Catalytic Enantioselective Synthesis of Geminally-Bismetallated Organic Compounds

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Project Summary/Abstract The development of new catalytic enantioselective synthesis of chiral molecules is a vitally important subject in synthetic organic chemistry. The objective of the proposed research is to invent efficient synthetic methods for the construction of optically active geminally-bisfunctionalized organic molecules. Considering that the majority of therapeutic agents and drugs are single enantiomers of chiral entities, easy accessibility and utility of such chiral molecules are regarded significantly important. The long-term goal of the PI's research program is to develop general strategies for enantioselective synthesis of challenging poly-functionalized molecular frameworks found in important therapeutic agents. Toward this end, the proposed research seeks to invent novel metal-catalyzed and organocatalytic synthesis of geminally-bismetallated chiral molecules. This general approach toward enantioselective synthesis of geminally-bismetallated organic compounds is unknown. Our hypothesis is that transition- metal catalysts and organocatalysts can effectively activate silicon-boron (Si-B) bonds to generate geminally bismetallated species in enantioenriched form. Our rationale for the development of catalytic synthesis of geminally-bismetallated organic species is that they are prepared from readily available starting materials. Furthermore, the resulting organo gem-bismetallic species can participate in subsequent synthetic transformations to rapidly build up molecular complexity. To achieve this goal, the PI proposes the following specific aims. (1) The PI's group will develop transition-metal catalyzed silicon- boron (Si-B) bond activation. A new activation mode of silicon-boron bond will be invented using transition-metal catalysts. (2) We will invent catalytic enantioselective synthesis of geminally- bisfunctionalized organic compounds. Suitable chiral catalysts will accelerate the reaction rate and will induce enantiomeric excess in the product. The preparation of chiral gem-bismetallic organic molecules will be demonstrated. (3) Our group will develop organocatalytic method to enantioenriched geminally- bismetallated chiral molecules. A novel catalytic enantioselective method will be developed using organocatalysts. The method will disclose a new mode of asymmetric catalysis, and the mechanistic studies will be performed to elucidate the new catalytic cycle. Improving human health is deeply related to the ability to prepare enantioenriched chiral molecules with high efficiency and selectivity. The proposed research will address this need by developing enantioselective catalysis to prepare pharmaceutical intermediates and biologically active molecules.