Selective formation of the rctt chair stereoisomers of octa-O-alkyl resorcin[4]arenes using Brønsted acid catalysis

Abstract

New synthetic conditions are described for the fully selective formation of the rctt chair stereoisomers of octa-O-alkyl resorcin[4]arenes; these offer a clean route into the chair conformer of these interesting receptor molecules. Brønsted acid catalysis in acetic acid solutions results in the formation of the single isomer when 1,3-dimethoxybenzene is heated at 80 °C with a range of aldehydes, straight- and branched-chain or aromatic, and with an aldehyde synthon. An investigation of reaction conditions indicated that, in this case, the rctt chair stereoisomer was the thermodynamic product, a result confirmed by molecular modelling studies that show that this stereoisomer is of lower energy than the expected rccc boat stereoisomer.