A convergent total synthesis of pumiliotoxins A and B via palladium-catalyzed cross-coupling reaction of homoallylic organozinc compounds with vinyl iodides

Abstract

A versatile convergent approach for preparing the pumiliotoxin alkaloids has been developed employing a Pd(0)-catalyzed cross-coupling reaction between homoallylic organozincs and vinyl iodides, which led to the asymmetric total synthesis of (+)-pumiliotoxins A ( 1) and B ( 2). The ( Z)-alkylideneindolizidine, which is a common organic part of the organozinc reagents in this approach, was synthesized with a high degree of stereocontrol upon using HfCl 4-mediated addition of the allenylsilane to ( S)-2-acetylpyrrolidine. The ( Z)-iodoalkylideneindolizidine ( 31) thus obtained as an advanced common intermediate was converted into the homoallylzinc chloride derivative 32, which underwent homoallyl-vinyl cross-coupling with the ( E)-vinyl iodide ( 13) using Pd(PPh 3) 4 catalyst to afford the 1,5-diene product 33. Subsequent deprotection provided (+)-pumiliotoxin A. On the other hand, 31 was transformed into the homoallyl- tert-butyl zinc intermediate 39, which was cross-coupled with the ( E)-vinyl iodide ( 36) in the presence of the Pd(0) catalyst. The resulting 1,5-diene product 40 underwent subsequent deprotection to afford (+)-pumiliotoxin B.