Direct Use of Benzylic Alcohols for Gold(III)-Catalyzed S-Benzylation of Mercaptobenzoic Acids in Water

Abstract

We demonstrate the gold(III)-catalyzed direct substitution of benzylic alcohols in water. These atom economic and environmentally benign protocols afford S-benzylated products in moderate to excellent yields. In contrast, common Lewis or Brønsted acids as catalyst, and organic solvents such as dichloromethane or toluene were ineffective for the S-benzylation of mercaptobenzoic acids. Water can be an attractive tool for new transition metal-catalyzed reactions. A Hammett study for the rate constants with various substituted alcohols shows a good correlation (R2=0.97) between the log(kX/kH) and the σ+ value of the respective substituents. From the slope negative ρ values of 2.35 are obtained, suggesting that there is a build-up of positive charge in the transition state. Our catalytic system can be performed with the use of only 2 mol% of gold(III) catalyst without any other additives in water, and scaled up to 10 mmol scale (85% isolated yield). Notably, the present method can accomplish the S-benzylation of unprotected mercaptobenzoic acids, which is chemoselective and leaves the carboxyl group intact. Furthermore, the direct substitution of allylic and propargylic alcohols also proceeded smoothly in good yields.