The effect of sulfoxides on the stereoselective construction of tetrahydrofurans: total synthesis of (+)-goniothalesdiol.

ABSTRACT

Good to excellent stereoselectivities were achieved in the reductive cyclization (with Et(3)SiH/trimethylsilyl trifluoromethanesulfonate (TMSOTf)) of enantiopure hydroxy sulfinyl ketones en route to 2,5-cis-disubstituted tetrahydrofuran skeletons. Electrostatic effects of the exocyclic sulfoxide, which stabilized the reactive intermediate oxocarbenium conformations, were responsible for the observed stereocontrol. A model is proposed to explain the results. The use of this reaction and the asymmetric ß-ketosulfoxide reduction as key steps facilitated the total enantioselective synthesis of the natural ß-C-aryl glycoside (+)-goniothalesdiol.