Issue 36, 2021

Structure–function relationships in aryl diazirines reveal optimal design features to maximize C–H insertion

Abstract

Diazirine reagents allow for the ready generation of carbenes upon photochemical, thermal, or electrical stimulation. Because carbenes formed in this way can undergo rapid insertion into any nearby C–H, O–H or N–H bond, molecules that encode diazirine functions have emerged as privileged tools in applications ranging from biological target identification and proteomics through to polymer crosslinking and adhesion. Here we use a combination of experimental and computational methods to complete the first comprehensive survey of diazirine structure–function relationships, with a particular focus on thermal activation methods. We reveal a striking ability to vary the activation energy and activation temperature of aryl diazirines through the rational manipulation of electronic properties. Significantly, we show that electron-rich diazirines have greatly enhanced efficacy toward C–H insertion, under both thermal and photochemical activation conditions. We expect these results to lead to significant improvements in diazirine-based chemical probes and polymer crosslinkers.

Graphical abstract: Structure–function relationships in aryl diazirines reveal optimal design features to maximize C–H insertion

Supplementary files

Article information

Article type
Edge Article
Submitted
04 Jul 2021
Accepted
10 Aug 2021
First published
10 Aug 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, 12138-12148

Structure–function relationships in aryl diazirines reveal optimal design features to maximize C–H insertion

S. F. Musolino, Z. Pei, L. Bi, G. A. DiLabio and J. E. Wulff, Chem. Sci., 2021, 12, 12138 DOI: 10.1039/D1SC03631A

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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