A highly efficient and practical approach to chiral quaternary 3-aminooxindoles was developed via Et2Zn catalyzed diastereoselective addition of Grignard reagents to isaltin-derived N-tert-butanesulfinyl ketimines giving good to excellent yields and diastereoselectivities with broad substrates and reagent scopes promoted by zinc(II) chloride.

A highly efficient and practical approach to chiral quaternary 3-aminooxindoles was developed via Et2Zn catalyzed diastereoselective addition of Grignard reagents to isaltin-derived N-tert-butanesulfinyl ketimines giving good to excellent yields and diastereoselectivities with broad substrates and reagent scopes promoted by zinc(II) chloride.

Chemical sensors are powerful for the fast recognition of chiral compounds. However, the established sensing systems are less effective for chiral tertiary alcohols. The chiral tertiary alcohol group is an important structural unit in natural products and drug molecules, and its enantioselective recognition represents a significant and challenging task. In this paper, a novel type of chiral bisselenourea sensor was first synthesized and used as a strong hydrogen-bonding donor for highly efficient chiral recognition of a diverse range of tertiary alcohols. The obtained sharply split NMR signals are well-distinguishable with a large (up to 0.415 ppm) chemical shift nonequivalence. The NMR signal of the hydroxyl hydrogen atom was first employed for enantiomeric excess determination of tertiary alcohols, giving accurate results with <2% absolute errors. The 2D NOESY spectra and computational studies suggest that the geometrical differentiation of the formed diastereomeric complexes between the sensor and tertiary alcohols enables the chiral discrimination of the hydroxyl hydrogen signals of the tertiary alcohol in the 1H NMR spectrum.

A chiral thiophosphoroamide 4 derived from (1R,2R)-1,2-diaminocyclohexane is used as a highly effective chiral sensor for the chiral recognition of varied acids via ion-pairing and hydrogen-bonding interactions using 1H, 19F and 31P NMR.

•A highly efficient and versatile NMR chiral sensor was developed for rapid chiral discrimination and ee determination of a wide range of chiral compounds.•Using a simple one-step synthesized bisthiourea as the NMR chiral sensor can give distinguishable split signals for chiral compounds with a diverse range of structures and functional groups.•The NMR chiral sensing method is rapid, practical and simple to operate, which can be used as a general tool for chiral discrimination and ee determination of various chiral compounds.A simple one-step synthesized bisthiourea has been used as a highly efficient and versatile chiral sensor for rapid chiral discrimination and enantiomeric excess determination of a wide range of chiral compounds containing alcohol, sulfoxide, lactone, epoxide, amino alcohol, amide, β-chiral carboxylic acid and remote chiral carboxylic acid with the use of 1H NMR signals.

An efficient method for the catalytic asymmetric additions to aldehydes using organolithium reagents and titanium(IV) isopropoxide in the presence of commercially available and relatively inexpensive diol ligands, such as (S)-BINOL or d-TADDOL has been developed. Good to excellent yields (up to 92%) and enantioselectivities (up to 94%) of the corresponding secondary alcohol products can be obtained following a simple procedure at relatively mild reaction temperatures.(R)-1-Phenylpentan-1-olC11H16O[α]D25.3 = +32.3 (c 2.0, CHCl3), 92% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-p-Tolylpentan-1-olC12H18O[α]D29.4 = +15.9 (c 1.0, C6H6), 92% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(4-(Trifluoromethyl)phenyl)pentan-1-olC12H15F3O[α]D31.7 = +8.1 (c 1.0, CHCl3), 93% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(4-Fluorophenyl)pentan-1-olC11H15FO[α]D29.2 = +11.5 (c 1.0, CHCl3), 88% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(4-Chlorophenyl)pentan-1-olC11H15ClO[α]D28.5 = +17.4 (c 1.0, C6H6), 94% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(Naphthalen-2-yl)pentan-1-olC15H18O[α]D29.7 = +13.4 (c 1.0, CHCl3), 86% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(Thiophen-2-yl)pentan-1-olC9H14OS[α]D30.5 = +12.2 (c 1.0, CHCl3), 63% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R,E)-1-Phenylhept-1-en-3-olC13H18O[α]D29.8 = −1.0 (c 1.0, CHCl3), 67% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-Cyclohexylpentan-1-olC11H22O[α]D24.1 = +6.3 (c 2.0, CHCl3), 68% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-PhenylethanolC8H10O[α]D25.6 = +42.1 (c 1.0, CHCl3), 82% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(4-Fluorophenyl)ethanolC8H9OF[α]D30.4 = +18.3 (c 1.0, CHCl3), 84% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-p-TolylethanolC9H12O[α]D26.2 = +35.0 (c 1.0, CHCl3), 81% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-Phenylheptan-1-olC13H20O[α]D30.2 = +25.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-(4-(Trifluoromethyl)phenyl)phenylmethanolC14H11F3O[α]D30.5 = −25.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

A highly effective 1H NMR method for determining the absolute configurations of various chiral α-hydroxyl acids and their derivatives has been developed with the use of bisthioureas (R)-CSA 1 and (S)-CSA 1 as chiral solvating agents in the presence of DABCO, giving distinguishable proton signals with up to 0.66 ppm chemical shift nonequivalence. Computational modeling studies were performed with Gaussian09 to reveal the chiral recognition mechanism.

