Head-to-Tail Packing to Facilitate [2+2] Cycloaddition for Green Synthesis of Cyclobutane Derivatives in Specific Configuration.

Topological [2+2] cycloaddition is known to provide a convenient synthetic route for cyclobutane derivatives from favorably dispositioned dienes. In this study, new (2Z,4E)-2-(2,4-difluorophenyl)-5-phenylpenta-2,4-dienenitrile (HDE), (2Z,4E)-2-(2,4-difluorophenyl)-5-(p-tolyl)penta-2,4-dienenitrile (MeDE), (2Z,4E)-5-(4-chlorophenyl)-2-(2,4-difluorophenyl)penta-2,4-dienenitrile (ClDE), (2Z,4E)-5-(4-bromophenyl)-2-(2,4-difluorophenyl)penta-2,4-dienenitrile (BrDE), (2Z,4E)-2-(2,4-difluorophenyl)-5-(4-methoxyphenyl) penta-2,4-dienenitrile (MeODE), and (2Z,4E)-2-(2,4-difluorophenyl)-5-(4-(dimethylamino)phenyl)penta-2,4-dienenitrile (MeNDE) were synthesized, and their reactivity and selectivity were investigated in relation to their molecular packing in the respective crystals. HDE and MeDE, with head-to-tail (HT) arrangement, yielded only one type of photodimer. On the contrary, ClDE and BrDE, with head-to-head (HH) packing, and where the "olefin pairsα,β-α,β" and "olefin pairsγ,δ-γ,δ" satisfy Schimdt's criteria, reacted to a mixture of photoproducts. Kinetics analysis suggests that the reaction rates of HDE and MeDE are higher than those of ClDE and BrDE. This observation may be due to the strong non-covalent interactions between the potentially reactive olefin pairs as suggested by energy decomposition analysis. Furthermore, the reaction activation energies for photodimerization of the HT-packed olefin pairs are indeed lower than those of the HH-arranged ones. The HT packing of the diphenyldienes not only enhances the reactivity in the topological [2+2] cycloaddition but also contributes chemospecificity, regiospecifity, and stereospecificity, all of which are essential for the preparation of specific cyclobutanes derivatives based on photodimerization.