Since 18251, compounds with the molecular formula C6H6-most notably benzene-have been the subject of rigorous scientific investigation2-7. Of these compounds, 1,2,3-cyclohexatriene has been largely overlooked. This strained isomer is substantially (approximately 100 kcal mol-1) 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 known8-12. 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 C6H6 isomer 1,2,3-cyclohexatriene and its derivatives, as well as their application in the synthesis of important compounds.