hr, at which time a GLC analysis
revealed the reaction was completed. The reaction was cooled to
room temperature. The reaction mixture was diluted with 100 mL of
ether and washed with 200 mL each of water and sat. aqueous NaCl,
dried over anhydrous sodium sulfate, filtered and concentrated in
vacuo, affording 20.1 g of a red oil as crude product. The crude
material was chromatograghed through a 6.times.15 cm silica gel
column (1-5% step gradient of ether in hexanes). During this
operation, the acetal was partially hydrolyzed. The fractions
containing the acetal and the aldehyde were combined and
concetrated in vacuo, affording 16.61 g of a yellow viscous oil.
The oil was stirred in a mixture of THF (50 mL), water (25 mL), and
acetic acid (25 mL) at 22.degree. C. for 1 hr. THF was removed by
evaporation and 200 mL of ether was added. The organic phase was
washed with 100 mL each of water and sat. aqueous sodium
bicarbonate, dried over anhydrous sodium sulfate, filtered and
concentrated in vacuo, affording 14.47 g of a deep yellow viscous
oil (97%). A GLC analysis and H-NMR analysis indicated this
material was pure. .sup.1H NMR (CDCl.sub.3, 300 MHz): 9.97 (s, 1H),
9.50 (s, 1H), 7.56 (d, J=7.8 Hz, 1H), 7.3-7.2 (m, 4H), 6.98 (s,
2H), 6.74 (t, J=7.5 Hz, 1H), 6.24 (d, J=8.4 Hz, 1H), 2.34 (s, 3H),
2.16 (s, 6H) ppm. .sup.13C NMR (CDCl.sub.3, 75 MHz): 194.3, 149.9,
136.5, 136.4, 136.3, 135.7, 133.6, 129.2, 118.3, 115.7, 112.3,
20.9, 18.1 ppm.
Example 6
[0083] 2-[2',6'-(diisopropylphenyl)amino]benzaldehyde (3a-2). In an
oven-dryed 250 mL Schlenk flask were added sodium t-butoxide (2.88
g, 30.0 mmol, Aldrich), Pd(dba).sub.2 (72 mg, 0.13 mmol, ACROS),
ligand A (87 mg, 0.25 mmol). Toluene (100 mL, anhydrous, Aldrich),
1 (5.70 g, 24.6 mmol), and 2,6-diisopropylaniline (4.37 g, 24.6
mmol, Aldrich) were added and the reaction was heated to 105 C for
14 hrs, at which time a GLC analysis revealed the reaction was
completed. The reaction was cooled to room temperature. The
reaction mixture was stirred with 50 mL of water and filtered to
remove insoluble materials. The organic layer was separated and
washed with 50 mL of sat. aqueous NaCl, dried over anhydrous sodium
sulfate, filtered and concentrated in vacuo, affording 8.88 g of a
red oil as crude product. The crude material was subjected to
hydrolysis in the similar way as 3a-1 (THF (50 mL), water (25 mL),
and acetic acid (25 mL) at 22 C for 1 hr). The crude product was
purified by flash chromatography on a 7.times.20 cm silica gel
column (2.5% ether in hexanes), affording 6.68 g of a very yellow
viscous oil (96%). IR (liquid film) 3292, 1660 cm.sup.-1.
.sup.1H-NMR (300 MHz, CDCl.sub.3) .delta. 1.08 (d, 3H, J=6.9 Hz),
1.13 (d, 3H, J=6.9 Hz), 3.04 (sept, 2H, J=6.9 Hz), 6.20 (d, 1H,
J=8.5), 6.70 (t, 1H, J=7.4 Hz), 7.18-7.23 (m, 3H), 7.32 (t, 1H,
J=7.6 Hz), 7.53 (dd, 1H, J=7.8, 1.5 Hz), 9.54 (br.s, 1H), 9.94 (s,
1H). .sup.13C-NMR (75 MHz, CDCl.sub.3) .delta. 23.0, 24.5, 28.4,
112.5, 115.7, 118.0, 123.9, 128.0, 133.4, 135.5, 136.1, 147.3,
151.0, 194.2. Mass spectrum (EI+) m/e 281 (M+), 266 (bp).
Example 7
[0084] This example is a general procedure for the formation of
2-mesitylaminobenzaldehyde imines: To a solution of
2-mesitylaminobenzaldehyde 3a-1 (957 mg, 4 mmol) in dichloroethane
(6 mL) was added benzylamine (429 mg, 4 mmol) via syringe, followed
by a catalytic amount of p-toluenesulfonic acid monohydrate (18 mg,
.about.1%) and 4 .ANG. molecular sieves. The reaction was heated to
reflux overnight while stirring under argon. The disappearance of
the aldehyde and formation of the imine was followed by GC/MS. To
the crude product was added amino propyl silica and the mixture was
shaken. The mixture was then filtered and the resulting solution
was concentrated. The product was then precipitated with hexanes.
The precipitate was washed with cold hexanes and dried in vacuo.
