Origins of Selectivity for the [2+2] Cycloaddition of α,β-unsaturated Ketones within a Porous Self-assembled Organic Framework

This article studies the origins of selectivity for the [2+2] cycloadditions of α,β-unsaturated ketones within a porous crystalline host. The host, formed by the self-assembly of a bis-urea macrocycle, contains accessible channels of ∼6 A diameter and forms stable inclusion complexes with a variety of cyclic and acyclic α,β-unsaturated ketone derivatives. Host 1 crystals provide a robust confined reaction environment for the highly selective [2+2] cycloaddition of 3-methyl-2-cyclopentenone, 2-cyclohexenone, and 2-methyl-2-cyclopentenone, forming their respective exo head-to-tail dimers in high conversion. The products are readily extracted from the self-assembled host and the crystalline host can be efficiently recovered and reused. Molecular modeling studies indicate that the origin of the observed selectivity is due to the excellent match between the size and shape of these guests to dimensions of the host channel and to the preorganization of neighboring enones into favorable reaction geometries. Small...