A Dual Role for the N‑Perfluorobutanesulfinamide Auxiliary in an Asymmetric Decarboxylative Mannich Reaction

Herein, we demonstrate that the enhanced electrophilicity of N-perfluorobutanesulfinamide auxiliary-derived imines enables a highly selective decarboxylative Mannich reaction under mild conditions. The molecular sieves-mediated transformation tolerates a broad substrate scope and produces chiral β-a...

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Bibliographic Details
Published in:Organic letters 2024-10, Vol.26 (41), p.8810-8815
Main Authors: Namitharan, Kayambu, Cellnik, Torsten, Mukanova, Assel, Kim, Shinwon, Healy, Alan R.
Format: Article
Language:English
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Letter
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Summary:Herein, we demonstrate that the enhanced electrophilicity of N-perfluorobutanesulfinamide auxiliary-derived imines enables a highly selective decarboxylative Mannich reaction under mild conditions. The molecular sieves-mediated transformation tolerates a broad substrate scope and produces chiral β-amino thioesters in high yield. Additionally, we demonstrate that the N-perfluoroalkyl sulfinyl group can function as a phase tag for fluorous purification, thus enabling the rapid isolation of the chiral amine products by solid-phase extraction. The synthetic utility of this method is illustrated by the synthesis of sitagliptin, ruspolinone, and the natural product negamycin.
ISSN:1523-7060
1523-7052
1523-7052
DOI:10.1021/acs.orglett.4c03139