β-Selective C-arylation of silyl protected 1,6-anhydroglucose with arylalanes: The synthesis of SGLT2 inhibitors

Article abstract of DOI:10.1021/jo502839e

The stereoselective arylation of hydroxy protected 1,6-anhydro-β-d-glucose with arylalanes to provide β-C-arylglucosides is reported. Modification of triarylalanes, Ar₃Al, with strong Br?nsted acids (HX) or AlCl₃ produced more reactive arylating agents, Ar₂AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me₃Al and i-Bu₂AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.