Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1998-11-12
2001-07-03
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C502S152000
Reexamination Certificate
active
06255493
ABSTRACT:
BACKGROUND OF THE INVENTION
Molecular chirality plays an important role in science and technology. The biological activities of many pharmaceuticals, fragrances, food additives and agrochemicals are often associated with their absolute molecular configuration. While one enantiomer gives a desired biological function through interactions with natural binding sites, another enantiomer usually does not have the same function and sometimes has deleterious side effects. A growing demand in pharmaceutical industries is to make chiral drugs in enantiomerically pure form. To meet this fascinating challenge, chemists have explored many approaches for acquiring enantiomerically pure compounds ranging from optical resolution and structural modification of naturally occurring chiral substances to asymmetric catalysis using synthetic chiral catalysts and enzymes. Among these methods, asymmetric catalysis is perhaps the most efficient because a small amount of a chiral catalyst can be used to produce a large quantity of a chiral target molecule. During the last several decades, great attention has been devoted to discovering new asymmetric catalysts and more than a half-dozen commercial industrial processes have used asymmetric catalysis as the key step in the production of enantiomerically pure compounds. The worldwide sales of chiral drugs in 1997 was nearly $90 billion.
Many chiral phosphines have been made to facilitate asymmetric reactions. Among these ligands, BINAP is one of the most frequently used bidentate chiral phosphines. The axiallay dissymmetric, fully aromatic BINAP ligand has been demonstrated to be highly effective for many asymmetric reactions. DUPHOS and related ligands have also shown impressive enantioselectivities in numerous reactions. However, these phosphines are difficult to make and some of them are air sensitive. Recently, chiral nitrogen ligands have been extensively studied for asymmetric reactions. Particularly, oxazolinyls derived from chiral amino alcohols are popular ligands. Recognition of secondary interaction between ligands and substrates have also been used to design asymmetric catalysts. For example, primary and secondary amines may form H-bonds with substrates.
SUMMARY OF THE INVENTION
An object of the present invention is the development of novel transition metal complexes with new families of amine oxazolinyl ligands for practical asymmetric synthesis. Several new families of chiral amine oxazolinyl ligands for asymmetric catalysis are embodied herein, including secondary amine oxazolinyl ligands, and amine oxazolinyl ligands having more than one oxazolinyl group.
A further object of the invention is the preparation of the chiral oxazolinyl from chiral amino alcohols.
A further object of the invention is the discovery of chiral tridentate and tetradentate ligands suitable for asymmetric catalysis. Particularly, these ligands have been demonstrated to be highly effective for Ru-catalyzed transfer hydrogenation of ketones and imines.
A further object of the invention is the improved catalysis of transition metal facilitated reactions such as hydrogenation, hydride transfer reaction, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, allylic alkylation, cyclopropanation, Diels-Alder reaction, Aldol reaction, Heck reaction, Michael addition, and rearrangement reactions, leading to efficient and practical methods for producing important chiral drugs and agrochemicals.
To achieve the objects and in accordance with the purpose of the invention as embodied and broadly described herein, the invention comprises a chiral ligand that forms a catalyst providing enhanced enantiomeric selectivity in asymmetric reactions, having a structure selected from the group consisting of the enantiomers of the following formulas (I) through (IV):
wherein R, R
1
, R
2
, R
3
, R
4
, R
5
, R
6
and R
7
are independently hydrogen, alkyl, aryl, substituted alkyl or substituted aryl, wherein any two of R
1
, R
2
, R
3
and R
4
, may be linked to each other to form ring structures, wherein any two of R
5
, R
6
and R
7
may be linked to each other to form a ring structure, and wherein n is 1 or 2.
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Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Higel Floyd D.
The Penn State Research Foundation
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