4a-1: .sup.1H NMR (CDCl.sub.3, 300 MHz): 10.49 (s, 1H), 8.57 (s,
1H), 7.4-7.25 (m, 6H), 7.12 (t, J=8 Hz, 1H) 7.01 (s, 1H), 6.69 (t,
J=8 Hz, 1H), 6.26 (d, J=8 Hz, 1H), 4.69 (s, 2H), 2.32 (s, 3H), 2.13
(s, 6H) ppm. .sup.13C NMR (CDCl.sub.3, 75 MHz): 165.3, 148.3,
139.8, 136.3, 135.5, 135.2, 133.8, 131.2, 128.9, 128.4, 127.6,
126.8, 116.9, 115.1, 111.5, 65.12, 20.9, 18.2 ppm. GC-MS: m/z 328
(M).sup.+. 4a-2: .sup.1H NMR (CDCl.sub.3, 300 MHz): 10.7 (s, 1H),
8.74 (s, 1H), 7.48 (d, J=8 Hz, 1H), 7.33 (d, J=8 Hz, 1H), 7.2 (m,
4H), 7.05 (s, 2H), 6.79 (t, J=8 Hz, 1H), 6.35 (d, J=8 Hz, 1H), 3.01
(m, 6.9 Hz, 1H), 2.40 (s, 3H), 2.28 (s, 6H), 1.34 (d, J=6.9 Hz, 6H)
ppm. .sup.13C NMR (CDCl.sub.3, 75 MHz): 162.3, 148.5, 146.5, 136.3,
135.7, 135.1, 134.5, 131.9, 129.0, 127.1, 120.9, 117.3, 115.4,
111.8, 33.7, 24.1, 20.9, 18.3 ppm. GC-MS: m/z 356 (M).sup.+.
Example 8
[0085] This example is a general procedure for the formation of
2-(2,6-diisopropylphenyl)aminobenzaldehyde imines. To a solution of
2-[(2,6-diisopropylphenyl) amino]benzaldehyde 3a-2 (126 mg, 0.45
mmol) in dichloroethane (500 .mu.L) was added
2,6-diisopropylaniline (84 .mu.L, 0.45 mmol) via syringe, followed
by a catalytic amount ofp-toluenesulfonic acid monohydrate (10 mg,
10%). The resulting solution was concentrated and the resulting oil
was heated overnight (external temperature 120.degree. C.). The
disappearance of the aldehyde and formation of the imine was
followed by GC/MS. To the crude product was added dichloroethane (1
mL) followed by amino propyl silica and the mixture was shaken. The
mixture was then filtered and the resulting solution was
concentrated. The product was then precipitated with methanol. The
precipitate was washed with cold methanol and dried in vacuo. 4a-3:
.sup.1H NMR (CDCl.sub.3, 300 MHz): 10.56 (s, 1H), 8.40 (s, 1H),
7.4-7.1 (m, 8H), 6.74 (t, J=7 Hz, 1H), 6.34 (d, J=8 Hz, 1H), 3.25
(m, 2H), 3.14 (m, 2H), 1.3-1.1 (m, 24H) ppm. .sup.13C NMR
(CDCl.sub.3, 75 MHz): 166.2, 150.4, 147.9, 138.6, 134.9, 134.8,
132.6, 127.9, 124.8, 124.2, 123.5, 116.6, 115.5, 112.4 ppm. GC-MS:
m/z 440 (M).sup.+.
Example 9
[0086] This example is a general procedure for the formation of
2-mesitylaminobenzaldehyde 2-aminomethylenes. To 4a-2 (0.17 mmol,
60 mg) in dichloroethane (2 mL) was added acetic acid (60 .mu.L)
followed by NaBH(OAc).sub.3 (0.34 mmol, 70 mg). The resulting
mixture was shaken at room temperature for 2 hours. The crude
product was extracted from an aqueous Na.sub.2CO.sub.3 solution
with dichloroethane (3.times.2 mL) then passed through a plug of
silica gel and concentrated to afford a pale yellow oil. 5a-1:
.sup.1H NMR (CDCl.sub.3, 300 MHz): 7.27 (d, J=7.4 Hz, 1H), 7.3-7.1
(m, 3H), 6.97 (s, 2H), 6.9-6.7 (m, 3H), 6.61 (s, 2H), 6.29 (d, J=8
Hz, 1H), 4.42 (s, 2H), 2.91 (m, J=6.9 Hz, 1H), 2.36 (s, 3H), 2.19
(s, 6H), 1.30 (d, J=6.9 Hz, 6H) ppm. .sup.13C NMR (CDCl.sub.3, 75
MHz): 146.0, 145.8, 139.5, 135.8, 134.7, 134.6, 130.0, 129.1,
128.9, 127.2, 122.8, 117.4, 114.2, 112.2, 48.2, 33.2, 24.2, 20.6,
18.2 ppm. GC-MS: m/z 358 (M).sup.+
[0087] It is to be understood that the above description is
intended to be illustrative and not restrictive. Many embodiments
will be apparent to those of skill in the art upon reading the
above description. The scope of the invention should, therefore, be
determined not with reference to the above description, but should
instead be determined with reference to the appended claims, along
with the full scope of equivalents to which such claims are
entitled. The disclosures of all articles and references, including
patent applications and publications, are incorporated herein by
reference for all purposes.
* * * * *