Fe-Catalyzed α-C(sp 3 )-H Amination of N-Heterocycles.

Autor: Geraci A; University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056, Basel, Switzerland., Baudoin O; University of Basel, Department of Chemistry, St. Johanns-Ring 19, 4056, Basel, Switzerland.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Oct 16, pp. e202417414. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1002/anie.202417414
Abstrakt: Nitrogen-heterocycles are privileged structures in both marketed drugs and natural products. On the other hand, C-H amination reactions furnish unconventional and straightforward approaches for the construction of C-N bonds. Yet, most of the known methods rely on precious metal catalysts. Herein we report a site-selective intermolecular C(sp 3 )-H amination of N-heterocycles, catalyzed by inexpensive FeCl 2, which allows the functionalization of a wide range of pharmaceutically relevant cyclic amines. The C-H amination occurs site-selectively in α-position to the nitrogen atom, even when weaker C-H bonds are present, and furnishes Troc-protected aminals or amidines. The method employs the N-heterocycle as limiting reagent and is applicable to the late-stage functionalization of complex molecules. Its synthetic potential was further illustrated through the derivatization of α-aminated products and the application to a concise total synthesis of the reported structure for senobtusin. Mechanistic studies allowed to propose a plausible reaction mechanism involving a turnover-limiting Fe-nitrene generation followed by fast H atom transfer and radical rebound.
(© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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