The asymmetric addition reactions between varied nonaromatic aldehydes and diethylzinc catalyzed by chiral phosphoramide L1 and thiophosphorodiamide L4 were thoroughly investigated. Both ligands worked very well for α-branched aliphatic and α-branched α,β-unsaturated aldehydes. For α-nonbranched aliphatic aldehydes, L4 behaved much better than L1. For α-nonbranched α,β-unsaturated aldehydes, L4 showed high enantioselectivities and L1 only gave racemic alcohol products.

The catalytic asymmetric β-hydrogen transfer reduction of α-trifluoromethyl ketones using diethylzinc as the β-hydrogen donor was developed with the use of phosphinamide chiral ligand. The corresponding alcohol products were afforded in good yields with up to 73% ee. This method was successfully applied to the chemo- and enantioselective reduction of α-methyl/trifluoromethyl diketone, affording 88% yield and 70% ee of the fluorinated hydroxylketone product.(R)-2,2,2-Trifluoro-1-phenylethanoneC8H7F3O[α]D30.5 = −16.1 (c 0.50, CH2Cl2), 73% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-2,2,2-Trifluoro-1-(4-fluorophenyl)ethanolC8H6F4O[α]D29.5 = −16.5 (c 0.50, CH2Cl2), 61% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(4-Chlorophenyl)-2,2,2-trifluoroethanolC8H6ClF3O[α]D30.6 = −10.8 (c 0.50, CH2Cl2), 60% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-2,2,2-Trifluoro-1-p-tolylethanolC9H9F3O[α]D28.5 = −14.7 (c 0.50, CH2Cl2), 61% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-2,2,2-Trifluoro-1-(naphthalen-6-yl)ethanolC12H9F3O[α]D29.9 = −11.8 (c 1.00, CH2Cl2), 40% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-2-Chloro-2,2-difluoro-1-phenylethanolC8H7ClF2O[α]D30.1 = −9.1 (c 0.50, CHCl3), 71% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)(R)-1-(4-(2,2,2-Trifluoro-1-hydroxyethyl)phenyl)ethanoneC10H9F3O2[α]D30.2 = −13.1 (c 1.00, CH2Cl2), 70% eeSource of chirality: Asymmetric synthesisAbsolute configuration: (R)

Using a single chiral phosphoramide–Zn(II) complex as the catalyst, the asymmetric β-H transfer reduction of aromatic α-trifluoromethyl ketones and enantioselective addition of aromatic aldehydes with Et2Zn in one pot were successfully realized, affording the corresponding additive products of secondary alcohols in high yields (up to 99%) with excellent enantioselectivities (up to 98% ee) and the reduction products of α-trifluoromethyl alcohols in good to excellent yields with up to 77% ee.

•The difference of binding activity between CIT–BSA and CIT–HSA is first reported.•Use spectroscopic, thermodynamic, and NMR methods.•CIT exhibits higher binding affinity to BSA than to HSA.•The binding forces between CIT and SA have been investigated.•The complexation of CIT–SA induces the conformational change of SA.The binding interactions of citalopram (CIT), an efficient antidepressant, with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated by a series of spectroscopic methods including fluorescence, UV–vis absorption, circular dichroism (CD) and 1H nuclear magnetic resonance (1H NMR). The fluorescence quenching and UV–vis absorption studies reveal that CIT could form complexes with both HSA and BSA. The CIT–BSA complex exhibits higher binding affinity than CIT–HSA complex. The thermodynamic study further suggests that the interactions between CIT and SAs are mainly driven by hydrophobic forces and hydrogen bonds. The 1H NMR analysis indicates that the participation of different functional groups of CIT is unequal in the complexation of CIT–HSA and CIT–BSA. Site marker competitive experiments show that the interactions between CIT and SAs primarily locate at sub-domain II A (site I). The effects of CIT on the conformation of SAs are further analyzed via synchronous fluorescence, three-dimensional fluorescence and CD spectra techniques. The results prove that the presence of CIT decreases the α-helical content of both SAs and induces the slight unfolding of the polypeptides of protein. Additionally, the conformational change of BSA induced by CIT is larger than that of HSA.

