Catalytic compositions and methods for asymmetric allylic...

Details Catalytic compositions and methods for asymmetric allylic... Catalytic compositions and methods for asymmetric allylic...

2001-09-07

2003-04-01

Barts, Samuel (Department: 1621)

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

Organic compounds

Carboxylic acid esters

C560S081000, C560S082000, C560S083000, C560S009000, C560S010000, C560S051000, C560S053000, C560S203000, C560S121000, C549S427000, C549S500000, C554S162000, C554S163000

Reexamination Certificate

active

06541655

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to catalytic methods and compositions for use in highly regioselective and enantioselective alkylations of allylic substrates. Molybdenum, tungsten and chromium complexes of chiral ligands having such catalytic activity, particularly the molybdenum complexes, are described, along with methods for their use.
REFERENCES
Adolfsson, H. and Moberg, C.,
Tetrahedron: Asymmetry
6:2023 (1995).
Dvorak, D. et al.,
J. Am. Chem. Soc
. 117:6130 (1995) and references cited therein.
Fenton, R. R. et al.,
J. Coord. Chem
. 23:291 (1991).
Godleski, S. A., in “Comprehensive Organic Synthesis,” Trost, B. M., Fleming, I., and Semmelhack, M. F., eds.; Permagon Press, Oxford, 1991, Vol. 4, pp 585-662.
Hammen, P. D. et al.,
Synth. Commun
. 21:2157 (1991).
Merlic, C. A., Ph.D. Thesis, University of Wisconsin (1988).
Pretot, R. and Pfalz, A.,
Angew. Chem. Int. Ed. Engl
. 37: 323 (1998).
Rubio, A. and Liebeskind, L. S.,
J. Am. Chem. Soc
. 115: 891 (1993).
Saigo, K. etal.,
Bull. Chem. Soc. Japan
59(3):931 (1986).
Trost, B. M. et al.,
J. Am. Chem. Soc
. 109: 2176 (1987).
Trost, B. M. and Hachiya, I.,
J. Am. Chem. Soc
. 120:1104 (1998).
Trost, B. M. and Hung, M.-H.,
J. Am. Chem. Soc
. 105:7757 (1983).
Trost, B. M. and Lautens, M.,
J. Am. Chem. Soc
. 104:5543 (1982).
Trost, B. M. and Lautens, M.,
J. Am. Chem. Soc
. 109:1469 (1987).
Trost, B. M. and Lautens, M.,
Tetrahedron
43: 4817 (1987).
Trost, B. M. and Merlic, C. A.,
J. Am. Chem. Soc
. 112:9590 (1990).
BACKGROUND OF THE INVENTION
Interest in molybdenum- and tungsten-catalyzed reactions of allyl substrates with nucleophiles has been promoted by the regioselectivity shown by these complexes, as compared to that of palladium complexes. See, for example, for molybdenum, Trost and Merlic, 1990, Rubio and Liebeskind, 1993, Trost and Hachiya, 1998; and for tungsten, Trost and Hung, 1983, and Trost et al., 1987. Palladium catalyzed reactions generally provide products from attack at the less substituted terminus. This regiochemistry (shown at eq 1, path a in
FIG. 1
) is particularly favored for alkylation of aryl-substituted allyl systems, even with catalysts having chiral ligands (Godleski, 1991). Molybdenum and tungsten catalysts, on the other hand, generally favor attack at the more substituted terminus (eq 1, path b). Complexes of these metals are also less costly than palladium catalysts.
Products of the type shown in reaction path (b), having high optical purity, find great value as building blocks in the synthesis of biologically useful compounds. A low-cost, versatile, stereoselective catalytic route to such compounds would thus be desirable.
SUMMARY OF THE INVENTION
In one aspect, the invention provides a catalytic organometallic composition, effective to catalyze the enantioselective alkylation of an allyl group bearing a leaving group at an allylic position. The composition comprises a metal atom selected from the group consisting of molybdenum, tungsten, and chromium, which is preferably molybdenum or tungsten and most preferably molybdenum, and coordinated thereto, a chiral ligand L
1
. The chiral ligand comprises a chiral component derived from a chiral diamine, and having first and second carbon atoms each bearing a binding group —NH—(C═O)—B, wherein:
the above-referenced carbon atoms are connected by a direct bond or by a chain of one to three atoms comprising linkages selected from alkyl, alkyl ether, alkyl amino, and combinations thereof,
each group B is independently selected from alkyl, cycloalkyl, heterocycle, aryl, and aralkyl, as defined herein;
at least one group B is a N-heterocyclic or N-heteroaryl group CyN having an sp
2
hybridized ring nitrogen atom effective to coordinate to said metal atom, and
at least one of the above-referenced carbon atoms is a chiral carbon atom bearing a further substituent effective to create a conformationally biased system containing the carbon atoms and the binding groups.
