Strain-promoted reactions of 1,2,3-cyclohexatriene and its derivatives.

Since 1825, compounds with the molecular formula CH-most notably benzene-have been the subject of rigorous scientific investigation. Of these compounds, 1,2,3-cyclohexatriene has been largely overlooked. This strained isomer is substantially (approximately 100 kcal mol) higher in energy compared with benzene and, similar to its relatives benzyne and 1,2-cyclohexadiene, should undergo strain-promoted reactions. However, few experimental studies of 1,2,3-cyclohexatriene are known. Here we demonstrate that 1,2,3-cyclohexatriene and its derivatives participate in a host of reaction modes, including diverse cycloadditions, nucleophilic additions and σ-bond insertions. Experimental and computational studies of an unsymmetrical derivative of 1,2,3-cyclohexatriene demonstrate the potential for highly selective reactions of strained trienes despite their high reactivity and short lifetimes. Finally, the integration of 1,2,3-cyclohexatrienes into multistep syntheses demonstrates their use in rapidly assembling topologically and stereochemically complex molecules. Collectively, these efforts should enable further investigation of the strained CH isomer 1,2,3-cyclohexatriene and its derivatives, as well as their application in the synthesis of important compounds.