Issue 6, 2021

Hydantoin-bridged medium ring scaffolds by migratory insertion of urea-tethered nitrile anions into aromatic C–N bonds

Abstract

Bicyclic or tricyclic nitrogen-containing heterocyclic scaffolds were constructed rapidly by intramolecular nucleophilic aromatic substitution of metallated nitriles tethered by a urea linkage to a series of electronically unactivated heterocyclic precursors. The substitution reaction constitutes a ring expansion, enabled by the conformationally constrained tether between the nitrile and the heterocycle. Attack of the metallated urea leaving group on the nitrile generates a hydantoin that bridges the polycyclic products. X-ray crystallography reveals ring-dependant strain within the hydantoin.

Graphical abstract: Hydantoin-bridged medium ring scaffolds by migratory insertion of urea-tethered nitrile anions into aromatic C–N bonds

Supplementary files

Article information

Article type
Edge Article
Submitted
10 Nov 2020
Accepted
11 Dec 2020
First published
14 Dec 2020
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, 2091-2096

Hydantoin-bridged medium ring scaffolds by migratory insertion of urea-tethered nitrile anions into aromatic C–N bonds

M. J. Millward, E. Ellis, J. W. Ward and J. Clayden, Chem. Sci., 2021, 12, 2091 DOI: 10.1039/D0SC06188C

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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