Chemical compounds that exist in multiple crystalline forms are said to exhibit polymorphism. Polymorphs have the same composition, but their structures and properties can vary markedly. In many fields, conditions for crystallizing compounds of interest are screened exhaustively to generate as many polymorphs as possible, from which the most advantageous form can be selected. We report new ways to search for polymorphs and increase polymorphic diversity, based on crystallization induced by suitably designed mixed-crystal seeds. The potential of the strategy has been demonstrated by using it to produce new polymorphs of the benchmark compound ROY as single crystals structurally characterized by X-ray diffraction. This allows ROY to reclaim its crown as the most polymorphic compound in the Cambridge Structural Database. More generally, the methods promise to become valuable tools for polymorphic screening in all fields where crystalline solids are used.

Sixfold phenyl embraces are well-established aromatic interactions that are strong and directional. In addition, functional groups that are able to participate, such as triphenylmethyl (trityl), are easily incorporated in molecular structures. As a result, embraces offer a possible way to control molecular organization in materials. To test this notion, we used a hybrid organic–inorganic strategy to make compounds with multiple trityl groups. Trityl-substituted alkynylpyridines 3–5 react with Pd­(II) to form square-planar 4:1 complexes with multiple divergent trityl groups poised to engage in embraces. The complexes were crystallized, and their structures were determined by X-ray diffraction. Surprisingly, few structures in this set of compounds were found to incorporate sixfold embraces. Our observations suggest that predictable molecular organization cannot normally be achieved using these embraces, which must compete with alternative aromatic interactions of similar energy.

A formal total synthesis of ivorenolide A has been accomplished employing a Z-selective olefin cross metathesis and a macrocyclic Glaser-Hay coupling as key steps. The macrocyclization protocol employed a phase separation/continuous flow manifold whose advantages include catalysis, fast reaction times, high concentrations, and facile scale-up.