α,β-Unsaturated diazoketones as platforms in the asymmetric synthesis of hydroxylated alkaloids. Total synthesis of 1-deoxy-8,8a-diepicastanospermine and 1,6-dideoxyepicastanospermine and formal synthesis of pumiliotoxin 251D.

A versatile and concise approach for the stereoselective synthesis of mono-, di-, and trihydroxylated indolizidines is presented in four to six steps from Cbz-prolinal and a diazophosphonate. The key steps involved a Wolff rearrangement, followed by a stereoselective dihydroxylation/epoxidation reaction, from an α,β-unsaturated diazoketone. The strategy also permits extension to the synthesis of many natural hydroxylated indolizidine alkaloids as demonstrated in the formal synthesis of pumiliotoxin 251D.