Tandem cyclohexen-3-yne and 1,2,3-cyclohexatriene reactions

There are three classes of neutral 6-membered reactive species, namely didehydrobenzene (benzyne (1)), dihydrobenzenes (cyclohexyne (2) and 1,2-cyclohexadiene (3)), and benzene isomers (cyclohexen-3-yne (4), 1,2,3-cyclohexatriene (5), and 1,2,4-cyclohexatriene (6)). Although intermediates 1-3 have found broad synthetic applications, the benzene isomers 4-6 received only sporadic attention. To further explore their synthetic utility and, more importantly, to uncover their potential in preparing polysubstituted 1,3-cyclohexadienes, we successfully incorporate cyclohexen-3-yne and 1,2,3-cyclohexatriene into several cascade transformations, such as 1,3-diamination, nucleophilic addition-ene reaction, and nucleophilic addition-[4+2] cycloaddition reaction. Additionally, a 1,5-sulfonyl group migration could occur to deliver a sulfone to the C4-position of the 1,3-cyclohexadiene framework. As a result, a series of 1,2-disubstituted, 1,2,3-trisubstituted, 1,2,4-trisubstituted, and 1,2,3,4-tetrasubstituted 1,3-cyclohexadienes bearing polycyclic ring systems can be efficiently prepared. This study offers a distinctive perspective on these aspects of reactive benzene isomers.