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. ? ?
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