Asymmetric synthesis is of paramount importance to modern medicinal chemistry. Many bioactive compounds are chiral, and their potencies, pharmacological profiles, and side effects often depend on the absolute configuration of chiral centers in their molecules. This is why every effort is made to find effective and economical ways of producing chiral pharmaceuticals in the form of pure, individual enantiomers. Catalytic methods are particularly attractive in this respect, since they allow generation or differentiation of chiral centers using only small amounts of chiral catalysts. ? ? The primary focus of this proposal is on the development of a new class of asymmetric nucleophilic catalysts based on the previously unexplored 2,3-dihydroimidazo[1,2-a]pyridine heterocyclic system. Our preliminary data indicate that these compounds, prepared in only two steps from commercially available starting materials, are effective acylation catalysts showing high levels of enantioselectivity in kinetic resolution of racemic secondary alcohols. The objectives of the proposed research are: ? ? a) To develop asymmetric catalysts that general synthetic practitioners will be able to use; ? b) To probe the mechanism of chiral recognition in the asymmetric acyl transfer reaction; ? c) To investigate reactivity of previously unexplored classes of substrates for enantioselective acylation, especially those that will lead to useful intermediates for asymmetric synthesis; ? d) To discover new applications of asymmetric nucleophilic catalysis taking advantage of the flexibility of our catalyst design. ? ?

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Medicinal Chemistry Study Section (MCHA)
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Schwab, John M
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Washington University
Schools of Arts and Sciences
Saint Louis
United States
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Li, Ximin; Jiang, Hui; Uffman, Eric W et al. (2012) Kinetic resolution of secondary alcohols using amidine-based catalysts. J Org Chem 77:1722-37
Yang, Xing; Bumbu, Valentina D; Liu, Peng et al. (2012) Catalytic, enantioselective N-acylation of lactams and thiolactams using amidine-based catalysts. J Am Chem Soc 134:17605-12
Zhang, Yuhua; Birman, Vladimir B (2009) Effects of Methyl Substituents on the Activity and Enantioselectivity of Homobenzotetramisole-Based Catalysts in the Kinetic Resolution of Alcohols. Adv Synth Catal 351:2525-2529
Yang, Xing; Birman, Vladimir B (2009) Homobenzotetramisole-Catalyzed Kinetic Resolution of alpha-Aryl-, alpha-Aryloxy-, and alpha-Arylthioalkanoic Acids. Adv Synth Catal 351:2301-2304
Boppisetti, Jagadish K; Birman, Vladimir B (2009) Asymmetric oxidation of o-alkylphenols with chiral 2-(o-iodoxyphenyl)-oxazolines. Org Lett 11:1221-3
Yang, Xing; Birman, Vladimir B (2009) Acyl transfer catalysis with 1,2,4-triazole anion. Org Lett 11:1499-502
Li, Ximin; Liu, Peng; Houk, K N et al. (2008) Origin of enantioselectivity in CF3-PIP-catalyzed kinetic resolution of secondary benzylic alcohols. J Am Chem Soc 130:13836-7
Birman, Vladimir B; Li, Ximin (2008) Homobenzotetramisole: an effective catalyst for kinetic resolution of aryl-cycloalkanols. Org Lett 10:1115-8
Birman, Vladimir B; Jiang, Hui; Li, Ximin (2007) Enantioselective synthesis of lobeline via nonenzymatic desymmetrization. Org Lett 9:3237-40
Birman, Vladimir B; Li, Ximin; Han, Zhenfu (2007) Nonaromatic amidine derivatives as acylation catalysts. Org Lett 9:37-40

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