Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-11-15
2002-11-05
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C548S237000, C548S312400, C548S146000, C502S152000
Reexamination Certificate
active
06476233
ABSTRACT:
SUMMARY OF THE INVENTION
This invention covers several new families of chiral amine oxazolinyl ligands and related ligands for asymmetric catalysis. There are many examples of oxazolinyl ligands linked with O, N, P, S, Se, in the of the groups. Oxazolinyl groups can be easily made from chiral amino alcohols. These ligands can be used for many asymmetric catalytic reactions. For examples, chiral tridentate ligands are highly effective for Ru-catalyzed transfer hydrogenation and direct hydrogenation of ketones and imines. Many other transition metal-catalyzed reactions such as hydrogenation, hydride transfer reaction, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, arrangement, allylic alkylation, cycloproprantion, Diels-Alder reaction, Aldol reaction, Heck reaction and Michael addition are also possible.
The invention covers ligands as well as procedures for asymmetric catalytic reactions.
FIG. 2
describes the general structure of this ligand. In these ligands, R, R1, R2, R3, R4, R5, R6, R7, R8=H, alkyl, aryl, substituted alkyl, substituted aryl. Ring structure is also possible by linking any two R groups from R1 to R4. The ring can be alkyl, substituted alkyl, aryl, and substituted aryl. X=PR′, PH, O, S, Se, AsR′, AsH, SiR′H, GeR′H, NH, NR′, NR′2, NCOR′, NOH, NNHR′, NNHCOR′ wherein R′=alkyl, aryl, substituted alkyl, and substituted aryl, n=1, 2.
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 market a chiral drug 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 two 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 1994 is 45.3 billion dollars, which enjoy 27% increase from the sales in 1993 (35.6 billions).
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 axially 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 are also used to design asymmetric catalysts. For example, primary and secondary NH may form H-bond with substrates. Part of this invention is the development of transition metal complexes with families of amine oxazolinyl ligands for practical asymmetric synthesis. A Ru-ambox complex can be used as an effective catalyst for asymmetric transfer hydrogenation of ketones. The current invention emphasizes the chemistry of Ru-catalyzed direct hydrogenation of ketones, a more practical method for making chiral alcohols. In addition, many other ligands are also disclosed.
A variety of asymmetric reactions such as hydrogenation, hydride transfer reaction, hydrosilylation, hydroboration, hydrovinylation, hydroformylation, hydrocarboxylation, allylic alkylation, cyclopropanation, Diels-Alder reaction, Aldol reaction, Heck reaction and Michael addition will be explored based on these innovative ligand systems. The success of this approach would lead to efficient and practical methods for producing important chiral drugs and agrochernicals.
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Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Higel Floyd D.
Saeed Kamal
The Penn State Research Foundation
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