Highly Stereodivergent Synthesis of Chiral C4-Ester-Quaternary Pyrrolidines: A Strategy for the Total Synthesis of Spirotryprostatin A
Zhigang Chen, Wei Zhong, Sihua Liu, Ting Zou, Kaiqiang Zhang, Chuliang Gong, Wenyan Guo, Feizhi Kong, Libo Nie, Shunqin Hu, Haifei Wang
Abstract
In this work, we disclose two sets of highly diastereo- and enantioselective [3 + 2] cycloadditions of iminoesters with various α-substituted acrylates, especially for sterically hindered and weakly activated α-aryl or alkyl-substituted acrylates and alkenal, alkynal, or unstable aliphatic aldehyde-derived iminoesters, catalyzed by the AgHMDS/DTBM-Segphos or Ag 2 O/CA-AA-Amidphos catalytic system, achieving the stereodivergent synthesis of chiral C4-ester-quaternary exo - or endo -pyrrolidines with high yields and excellent diastereo- and enantioselectivities (up to >99:1 dr and >99% ee). More importantly, the gram-scale synthetic exo -adduct displays significant applications in the aspect of realizing the total synthesis of the spirotryprostatin A alkaloid via nine steps in a 36% overall yield.