Exploring the Glycosylation Reaction Inside the Resorcin[4]arene Capsule

Abstract

In the past decade, there has been an increased interest in applying supramolecular capsule and cage catalysis to the current challenges in synthetic organic chemistry. In this context, we recently reported the resorcin[4]­arene capsule-catalyzed conversion of α-glycosyl halides into β-glycosides with high selectivity. Interestingly, this methodology enabled the formation of a wide range of β-pyranosides as well as β-furanosides, although these two donor classes exhibit different reactivities and usually require different reaction conditions and catalysts. Evidence was provided that a proton wire plays a key role in this reaction by enabling dual activation of the glycosyl donor and acceptor. Here, we describe a detailed investigation of several aspects of this reactivity. Besides a mechanistic study, we elucidated the size limitation, the origin of catalytic turnover, and the electrophile scope of nonglycosylic halides. Moreover, a screening of the sensitivity to changes in the reaction conditions provides guidelines to facilitate reproducibility. Furthermore, we demonstrate the compatibility with environmentally benign solvent alternatives, including the renewable solvent limonene.

Window[1]resorcin[3]arenes: A Novel Macrocycle Able to Self-Assemble to a Catalytically Active Hexameric Cage

“…The substrate conversion was high (>90%), while the yield plateaued at approximately 60%, likely due to capsule/cage alkylation as also observed in previous studies. 83 − 85 Importantly, no background reaction was observed in the absence of the capsule or cage (see SI Section 7.2 ). As indicated by the encapsulation studies discussed before, the “open window” of cage II should enable the binding of large substrates excluded in capsule I .…”