Facile one-pot synthesis of cinchona alkaloid-based P,N ligands and their application to Pd-catalyzed asymmetric allylic alkylation

A novel class of bidentate chiral P,N donor ligands based on cinchona alkaloids is described. These ligands are easily synthesized in one-pot from commercially available enantiopure 1,2-diphenyl-1,2-ethanediol and cinchona alkaloids in two steps. Their application to the palladium(II)-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate gave the corresponding products in excellent yields and up to 94% ee. The effect of ligands, substrates, nucleophiles, and temperature on the reaction was also investigated.

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(4S,5S)-2-Cinchoninyl-4,5-diphenyl-1,3,2-dioxaphospholaneC33H33N2O3P[α]D25=-108 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-2-Cinchonidinyl-4,5-diphenyl-1,3,2-dioxaphospholaneC33H33N2O3P[α]D25=-35 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-2-Quininyl-4,5-diphenyl-1,3,2-dioxaphospholaneC34H35N2O4P[α]D25=-29.5 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)

(4S,5S)-2-Quindinyl-4,5-diphenyl-1,3,2-dioxaphospholaneC34H35N2O4P[α]D25=-69.6 (c 1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (4S,5S)