N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp3 )-H Amination of Alkyl Azides

Ka-Pan Shing; Yungen Liu; Bei Cao; Xiao-Yong Chang; Tingjie You; Chi-Ming Che

doi:10.1002/anie.201806059

N-Heterocyclic Carbene Iron(III) Porphyrin-Catalyzed Intramolecular C(sp³ )-H Amination of Alkyl Azides

Angew Chem Int Ed Engl. 2018 Sep 10;57(37):11947-11951. doi: 10.1002/anie.201806059. Epub 2018 Aug 16.

Authors

Ka-Pan Shing¹, Yungen Liu², Bei Cao¹, Xiao-Yong Chang¹, Tingjie You², Chi-Ming Che^{1

3}

Affiliations

¹ State Key Laboratory of Synthetic Chemistry, Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
² Department of Chemistry, South University of Science and Technology of China, Shenzhen, Guangdong, 518055, China.
³ HKU Shenzhen Institute of Research and Innovation, Shenzhen, 518053, China.

PMID: 30055031
DOI: 10.1002/anie.201806059

Abstract

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(sp³ )-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.

Keywords: C−H amination; alkyl azides; homogeneous catalysis; iron; porphyrinoids.

Publication types

Research Support, Non-U.S. Gov't