A palladium-catalyzed dehydrative N-benzylation/C–H benzylation cascade of 2-morpholinoanilines on water

Abstract

A strategy for the palladium-catalyzed dehydrative tandem benzylation of 2-morpholinoanilines with benzyl alcohols has been developed. This cascade reaction is devised as a straightforward and efficient synthetic route for N-(1,2-diphenylethyl)-2-morpholinoanilines.

A Borrowing Hydrogen Strategy for Dehydrative Coupling of Aminoisoquinolines with Benzyl Alcohols in Water

“…On the basis of these results and our previous report, [18] we propose a catalytic mechanism for the dehydrative coupling of 1-aminoisoquinoline (1a) with benzyl alcohol (2a) in water as illustrated in Scheme 5. First, oxidative addition of hydrated alcohol 2a to the water-soluble Pd 0 /TPPMS catalyst affords the cationic π-benzylpalladium(II) complex A (step 1).…”

“…[17] We recently developed a new environmentally benign borrowing hydrogen methodology for dehydrative coupling of 2-aminopyridines under basefree aqueous conditions. [18] However, we could not provide enough support for the catalytic pathway and the scopes of the pyridine nucleophiles were limited. In this paper, we describe new insights into the chemistry of the palladium-catalyzed N-benzylation pathway via π-benzylpalladium(II) complexes in water and the development of a borrowing hydrogen process as a new synthetic route for series of N-benzylated aminoisoquinolines (Scheme 1B).…”

“…We have been developing a unique strategy for dehydrative benzylation by the π‐benzylpalladium(II) species generated from Pd 0 /sodium diphenylphosphinobenzene‐3‐sulfonate (TPPMS) and benzyl alcohol in water . We recently developed a new environmentally benign borrowing hydrogen methodology for dehydrative coupling of 2‐aminopyridines under base‐free aqueous conditions .…”

Chennat‐Type Synthesis of 1,4‐Dihydropyridine Derivatives in Water: Role of a Hydrogen‐Bonding Network

“…Recently, Hikawa et al. reported a palladium‐catalyzed dehydrative N‐benzylation with benzyl alcohol in water . They suggested that water activated the sp 3 C−O bond of the alcohol via hydrogen bonding with formation of the π‐benzylpalladium(II) complex.…”

“…In the next step, a second amine and methyl propiolate react with the dehydrated compound with benzyl alcohol in water. [19,20] They suggested that water activated the sp 3 CÀ O bond of the alcohol via hydrogen bonding with formation of the π-benzylpalladium(II) complex. A similar type of effect, based on a hydrogen-bonding network of water molecules, could accelerate the hydroxyl group elimination in our 1,4-DHP formation.…”