Exploring crystal-state vs. solution-based reactivity of donor–acceptor cyclopropanes

Donor–acceptor cyclopropanes (DACs) are highly reactive building blocks in organic synthesis due to their combination of electronic bond polarization and ring strain. This work explores three modes of activation, thermal, photochemical, and catalytic, applied to the same vinologous DAC precursor, both in solution and in the solid state. In solution, thermal activation enables the regio- and stereoselective formation of eight-membered carbocyclic frameworks, without the need for catalysts or reagents, thanks to a rational precursor design based on electronic and steric considerations. Depending on the nature of the substituents, either a concerted or a stepwise mechanism is involved. Additionally, and still in solution, a Lewis-acid-promoted cascade reaction leads to benzocyclobutene scaffolds, with complete transfer of stereochemistry into the regioselectivity of the final product. In the solid state, exposure to X-ray radiation induces a rare single-crystal-to-single-crystal photopolymerization, governed by precise molecular preorganization and a degree of crystal lattice flexibility. Overall, this study highlights how DAC reactivity is modulated by both the mode of activation and the physical environment, thereby offering new strategies for the construction of complex molecules.