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, transesterification, and epimerization. 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. Et₃Al provided the best balance between rate and control, yielding well-defined polymers with quantitative conversions and monomodal size exclusion chromatography (SEC) traces. MALDI-TOF mass spectrometry revealed exclusively DKP-telechelic polyether structures, and attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) confirmed the absence of transesterification or epimerization. In contrast, Et₃B afforded rapid polymerizations with low dispersities (Đ = 1.13) but induced partial epimerization of the DKP stereogenic centers, 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.