Precipitation-driven diastereo- and regioselective macrocyclization via benzoin condensation: effects of solvents and alkyl chain lengths

Abstract

The benzoin condensation of a designed dialdehyde 1 with a terphenyl framework was investigated. When the reaction was carried out in mixed solvents composed of an alcohol and a co-solvent, a precipitate primarily consisting of the cyclic dimer meso-2 was obtained, indicating a precipitation-driven diastereo- and regioselective self-assembly process. Using this system as a model for precipitation-induced self-assembly based on reversible C–C bond formation, we comprehensively investigated the effects of the alcohol, co-solvent, and alkyl chain length of the substrate on the outcome of the reaction. Notably, the reaction of ethoxy-substituted dialdehyde 1 in MeOH/toluene mixture reached equilibrium efficiently, affording a crystalline precipitate incorporating macrocycle meso-2 and toluene, from which meso-2 was isolated in good yield.