Very Short Highly Enantioselective Grignard Synthesis Of 2,2-Disubstituted Tetrahydrofurans And Tetrahydropyrans

Phenones with elongated chains are shown to be excellent substrates for ligand-promoted asymmetric Grignard synthesis of tertiary alcohols. In turn this enables the simple, short and highly enantioselective (up to 96% ee) preparation of chiral 2,2-disubstituted THFs and THPs. Thus, asymmetric addition of Grignard reagents to gamma-chlorobutyrophenones and delta-chlorovalerophenones takes place in the presence of a chiral diaminocyclohexyl-derived tridentate ligand and subsequent base-promoted intramolecular cyclisation occurs with complete retention of asymmetry. As examples of the methodology, we report the shortest syntheses of gossonorol, gamma-ethyl-gamma-phenylbutyrolactone and delta-methyl-delta-tolylvalerolactone, the joint-shortest and flexible synthesis of boivinianin A and the shortest formal syntheses of boivinianin B and yingzhaosu C.