Substrate-dependent regiodivergence in 3 + 2 annulation reactions of 2-(phenacylethylidene)cyclobutanones with thioureas

• Published in: Organic & biomolecular chemistry 2024-10, Vol.22 (39), p.8048
• Main Authors: Barranco, Stefano, Pagnanini, Alessio, Cuccu, Federico, Caboni, Pierluigi, Guillot, Régis, Aitken, David J, Frongia, Angelo
• Format: Article
• Language: English
• ISSN: 1477-0539; 1477-0539
• DOI: 10.1039/d4ob01103a

The [3 + 2] annulation reaction between a thiourea, an ambident dinucleophile, and a 2-(phenacylethylidene)cyclobutanone, containing a novel pull-pull alkene system, could in principle proceed with several chemo- and regioselectivity profiles. Here we describe a convenient synthesis of the functionalized cyclobutanone substrates and show that they react with thioureas in a manner that is rationalized mechanistically in terms of the steric and electronic effects at play. The [3 + 2] annulation proceeds in mild, additive-free conditions to provide access to previously unknown cyclobutane-fused imidazolidine-2-thione and thiazolidine-2-imine derivatives in good yields.The [3 + 2] annulation reaction between a thiourea, an ambident dinucleophile, and a 2-(phenacylethylidene)cyclobutanone, containing a novel pull-pull alkene system, could in principle proceed with several chemo- and regioselectivity profiles. Here we describe a convenient synthesis of the functionalized cyclobutanone substrates and show that they react with thioureas in a manner that is rationalized mechanistically in terms of the steric and electronic effects at play. The [3 + 2] annulation proceeds in mild, additive-free conditions to provide access to previously unknown cyclobutane-fused imidazolidine-2-thione and thiazolidine-2-imine derivatives in good yields.