Enantioselective addition of diethylzinc to benzaldehyde in the presence of sulfur-containing pyridine ligands

Diastereomerically pure hydroxy and thiol derivatives of (5S,7S)-5,7-methane-6,6-dimethyl-2-phenyl-5,6,7,8-tetrahydroquinoline were prepared and assessed in the enantioselective addition of diethylzinc to benzaldehyde: enantioselectivities up to 62% were obtained.     

Enantioselective addition of diethylzinc to aldehydes in the presence of chiral aprotic ligands

Optically active amino thiocyanate derivatives of (−)-norephedrine were found to act as effective aprotic ligands for enantioselective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 96%.     

Enantioselective addition of n-butyllithium to benzaldehyde in the presence of chiral lithium amides

The reaction of n-butyllithium with benzaldehyde in the presence of chiral lithium amides 1a-–e gives 1-phenyl-1-pentanol with optical yields up to 90%.     

Enantioselective addition of diethylzinc to benzaldehyde catalyzed by ferrocenic amino-alcohols combining centered and planar chiralities

Diastereomeric ferrocenic amino-alcohols combining three elements of chirality (one of which is a ferrocenic plane) are tested as catalysts in the alkylation of benzaldehyde with diethylzinc. Good to excellent yields and ees were obtained and show correlation between the metallocenic chirality and the configuration of the resulting 1-phenyl-1-propanol.     

Enantioselective addition of diethylzinc to aldehydes in the presence of chiral hydrazone and imine ligands

Optically active hydrazone and imine were found to act as effective ligands for enantioselective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 71%.     

Dramatic catalyst evolution in the asymmetric addition of diethylzinc to benzaldehyde

We have observed product ee's that begin at 20% at low reaction conversion and rise to 79% ee at the completion of the reaction in the asymmetric addition of alkyl groups to benzaldehyde. This rare behavior is attributed to autoinduction, in which the catalyst evolves by incorporation of the product. Based on this, we have been able to optimize the catalyst by variation of achiral, rather than enantiopure ligands.     

Enantioselective addition of diethylzinc to benzaldehyde catalyzed by a small amount of chiral 2-amino-1-alcohols

The reaction of diethylzinc with benzaldehyde catalyzed by a small amount of chiral 2-amino-1-alcohols in toluene at room temperature gave optically active 1-phenylpropan-1-ol almost quantitatively in ～, 50% ee.     

Hydroxyamides versus amino alcohols in the enantioselective addition of diethylzinc to benzaldehyde

Two series of structurally related enantiopure isoborneols (10-amino- and 10-amino-10-oxoisoborneols) have been obtained from ketopinic acid and compared as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde in the absence of Ti(O-i-Pr)₄. The results obtained (chemical yields and enantiomeric excesses) show that identical structural factors (functionalization grade and symmetry group) exert very different effects on both series. The observed differences have been rationalized on the basis of the coordination ability of each ligand type to form the corresponding reactive zinc-chelate catalyst.     

Chiral tetrahedral complex catalyzing asymmetric addition of diethylzinc to benzaldehyde

The optical active alkyne-bridged Mo-Co heterometal complexes are synthesized by the chiral phase transfer catalyst (N-benzylcinchorin chloride) induced metal exchange reaction. The complex is used as catalyst to promote the asymmetric addition of diethylzinc to benzaldehyde. The ee value of the product alcohol is 5.7%, which illustrates the asymmetric induction of the tet-rahedral framework chirality in asymmetric catalysis reaction for the first time.     

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.     

Polyoxygenated ketopinic-acid-derived γ-amino alcohols in the enantioselective diethylzinc addition to benzaldehyde

Three N,N-dialkylated γ-amino alcohols, specifically 10-(dialkylamino)isoborneols, with different grades of oxygenation in the nitrogen’s alkyl groups (alkoxyalkyl groups), have been obtained from commercial (+)-ketopinic acid and tested as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde, in order to evaluate the effect of polyoxygenation on the ligand’s catalytic activity. An interesting effect of the oxygen atoms on the ligand activity is observed. The observation is in agreement with two unique previous results on amino-acid-derived polyoxygenated β-amino alcohols. A noticeable dependence of the observed effect with the conformational flexibility of the polyoxygenated chains is also demonstrated. The effect is explained by a pincer role of the polyoxygenated dialkylamino moiety, activating and directing a diethylzinc molecule.     

