β‑Selective <i>C</i>‑Arylation
of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis
of Canagliflozin without Recourse to Conventional Protecting Groups
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Abstract
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 aryl(chloro)alanes 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