A Type of Chiral C2‑Symmetric Arylthiol Catalyst for Highly Enantioselective Anti-Markovnikov Hydroamination

The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation of asymmetric organocatalyzed reactions via an enantioselective hydrogen atom transfer (HAT) process. Herein, an unprecedented type of chiral C2-symmetric arylthiol catalysts derived from readily availa...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2024-05, Vol.146 (23), p.16248-16256
Main Authors: Tang, Lin, Shen, Chaoren, Hao, Shaoyu, Dong, Kaiwu
Format: Article
Language:English
Subjects:
catalysts
enantioselectivity
hydrogen
lactic acid
moieties
piperidines
thiols
Online Access:Get full text
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Summary:The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation of asymmetric organocatalyzed reactions via an enantioselective hydrogen atom transfer (HAT) process. Herein, an unprecedented type of chiral C2-symmetric arylthiol catalysts derived from readily available enantiomeric lactate ester was developed. With these catalysts, an asymmetric anti-Markovnikov alkene hydroamination–cyclization reaction was established, affording a variety of pharmaceutically interesting 3-substituted piperidines with moderate to high enantioselectivity. Results of the designed control experiments and theoretical computation rationalized the origin of stereocontrol and disclosed the spatial effect of the moiety of chiral thiols on the enantioselectivity. We believed the facile synthesis, flexible tunability, and effective enantioselectivity-controlling capability of these catalysts would shed light on the development of versatile chiral HAT catalysts and related asymmetric reactions.
ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/jacs.4c04596