Development of highly efficient acid-base combination catalyses based on carbon-metal bonds activation in organometallic reagents

Abstract

For synthesis of secondary and tertiary alcohols, practical carbon-carbon bond forming reactions between organometallic reagents and carbonyl compounds have been developed over a century since the discovery of Grignard reaction in 1900. Traditional organometallic reagents (i.e. Li, Mg, Si, Cu, and Zn reagents) should involve some fundamental functions, such as alkylating reagents, Lewis acids, and Brønsted bases. Thus, in principle, the efficiency of the nucleophilic addition should significantly increase if a carbon-metal bond in organometallic reagents can be activated by Lewis base catalysts and the substrates can be activated by native Lewis acid function of organometallic reagents. We report here that the highly efficient catalytic carbon-carbon bond forming reactions via carbon-metal bond activation in organometallic reagents using simple metal salt catalysts. A variety of acid-base promoting catalytic reactions, such as Grignard reaction, organozinc addition, 1,4-addition of organocopper reagents, trimethylsilylcyanation, and Mukaiyama aldol reaction, were achieved toward the efficient asymmetric catalyses.