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

Treatment of an achiral mol. ladder of C2h symmetry composed of five edge-sharing cyclobutane rings, or a [5]-ladderane, with acid results in cis- to trans-isomerization of end pyridyl groups. Soln. NMR spectroscopy and quantum chem. calcns. support the isomerization to generate two diastereomers. The NMR data, however, could not lead to unambiguous configurational assignments of the two isomers. Single-crystal X-ray diffraction was employed to det. each configuration. One isomer readily crystd. as a pure form and X-ray diffraction revealed the mol. as being achiral based on Ci symmetry. The second isomer resisted crystn. under a variety of conditions. Consequently, a strategy based on a cocrystn. was developed to generate single crystals of the second isomer. Cocrystn. of the isomer with a carboxylic acid readily afforded single crystals that confirmed a chiral ladderane based on C2 symmetry. The chiral ladderane and acid self-assembled to generate a five-component hydrogen-bonded complex that packs to form large solvent-filled homochiral channels of nanometer-scale dimensions. Whereas cocrystns. are frequently applied to structure detns. of proteins, our study represents the first application of a cocrystn. to confirm the relative configuration of a small-mol. diastereomer generated in a soln.-phase org. synthesis. [on SciFinder(R)]