Proline Derived Bicyclic Derivatives through Metal Catalysed Cyclisations of Allenes: Synthesis of Longamide B, Stylisine D and their Derivatives

Abstract

Annulations of allene-substituted proline derivatives promoted by transition metals have been investigated as a general way to access bicyclic structures with a bridgehead nitrogen. Two processes, Pd- and Ag-catalysed cyclisations, have been employed complementary to control the substitution pattern of the product. The investigated methodologies afforded the bicyclic derivatives in comparable yields, while Ag-catalysis showed higher level of diastereoselectivity. Both processes have been utilized in the synthesis of naturally occurring pyrroles longamide B, stylisine D and their derivatives.