In this work, we thoroughly investigated the effect of structural differentiation of a series of N,N-disubstituted chiral diamine ligands on the catalytic asymmetric aldol reactions between trifluoromethyl ketones and linear aliphatic ketones for the construction of chiral trifluoromethyl tertiary alcohols. A highly efficient primary–tertiary diamine ligand derived from (1R,2R)-1,2-diphenylethylenediamine was developed, which catalyzed the reactions with up to 99% yield and up to 94% enantioselectivity in the presence of p-toluenesulfonic acid (TsOH) using toluene as solvent.

In this study, a series of mono- and dialkylated chiral 1,2-amino phosphinamide ligands derived from modular (1R,2R)-diphenylethylenediamine were successfully applied in the chiral 1,2-amino phosphinamide-Zn(II) catalyzed asymmetric Henry reaction between benzaldehyde and nitromethane. Although the chiral N-monosubstituted and N,N-disubstituted 1,2-amino phosphinamide ligands gave the main alcohol products with opposite configurations, a validated quantitative structure–activity relationship (QSAR) mathematical model could be constructed between the physical Sterimol steric parameters of the N-substituents of the chiral ligands and the enantiomeric ratios of the alcohol products produced in the asymmetric Henry reaction. Since two sets of N-substituents are involved in the QSAR model construction, the key factor to succesfully construct a highly correlative and predictive model is to appropriately assign the N-substitutents. Ligand optimization based on the established QSAR model led to chiral 1,2-amino phosphinamide ligand 2r, which produced (R)-β-nitroalcohol in excellent yield and enantioselectivity (99% yield and 92% ee). In addition, a quantitative correlation could also be established with the use of subtractive Sterimol parameters.

We have developed a series of new chiral thiophosphorodiamide ligands derived from (1R,2R)-(+)-1,2-diphenylethylenediamine, which are the structural relatives of thioureas. An investigation into their catalytic properties in asymmetric additions of diethylzinc to aldehydes has shown that N,N,N′,N′-tetra-substituted chiral thiophosphorodiamides can give (R)-secondary alcohols with up to 98% yield and 98% ee, while N,N′-di-substituted chiral thiophosphorodiamides give (S)-secondary alcohols with up to 99% yield and 97% ee values. The enantioselectivity switch is highly efficient with a broad substrate scope. We have also proposed hypothetical reaction pathways, which result in an enantioselectivity switch.(1R,2R)-N-Phthaloyl-1,2-diphenylethylenediamineC22H18N2O2[α]D31=+80.5 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N,N-Dimethyl-N′-phthaloyl-1,2-diphenylethylenediamineC24H22N2O2[α]D31=-89.5 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N,N-Diethyl-N′-phthaloyl-1,2-diphenylethylenediamineC26H26N2O2[α]D31=-213.0 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)2-[(1R,2R)-1,2-Diphenyl-2-(pyrrolidin-1-yl)ethyl]-2,3-dihydro-1H-isoindole-1,3-dioneC26H24N2O2[α]D31=-111.1 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)2-[(1R,2R)-1,2-Diphenyl-2-(piperidin-1-yl)ethyl]-2,3-dihydro-1H-isoindole-1,3-dioneC27H26N2O2[α]D31=-110.9 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Ethyl-N′-phthaloyl-1,2-diphenylethylenediamineC24H22N2O2[α]D31=+32.2 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Isopropyl-N′-phthaloyl-1,2-diphenylethylenediamineC25H24N2O2[α]D31=+16.5 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Pentyl-N′-phthaloyl-1,2-diphenyl ethylenediamineC27H28N2O2[α]D31=+19.0 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Ethyl-N-methyl-N′-phthaloyl-1,2-diphenylethylenediamineC25H24N2O2[α]D31=-135.5 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Isopropyl-N-methyl-N′-phthaloyl-1,2-diphenylethylenediamineC26H26N2O2[α]D31=-104.7 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Pentyl-N-methyl-N′-phthaloyl-1,2-diphenylethylenediamineC28H30N2O2[α]D31=+107.1 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Acetyl-N′-phthaloyl-1,2-diphenylethylenediamineC24H20N2O3[α]D31=+9.9 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Boc-N′-phthaloyl-1,2-diphenylethylenediamineC27H26N2O4[α]D31=-29.2 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-Cbz-N′-phthaloyl-1,2-diphenylethylenediamineC30H24N2O4[α]D31=+23.8 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-2-(Dimethylamino)-1,2-diphenylethyl]({[(1R,2R)-2-(dimethylamino)-1,2-diphenylethyl]amino}(phenyl)thiophosphoryl)amineC38H43N4PS[α]D31=+141.0 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-2-(Diethylamino)-1,2-diphenylethyl]({[(1R,2R)-2-(diethylamino)-1,2-diphenylethyl]amino}(phenyl)thiophosphoryl)amineC42H51N4PS[α]D31=+69.7 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-1,2-Diphenyl-2-(pyrrolidin-1-yl)ethyl]({[(1R,2R)-1,2-diphenyl-2-(pyrrolidin-1-yl)ethyl]amino}(phenyl)thiophosphoryl)amineC42H47N4[α]D31=+67.1 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-1,2-Diphenyl-2-(piperidin-1-yl)ethyl]({[(1R,2R)-1,2-diphenyl-2-(piperidin-1-yl)ethyl]amino}(phenyl)thiophosphoryl)amineC44H51N4PS[α]D31=+118.4 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-2-[Ethyl(methyl)amino]-1,2-diphenylethyl]({[(1R,2R)-2-[ethyl(methyl)amino]-1,2-diphenylethyl]amino}(phenyl)thiophosphoryl)amineC40H47N4PS[α]D31=+140.2 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-2-[Methyl(propan-2-yl)amino]-1,2-diphenylethyl]({[(1R,2R)-2-[methyl(propan-2-yl)amino]-1,2-diphenylethyl]amino}(phenyl)thiophosphoryl)amineC42H51N4PS[α]D31=+140.2 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)[(1R,2R)-2-[Methyl(pentyl)amino]-1,2-diphenylethyl]({[(1R,2R)-2-[methyl(pentyl)amino]-1,2-diphenylethyl]amino}(phenyl)thiophosphoryl)amineC46H59N4PS[α]D31=+104.6 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)N-[(1R,2R)-2-[({[(1R,2R)-2-Acetamido-1,2-diphenylethyl]amino}(phenyl)thiophosphoryl)amino]-1,2-diphenylethyl]acetamideC38H39O2N4PS[α]D31=+65.0 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)tert-Butyl N-[(1R,2R)-2-[({[(1R,2R)-2-{[(tert-butoxy)carbonyl]amino}-1,2-diphenyl ethyl]amino}(phenyl)thiophosphoryl)amino]-1,2-diphenylethyl]carbamateC44H51O4N4PS[α]D31=+30.8 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)Benzyl N-[(1R,2R)-2-[({[(1R,2R)-2-{[(benzyloxy)carbonyl]amino}-1,2-diphenyl ethyl]amino}(phenyl)thiophosphoryl)amino]-1,2-diphenylethyl]carbamateC50H47O4N4PS[α]D31=+28.8 (c 1.00, CH2Cl2)Source of chirality: (1R,2R)-(+)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)

