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·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 σ-bonds and three new stereogenic centers
were generated in a one-pot process.