Highly Stereodivergent Synthesis of Chiral C4-Ester-Quaternary Pyrrolidines: A Strategy for the Total Synthesis of Spirotryprostatin A

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-...

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Bibliographic Details
Published in:Organic letters 2023-05, Vol.25 (19), p.3391-3396
Main Authors: Chen, Zhigang, Zhong, Wei, Liu, Sihua, Zou, Ting, Zhang, Kaiqiang, Gong, Chuliang, Guo, Wenyan, Kong, Feizhi, Nie, Libo, Hu, Shunqin, Wang, Haifei
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Language:English
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Summary: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 Ag2O/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.
ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.3c00904