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Peer-reviewedCC BY-NC-ND 4.0Organic Letters

Carbon Quaternization at the α‑Position of Thiazoles: Iron-Catalyzed Hydroheteroarylation Using Unactivated Alkenes

  • Jinwoo Lee1
  • Chaeryn Jeong1
  • Hyungwoo Choi1
  • Seok Beom Lee1
  • Joonseok Jang1
  • Sangmyung Han1
  • Yohan Park2
  • Suckchang Hong1,3
  1. 1Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
  2. 2College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 34134, Republic of Korea
  3. 3Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
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Abstract

Thiazoles are privileged N-heterocyclic scaffolds ubiquitous in FDA-approved drugs, yet their clinical utility can be compromised by oxidative metabolism at the heterobenzylic position. Inspired by the metabolic-blocking strategy used in dabrafenib development, herein we report an iron-catalyzed strategy for direct α-quaternization of (benzo)­thiazoles using unactivated alkenes. Under the proposed pathway, alkene-derived carbon-centered radicals undergo regioselective C2 addition and oxidative rearomatization, providing α-quaternary products without heteroarene preactivation or stoichiometric Lewis acids, thereby enabling analogue diversification.

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Cite

BibTeXRIS
BibTeX
@article{lee2026carbon,
  title = {{Carbon Quaternization at the α‑Position of Thiazoles: Iron-Catalyzed Hydroheteroarylation Using Unactivated Alkenes}},
  author = {Jinwoo Lee and Chaeryn Jeong and Hyungwoo Choi and Seok Beom Lee and Joonseok Jang and Sangmyung Han and Yohan Park and Suckchang Hong},
  journal = {Organic Letters},
  year = {2026},
  month = oct,
  doi = {10.1021/acs.orglett.6c04036},
  url = {https://doi.org/10.1021/acs.orglett.6c04036},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Carbon Quaternization at the α‑Position of Thiazoles: Iron-Catalyzed Hydroheteroarylation Using Unactivated Alkenes
AU  - Jinwoo Lee
AU  - Chaeryn Jeong
AU  - Hyungwoo Choi
AU  - Seok Beom Lee
AU  - Joonseok Jang
AU  - Sangmyung Han
AU  - Yohan Park
AU  - Suckchang Hong
PY  - 2026
DA  - 2026/10/08
JO  - Organic Letters
DO  - 10.1021/acs.orglett.6c04036
UR  - https://doi.org/10.1021/acs.orglett.6c04036
AB  - Thiazoles are privileged N-heterocyclic scaffolds ubiquitous in FDA-approved drugs, yet their clinical utility can be compromised by oxidative metabolism at the heterobenzylic position. Inspired by the metabolic-blocking strategy used in dabrafenib development, herein we report an iron-catalyzed strategy for direct α-quaternization of (benzo)­thiazoles using unactivated alkenes. Under the proposed pathway, alkene-derived carbon-centered radicals undergo regioselective C2 addition and oxidative rearomatization, providing α-quaternary products without heteroarene preactivation or stoichiometric Lewis acids, thereby enabling analogue diversification.
SN  - 1523-7060
SN  - 1523-7052
ER  -