Microwave assisted heterocyclization promoted by Lawesson's reagent: Synthesis of benzo[c]thiophen-1(3H)-ones and 1H-isothiochromene-1-ones

Intramolecular heterocyclization is a well exploited process for the preparation of a variety of heterocyclic systems. In this context, the broad synthetic potential of polyfunctional acetylenes continues to draw the attention of organic and medicinal chemists: the cyclization of propargylic compounds, promoted by the attack of a variety of nucleophiles in a close proximity to the triple bond, is a very efficient method to produce furans, pyrroles, thiazoles, indoles, imidazoles, indolizines, oxazoles, pyridines, quinolines, thiophenes 1. In particular, the heterocyclization process of o-alkynylbenzoic acids, o-alkynylbenzamides and their derivatives have been of great significance in the formation of heterocyclic compounds such as isocoumarins, 3-alkylidenephthalides, 2H-isoquinolin-1-ones, 3-aryl(alkyl)idene-isoindolones and 3-benzazepinones. Recently, we have reported the selective formation of functionalized isoindolinone and isobenzofuranimine through the oxidative carbonylation of 2-ethynylbenzamides, followed by the intramolecular nucleophilic attack of the nitrogen atom in the benzamide moiety to the conjugated triple bond.2 The recognition that thioacids are exploitable nucleophiles makes these compounds as interesting substrates for heterocyclization reactions, promoted by the intramolecular attack of the sulphur atom at the triple bond of the propargylic unit. In this work, starting from o-alkynyl benzoic acids, benzo[c]thiophen-1(3H)-ones or 1H-isothiochromene-1-ones have been selectively synthesized by an intramolecular cyclization process performed by treatment with Lawesson’s reagent under microwave irradiation. Two alternative reaction routes are controlled by the nature of the substituent at the distal position of the carbon-carbon triple bond.