Platinum(ii)-catalyzed dehydrative C3-benzylation of electron-deficient indoles with benzyl alcohols

Abstract

A synthetic strategy for the water-promoted direct dehydrative coupling of indoles with benzyl alcohols catalyzed by PtCl₂(PhCN)₂ in 1,2-dichloroethane has been developed. Water molecules significantly accelerate C–C bond formation, whereas the reaction proceeds slowly under anhydrous conditions. Comparative rate plots for reactions in the presence of H₂O and D₂O show a kinetic solvent isotope effect (KSIE) of 1.5. A Hammett study of the dehydrative reaction of para-substituted benzhydrols shows negative ρ values, indicating a build-up of cationic charge during the rate-determining sp³ C–O bond cleavage step. Our catalytic system can be used on the gram scale with simplified product isolation and catalysis is performed using 1 mol% of a Pt(II) catalyst with an additional molecule of water.