Now, writing in Angewandte Chemie International Edition, Liu and co-workers report a molecular-strain engineering (MSE) approach to control the regioselectivity of a reaction within a macrocyclic structure resembling a molecular bow. By introducing ring strain into a 1,4-dimethoxy-2,5-cyclohexadiene moiety that forms the bow-limb of a bow-shaped molecule, two consecutive [1,2]-aryl shifts occur to give the meta-disubstituted and subsequently, the ortho-disubstituted product (pictured). “This seemingly impractical [1,3]-aryl shift is realized through applying intramolecular strain in a precise way,” says Liu.
The macrocyclic structure comprises a 1,4-dimethoxy-2,5-cyclohexadiene group and a flexible chain, which serves the function of the bowstring. Two macrocycles — with either a cis-butene or a trans-butene bowstring — are synthesized. In both cases, the length of the bowstring is shorter than the length of the bow-limb, which induces ring strain as well as results in a taut bow-limb after the first [1,2]-aryl shift. In the macrocycle containing the cis-butene bowstring, the bent angle of the meta-disubstituted bow-limb is around 70°, compared with an angle of 120° in the non-strained meta-diphenyl-substituted benzene. “This difference indicates the large strain in the meta-disubstituted molecular bow, which is the driving force to enable the second [1,2]-aryl shift, thus facilitating the formal [1,3]-aryl shift,” says Liu.
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