Benzyl Deprotection of Alcohols

08 Feb

Benzyl Deprotection of Alcohols

Benzyl groups are often used to protect alcohols in multi-step synthetic reactions. To deprotect, the benzyl ether first undergoes oxidative addition to the Pd(0) catalyst, forming a Pd(II) complex. Hydrogen coordination and transfer then facilitates the release of the alcohol. Reductive elimination expels toluene and regenerates the palladium catalyst.

Reagents: Pd/C, H₂, Solvent (EtOH, MeOH, THF, Toluene etc.)
Reactant: Benzyl protected alcohol
Product: Alcohol, Toluene
Type of Reaction: Hydrogenolysis

Lab Tips

Various other protocols have been developed, including using 1,4-cyclohexadiene as a hydrogen transfer source, ^[1] deprotection under mild, oxidative conditions, ^[2] or removal with chlorosulfonyl isocyanate-sodium hydroxide. ^[3][3][3][3]

_{1. Quinn et al. 1,4-Cyclohexadiene with Pd/C as a rapid, safe transfer hydrogenation system with microwave heating. Tetrahedron Lett. 2008, 49(42), 6137-6140.
2. Weinreb et al. Efficacious cleavage of the benzyl ether protecting group by electrochemical oxidation. J. Org. Chem. 1975, 40(9) 1356-1358.
3. Wuts, P. G. M. (2014). Greene’s Protective Groups in Organic Synthesis (Fifth Ed.). Hoboken, New Jersey: John Wiley & Sons.}