In preferred embodiments, the substituent (or substituents) on the above-referenced carbon atom(s) are independently selected from aryl, aralkyl, carbocycle, heterocycle, and secondary or tertiary alkyl having 3 or more, preferably 4 or more, carbon atoms. In one such embodiment, the substituents are aryl groups. In another embodiment, where both of the above-referenced carbon atoms are chiral and are adjacent, the substituents on these carbon atoms may together form a ring. This ring is typically a 5- to 7-membered carbocyclic ring, or a 5- to 7-membered heterocyclic ring having 1-3, preferably 1-2, ring atoms selected from oxygen, nitrogen and sulfur, and the remaining ring atoms carbon. It may be fused to one or more additional rings, preferably no more than two, and more preferably one or none. The ring or other substituents, particularly he cyclic substituents, may themselves be substituted with one or more groups selected rom alkyl, alkenyl, aryl, aralkyl, alkoxy, aryloxy, acyl, acyloxy, carboxylic ester, amide, tertiary amine, nitro, and halogen.
In further embodiments, each said group B is a group CyN as defined above, and/or each said carbon atom is a chiral carbon atom bearing a substituent effective to create a conformationally biased system containing said carbon atoms and said binding groups. The carbon atoms are preferably connected by a direct bond.
Examples of the groups B described above as CyN, which may be the same or different on a given ligand, include, but are not limited to, pyridyl, quinolinyl, isoquinolyl, pyrimidyl, triazinyl, tetrazinyl, pyrazinyl, pyrazolyl, triazolyl, tetrazolyl, oxazinyl, oxazolyl, thiazolyl, imidazolyl, benzoxazole, benzimidazole, and dihydro derivatives of the above. N-heteroaryl groups are generally preferred. In one embodiment, at least one group B is a group CyN having an Sp
2
hybridized ring nitrogen which is &agr; to a nrng carbon atom which is linked to the carbonyl (C═O) carbon of the binding group (referred to herein as an “&agr;-linked” CyN). Examples of these groups include 2-pyridyl, 2-quinolinyl, 1- or 3-isoquinolyl, 2- or 4-pyrimidyl, 2-triazinyl, 4-tetrazinyl, 2-pyrazinyl, 3- or 5-pyrazolyl, 3- or 5-triazolyl, 2-tetrazolyl, 2-oxazinyl, 2- or 5-oxazolyl, 2- or 5-thiazolyl, 2- or 4-imidazolyl, 2-benzoxazole, 2-benzimidazole, and dihydro derivatives of the above.
The above-referenced carbon atoms of the chiral component are connected by a direct bond or by a chain of one to three atoms comprising linkages selected from alkyl, alkyl ether, alkyl amino, and combinations thereof. Preferably, they are connected by a direct bond, such that the chiral scaffold is derived from a 1,2-diamine. Examples of chiral 1,2-diamines that may be used as chiral scaffolds include 1R,2R-trans-diaminocyclohexane, 1R,2R-trans-diphenyl-1,2-ethanedi amine, 3R,4R-trans-3,4-diamino-N-benzylpyrrolidine, 1R,2R-trans-diarninocycloheptane, 5R,6R-trans-5,6-diaminoindan, 1S-phenyl-1,2-ethanediamine, and the mirror image counterpart of any of the above. Examples of chiral ligands of the invention include those represented herein as ligands I-XV and their mirror image counterparts.
The catalytic organometallic composition of the invention is the product of a process which comprises contacting, in a suitable solvent, a chiral ligand L
1
, as defined above, with a complex (also referred to herein as the starting complex or precomplex) of a metal selected from tungsten (0), chromium (0), and molybdenum(0), ligands which form a stable complex with the metal and are displaceable by ligand L
1
under the conditions of said contacting. Such ligands include CO, cycloheptatriene, lower alkyl nitrile, and lower alkyl isonitrile. Preferred precomplexes for the preparation of the molybdenum catalysts include Mo(h
3−
C
7
H
8
)(CO)
3
(cycloheptatriene molybdenum tricarbonyl), Mo(CO)
3
(CH
3
CH
2
CN)
3
, and Mo(CO)
6
. Tungsten and molybdenum complexes are preferred, with molybdenum being particularly preferred. Upon such contacting, the complex undergoes a ligand exchange reaction, such that L
1
becomes coordinated to the metal atom. T

Affiliated with

Also associated with

Rating

Catalytic compositions and methods for asymmetric allylic... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Catalytic compositions and methods for asymmetric allylic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Catalytic compositions and methods for asymmetric allylic... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3059233