Issue 11, 2019

Enantioselective intramolecular C–H amination of aliphatic azides by dual ruthenium and phosphine catalysis

Abstract

The catalytic enantioselective intramolecular C(sp3)-H amination of aliphatic azides represents an efficient method for constructing chiral saturated cyclic amines which constitute a prominent structural motif in bioactive compounds. We report a dual catalytic system involving a chiral-at-metal bis(pyridyl-NHC) ruthenium complex and tris(4-fluorophenyl)phosphine (both 1 mol%), which facilitates the cyclization of aliphatic azides to chiral α-aryl pyrrolidines with enantioselectivities of up to 99% ee, including a pyrrolidine which can be converted to the anti-tumor alkaloid (R)-(+)-crispine. Mechanistically, the phosphine activates the organic azide to form an intermediate iminophosphorane and transfers the nitrene unit to the ruthenium providing an imido ruthenium intermediate which engages in the highly stereocontrolled C–H amination. This dual catalysis combines ruthenium catalysis with the Staudinger reaction and provides a novel strategy for catalyzing enantioselective C–H aminations of unactivated aliphatic azides.

Graphical abstract: Enantioselective intramolecular C–H amination of aliphatic azides by dual ruthenium and phosphine catalysis

Supplementary files

Article information

Article type
Edge Article
Submitted
04 janv. 2019
Accepted
28 janv. 2019
First published
29 janv. 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2019,10, 3202-3207

Enantioselective intramolecular C–H amination of aliphatic azides by dual ruthenium and phosphine catalysis

J. Qin, Z. Zhou, T. Cui, M. Hemming and E. Meggers, Chem. Sci., 2019, 10, 3202 DOI: 10.1039/C9SC00054B

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