2 research outputs found
β‑Selective <i>C</i>‑Arylation of Silyl Protected 1,6-Anhydroglucose with Arylalanes: The Synthesis of SGLT2 Inhibitors
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
β‑Selective <i>C</i>‑Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups
The β-selective phenylation
of benzyl and boronate protected
1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose
(<b>10</b>), pretreated with <i>i</i>-Bu<sub>2</sub>AlH, <i>i</i>-Bu<sub>3</sub>Al, Et<sub>3</sub>Al, Me<sub>3</sub>Al, or <i>n</i>-octyl<sub>3</sub>Al, with triphenylalane
or arylÂ(chloro)Âalanes is reported. The utility of the unprotected
version of the method is demonstrated by the synthesis of the SGLT2
inhibitor, canagliflozin (<b>1a</b>), from commercially available <b>10</b> in one C–C bond-forming step. This approach circumvents
the need for conventional protecting groups, and therefore no formal
protection and deprotection steps are required