Synthetic studies toward the pyran core and the amide side chain of psymberin

A synthetic approach to the polysubstituted pyran core and amide side chain of psymberin (irciniastatin A) using stereoselective organoboron methodology is described. An advanced oxyranyl pyran intermediate was prepared using a catalytic enantioselective and diastereoselective three-component reaction involving first an inverse electron-demand hetero 4+2] cycloaddition between 3-boronoacrolein pinacolate and 1-ethoxy-2-methylpropene, followed by an allylboration of ethyl glyoxylate. The amide side chain was prepared highly efficiently using the first example of a doubly diastereoselective allylboration of a chiral α-alkoxy aldehyde under the Lewis acid-catalyzed reaction manifold.