Palladium-mediated C-N, C-C, and C-O functionalization of azolopyrimidines: a new total synthesis of variolin B

Abstract

A new total synthesis of the alkaloid variolin B is achieved by a selective and sequential palladium-mediated functionalization of a trihalo-substituted pyrido[30 ,20 :4,5]pyrrolo[1,2-c]pyrimidine. This intermediate is obtained by a new heterocyclization reaction between an appropriate bromomethyl azaindole and N-tosylmethyl dichloroformimide. The methodology may be effective for the synthesis of some analogs by substitution on the relatively unexplored C4 and C9 positions of the alkaloid.