Iterative Direct Aldol Strategy for Polypropionates: Enantioselective Total Synthesis of (-)-Membrenone A and B

An iterative direct aldol reaction using a C3 propionate unit as an aldol donor offers expeditious access to polyketide assembly in a highly diastereo- and enantioselective manner. An all-syn polyketide array with four consecutive stereogenic centers was efficiently constructed by an aldol reaction of thiopropionamide via soft Lewis acid/hard Bronsted base cooperative catalysis. This iterative aldol strategy led to an enantioselective synthesis of (-)-membrenone A and B.