Extending Aryne Chemistry: Application to Insertion Reactions, Multicomponent Couplings, Molecular Rearrangements and Arylation Reactions

Abstract

Arynes are highly reactive electrophilic intermediates, which can be utilized in various carbon-carbon bond-forming reactions including pericyclic reactions, insertion reactions, multicomponent couplings (MCCs), molecular rearrangements, and transition-metal-catalyzed reactions. In this context, we have developed a transition-metal-free protocol for the synthesis of biologically important o-sulfanylaniline derivatives using the thioamination of arynes via the insertion of arynes into the S-N σ-bond of sulfenamides. Using this methodology, we have successfully synthesized an antidepressant drug vortioxetine. The use of organoselenium compounds as an electrophilic source in aryne MCCs initiated by tertiary amines resulted in the aminoselenation of arynes. Moreover, the synthesis of functionalized enol ethers by a umpolung oxa-[2,3] sigmatropic rearrangement of β-keto thioethers employing arynes has been achieved. This chemistry has been extended to the synthesis of a variety of oxazole derivatives employing arynes via the [2,3] sigmatropic rearrangement followed by cyclization using βacetonitrile thioethers. In the final phase of our work, transition-metal-free route employing arynes for the generation of aryl anion equivalents and subsequent reaction with aldehydes for the synthesis of benzhydrol derivatives has been developed.