Modular amino acid amide chiral ligands for enantioselective addition of diethylzinc to aromatic aldehydes

Enantioselective addition of diethylzinc to a series of aromatic aldehydes was developed using a modular amino acid amide chiral ligand (2S)‐3‐phenyl‐N‐((R)‐1‐phenyl‐ethyl)‐2‐(tosylamino)propanamide without using titanium complex. The catalytic system employing 10 mol% of 1g was found to promote the addition of diethylzinc (ZnEt₂) to a wide range of aromatic aldehydes with electron‐donating and electron‐withdrawing substituents, giving up to 82% ee of the corresponding secondary alcohol under mild conditions. Copyright © 2011 John Wiley & Sons, Ltd.     

3,3'-dipyridyl BINOL ligands. Synthesis and application in enantioselective addition of Et2Zn to aldehydes

3,3'-di(2-pyridyl) BINOLs (4), prepared in three steps from commercial substances by a combined directed ortho metalation-Negishi cross-coupling protocol, constitute new members of the BINOL ligand family. They are among the most selective, general ligands, providing equal or greater stereoselectivities in the Et2Zn addition to benzaldehydes and cinnamaldehydes (Table 3) than any single BINOL ligand reported to date.     

Modular ligands derived from amino acids for the enantioselective addition of organozinc reagents to aldehydes

A new series of modular chiral ligands that are derived from amino acids were prepared and tested for their ability to catalyze the asymmetric addition of alkylzinc reagents to aromatic and aliphatic aldehydes. The ligands contain a tertiary amine, an amino acid side chain, and a carbamate or amide functional group. One ligand, which was synthesized from Ile, catalyzes the addition of diethylzinc to cyclohexanecarboxaldehyde in 99% ee.     

Modular amino acids and β‐amino alcohol‐based chiral ligands for enantioselective addition of diethylzinc to aromatic aldehydes

Enantioselective addition of diethylzinc to a series of aromatic aldehydes was developed using a modular amino acids and ${\bf \beta}$ ‐amino alcohol‐based chiral ligand (2R)‐N‐[(1R,2S)‐1‐hydroxy‐1‐phenylpropan‐2‐yl]‐3‐phenyl‐2‐(tosylamino) propanamide ( 1f ) without using titanium complex. The catalytic system employing 15 mol% of 1f was found to promote the addition of diethylzinc (ZnEt₂) to a wide range of aromatic aldehydes with electron‐donating and electron‐withdrawing substituents, giving up to 97% ee of the corresponding secondary alcohol under mild conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by novel chiral imino alcohol ligands

The enantioselective alkylation of aryl aldehydes by diethylzinc in the presence of catalytic amounts of several novel chiral imino alcohol ligands, synthesized from the reaction of (R)-2-amino-1-butanol with aromatic aldehydes, was studied. The influence of temperature and ligand structure was investigated and enantioselectivity up to 81% was obtained.     

A new pyrrolidine-derived atropisomeric amino alcohol as a highly efficient chiral ligand for the asymmetric addition of diethylzinc to aldehydes

A highly efficient pyrrolidine-derived atropisomeric amino alcohol, (S_a)-1-[2-diphenylhydroxymethyl-6-(trifluoromethyl)phenyl]-2-(1-pyrrolido)methyl-1H-pyrrole, has been synthesized as a chiral ligand for the enantioselective addition of diethylzinc to some prochiral aldehydes to afford (S)-alcohols. The conversion rates were close to quantitative with good to excellent enantiomeric excesses (up to 95% ee).     

Polystyrene-supported amino alcohol ligands for the heterogeneous asymmetric addition of phenyl zinc reagents to aldehydes

A family of polystyrene-supported amino alcohols, characterized by a high catalytic activity in alkyl transfer from zinc to formyl groups has been successfully tested in the enantioselective addition of phenyl zinc reagents to aldehydes to afford chiral diarylmethanols. Enantioselectivities higher than 90% (mean ee 90.5%; eight examples) are recorded with aromatic aldehydes in what represents the first successful use of heterogeneous, polymeric reagents for enantiocontrol in the phenylation of aldehydes.     

Aminosubstituted tert-butylsulfinylferrocenes as a new family of chiral ligands: asymmetric addition of diethylzinc to aldehydes

A ready access to a new family of planar chiral ferrocenes, the (RFc,RS)-2-amino substituted 1-tert-butylsulfinylferrocenes, is described; in the case of the sulfonamide series enantioselectivities of up to 96% were obtained in the addition of Et2Zn to aromatic aldehydes.     

2-amino-substituted 1-sulfinylferrocenes as chiral ligands in the addition of diethylzinc to aromatic aldehydes

A simple and modulable access to a structural variety of enantiopure amino-substituted ferrocenyl sulfoxides and their use as chiral catalysts in the asymmetric addition of diethylzinc to aromatic aldehydes is described. Moderate to high enantioselectivities (up to 96% ee) were obtained in the case of the arylsulfonamide ligands (R(Fc), R(S))-4h and (R(Fc), R(S))-4i. It has been demonstrated that the planar chirality of the ferrocene unit is the decisive chiral element involved in the reaction.     

Camphordisulfonamides: good chiral ligands for the addition of dialkylzinc to aliphatic aldehydes

The preparation of several disulfonamides derived from camphor and their use in the titanium tetraisopropoxide-promoted enantioselective addition of dialkylzinc to aldehydes is described. The enantiomeric ratio is up to 98:2, the best results being obtained for aliphatic aldehydes.     

