Nickel-Catalyzed Preparation of Bicyclic Heterocycles:  Total Synthesis of (+)-Allopumiliotoxin 267A, (+)-Allopumiliotoxin 339A, and (+)-Allopumiliotoxin 339B

A new method for the reductive cyclization of ynals involving a Ni(COD)₂/PBu₃ catalyst system to produce allylic alcohols was developed. The triethylsilane-mediated procedure allows preparation of functionally rich pyrrolizidine, indolizidine, and quinolizidine alkaloid frameworks. The method allows the direct introduction of an allylic alcohol moiety with completely stereoselective creation of an exocyclic double bond and highly diastereoselective alcohol introduction relative to preexisting chirality. The total syntheses of (+)-allopumiliotoxin 267A, (+)-allopumiliotoxin 339A, and (+)-allopumiliotoxin 339B were accomplished utilizing an ynal cyclization as the key step. These syntheses provide short and efficient entries to the allopumiliotoxins and highlight the utility of nickel-catalyzed ynal cyclizations in complex synthetic strategies.