Divergent Multicomponent Tandem Palladium-Catalyzed Aminocarbonylation-Cyclization Approaches to Functionalized Imidazothiazinones and Imidazothiazoles

The reactivity of 2-(prop-2-ynylthio)imidazoles under PdI2/KI-catalyzed oxidative aminocarbonylation conditions has been studied. Under relatively mild conditions, 0.33-1mol% of catalyst at 100 degrees C in MeCN and under 20atm (at 25 degrees C) of a 4:1 mixture of CO/air, and in the presence of an equimolar amount of a secondary nucleophilic amine, substrates that are unsubstituted or bear a single substituent on the imidazole ring were converted directly in a multicomponent fashion into functionalized imidazothiazinones. This transformation occurred through a new auto-tandem catalysis process that involves two concatenated catalytic cycles both catalyzed by PdI2: oxidative aminocarbonylation of the terminal triple bond/cyclocarbonylation. However, in the presence of an excess of secondary amine, 4,5-disubstituted substrates led selectively to functionalized imidazothiazoles through an oxidative aminocarbonylation/conjugate addition process.