The hexadehydro-Diels–Alder reaction

• Published in: Nature (London) 2012-10, Vol.490 (7419), p.208-212
• Main Authors: Hoye, Thomas R., Baire, Beeraiah, Niu, Dawen, Willoughby, Patrick H., Woods, Brian P.
• Format: Article
• Language: English
• Subjects: 639/638/403/934; Agrochemicals; Analytical, structural and metabolic biochemistry; Benzene; Biological and medical sciences; Chromatography; Diels-Alder reaction; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Molecular and cellular biology; multidisciplinary; Polymers; Reagents; Science; Small mammals
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature11518

Arynes (aromatic systems containing, formally, a carbon–carbon triple bond) are among the most versatile of all reactive intermediates in organic chemistry. They can be ‘trapped’ to give products that are used as pharmaceuticals, agrochemicals, dyes, polymers and other fine chemicals. Here we explore a strategy that unites the de novo generation of benzynes—through a hexadehydro-Diels–Alder reaction—with their in situ elaboration into structurally complex benzenoid products. In the hexadehydro-Diels–Alder reaction, a 1,3-diyne is engaged in a [4+2] cycloisomerization with a ‘diynophile’ to produce the highly reactive benzyne intermediate. The reaction conditions for this simple, thermal transformation are notable for being free of metals and reagents. The subsequent and highly efficient trapping reactions increase the power of the overall process. Finally, we provide examples of how this de novo benzyne generation approach allows new modes of intrinsic reactivity to be revealed. The de novo generation of benzynes—through a hexadehydro-Diels–Alder reaction—followed by their in situ elaboration is reported; the reaction is metal-free and reagent-free, and reveals new modes of intrinsic benzyne reactivity. A new approach to aryne syntheses Arynes are reactive intermediates derived from aromatic systems, which can be 'trapped' to give products that find use as chemical reagents and in pharmaceuticals, agrochemicals, dyes and polymers. This study explores a new synthetic strategy that combines de novo generation of benzynes — through a hexadehydro-Diels–Alder reaction — with their in situ elaboration into structurally complex benzenoid products. The reaction is metal-free and reagent-free, and the authors provide examples of how this approach allows new modes of intrinsic reactivity to be revealed.