Nickel-Catalyzed Preparation of Bicyclic Heterocycles: Total
Synthesis of (+)-Allopumiliotoxin 267A, (+)-Allopumiliotoxin 339A,
and (+)-Allopumiliotoxin 339B
posted on 2000-07-11, 00:00authored byXiao-Qing Tang, John Montgomery
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.