Removal of Acyl Protecting Groups Using Solid NaOH and a Phase Transfer Catalyst

R. David Crouch*, Jennifer S. Burger, Karolina A. Zietek, Amy B. Cadwallader, James E. Bedison, Magda M. Smielewska

*Department of Chemistry, Dickinson College, Box 1773, Carlisle, PA 17013-2896, USA, Email: crouchdickinson.edu

R. D. Crouch, J. S. Burger, K. A. Zietek, A. B. Cadwallader, J. E. Bedison, M. M. Smielewska, Synlett, 2003, 991-992.

DOI: 10.1055/s-2003-39309

Abstract

Acetyl-, benzoyl- and pivoyl-protected alcohols and phenols undergo smooth deacylation in a two-phase system of powdered NaOH and Bu₄NHSO₄ in THF or CH₂Cl₂.

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Details

The document discusses a method for removing acyl protecting groups from alcohols and phenols using solid NaOH and a phase transfer catalyst (Bu4NHSO₄) in a two-phase system with THF or CH₂Cl₂ as solvents. The study found that THF provided slightly better yields than CH₂Cl₂, with 10 equivalents of NaOH being optimal. The method is effective for acetyl-, benzoyl-, and some pivoyl-protected alcohols, including primary and secondary alcohols. Notably, pivoyl-protected secondary alcohols required longer reaction times for satisfactory yields. The method also demonstrated stability for silyl-protected alcohols, while aryl silyl ethers underwent desilylation. For acyl-protected phenols, conducting the reaction under an inert atmosphere significantly improved yields and reduced by-product formation. The procedure involves combining the acyl-protected alcohol, powdered NaOH, Bu₄NHSO₄, and THF, purging with argon, and stirring under an inert atmosphere. The reaction typically completes in 3 hours, followed by filtration and column chromatography to isolate the deprotected alcohol. This method offers advantages such as ease of application, simple workup, and the use of inexpensive, relatively safe reagents. The research was supported by the Whitaker Foundation, Dickinson College, and the Research and Development Committee of Dickinson College.

Key Words

protecting groups, alcohols, phase-transfercatalysis, acyl groups, deacylation, deprotection (acetic acid esters, pivalic acid esters)

ID: J60-Y2003-1990