Supramolecular Capsule-Catalyzed Highly fl-Selective Furanosylation Independent of the SN1/SN2 Reaction Pathway

The resorcin[4]arene capsule was found to catalyze fi-selective furanosylation reactions for a variety of different furanosyl donors: alpha-D- and alpha-L-arabinosyl-, alpha-L-fucosyl-, alpha-D- ribosyl-, alpha-D-xylosyl-, and even alpha-D-lyxosyl fluorides. The scope is only limited by the inherently finite volume inside the closed capsular catalyst. The catalyst is readily available on a multi-100 g scale and can be recycled for at least seven rounds without significant loss in activity, yield, and selectivity. The mechanistic investigations indicated that the furanosylation mechanism is shifted toward an SN1 reaction on the mechanistic continuum between the prototypical SN1 and SN2 substitution types, as compared to the pyranosylation reaction inside the same catalyst. This is especially true for the lyxosyl donor, as indicated by the nucleophile reaction order of 0.26, and supported by metadynamics calculations. The mechanistic shift toward SN1 is of high interest as it indicates that this catalyst not only enables fi-selective furanosylations and pyranoslyations independently of the substrate configuration but in addition also independently of the operating mechanism. To our knowledge, there is no alternative catalyst available that displays such properties.