Catalytic Enantioselective C-C Coupling of Alcohols for Polyketide Total Synthesis beyond Chiral Auxiliaries and Premetalated Reagents.

Catalytic enantioselective hydrogen autotransfer reactions for the direct conversion of lower alcohols to higher alcohols are catalogued and their application to the total synthesis of polyketide natural products is described. These methods exploit a redox process in which alcohol oxidation is balanced by reductive generation of organometallic nucleophiles from unsaturated hydrocarbon pronucleophiles. Unlike classical carbonyl additions, premetalated reagents, chiral auxiliaries and discrete alcohol-to-aldehyde redox reactions are not required. Additionally, chemoselective dehydrogenation of primary alcohols in the presence of secondary alcohols enables C-C coupling in the absence of protecting groups.