The long term objectives of this project are to design and construct chiral dirhodium(II) tetrakis(carboxamides) whose catalytic applications will provide convenient and effective asymmetric syntheses of molecules having biomedical importance. These catalysts have a unique geometry in which four chiral carboxamide ligands are oriented so that each rhodium possesses two adjacent Rh-N bonds. As a result, reactive substrates have relatively unimpeded access to rhodium, and the resulting reaction intermediates are advantageously arranged for enantioselective intermolecular transformations and, especially, intramolecular cyclizations. As indicated by results obtained with intramolecular cyclopropanation reactions for which enantiomeric excesses of > 94% have been achieved, chiral rhodium(II) carboxamides are particularly suitable for highly selective catalytic metal carbene processes involving diazo compounds. Furthermore, the design of these catalysts allows placement of a polar substituent at the asymmetric center of the ligand over the carbene center to provide electronic stabilization to the rhodium-bound carbene, orientation of carbene substituents into an electronically and sterically preferred configuration, and control over the direction of approach by nucleophiles to the carbene center. Focus will be placed on chiral dirhodium(II) catalyst applications to carbenoid transformation including cyclopropanation, aromatic cycloaddition, carbon-hydrogen insertion, and metal-stabilized ylide reactions. Based on preliminary investigations, exceptional enantiocontrol is expected from intramolecular cyclopropanation and aromatic cycloaddition processes resulting in lactones, lactams, and cyclopentanones. Further developments in catalyst design are predicted to advance C-H insertion, cyclopropanation, and ylide transformations to similar high levels of enantioselectivity. Chiral dirhodium(II) catalysts will be designed and developed to achieve high enantioselectives in carbenoid transformations of disubstituted diazomethanes. Addition reactions of organoboranes for which these chiral catalysts are effective will also be investigated. The advantages of chiral dirhodium(II) carboxamides, especially those possessing chiral oxazolidinone or 2-pyrrolidone-5-carboxylate ligands, extends to their ease of preparation, their stability, and the convenience of synthetic access to structurally modified ligands.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Medicinal Chemistry Study Section (MCHA)
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Trinity University
Schools of Arts and Sciences
San Antonio
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Cheng, Qing-Qing; Deng, Yongming; Lankelma, Marianne et al. (2017) Cycloaddition reactions of enoldiazo compounds. Chem Soc Rev 46:5425-5443
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Xu, Xinfang; Zavalij, Peter Y; Doyle, Michael P (2013) Highly enantioselective dearomatizing formal [3+3] cycloaddition reactions of N-acyliminopyridinium ylides with electrophilic enol carbene intermediates. Angew Chem Int Ed Engl 52:12664-8
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