New bis-steroidal axially chiral diols as ligands for the asymmetric addition of diethylzinc to aldehydes

New axially chiral steroidal binaphthols, prepared from estrone, were applied in the form of their Ti-alkoxides as catalysts for the addition of diethylzinc to aldehydes. The addition reactions proceeded with high yields and enantioselectivities up to 86%.     

Synthesis of chiral ligands containing the N-(S)-α-phenylethyl group and their evaluation as activators in the enantioselective addition of Et2Zn to benzaldehyde

The synthesis of chiral ligands 4–18 derived from N-[(S)-α-phenylethyl]-trans-β-aminocyclohexanols (S,S,S)-1a and (R,R,S)-2 is described. Addition of diethylzinc to benzaldehyde catalyzed by ligands 4–18 (6 mol %) proceeds in fair to good yield (45–86%), and low to good enantioselectivities (1–76% ee). Highest enantioselectivities were induced by ligands (S,S,S)-4 and (S,S,S,S,R,R)-18 (76% and 68% ee, respectively). The configuration of the major enantiomer of carbinol 3 is (R) in both cases.     

Enantioselective addition of organometallics to aldehydes using camphor derived chiral 1,4-aminoalcohols as ligands

(+)-Camphor derived enantiomerically pure 1,4-aminoalcohols have been used as ligands in the addition reactions of n-BuLi and n-BuMgBr to benzaldehyde and in the reaction of diethylzinc with benzaldehyde and hexanal. All chiral secondary alcohols were obtained in good chemical yields and enantioselectivities were up to 87% ee in the addition of diethylzinc.     

Synthesis and application of oxadiazines as chiral ligands for the enantioselective addition of diethylzinc to aldehydes

A series of oxadiazines derived from l-phenylalanine bearing phenolic substituents have been synthesized in a multistep, one pot process. This process involves the reaction of a mixed anhydride with a β-hydrazino alcohol, methanesulfonylation of the alcohol moiety, and base induced cyclization. The resultant oxadiazines were employed in the asymmetric addition of diethylzinc to aldehydes.     

Efficient asymmetric addition of diethylzinc to aldehydes using C2‐novel chiral pyridine β‐amino alcohols as chiral ligands

A series of novel C₂‐symmetric chiral pyridine β‐amino alcohol ligands have been synthesized from 2,6‐pyridine dicarboxaldehyde, m‐phthalaldehyde and chiral β‐amino alcohols through a two‐step reaction. All their structures were characterized by ¹H NMR, ¹³C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)‐2,2′‐((pyridine‐2,6‐diylbis(methylene))bisazanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)‐2,2′‐((1,3‐phenylenebis(methylene))bis(azanediyl))bis(4‐methyl‐1,1‐diphenylpentan‐1‐ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

New chiral tetraaza ligands for the efficient enantioselective addition of dialkylzinc to aromatic aldehydes

A series of chiral tetraaza ligands were studied for the enantioselective addition of dialkylzinc to aldehydes. These bis(amino amide) ligands show high enantioselectivity in the addition of organozincs to aromatic aldehydes. Different structural elements on the ligands seem to play an important role in determining the observed enantioselectivity. Ligand 4b (N,N′-bis(N-l-valinyl)-1,3-diaminopropane, with an aliphatic spacer with 3C atoms) catalyzed the addition of Et₂Zn to benzaldehyde, 1-naphtaldehyde, 4-methoxybenzaldehyde, and 4-chlorobenzaldehyde to give the corresponding alcohol products with excellent conversions and selectivities and with enantioselectivities of 99, 97, 98, and 82%, respectively. DFT calculations provide an understanding of the mechanism of the enantioselection process.     

The synthesis of chiral amino diol tridentate ligands and their enantioselective induction during the addition of diethylzinc to aldehydes

A series of C₂-symmetric chiral amino diol tridentate ligands 3a–g were prepared from achiral bulky organolithiums, achiral bulky primary amines, and optically active epichlorohydrin (ECH). The prepared C₂-symmetric chiral amino diol tridentate ligands were capable of inducing enantioselectivity in the model reaction of aromatic and aliphatic aldehydes with diethylzinc with an ee of up to 96%. The enantioselectivity can be modulated by adjusting the steric hindrance of the achiral reagents employed in the synthesis of the chiral ligand. The configuration of the addition product depended on the configuration of the amino diol ligands, which can be simply controlled as desired by using the ECH with the desired configuration during the preparation of the ligand.     

Chiral bis(amino alcohol)oxalamides as ligands for asymmetric catalysis. Ti(IV) catalyzed enantioselective addition of diethylzinc to aldehydes

Several chiral bis(aminoalcohol)oxalamides with C₂-symmetry have been prepared and used as ligands for the enantioselective addition of diethylzinc to aromatic and aliphatic aldehydes. The reaction proceeds in the presence of titanium isopropoxide to give the corresponding (S)-alcohols with ee up to 78%. In the absence of Ti(IV), the alcohols with the opposite configuration are obtained.     

Efficient asymmetric addition of diethylzinc to aldehydes using 3‐hydroxyazetidine derivatives as chiral ligands

A new series of chiral 3‐hydroxyazetidines has been prepared from (S)‐1‐(4‐methoxyphenyl)ethylamine. These ligands have shown excellent catalytic activities and enantiomeric selectivities in asymmetric addition of diethylzinc to aromatic aldehydes. Copyright © 2008 John Wiley & Sons, Ltd.     

An efficient method for catalytic enantioselective addition of diethylzinc to aryl aldehydes by a C2-symmetric chiral imino alcohol

The enantioselective alkylation of aryl aldehydes with diethylzinc in the presence of a C₂-symmetric chiral ligand derived from 2-hydroxy-3-pinanone was achieved at room temperature with high enantiomeric excesses.