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 Å 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 substrates, such as acrylic
acid and methylvinylketone, were bound by the host and were protected from photoreactions. Larger
substrates, such as 4,4-dimethyl-2-cyclohexenone and mesityl oxide, do not undergo selective [2+2]
cycloaddition reactions. In an effort to understand these differences in reactivity, we examined these host−guest complexes by thermogravimetric analysis (TGA), NMR, powder X-ray diffraction (PXRD) and molecular
modeling.