Phosphino-aminophosphines

Details Phosphino-aminophosphines Phosphino-aminophosphines

2001-09-20

2003-07-08

Nazario-Gonzalez, Porfirio (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heavy metal containing

C556S144000, C556S148000, C502S162000, C585S276000, C568S846000

Reexamination Certificate

active

06590115

ABSTRACT:

FIELD OF THE INVENTION
This invention pertains to novel, substantially enantiomerically pure bis-phosphine compounds possessing the unique feature of having both a carbon-bonded phosphine and a nitrogen-bonded phosphine connected by a divalent chiral group. The compounds are useful as ligands for metal catalysts for asymmetric reactions and have demonstrated surprising stability as well as excellent results, in particular as rhodium complexes for asymmetric hydrogenation. This invention also pertains to novel processes and intermediate compounds useful for the preparation of the bis-phosphine compounds and to compounds comprising one or more of the bis-phosphine compounds in complex association with one or more Group VIII metals and their use for asymmetric hydrogenation.
BACKGROUND OF THE INVENTION
Asymmetric catalysis is the most efficient method for the generation of products with high enantiomeric purity, as the asymmetry of the catalyst is multiplied many times over in the generation of the chiral product. These chiral products have found numerous applications as building blocks for single enantiomer pharmaceuticals as well as in some agrochemicals. The asymmetric catalysts employed can be enzymatic or synthetic in nature. The latter types of catalyst have much greater promise than the former due to much greater latitude of applicable reaction types. Synthetic asymmetric catalysts are usually composed of a metal reaction center surrounded by an organic ligand. The ligand usually is generated in high enantiomeric purity, and is the agent inducing the asymmetry. These ligands are, in general, difficult to make and therefore expensive.
As is described by Richards, C. J.; Locke, A. J.
Tetrahedron: Asymmetry
1998, 9, 2377-2407, asymmetric ferrocene derivatives have found great utility as ligands for asymmetric catalysis in reactions as varied as asymmetric hydrogenations, asymmetric Aldol reactions, asymmetric organometallic additions, and asymmetric hydrosilations. These ferrocene species usually are bidentate in nature, using a variety of ligating species. In the cases where the ligands are phosphines they invariably are carbon-linked phosphines. In no cases do these ferrocene-based ligands have heteroatom linkage to the phosphorus atom. Fiorini, M. and Giongo, G. M.
J. Mol. Cat.
1979, 5, 303-310, and Pracejus, G.; Pracejus, H.
Tetrahedron Lett.
1977, 3497-3500, report that bis-aminophosphine-based asymmetric ligands afford moderate results for asymmetric hydrogenations (<90% enantiomeric excess—ee), but in no cases have these ligands had either a metallocenyl moiety or a mixture of carbon and nitrogen-bonded phosphines included therein. Indeed, there appear to be no reports of chiral, non-racemic, bis-phosphine ligands where one phosphine is bonded to three carbon atoms and the other is bonded to two carbons and one nitrogen.
BRIEF SUMMARY OF THE INVENTION
The novel bis-phosphine compounds provided by our invention are substantially enantiomerically pure bis-phosphine compounds comprising a substantially enantiomerically pure chiral backbone linking two phosphine residues wherein one of the phosphine residues has three phosphorus-carbon bonds and the other phosphine residue has two phophorus-carbon bonds and one phosphorus-nitrogen bond wherein the nitrogen is part of the chiral backbone. These compounds are the first examples of chiral bis-phosphines combining a tri-hydrocarbylphosphine with a dihydrocarbylaminophosphine. These species can be utilized as bidentate ligands for asymmetric catalysis for a variety of reactions. They are of particular interest for asymmetric hydrogenations, and as the rhodium complex they have afforded hydrogenation products with high enantiomeric excess, in particular for the rhodium-catalyzed hydrogenation of prochiral olefins and ketones. The activity of these compounds is readily modified by the choice of the amine substituents.
