Palladium-Catalyzed Benzylic CH Benzylation via Bis-Benzylpalladium(II) Complexes in Water: An Effective Pathway for the Direct Construction of N-(1,2-Diphenylethyl)anilines

A strategy for the N‐benzylation/benzylic CH benzylation cascade of anilines by the π‐benzylpalladium system using a water‐soluble palladium(0)/sodium diphenylphosphinobenzene‐3‐sulfonate (TPPMS) catalyst and benzyl alcohol in water has been developed. This tandem process is devised as a novel and efficient synthetic route for N‐(1,2‐diphenylethyl)anilines. Benzylic CH activation of a mono‐N‐benzylated intermediate with a π‐benzylpalladium(II) complex affords a bis‐π‐benzylated palladium(II) intermediate. The nucleophilic η1‐σ‐benzyl anion ligand attacks the electrophilic η3‐π‐benzyl ligand to give a dibenzylated product. The intermolecular competition between mono‐N‐benzylaniline and its monodeuterated form (monodeuterated at the benzylic group) with benzyl alcohol gave a KIE=4.6, suggesting that CH bond cleavage was involved in the rate‐determining step. Hammett studies on the rate constants of benzylation by various substituted anthranilic acids and mono‐N‐benzylanilines show a good correlation between the log(kX/kH) and the σ values of the respective substituents. From the slope, negative ρ values are obtained, suggesting that there is a build‐up of positive charge in the transition state. The reaction of anilines with electron‐donating and electron‐withdrawing groups affords the corresponding N‐(1,2‐diphenylethyl)anilines in moderate to good yields (54–86%). Interestingly, the reaction of anthranilic acids proceeded smoothly to give only the corresponding dibenzylated products in good to excellent yields (70–87%). The carboxyl group of the anthranilic acids acts as a directing group in the benzylic CH activation process.