Benzene’s forgotten isomer takes centre stage in organic synthesis

Benzene’s forgotten isomer takes centre stage in organic synthesis

An overlooked benzene isomer could become a powerful and versatile reagent in organic synthesis.Researchers demonstrated that the high energy compound 1,2,3-cyclohexatriene readily participates
in a diverse range of cycloaddition, nucleophilic addition and σ-bond insertion reactions, enabling
chemists to construct complex molecular architectures in just a few steps.

Isomers of benzene have captured the imagination of organic chemists for decades and studies
of unusual strained structures such as Dewar-benzene and prismane have proven pivotal to our
understanding of resonance theory and aromaticity. High-energy relatives of benzene like benzyne
and 1,2-cyclohexadiene have likewise attracted significant interest, their propensity to undergo strain-promoted
reactions making them valuable synthetic intermediates.

Surprisingly, 1,2,3-cyclohexatriene has not received the same degree of attention. Unlike the alternating
conjugated double bonds of benzene, 1,2,3-cyclohexatriene’s three contiguous olefins lack any stabilising
aromaticity and the strained ring structure, resulting from the distortion of the sp-hybridised carbon’s naturally
linear geometry, led many to believe this isomer was simply too unstable to be synthetically useful. ‘If you were to
try to build this species with plastic models, you would certainly break them,’ says Frederick West, an
organic chemist from the University of Alberta, Canada. ‘The extreme angle strain that this intermediate
experiences renders it highly reactive and the release of strain in the final product makes its reactions highly
favourable thermodynamically.’