Vinylazaarenes as dienophiles in Lewis acid-promoted Diels–Alder reactions

Abstract

Described are the first examples of Lewis acid-promoted Diels–Alder reactions of vinylpyridines and other vinylazaarenes with unactivated dienes. Cyclohexyl-appended azaarenes constitute a class of substructures of rising prominence in drug discovery. Despite this, thermal variants of the vinylazaarene Diels–Alder reaction are rare and have not been adopted for synthesis, and Lewis acid-promoted variants are virtually unexplored. The presented work addresses this gap and in the process furnishes increased scope, dramatically higher yields, improved regioselectivity, and high levels of diastereoselectivity compared to prior thermal examples. These reactions provide scalable access to druglike scaffolds not readily available through other methods. More broadly, these studies establish a useful new class of dienophiles that, based on preliminary mechanistic studies, should be amenable to conventional strategies for enantioselective catalysis.

Graphical abstract: Vinylazaarenes as dienophiles in Lewis acid-promoted Diels–Alder reactions

Supplementary files

Article information

Article type
Edge Article
Submitted
15 Sep 2021
Accepted
24 Nov 2021
First published
24 Nov 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-NC license

Chem. Sci., 2021, Advance Article

Vinylazaarenes as dienophiles in Lewis acid-promoted Diels–Alder reactions

A. E. Davis, J. M. Lowe and M. K. Hilinski, Chem. Sci., 2021, Advance Article , DOI: 10.1039/D1SC05095H

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