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.’
The team used a method pioneered by Richard Johnson and Hiroshi Kobayashi in the 1990s to generate the reactive 1,2,3-cyclohexatriene intermediate from a silyl triflate precursor, probing the reaction scope by introducing a variety of trapping agents. Following a fluoride-induced elimination to form the triene, reactions with dienes, imines, ketene acetals and nucleophiles produced a diverse array of fused-ring adducts, each containing reactive handles to allow further manipulation. ‘What we see is mostly reactivity of the triene as a π-system, where the middle C=C bond gets consumed in various cycloaddition processes, leaving the other two alkenes present in the product as a 1,3-diene. Like benzynes, it also reacts well with nucleophiles,’ explains West. ‘There are few (if any) established ways to build similar products, at least in one step as done here.’
No comments:
Post a Comment