Benzoyl Shift: A New Approach to Reverse Regioselectivity in the Monoprotection of vic-Diols

Abstract

The benzoyl shift in monoprotected vic-diols is described. Triggered under mild conditions, this transformation allows regioselective protection of the least acidic hydroxyl function of an activated vic-diol.

Key words

protecting groups - regioselectivity - diols - benzoyl shift - acidity

• References and Notes


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• 9 See the Supporting Information for a NMR monitoring of the basic workup that evidences the benzoyl shift.
• 10 General Procedure for Monoprotection To a solution of diol (1 mmol) in CH₂Cl₂ (4 mL) at 0 °C were added Et₃N (2.2 mmol), DMAP (0.05 mmol), then slowly BzCl (1.1 mmol), and the reaction was allowed to warm to r.t. over 3 h. The reaction was quenched by addition of aq HCl (0.1 M, ca. 3 mL), EtOAc was added (ca. 2 mL), the organic phases separated and the aqueous phases extracted with EtOAc (3 × 2 mL). The combined organic phases were dried over MgSO₄, filtered, and concentrated under vacuum. The crude product was dissolved in MeOH–H₂O (4 mL, 9:1 v/v), solid NaHCO₃ (5 mmol) was added to the solution, and the reaction was stirred for 90 min at r.t. Water was added (ca. 4 mL), then EtOAc followed by extraction of the aqueous phase (3 times total). The combined organic phases were dried over MgSO₄, filtered, and concentrated under vacuum. The crude product was purified by column chromatography.
• 11 Compounds 6c and 6d were used as a mixture of syn- and anti-diols.
• 12 pK _a calculations were performed using ACDLabs.