C-C Bond Formation via Alkyl Cobaloxime Radical Chemistry: New Synthetic Reactions and Bio-Organic Applications

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The Organic and Macromolecular Program is supporting research directed toward the study of organometallic reagents related to vitamin B12. A series of novel chemical reactions have been discovered in which organo-cobalt (III) reagents mediate the cross coupling of varied structure types which leads to the construction of several biologically important compounds. Three different types of novel radical cross coupling reactions mediated via alkyl cobaloximes ıR-CoIII(dmgH)2py; dmgH = dimethylglyoxime monoanion! are being studied: (1) alkyl-alkenyl cross coupling, (2) alkyl-protonated heteroaromatic cross coupling, and (3) alkyl-nitroalkylanion cross coupling. A unique feature of these radical-mediated reactions, compared to other synthetically important radical reactions, is regeneration of the original olefin, protonated heteroaromatic, or nitroalkylanion functionality in the product. This research will continue the study of cobaloxime-mediated cross couplings and applications to (1) the development of a radical equivalent to the Grignard reaction, compatible with hydroxylic solvents and most of the common organic functional groups, via stoichiometric alkyl-nitroakylanion cross coupling, (2) a synthesis of the nucleoside antibiotic tunicamycin V and the development of a general strategy for the preparation of tunicamycins and analogs via stoichiometric alkyl-nitroalkylanion cross couplings, (3) a general strategy for the synthesis of C-di-, C-oligo-, and C-polysaccharides, essentially unexplored classes of bio-organically interesting and potentially significant unnatural analogs of natural products, via alkyl-nitroalkylanion cross coupling of valuable monosaccharides, and (4) preparation of two new classes of penicillin analogs, designed to be mechanism-based inhibitors of bacterial beta-lactamase self-defense enzymes, via alkyl-alkenyl or alkyl-protonated heteroaromatic cross couplings.