An efficient synthetic route to inherently chiral calix[4]arenes with an ABCD substitution pattern at the wide rim in the cone conformation was developed for the first time. For the synthesis of inherently chiral ABCD-type calix[4]arenes, first 5,11-dibromo-17-(3,5-dimethylphenyl)-25,26,27,28-tetrapropoxycalix[4]arene (9) was prepared as a key intermediate. Then, functionalization of the calix[4],arene 9 was examined, and highly regioselective monofunctionalization was achieved via selective monolithiation of bromo groups. Various multifunctionalized inherently chiral ABCD-type calix[4]arenes can be synthesized by using this method; thus, the synthesis of inherently chiral phosphine and carboxylic acid derivatives of ABCD-type calix[4]arene was demonstrated. In addition, the aminophenol derivative 1b of an ABCD-type calix[4]arene with a 3,5-dimethylphenyl group at the wide rim was synthesized and resolved into optically pure enantiomers. The chiral calix[4]arene 1b was used as an organocatalyst in asymmetric Michael addition reactions of thiophenols. The effect of the 3,5-dimethylphenyl group at the wide rim of calix[4]arene 1b on enantioselectivity was examined, and a positive effect of the 3,5-dimethylphenyl group was observed.
