Novel Frechet-type dendritic BINOL ligands and their applications in Ti（IV） complex catalyzed asymmetric addition of diethylzinc to aldehydes

New Frechet-type dendritic BINOL ligands bearing several BINOL units at the periphery have been successfully synthesized. The （dendritic BINOL） Ti（IV） complexes were proved to be efficient catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes. Moreover, these ligands could be quantitatively recovered and reused at least five times without a loss of the yield and enantioselectivity.     

The synthesis of silica-supported chiral BINOL: Application in Ti-catalyzed asymmetric addition of diethylzinc to aldehydes

Chiral BINOL was covalently anchored on two different pore sized mesoporous silica (SBA-15 (7.5 nm) and MCF (14 nm)). These heterogenized ligands were used in Ti-catalyzed asymmetric addition of diethylzinc to aldehydes. High catalytic activity with excellent enantioselectivity (up to 94% ee) for secondary alcohols was achieved using MCF supported chiral BINOL under heterogeneous reaction conditions. Good to excellent enantioselectivity (ee, 68–91%) was also achieved with various small to bulkier aldehydes. The MCF supported catalyst was reused in multiple catalytic runs without loss of enantioselectivity.     

3,3′-Functionalized octahydro-BINOL: a facile synthesis and its high enantioselectivity in the alkyne addition to aldehydes

A facile synthesis of an enantiomerically pure 3,3′-bismorpholinylmethyl H₈-BINOL ligand has been developed. This compound in combination with Et₂Zn and Ti(OⁱPr)₄ is found to catalyze the highly enantioselective reaction of phenylacetylene with aromatic aldehydes. The enantioselectivity of this catalytic process for the reactions of ortho-substituted benzaldehydes is significantly higher than that based on H₈-BINOL.     

Synthesis of 3 or 3,3′-substituted BINOL ligands and their application in the asymmetric addition of diethylzinc to aromatic aldehydes

Three new substituted BINOL ligands (R)-3-[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-1, (R)-3,3′-bis[4,6-bis(dimethylamino)-1,3,5-triazin-2-yl]-1,1′-bi-2-naphthol (R)-2 and 2,4-bis(2,2′-dihydroxy-1,1′-binaphthalen-3-yl)-6-(p-tolyl)-1,3,5-triazine (R,R)-3 have been obtained by directed ortho-lithiation or Suzuki cross-coupling process. Ligand (R)-1 shows improved catalytic properties for the asymmetric diethylzinc addition to aromatic aldehydes.     

Titanium (IV) as an essential promoter in the asymmetric addition of diethylzinc to aldehydes catalyzed by aminonaphthol and imine ligands based on 3-substituted binaphthol

By using indirect reductive amination and condensation, two types of aminonaphthol and imine ligands based on 3-substituted binaphthol have been synthesized, respectively. When their catalytic effectiveness was tested by the ethylation of aldehydes with diethylzinc, titanium tetraisopropoxide was found essential to get good results with ee up to 90%.     

2-Pyridylsulfinamides as effective catalysts in the asymmetric alkylation of aldehydes with diethylzinc

Chiral 2-pyridylsulfinamides were shown to be effective catalysts in the alkylation of aryl and alkyl aldehydes with diethylzinc providing the corresponding alcohols in excellent enantioselectivity. Sulfinamide catalysts possessing solitary chirality at the sulfur center produced the product phenethyl alcohol in good enantioselectivity. Diastereomeric sulfinamides possessing chirality at the carbon-bearing nitrogen and at the sulfur of the sulfinamide increased the enantioselectivity of the product alcohols up to >99%. However, there is no effect of the match-mismatch pair of sulfinamide diastereomers on the outcome of the chiral induction of the product phenethyl alcohols. It was conclusively proved that chirality at the sulfur center is mandatory for obtaining good enantioselectivity in the reaction.     

Highly enantioselective addition of linear alkyl alkynes to linear aldehydes

It is discovered that the use of biscyclohexylamine (Cy₂NH) as an additive can greatly enhance the enantioselectivity for the reaction of linear alkyl alkynes with linear aldehydes. The combination of (S)-BINOL (20 mol %), Cy₂NH (5 mol %), ZnEt₂ (2 equiv), and Ti(OⁱPr)₄ (0.5 equiv) catalyzes the reaction at room temperature in diethyl ether solution with 81-89% ee and 57-77% yield.     

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).     

Ionic liquids incorporating camphorsulfonamide units for the Ti-promoted asymmetric diethylzinc addition to benzaldehyde

New hydrophobic ionic liquids containing chiral camphorsulfonamide units were used as chiral auxiliaries in the titanium catalyzed asymmetric diethylzinc addition to benzaldehyde. The ionic catalyst system shows catalytic properties similar to those of related nonionic counterparts in terms of activity and enantioselectivity. Interestingly, the ionic ligands can easily be recycled and re-used without loss of activity or selectivity.     

Enantioselective phenyl transfer to aldehydes using 1,1′-bi-2-naphthol-3,3′-dicarboxamide as chiral auxiliary

N,N,N′,N′-Tetra-n-butyl-BINOL-3,3′-dicarboxamide 5d was found to promote phenyl transfer from ethylphenylzinc to both aromatic and aliphatic aldehydes with high enantioselectivity up to 96% ee in tert-butyl methyl ether.     

