The syntheses of three novel chiral 4,4′BOX ligands are described. The three ligands each have a chiral backbone and chiral sidearms, two of which are diastereomeric. These new ligands have been applied as copper complexes to asymmetric cyclopropanation reaction of styrene with ethyldiazoacetate. Enantioselectivities of up to 70% were obtained, which is the highest ee reported from the use of this ligand class in this reaction to date. The multiple stereogenic centres in the ligand resulted in a substantial additive effect and this is discussed along with interpretation of the results for previously described 4,4′BOX ligands, and a major computational study of the multiple reaction channels involved with ligands of this type. The use of complexes of 4,4′BOX ligands, as catalysts, in an allylic alkylation is also reported for the first time and ee’s of >70% have been achieved in this reaction. These ligands were also applied to a Diels–Alder test reaction and again outperformed previous examples of this ligand type.(2S)-N-[(1S,3S)-4-(tert-Butyl(dimethyl)silyl)oxy-1-[(tert-butyl(dimethyl)silyl)oxymethyl]-3-[[(2S)-2-methylbutanoyl]amino]butyl]-2-methyl-butanamideC27H58N2O4Si2[α]D20=-15.2 (c 0.003, CH3CN)Sources of chirality: d-(+)-Arabitol(2S)-2-Methylbutanoic acid(2S)-N-[(1S,3S)-4-(tert-Butyl(dimethyl)silyl)oxy-1-[(tert-butyl(dimethyl)silyl)oxymethyl]-3-[[(2S)-2-phenylbutanoyl]amino]butyl]-2-phenyl-butanamideC37H62N2O4Si2[α]D20=-13.6 (c 0.003, CH3CN)Sources of chirality: d-(+)-Arabitol(2S)-2-Phenylbutanoic acid(2S)-N-[(1R,3R)-4-(tert-butyl(dimethyl)silyl)oxy-1-[(tert-butyl(dimethyl)silyl)oxymethyl]-3-[[(2S)-2-phenylbutanoyl]amino]butyl]-2-phenyl-butanamideC37H62N2O4Si2[α]D20=+18.3 (c 0.003, CH3CN)Sources of chirality: l-(−)-Arabitol(2S)-2-Phenylbutanoic acid2-[(1S)-1-Methylpropyl]-4-[[(4S)-2-[(1S)-1-methylpropyl]-4,5-dihydrooxazol-4-yl]methyl]-4,5-dihydrooxazoleC15H26N2O2[α]D20=+17.6 (c 0.003, CH3CN)Sources of chirality: d-(+)-Arabitol(2S)-2-Methylbutanoic acid2-[(1S)-1-Phenylpropyl]-4-[[(4S)-2-[(1S)-1-phenylpropyl]-4,5-dihydrooxazol-4-yl]methyl]-4,5-dihydrooxazoleC25H30N2O2[α]D20=-18.7 (c 0.003, CH3CN)Sources of chirality: d-(+)-Arabitol(2S)-2-Phenylbutanoic acid2-[(1S)-1-Phenylpropyl]-4-[[(4R)-2-[(1S)-1-phenylpropyl]-4,5-dihydrooxazol-4-yl]methyl]-4,5-dihydrooxazoleC25H30N2O2[α]D20=+59.8 (c 0.003, CH3CN)Sources of chirality: l-(−)-Arabitol(2S)-2-Phenylbutanoic acid

Asymmetric ligands whose key functional component consists of an amide and hydroxyl functional groups, in the absence of other co-ordinating groups, are a relatively recent development in asymmetric catalysis. These ligands in combination with ruthenium, zinc, or titanium have catalyzed a range of key organic reactions showing high activity and selectivity. This review looks at the ligands reported and their performance as catalysts.Keywords: asymmetric synthesis; catalyst; hydroxyamide; ligand; organic synthesis;

The synthesis of a series of chiral hydroxy amide ligands is described. These ligands were used in a ruthenium-catalysed transfer hydrogenation reaction where one ligand gave the product in 72% ee. The ligands were also used in two titanium-catalysed reactions, an alkylation where ee’s of up to 74% were achieved and a phenyl acetylene addition where more modest selectivities were observed.Figure optionsDownload full-size imageDownload as PowerPoint slide(2S)-N-[(1R)-2-Hydroxy-1-phenyl-ethyl]-5-oxo-pyrrolidine-2-carboxamideC13H16N2O3[α]D20=-81.6 (c 1, MeOH)Sources of chirality: (S)-(−)-2-pyrrolidone-5-carboxylic acid(R)-(+)-2-PhenylglycinolAbsolute configuration: 2S,1′R(2S)-N-[(1S)-1-Hydroxymethyl)-2-methyl-propyl]-5-oxo-pyrrolidine-2-carboamideC10H18N2O3[α]D20=-14.1 (c 0.8, H2O)Sources of chirality: (S)-(−)-2-pyrrolidone-5-carboxylic acid(S)-(+)-ValinolAbsolute configuration: 2S,1′S(2S)-N-[(1S)-1-benzyl-2-hydroxy-ethyl]-5-oxo-pyrrolidine-2-carboxamideC14H18N2O3[α]D20=-32.9 (c 1, MeOH)Sources of chirality: (S)-(−)-2-pyrrolidone-5-carboxylic acid(S)-(+)-2-PhenylalaninolAbsolute configuration: 2S,1′S(2S)-N-[(1S)-1-(Hydroxymethyl)-2-methyl-butyl]-5-oxo-pyrrolidine-2-carboxamideC11H20N2O3[α]D20=-21.9 (c 1, H2O)Sources of chirality: (S)-(−)-2-pyrrolidone-5-carboxylic acid(S)-(+)-LeucinolAbsolute configuration: 2S,1′S

The synthesis of two new 4,4′ bisoxazoline ligands is described. The use of copper complexes of these and three other recently described related ligands as catalysts in a cyclopropanation reaction is discussed. The first structural data on one such chiral copper complex is reported herein.