Synthesis of β-cyclodextrin derivatives substituted at larger or smaller rims via amine-catalyzed ring-opening oligomerization of ε-caprolactone

Abstract

The involvement of cyclodextrins in transesterification reactions with active esters has been described to mimic enzyme-catalyzed reactions, making cyclodextrin molecules suitable as enzyme models. Cyclodextrin-catalyzed ring-opening of cyclic esters in bulk reaction conditions was considered to proceed similarly. However, the mechanism of activating cyclic esters through inclusion in the cyclodextrin cavity remains incompletely understood to date. The present research is focused on observing the transesterification of ε-caprolactone in the presence of β-cyclodextrin and additional amine organocatalysts within dimethyl sulfoxide solutions. The conducted experiments provide insights into the structural changes caused by various catalytic conditions in terms of the substitution pattern of the cyclodextrins. Our results are supported by a deep structural characterization through NMR and MALDI MS, which revealed the prospect of promoting rim-selective substitution of β-cyclodextrin at either secondary or primary hydroxyl groups using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) organocatalysts. This offers the possibility to prepare cyclodextrin derivatives with specific substitution patterns. Based on the acquired structural information, the particular pathway in which β-cyclodextrin influences the ring-opening of ε-caprolactone is delineated as follows: monomer complexation, substitution at the larger rim, chain elongation, and intramolecular transfer toward the smaller rim.