Issue 9, 2017

Nickel-catalyzed transamidation of aliphatic amide derivatives

Abstract

Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C–N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date.

Graphical abstract: Nickel-catalyzed transamidation of aliphatic amide derivatives

Supplementary files

Article information

Article type
Edge Article
Submitted
03 May 2017
Accepted
08 Jul 2017
First published
10 Jul 2017
This article is Open Access

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

Chem. Sci., 2017,8, 6433-6438

Nickel-catalyzed transamidation of aliphatic amide derivatives

J. E. Dander, Emma L. Baker and N. K. Garg, Chem. Sci., 2017, 8, 6433 DOI: 10.1039/C7SC01980G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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