Catalytic Asymmetric Vinylogous Prins Cyclization: A Highly Diastereo- and Enantioselective Entry to Tetrahydrofurans

We describe the design and development of the first catalytic asymmetric vinylogous Prins cyclization. This reaction constitutes an efficient approach for highly diastereo- and enantioselective synthesis of tetrahydrofurans (THFs) and is catalyzed by a confined chiral imidodiphosphoric acid (IDP). Aromatic and heteroaromatic aldehydes react with various 3,5-dien-1-ols to afford 2,3-disubstituted THFs in excellent selectivity (d.r. > 20:1, e.r. up to 99:1). Aliphatic aldehydes react with similarly excellent results when a highly acidic imidodiphosphorimidate (IDPi) catalyst is used. With a racemic dienyl alcohol, the reaction proceeds via a kinetic resolution. DFT calculations suggest an explanation for unusually high stereoselectivity.