Cobalt-Catalyzed Enantioconvergent Decarboxylative N-Alkylation
Introduction of alkyl substituents onto nucleophilic nitrogen atoms in amines is a central synthetic strategy for increasing molecular complexity and structural diversity in medicinal chemistry, organic synthesis, and materials science. Although the direct transfer of a stereogenic alkyl group onto a nitrogen atom by N-alkylation is one of the most efficient approaches to asymmetric C(<i>sp</i><sup>3</sup>)-N bond formation, few methods are available for the enantioconvergent N-alkylation of amines with racemic alkyl transfer reagents. We report herein a previously unexplored enantioconvergent decarboxylative N-alkylation of aromatic amines with racemic carboxylic acids. The reaction is enabled by a merger of acridine photocatalysis with Co(salen)-catalyzed asymmetric radical-polar crossover (RPC). The study provides a simple synthetic segue to medicinally and synthetically valuable α-chiral benzylic amines and unravels the structural, electronic, and bonding effects that govern the stereocontrol imparted by the privileged Co(salen)-based asymmetric RPC catalytic system.
Authors
- Xiyuan Xu (ORCID: https://orcid.org/0000-0003-0440-323X)
- Min He (ORCID: https://orcid.org/0000-0002-0361-5604)
- Bo Gao (ORCID: https://orcid.org/0000-0002-2491-534X)
- William B. Hughes
- Arka Porey (ORCID: https://orcid.org/0009-0002-9785-1890)
- Shengfei Jin (ORCID: https://orcid.org/0000-0001-9349-7332)
- Vy T. Nguyen (ORCID: https://orcid.org/0000-0002-7130-6379)
- Xin Tian (ORCID: https://orcid.org/0000-0003-1896-2462)
- Chao Huang
- Wenhan Yang (ORCID: https://orcid.org/0000-0002-1692-0069)
- Ramon Trevino
- Maosheng Cheng (ORCID: https://orcid.org/0000-0001-9073-4806)
- Seth O. Fremin (ORCID: https://orcid.org/0000-0002-9744-557X)
- Shree Krishna Dhakal
- Yao Sun (ORCID: https://orcid.org/0009-0000-2663-7382)
- Bin Qin (ORCID: https://orcid.org/0000-0002-9180-0550)
- Yongxiang Liu (ORCID: https://orcid.org/0000-0003-0364-0137)
- Yingqian Jiang
- Chandan Kumar Giri (ORCID: https://orcid.org/0000-0003-1373-6116)
- Siwen Huang (ORCID: https://orcid.org/0009-0009-2909-1624)
- Oleg V. Larionov (ORCID: https://orcid.org/0000-0002-3026-1135)
- Dongqing Zuo (ORCID: https://orcid.org/0000-0002-6684-9467)
- Babu Raj Dhungana (ORCID: https://orcid.org/0009-0000-0615-7015)
Institutions
- Shenyang Pharmaceutical University (CN)
- The University of Texas at San Antonio (US)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-06-09
- DOI
- https://doi.org/10.1021/jacs.5c06317
- Citations
- 12
- Primary Topic
- Catalytic C–H Functionalization Methods
- Type
- article
- Field-Weighted Citation Impact
- 11.23
Funders
- National Natural Science Foundation of China
- Department of Education of Liaoning Province
- Liaoning Revitalization Talents Program
- Division of Chemistry