A facile synthesis and the asymmetric catalytic activity of BINOL-based thiazole (thiadiazole) thioether ligands

Four new BINOL-based thiazole (thiadiazole) thioether ligands (S)-1, (S)-2, (S,S)-3 and (S)-4 were prepared. When their catalytic effectiveness was tested, good results (up to 93% ee and 97% yield) were obtained in the asymmetric addition of diethylzinc to aldehydes while poor results were obtained in the asymmetric conjugate addition of diethylzinc to enones.     

1,1′-Binaphthyl ligands with bulky 3,3′-tertiaryalkyl substituents for the asymmetric alkyne addition to aromatic aldehydes

The BINOL ligand (R)-2 that contains bulky 3,3′-tertiaryalkyl groups shows improved catalytic properties over the previously reported 3,3′-substituted BINOL ligands in the asymmetric alkyne addition to aromatic aldehydes. It catalyzes the phenylacetylene addition to aromatic aldehydes with high enantioselectivity (86-94% ee) and good yields without using Ti(OⁱPr)₄ and a Lewis base additive. The catalytic properties of several analogs of (R)-2 in the asymmetric alkyne addition to aldehydes have also been studied.     

Synthesis of modified H4-BINOL ligands and their applications in the asymmetric addition of diethylzinc to aromatic aldehydes

Two new ligands (S,S)-3-(1,1′-bi-2-naphthol-3-yl)-5,6,7,8-tetrahydro-1,1′-bi-2-naphthol [(S,S)-1] and (S)-3-(morpholin-4-ylmethyl)-H₄-BINOL [(S)-2] have been synthesized via Suzuki cross-coupling reaction and a Mannich-type reaction, respectively. In the presence of titanium tetraisopropoxide, 0.8 mol % of ligand (S,S)-1 catalyzed the asymmetric addition of diethylzinc to aromatic aldehydes in good yield and with high enantioselectivity.     

The synthesis of dendritic BINOL ligands and their applications in the asymmetric addition of diethylzinc to benzaldehyde

The synthesis of Fréchet-type dendritic BINOL ligands is described. These dendritic BINOL ligands were found to be effective in the enantioselective addition of diethylzinc to benzaldehyde both in the presence and absence of Ti(O-i-Pr)₄. In the latter case, the novel dendritic chiral BINOL ligands showed slightly higher enantioselectivities than their monomeric analogue.     

Synthesis of new chiral 1,2,3,4-tertrahydroisoquinoline β-amino alcohol for asymmetric diethylzinc addition to aryl aldehydes (I)

Four new chiral 1,2,3,4-tetrahydroisoquinoline-derived β-amino alcohols were synthesized from commercially available L-DOPA.These ligands were evaluated in the asymmetric addition of diethylzinc to benzaldehydes and showed different catalytic activities (up to 86% ee).The solvent played an important role in the enantioselective process.The transition state models were proposed to explain the reversion of the product configuration.     

Furanoside phosphite-phosphoroamidite: new ligand class for the asymmetric nickel-catalyzed trialkylaluminium addition to aldehydes

We have described the first successful application of bidentate ligands in the asymmetric Ni-catalyzed trialkylaluminium addition to several aldehydes. The ligands are prepared from inexpensive d-(+)-xylose and d-(+)-glucose and have the advantage of carbohydrate and phosphite/phosphoroamidite moieties. After systematic variation of the position of the phosphoroamidite group at either C5 or C-3, the configuration of C-3 and the substituents in the biaryl phosphite/phosphoroamidite moieties, enantioselectivities up to 84% and high yields were obtained in the Ni-catalyzed trialkylaluminium addition to several aldehydes.     

Enantioselective addition of diethylzinc to aldehydes catalyzed by 5-cis-substituted proline derivatives

5-Cis-substituted prolinols, prolinamines, and prolinamine sulfonamides proved to be efficient ligands for the enantioselective addition of diethylzinc to aldehydes, providing up to 99% ee. The sense of asymmetric induction can be controlled by the nature of the exocyclic functional group (CPh₂OH vs. CH₂NHR vs. CH₂NHSO₃R). The additional 5-cis substituent exerts a strong beneficial effect on the chirality transfer since it rigidifies the catalyst structure. The stereochemical outcome of the reactions is discussed in detail on the respective transition states.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by 1,2,3,4-tetrahydroisoquinoline β-amino alcohol

<正>A highly effective,new chiral 1,2,3,4-tetrahydroisoquinoline catalyst 1 for the diethylzinc addition to aryl aldehydes has been investigated.Using 10 mol%of this chiral catalyst,secondary alcohols can be obtained in up to 87%yield and 99.5%ee under mild conditions.     

Fructose derived pyridyl alcohol ligands: synthesis and application in the asymmetric diethylzinc addition to aldehydes

Easily available chiral ketones were employed for the synthesis of optically active pyridyl alcohols, which were applied in the asymmetric diethylzinc addition to aldehydes, up to 89.4% e. e. was obtained using D-fructose-derived pyridyl alcohol.