Ti-mediated addition of diethylzinc to benzaldehyde. The effect of chiral additives

In the presence of a chiral tridentate bissulfonamide, the titanium-mediated addition of diethylzinc to benzaldehyde gave alkylated products ranging from the (R)-enantiomer, formed with an e.e. of 26%, to the (S)-enantiomer, formed in 72% e.e. The enantioselectivity was also affected by the presence of additional chiral mono- and bidentate ligands, with the reactions proceeding via complexes containing the chiral sulfonamide and the additive. The addition of (1R,2R)-1,2-diphenyl-1,2-ethanediamine and (1S,2S)-1,2-diphenyl-1,2-ethanediamine gave the (S)-product with e.e. of 49% and the (R)-product with 16% e.e., respectively, whereas without additives the (R)-product was obtained in 26% e.e. In the presence of (1R,2R)-1,2-diphenyl-1,2-ethanediamine only (i.e. without the chiral sulfonamide), the (S)-product formed with a 3% e.e.     

Enantioselective Cu-catalyzed conjugate addition of diethylzinc to acyclic aliphatic enones

[reaction: see text] A new P-chiral phosphine bis(sulfonamide) ligand has been developed that allows the Cu-catalyzed enantioselective conjugate addition of Et(2)Zn to acyclic aliphatic enones. The reactions proceed with excellent levels of enantioselectivity (90-95% ee) with a range of enone substrates, involve the use of only 1.2 equiv of Et(2)Zn, and give best results at ambient temperature.     

New silica-immobilized chiral amino alcohol for the enantioselective addition of diethylzinc to benzaldehyde

[reaction: see text] A readily available chiral amino alcohol has been immobilized on silica by sol-gel synthesis and grafting. The solid prepared according to the latter method led to the best enantioselectivity (77% ee) described for the asymmetric addition of diethylzinc to benzaldehyde using inorganic solids.     

Enantioselective addition of diethylzinc to benzaldehyde catalysed by chiral, bridged resorcinarenes: a stereoselectivity model based on chirality transfer

The enantioselective addition of diethylzinc to benzaldehyde catalysed by a range of chiral bridged resorcinarenes has been studied, and the results used as a means of probing cooperative effects in the resorcinarene bowl. A structure-activity relationship has emerged in which bridged resorcinarenes with little available room in the bowl (e.g., 3b, 3c) favour R-enantioselectivity in the product, while those promoting cooperative effects in the bowl via coordination sites in the bridge (3e) or strong donor protecting groups (3j) favour S-enantioselectivity. A mechanistic hypothesis based on Noyori's model to account for these trends has been put forward in which stereoselectivity is dependent on two factors as the ratio of axially diastereomeric anti-zincoxazines as well as the exo or endo bias of active zinc. The model explains why ee's are never greater than around 50% and indicates asymmetric induction to be due to the axial chirality in the bowl as a result of chirality transfer from the bridge, rather than due to induction via the central chirality in the line of the bridge. As a result, the model stimulates some new fascinating possibilities in enzyme mimicry.     

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.     

Synthesis of non-racemic nitrogen-containing diselenides as efficient precursor catalysts in the diethylzinc addition to benzaldehyde

Short synthetic procedures for the preparation of new chiral, non-racemic nitrogen-containing diselenides are described. Only 1 mol% of these diselenides can very efficiently catalyze the diethylzinc addition to benzaldehydes affording the secondary alcohols in high enantiomeric purities (up to 97% ee).     

N-Substituent effects on the diethylzinc addition to benzaldehyde catalysed by bicyclic 1,4-amino alcohols

Chiral enantiopure bicyclic 1,4-amino alcohols were synthesised by a new methodology that provided a common precursor, which was easily N-functionalised with a wide variety of substituents. The final compounds were used as chiral ligands in a model study of the enantioselective addition of diethyl zinc to benzaldehyde, aimed at understanding the influence of the N-substituent on both the rate and stereoselectivity of the reaction. This set of experiments also provided interesting insight into the non-catalysed addition that occurred by employing commercially available Et₂Zn solutions.     

Titanium-promoted enantioselective diethylzinc addition to benzaldehyde in the presence of C2-symmetrical bis(camphorsulfonamide) ligands

The synthesis of several C₂-symmetric bissulfonamides is described, starting from camphorsulfonyl chloride and various aromatic as well as aliphatic diamines. These compounds have been used as ligands for titanium tetraisopropoxide promoted diethylzinc addition to benzaldehyde. The best enantiomeric excess obtained in this study was 67%. The stereochemical outcome of the reaction is highly influenced both by the structure of ligand and the reaction parameters.     

Synthesis of novel chiral oligopyridine derivative ligands for the enantioselective addition of diethylzinc to benzaldehyde

Several chiral dipyridine and dithiophene derived ligands have been prepared from readily available homochiral materials such as ethyl L-lactate and naproxene methyl ester, based on the dialkylation strategy using heterocyclic organometallic reagents. Each of these chiral ligands was used for the catalytic enantioselective addition of diethylzinc to benzaldehyde. The best result was obtained for 3: 70% ee was achieved. A plausible mechanism for this asymmetric induction is offered, based on X-ray crystallographic data.