Issue 22, 2021

Generation and application of Cu-bound alkyl nitrenes for the catalyst-controlled synthesis of cyclic β-amino acids

Abstract

The advent of saturated N-heterocycles as valuable building blocks in medicinal chemistry has led to the development of new methods to construct such nitrogen-containing cyclic frameworks. Despite the apparent strategic clarity, intramolecular C–H aminations with metallonitrenes have only sporadically been explored in this direction because of the intractability of the requisite alkyl nitrenes. Here, we report copper-catalysed intramolecular amination using an alkyl nitrene generated from substituted isoxazolidin-5-ones upon N–O bond cleavage. The copper catalysis exclusively aminates aromatic C(sp2)–H bonds among other potentially reactive groups, offering a solution to the chemoselectivity problem that has been troublesome with rhodium catalysis. A combined experimental and computational study suggested that the active species in the current cyclic β-amino acid synthesis is a dicopper alkyl nitrene, which follows a cyclisation pathway distinct from the analogous alkyl metallonitrene.

Graphical abstract: Generation and application of Cu-bound alkyl nitrenes for the catalyst-controlled synthesis of cyclic β-amino acids

Supplementary files

Article information

Article type
Edge Article
Submitted
11 Mar 2021
Accepted
24 Apr 2021
First published
27 Apr 2021
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., 2021,12, 7809-7817

Generation and application of Cu-bound alkyl nitrenes for the catalyst-controlled synthesis of cyclic β-amino acids

R. K. Tak, F. Amemiya, H. Noda and M. Shibasaki, Chem. Sci., 2021, 12, 7809 DOI: 10.1039/D1SC01419F

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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