DETAILED DESCRIPTION
We have discovered a broad group of novel substantially enantiomerically pure bis-phosphine compounds comprised of one phosphine residue having three phosphorus-carbon bonds and the other having two phosphorus-carbon bonds and one phosphorus-nitrogen bond. Examples of the substantially enantiomerically pure, i.e., an enantiomeric excess of 90% or greater, compounds include phosphinometallocenylaminophosphines having the general formulas 1 and 2 (the enantiomer of 1):
wherein
R is selected from substituted and unsubstituted, branched- and straight-chain C
1
-C
20
alkyl, substituted and unsubstituted C
3
-C
8
cycloalkyl, substituted and unsubstituted C
6
-C
20
carbocyclic aryl, and substituted and unsubstituted C
4
-C
20
heteroaryl wherein the heteroatoms are selected from sulfur, nitrogen, and oxygen;
R
1
, R
2
, R
3
, R
4
, and R
5
are independently selected from hydrogen, substituted and unsubstituted, branched- and straight-chain C
1
-C
20
alkyl, substituted and unsubstituted C
3
-C
8
cycloalkyl, substituted and unsubstituted C
6
-C
20
carbocyclic aryl, and substituted and unsubstituted C
4
-C
20
heteroaryl wherein the heteroatoms are selected from sulfur, nitrogen, and oxygen;
n is 0 to 3;
m is 0 to 5; and
M is selected from the metals of Groups IVB, VB, VIB, VIIB and VIII.
The alkyl groups which may be represented by each of R, R
1
, R
2
, R
3
, R
4
, and R
5
may be straight- or branched-chain, aliphatic hydrocarbon radicals containing up to about 20 carbon atoms and may be substituted, for example, with one to three groups selected from C
1
-C
6
-alkoxy, cyano, C
2
-C
6
-alkoxycarbonyl, C
2
-C
6
-alkanoyloxy, hydroxy, aryl and halogen. The terms “C
1
-C
6
-alkoxy”, “C
2
-C
6
-alkoxycarbonyl”, and “C
2
-C
6
-alkanoyloxy” are used to denote radicals corresponding to the structures —OR
6
, —CO
2
R
6
, and —OCOR
6
, respectively, wherein R
6
is C
1
-C
6
-alkyl or substituted C
1
-C
6
-alkyl. The term “C
3
-C
8
-cycloalkyl” is used to denote a saturated, carbocyclic hydrocarbon radical having three to eight carbon atoms. The aryl groups which each of R, R
1
, R
2
, R
3
, R
4
, and R
5
may represent may include phenyl, naphthyl, or anthracenyl and phenyl, naphthyl, or anthracenyl substituted with one to three substituents selected from C
1
-C
6
-alkyl, substituted C
1
-C
6
-alkyl, C
6
-C
10
aryl, substituted C
6
-C
10
aryl, C
1
-C
6
-alkoxy, halogen, carboxy, cyano, C
1
-C
6
-alkanoyloxy, C
1
-C
6
-alkylthio, C
1
-C
6
-alkylsulfonyl, trifluoromethyl, hydroxy, C
2
-C
6
-alkoxycarbonyl, C
2
-C
6
-alkanoylamino and —O—R
7
, S—R
7
—SO
2
—R
7
, —NHSO
2
R
7
and —NHCO
2
R
7
, wherein R
7
is phenyl, naphthyl, or phenyl or naphthly substituted with one to three groups selected from C
1
-C
6
-alkyl, C
6
-C
10
aryl, C
1
-C
6
-alkoxy and halogen.
The heteroaryl radicals include a 5- or 6-membered aromatic ring containing one to three heteroatoms selected from oxygen, sulfur and nitrogen. Examples of such heteroaryl groups are thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, tetrazolyl, pyridyl, pyrimidyl, benzoxazolyl, benzothiazolyl, benzimidazolyl, indolyl and the like. The heteroaryl radicals may be substituted, for example, with up to three groups such as C
1
-C
6
-alkyl, C
1
-C
6
-alkoxy, substituted C
1
-C
6
-alkyl, halogen, C
1
-C
6
-alkylthio, aryl, arylthio, aryloxy, C
2
-C
6
-alkoxycarbonyl and C
2
-C
6
-alkanoylamino. The heteroaryl radicals also may be substituted with a fused ring system, e.g., a benzo or naphtho residue, which may be unsubstituted or substituted, for example, with up to three of the groups set forth in the preceding sentence. The term “halogen” is used to include fluorine, chlorine, bromine, and iodine.
The compounds of the invention which presently are preferred have formulas 1 and 2 wherein R is C, to C
6
alkyl; R
1
is hydrogen or C
1
to C
6
alkyl; R
2
is aryl (preferably phenyl), ethyl, isopropyl, or cyclohexyl; R
3
is aryl, most preferably phenyl; R
4
and R
5
are hydrogen; and M is iron, ruthenium, or osmium, most preferably iron.
The compounds of our in

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