Catalytic Redox-Neutral Decarboxylative Aromatization via Transfer Dehydrogenation

Abstract Arenes are fundamental structural motifs in organic molecules; therefore, methods for introducing aromatic rings are of broad importance. Traditional approaches that install arenes early followed by postfunctionalization sometimes struggle to achieve diverse substitution patterns, high chemoselectivity, or satisfactory processability. As an alternative, constructing arenes via late-stage aromatization of prearomatic intermediates could offer greater flexibility, improved processability, and orthogonal reactivity, which, however, has been underdeveloped. Particularly, there remain substantial challenges of using saturated cyclohexanes as benzene precursors. Here, we report a distinct catalytic strategy that uses carboxylic acids as traceless, multifunctional anchors to achieve chemoselective, redox-neutral aromatization of cyclohexanes via transfer dehydrogenation. This approach provides a rare means to selectively aromatize carboxylated cyclohexanes even in the presence of more reactive cyclohexenes and cyclohexanones. The Ir-catalyzed protocol delivers excellent yields, remarkable chemoselectivity, and broad functional-group compatibility. Combined experimental and computational studies support an unusual mechanism involving sequential dehydrogenation, anti-decarboxylation, β-hydrogen elimination, and further dehydrogenation. The utility of the method is demonstrated in site-selective, modular syntheses of diverse multisubstituted arenes through late-stage aromatization.