Stereoselective Synthesis of 2,3,5-Trisubstituted Tetrahydrofurans Initiated by a Titanium-BINOLate-Catalyzed Vinylogous Aldol Reaction

The enantioselective synthesis of 2,3,5-trisubstituted tetrahydrofurans 3 has been achieved using a chiral titanium- BINOL complex as catalyst for the vinylogous Mukaiyama aldol reaction of bis(silyl) diendiolate 1 and an aldehyde. The ensuing BF3 center dot OEt2-mediated Prins-type cyclization with a second aldehyde gave rise to 2,3,5-substituted tetrahydrofurans 3 with generally good yields and excellent stereocontrol. In this process, three new sigma-bonds and three new stereogenic centers were generated in a one-pot process.