Novel nitrogen ligands based on imidazole derivatives and their application in asymmetric catalysis

Recently prepared chiral amines have been used in the preparation of novel tridentate ligands based on an imidazole ring with an additional (hetero)ring. The synthesis was carried out by the reaction of chiral amines with suitable aldehydes (2-phenylimidazole-4-carbaldehyde, 2-hydroxybenzaldehyde or pyridine-2-carbaldehyde) under reductive conditions (H2/Pd or NaBH4). All ligands prepared showed strong hydrogen bonds in d6-DMSO solution, which resulted in hindered imidazole tautomerism. The observed hindered tautomerism was studied by 1H NMR spectroscopy. The structures of the prepared ligands were also confirmed by APCI mass spectroscopy. Both chiral amines and tridentate compounds have been applied as ligands in copper (II)-catalyzed nitroaldol reactions (Henry reaction). Various reaction conditions for the Henry reaction have been studied (influence of temperature, molar ratio, solvent or copper (II) precursors). The compounds prepared with the two imidazole rings showed fast reaction times and a reversal in enantioselectivity compared to other chiral amines.

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(1S)-1-(2-Phenyl-1H-imidazol-4-yl)-N-(2-phenyl-1H-imidazol-4-ylmethyl) ethanamineC21H21N5Ee = 99%[α]D20=-43.0 (c 0.5, CH3OH)Source of chirality: (S)-AlaAbsolute configuration: (S)

(1S)-2-Methyl-1-(2-phenyl-1H-imidazol-4-yl)-N-(2-phenyl-1H-imidazol-4-ylmethyl) propanamineC23H25N5Ee = 99%[α]D20=-66.2 (c 0.5, CH3OH)Source of chirality: (S)-ValAbsolute configuration: (S)

(1S)-3-Methyl-1-(2-phenyl-1H-imidazol-4-yl)-N-(2-phenyl-1H-imidazol-4-ylmethyl) butanamineC24H27N5Ee = 99%[α]D20=-30.8 (c 0.5, CH3OH)Source of chirality: (S)-LeuAbsolute configuration: (S)

(1S)-2-Phenyl-1-(2-phenyl-1H-imidazol-4-yl)-N-(2-phenyl-1H-imidazol-4-ylmethyl) ethanamineC27H25N5Ee = 99%[α]D20=-10.0 (c 0.5, CH3OH)Source of chirality: (S)-PheAbsolute configuration: (S)

(1S)-2-Methyl-1-(2-phenyl-1H-imidazol-4-yl)-N-(pyridine-2-ylmethyl) propanamineC19H22N4Ee = 99%[α]D20=-49.8 (c 0.5, CH3OH)Source of chirality: (S)-ValAbsolute configuration: (S)

(1S)-3-Methyl-1-(2-phenyl-1H-imidazol-4-yl)-N-(pyridine-2-ylmethyl) butanamineC20H24N4Ee = 99%[α]D20=-29.4 (c 0.5, CH3OH)Source of chirality: (S)-LeuAbsolute configuration: (S)

(1S)-2-Phenyl-1-(2-phenyl-1H-imidazol-4-yl)-N-(pyridine-2-ylmethyl) ethanamineC23H22N4Ee = 99%[α]D20=34.0 (c 0.5, CH3OH)Source of chirality: (S)-PheAbsolute configuration: (S)

2-[(1S)-N-(3-Methyl-1-(2-phenyl-1H-imidazol-4-yl)butyl)aminomethyl]phenolC21H25N3OEe = 99%[α]D20=-28.0 (c 0.5, CH3OH)Source of chirality: (S)-LeuAbsolute configuration: (S)