Design and application of new methods for asymmetric carbon-carbon bond formation

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The objective of this proposal is to investigate new methods for the asymmetric construction of carbon-carbon bonds. New organocatalysts and chiral scaffolds will be developed and their applications in asymmetric synthesis will be examined.Asymmetric Organocatalysis: One aim of this proposal is the development of new organocatalysts for fundamental processes such as stereoselective conjugate additions of carbon nucleophiles to enones and nitroalkenes as well as carbocyclization reactions of aminodienes with acrylates or nitroalkenes. The catalyst types that will be examined are: a) chiral guanidines, b) chiral diamines and triamines. The catalysts will be elaborated from enantiomerically pure amino acids, amino alcohols and terpenoids.A study of the nature and positioning of hydrogen bond donor groups in chiral pyrrolidine-based organocatalysts will be undertaken. The utility of these catalysts in conjugate addition and carbocyclization reactions will be studied. Application to the synthesis of bioactive molecules such as the lycorane class of alkaloids will be examined.2. Asymmetric Synthesis on Chiral Templates: The synthesis and asymmetric functionalization reactions of chiral morpholine templates will be examined. The focus is the development of templates that offer good stereocontrol and easy recovery of the chiral regulator. The use of these templates in stereoselective alkylation, carbonyl addition and aziridination reactions will be studied. The construction of highly functionalized carbocycles, oxacycles and azacycles as well as peptide isosteres will be explored.The research will provide new methods for the enantioselective synthesis of molecules that are useful in organic chemistry and medicinal chemistry, and provide training to employ students in the pharmaceutical industry or in academia.