The electrochemical reduction of geminal dihalides in the presence of electrophilic reagents has several disadvantages (poor chemoselectivity and stereoselectivity) for the synthesis of mono-and bis-substituted materials. The process will be catalyzed with cobalt (I) macrocyclic complexes, including vitamin B12, cobalt bis-salicylideneethylenediamine, and cobaloximes. The strategy is to reduce the cobalt species to the reactive Co(I) state, which is expected to undergo rapid oxidative addition with a geminal dihalide in the medium. The resulting adduct, a Co(III) species, will be reduced in situ to eject the desired carbanion for reaction with an electrophile in the medium. In effect, the cobalt macrocycle will catalyze the reduction of the geminal halide to the corresponding alpha-halocarbanion. The catalytic process is expected to occur in far higher stereoselectivity and chemoselectivity than the direct electrochemical process, and permit conversions not possible at all by the direct process. Furthermore, by carrying out the electrolysis at potentials where oxidative addition to Co(I) takes place but the Co(III) adduct is stable, it will be possible to make radicals by thermal or photochemical decomposition of the latter. A number of synthetic applications, including reductive electrophilic substitution on geminal dihalides (including both open chain and cyclic systems), synthesis of substituted cyclopropanes, arenes, and polycyclic systems, and synthesis of alkenes, based on these principles, will be undertaken. These principles will be further extended to electrocatalytic generation of carbanions from substrates other than alkyl halides. The Organic Synthesis Program is supporting this research to develop cobalt macrocycle-catalyzed electrochemical coupling reactions. This research will lead to a new and novel route to synthetically useful reactive intermediates that can be used to synthesize the increasingly complex substances needed in our economy.
