β‑Selective <i>C</i>‑Arylation
of Silyl Protected 1,6-Anhydroglucose with Arylalanes: The Synthesis
of SGLT2 Inhibitors
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Abstract
The stereoselective arylation of
hydroxy protected 1,6-anhydro-β-d-glucose with arylalanes
to provide β-<i>C</i>-arylglucosides is reported.
Modification of triarylalanes, Ar<sub>3</sub>Al, with strong Brønsted
acids (HX) or AlCl<sub>3</sub> produced more reactive arylating agents,
Ar<sub>2</sub>AlX, while
the incorporation of alkyl dummy ligands into the arylating agents
was also viable. Me<sub>3</sub>Al and <i>i</i>-Bu<sub>2</sub>AlH were found useful in the <i>in situ</i> blocking of
the C3-hydroxyl group of 2,4-di-<i>O</i>-TBDPS protected
1,6-anhydroglucose. The utility of the method was demonstrated by
the synthesis of the SGLT2 inhibitor, canagliflozin
