ABSTRACT
Herein, we disclose a general method for the assembly of C-allyl glycosides containing gem-difluoroalkene groups via a radical-polar crossover strategy. Central to the success of this process is the polarity matching between the benzenesulfinate radical and the glycosyl donor, which facilitates the initiation of the glycosyl radical and the subsequent formation of gem-difluoroalkene sugar derivatives. This method demonstrated good compatibility with various glycosyl donors and functional groups. Furthermore, we showcase the utility of this method in modifying amino acids, potentially paving the way for analogous modifications to peptides.
ABSTRACT
Despite their importance in life and material sciences, the efficient construction of stereo-defined glycosides remains a challenge. Studies of carbohydrate functions would be advanced if glycosylation methods were as reliable and modular as palladium (Pd)-catalyzed cross-coupling. However, Pd-catalysis excels in forming sp2-hybridized carbon centers whereas glycosylation mostly builds sp3-hybridized C-O linkages. We report a glycosylation platform through Pd-catalyzed SN2 displacement from phenols toward bench-stable, aryl-iodide-containing glycosyl sulfides. The key Pd(II) oxidative addition intermediate diverges from an arylating agent (Csp2 electrophile) to a glycosylating agent (Csp3 electrophile). This method inherits many merits of cross-coupling reactions, including operational simplicity and functional group tolerance. It preserves the SN2 mechanism for various substrates and is amenable to late-stage glycosylation of commercial drugs and natural products.
