Varying the regiochemistry from a solid-state [2+2] cycloaddition reaction within a series of mixed co-crystals based upon isosteric resorcinols

A series of regioselective [2 + 2] cycloaddition reactions have been achieved in different mixed co-crystals based upon ( E )-methyl-3-(pyridin-3-yl)prop-2-enoate (3-PAMe) as the reactant molecule. The solid-state photoreaction occurred by utilizing a combination of three isosteric resorcinols, namely 4,6-dichlororesorcinol (4,6-diCl res), 4,6-dibromoresorcinol (4,6-diBr res), and 4,6-diiodoresorcinol (4,6-diI res) as hydrogen-bonding templates to align a pair of carbon-carbon double bonds in the correct orientation to photoreact. In each mixed co-crystal, the components form a discrete three-component hydrogen-bonded assembly when upon exposure to UV light produce either the head-to-head ( rctt )-dimethyl-3,4-bis(pyridin-3-yl)cyclobutane-1,2-dicarboxylate or the head-to-tail ( rctt )-dimethyl-2,4-bis(pyridin-3-yl)cyclobutane-1,3-dicarboxylate photoproducts. In particular, the mixed co-crystal (4,6-diCl/Br res)∙2(3-PAMe) yielded exclusively the head-to-head isomer while both (4,6-diBr/I res)∙2(3-PAMe) and (4,6-diCl/I res)∙2(3-PAMe) produced the head-to-tail isomer.