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

Since 1825 1 , studies of compounds with the molecular formula C 6 H 6 - most notably benzene - have been the subject of rigorous scientific investigation 2 , 3,4,5,6,7 . Of these compounds, 1,2,3-cyclohexatriene has been largely overlooked. This strained isomer is substantially (~100 kcal/mol) higher in energy compared to benzene and, like its relatives benzyne and 1,2-cyclohexadiene, should undergo strain-promoted reactions. However, few experimental studies of 1,2,3-cyclohexatriene are known 8,9,10,11,12 . 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, integration of 1,2,3-cyclohexatrienes into multistep synthetic sequences demonstrates their utility in rapidly assembling topologically and stereochemically complex molecules. Collectively, these efforts should fuel the further investigation of the strained C 6 H 6 isomer 1,2,3-cyclohexatriene and its derivatives, as well as their strategic application in the synthesis of important compounds.