Discussion Addendum for: The Direct Acyl-Alkylation of Arynes. Preparation of Methyl 2-(2-acetylphenyl)acetate

Abstract

For the past 50 years, benzynes and related arynes have been a major subject of study among physical organic chemists due to their unusual electronic and structural properties. However, the utility of these strained intermediates in the domain of chemical synthesis has only relatively recently undergone a vibrant expansion. The direct insertion of aryne and heteroaryne moieties into carbon-carbon and carbon-heteroatom σ bonds presents an intriguing and unique strategy for the rapid functionalization of aryl and heteroaryl systems. Following our 2009 Organic Syntheses article on the acyl-alkylation of arynes with β-ketoesters, there have been numerous reports of related transformations involving these highly reactive intermediates. This discussion addendum is intended to document advances made in the field of (hetero)arynes since our initial disclosure. Topics covered will be divided as follows: recent methods for the acyl-functionalization of arynes, syntheses of related strained systems, applications in heterocycle synthesis, miscellaneous transformations, and strategic uses in natural product synthesis. A supplemental review on aryne insertions into σ bonds is available. Applications of arynes in transition metal catalysis will not be discussed in detail, however there are thorough reviews on the subject.