The development of new amine–amide ligands for application in Cu(II)-catalyzed enantioselective Henry reactions

A new type of chiral tertiary amine ligand was designed and derived from l-proline and (R)-BINOL. These new chiral ligands chelated with Cu(II) showed highly catalytic efficiency in enantioselective Henry reactions. Excellent yields (up to 99%) and high enantioselectivities (up to 96% ee) were achieved for aromatic, hetero-aromatic and aliphatic aldehyde substrates, without an additional base additive or the need for air or moisture exclusion.

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(S)-1-(2-((R)-3H-Dinaphtho[2,1-c:1′,2′-e]azepin-4(5H)-yl)ethyl)-N-butylpyrrolidine-2-carboxamideC33H37N3O[α]D25 = −248.0 (c 0.51, CH2Cl2)Absolute configuration: (S,R)

(S)-1-(2-((R)-3H-Dinaphtho[2,1-c:1′,2′-e]azepin-4(5H)-yl)ethyl)-N-(tert-butyl)pyrrolidine-2-carboxamideC33H37N3O[α]D25 = −222.8 (c 0.5, CH2Cl2)Absolute configuration: (S,R)

(S)-1-(2-((R)-3H-Dinaphtho[2,1-c:1′,2′-e]azepin-4(5H)-yl)ethyl)-N-cyclohexylpyrrolidine-2-carboxamideC35H39N3O[α]D25 = −229.4 (c 0.5, CH2Cl2)Absolute configuration: (S,R)

(S)-1-(2-((R)-3H-Dinaphtho[2,1-c:1′,2′-e]azepin-4(5H)-yl)ethyl)-N-phenylpyrrolidine-2-carboxamideC35H33N3O[α]D25 = −297.4 (c 0.5, CH2Cl2)Absolute configuration: (S,R)

(S)-1-(2-((R)-3H-Dinaphtho[2,1-c:1′,2′-e]azepin-4(5H)-yl)ethyl)-N-(naphthalen-1-yl)pyrrolidine-2-carboxamideC39H36N3O[α]D31 = 239.0 (c 0.51, CH2Cl2)Absolute configuration: (S,R)

(R)-4-(2-(Pyrrolidin-1-yl)ethyl)-4,5-dihydro-3H-dinaphtho[2,1-c:1′,2′-e]azepineC28H28N2[α]D25 = +63.7 (c 0.19, CH2Cl2)Absolute configuration: (R)

(S)-1-(2-(Isoindolin-2-yl)ethyl)-N-(naphthalen-1-yl)pyrrolidine-2-carboxamideC25H28N3O[α]D25 = −79.4 (c 0.51, CH2Cl2)Absolute configuration: (R)