Crystal engineering rescues a solution organic synthesis in a cocrystallization that confirms the configuration of a molecular ladder.

Treatment of an achiral molecular ladder of C(2h) symmetry composed of five edge-sharing cyclobutane rings, or a [5]-ladderane, with acid results in cis- to trans-isomerization of end pyridyl groups. Solution NMR spectroscopy and quantum chemical calculations support the isomerization to generate two diastereomers. The NMR data, however, could not lead to unambiguous configurational assignments of the two isomers.

General application of mechanochemistry to templated solid-state reactivity: rapid and solvent-free access to crystalline supermolecules.

Supermolecules with olefins organized by hydrogen-bond donor and acceptor templates and that react in the solid state rapidly form co-crystals via solvent-free and liquid-assisted grinding.