A Highly Stereoselective Synthesis of Tetrahydrofurans

The development of a direct and highly stereoselective synthesis of 2,3,5-substituted tetrahydrofurans has been accomplished through a combination of batch- and microchip-MS-experiments. This sequential transformation comprises a Lewis acid-mediated reaction of bis(silyl) dienediolate 1 and a broad range of aldehydes, furnishing products with three new σ-bonds and three stereogenic centers in a one-pot process with typically good yields and excellent stereoselectivity. Key steps which have been elucidated primarily with microchip-MS-experiments include a vinylogous aldol reaction and a Prins-type cyclization. Furthermore, a titanium BINOL complex is a powerful chiral catalyst for this process. The products were further converted into bi- and tricylic products by carbonyl-ene reactions, proceeding with excellent yields and diastereoselectivity.