Diastereoselective synthesis of polysubstituted tetrahydropyrans and thiacyclohexanes via indium trichloride mediated cyclizations

Polysubstituted tetrahydropyrans and thiacyclohexanes were synthesized in h igh yields with excellent diastereoselectivities via indium trichloride med iated cyclizations between homoallyl alcohols and mercaptans with aldehydes . In the case of tetrahydropyran products, the stereochemistry of the produ ct was found to be directly correlated with the geometry of the homoallyl a lcohols; whereas the cross-cyclization of aldehydes with trans-homoallyl al cohols generated (up-down-up) 2,3,4-trisubstituted tetrahydropyran products exclusively, the reaction of aldehydes with cis-homoallyl alcohols provide d mainly (up-up-up) 2,3,4-trisubstituted products. When a trisubstituted ho moallyl alcohol was used, its cross-cyclization with aldehydes generated (u p-down-up-down-up) pentasubstituted tetrahydropyran derivatives with simult aneous controlling of five stereogenic centers. On the other hand, a cycliz ation-decyclization equilibrium was observed in the formation of thiacycloh exanes. The reaction of both cis- and trans-homoallyl mercaptans with aldeh ydes provided the same major diastereomers.