Influence of the nature of the Lewis acid on the AROP of epoxides initiated by 2,5-diketopiperazine

Abstract

The anionic ring-opening polymerization (AROP) of tert-butyl glycidyl ether (tBuGE) initiated by 2,5-diketopiperazines (DKPs) was systematically investigated, with emphasis on the influence of Lewis acid nature on polymerization control and side reaction suppression. DKPs are bio-based cyclic dipeptides bearing two secondary amide N–H functions that can act as bifunctional initiating sites upon deprotonation. However, polymerizations promoted by phosphazene bases alone (tBuP₄ or tBuP₂/tBuP₄) suffered from bimodal molar mass distributions, and side reactions. Three asymmetric DKPs—cyclo(Gly–Phe), cyclo(Gly–Val), and cyclo(Leu–Phe)—were examined with various Lewis acids: iBu₃Al, Et₃Al, Ph₃Al, and Et₃B. The addition of Lewis acids markedly altered the polymerization behavior. Aluminum-based Lewis acids (iBu₃Al and Et₃Al) promoted efficient monomer activation while reducing the reactivity of the propagating alkoxide through ate-complex formation. This led to improved agreement between theoretical and experimental molar masses, dispersities as low as Đ ≈ 1.1–1.3, and strong suppression of transesterification. Under optimized conditions, Et₃Al provided the best overall balance between polymerization rate and control, affording well-defined polymers with high to quantitative conversions and narrow dispersities. MALDI-TOF mass spectrometry predominantly revealed the expected DKP-telechelic polyether structures, while ATR-FTIR showed no detectable ester carbonyl band and no additional amide-I band under Et₃Al conditions, supporting suppression of transesterification and major DKP-environment changes. In contrast, Et₃B afforded rapid polymerizations with low dispersities (Đ = 1.13) but induced partial modification of the DKP carbonyl environment, most likely associated with epimerization and/or conformational differentiation of the DKP ring, as evidenced by ATR-FTIR. Comprehensive ¹H, ¹³C, and ¹⁵N NMR analyses confirmed quantitative bifunctional initiation and bidirectional chain growth. These results establish Lewis acid-assisted DKP initiation as an effective strategy for synthesizing well-defined bio-based DKP-telechelic polyethers with controlled architecture and narrow dispersity.