Benzyl Protection of Phenols under Neutral Conditions: Palladium-Catalyzed Benzylations of Phenols

Abstract

Benzyl protection of phenols under neutral conditions was achieved by using a Pd(eta3-C3H5)Cp-DPEphos catalyst. The palladium catalyst efficiently converted aryl benzyl carbonates into benzyl-protected phenols through the decarboxylative etherification. Alternatively, the nucleophilic substitution of benzyl methyl carbonates with phenols proceeded in the presence of the catalyst, yielding aryl benzyl ethers.

Transition Metal-Catalyzed Decarboxylative Allylation and Benzylation Reactions

“…157 For example, malonate-type nucleophiles, 158 boronic acids, 159 and more recently, direct arylation methods, 160 have been utilized to make new benzyl C–C bonds though palladium-benzyl intermediates. With respect to heteroatomic nucleophiles, catalytic benzylations of phenols, 161 amines, 158d and sulfonyl nucleophiles 162 have all been disclosed. Although this review focuses on the decarboxylative benzylation of relatively unstabilized nucleophiles (Scheme 85, B to C ), some relevant information can be gained by briefly discussing aspects of the previous catalytic benzylations of stabilized nucleophiles.…”

“…157b Conversely, decarboxylative benzylations are still in their infancy; decarboxylative benzylations of phenols, 161 diphenylglycinate imines, 164 acetylides, 165 and ketones 165 have only recently been reported.…”

“…161 Importantly, such benzyl ethers are frequently used as protecting groups in organic synthesis. In contrast to common methods for benzyl ether synthesis which require basic or acidic conditions and often utilize stoichiometric coupling reagents, 166 Kuwano’s palladium-catalyzed decarboxylative benzylation of alcohols allows benzyl ethers to be synthesized under neutral conditions with no stoichiometric additives.…”

Usage of the Carboxylate Leaving Group in Transition-metal-catalyzed Cross-coupling and Related Reactions

“…4). 29 Furthermore, DPEphos palladium catalyst is useful for the benzylation of sul nate salts 31 and phenols, 32 giving respectively the benzyl sulfones and aryl benzyl ethers 5 in high yields (eqs. 5 and 6).…”

“…7). 32 In the latter transformation, oxidative addition of 6 to palladium(0) and subsequent decarboxylation from the leaving group afford (π benzyl)palladium B and nucleophilic phenoxide (Scheme 2). The phenoxide attacks the electrophilic π Table 1.…”