Abstract
The most reliable method to determine the absolute configuration of chiral molecules is X-ray crystallography, but small molecules can be difficult to crystallize. We report rapid co-crystallization of tetraaryladamantanes with small molecules as different as n-decane to nicotine to produce crystals for X-ray analysis and the assignment of absolute configuration when the molecules are chiral. A screen of 52 diverse compounds gave inclusion in co-crystals for 88 % of all cases and a high-resolution structure in 77 % of cases. Furthermore, starting from three milligrams of analyte, a combination of NMR spectroscopy and X-ray crystallography produced a full structure in less than three days using an adamantane crystallization chaperone that encapsulates the analyte at room temperature.