Premium
N‐Heterocyclic Carbene Iron(III) Porphyrin‐Catalyzed Intramolecular C(sp 3 )–H Amination of Alkyl Azides
Author(s) -
Shing KaPan,
Liu Yungen,
Cao Bei,
Chang XiaoYong,
You Tingjie,
Che ChiMing
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201806059
Subject(s) - chemistry , amination , regioselectivity , intramolecular force , carbene , alkyl , porphyrin , nitrene , medicinal chemistry , organic chemistry , combinatorial chemistry , catalysis
Metal‐catalyzed intramolecular C−H amination of alkyl azides constitutes an appealing approach to alicyclic amines; challenges remain in broadening substrate scope, enhancing regioselectivity, and applying the method to natural product synthesis. Herein we report an iron(III) porphyrin bearing axial N‐heterocyclic carbene ligands which catalyzes the intramolecular C(sp 3 )–H amination of a wide variety of alkyl azides under microwave‐assisted and thermal conditions, resulting in selective amination of tertiary, benzylic, allylic, secondary, and primary C−H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5–H bond. Mechanistic studies revealed a concerted or a fast re‐bound mechanism for the amination reaction. The reaction has been applied to the syntheses of tropane, nicotine, cis ‐octahydroindole, and leelamine derivatives.