A Nitrone Based Route to Polyhydroxylated Lactams and Piperidines: An Expeditious Synthesis of rac-Fagomine

Abstract

The synthetic versatility of tetrahydrofuro[2,3-d]isoxazol-5(2H)-ones, obtained from TMSOTf-promoted addition of 2-trimethyl-silyloxyfuran to nitrones, is demonstrated in a two-step reductive sequence to give the title compounds. The cycloadducts obtained from a glycolaldehyde derived nitrone are first reduced with DIBAH, then hydrogenolyzed in the presence of Pd(OH)2 to give polyhydroxylated piperidines, including rac-fagomine. Direct hydrogenolysis of the same cycloadducts gives an easy entry to polyhydroxylated lactams.