The interactions between erlotinib (ET) and bovine serum albumin (BSA) in the absence and presence of Cu(II) and Fe(III) in aqueous solution were investigated by using fluorescence, circular dichroism and three-dimensional (3D) fluorescence spectroscopic methods under simulative physiological conditions. Erlotinib effectively quenched the intrinsic fluorescence of BSA with slight redshifts in the absence and presence of Cu(II) and Fe(III). Cu(II) decreased the binding affinity and reduced the binding sites of erlotinib to BSA, while Fe(III) increased the binding affinity and binding sites of erlotinib to BSA. The negative values of ΔH and ΔS illustrate that the binding is mainly driven by the hydrogen bond and van der Waals force. The conformation of BSA was changed through ET binding in the presence of Cu(II) and Fe(III), which was revealed by circular dichroism, synchronous fluorescence and 3D fluorescence spectroscopic methods. The results indicate that the binding capability of erlotinib to BSA is affected by the types of metal ions.Graphical abstractHighlights► Interaction of erlotinib (ET) with BSA in the presence of Cu(II) and Fe(III) was studied. ► Using various spectroscopic methods such as UV, CD, fluorescence and three-dimensional (3D) fluorescence. ► Effects of metal ions on the binding activity of ET to BSA have not been reported. ► Ternary system Cu(II)/Fe(III)–ET–BSA induced the conformational change of BSA.

Our investigation has shown that achiral quaternary ammonium salt has a significant synergistic effect on the asymmetric additions of diethylzinc to aldehydes catalyzed by chiral phosphoramide–Zn(II) complex. The addition of 10 mol % NBu4X can dramatically reduce the loading amount of chiral ligand without sacrificing the excellent reactivity and enantioselectivity of the asymmetric reaction.

A simple chiral bisthiourea has been used as a highly effective and practical chemical solvating agent (CSA) for diverse α-carboxylic acids in the presence of DMAP. Excellent enantiodiscrimination based on well-resolved α-H NMR signals of the enantiomers of carboxylic acids can be obtained without interference from the chiral bisthiourea and DMAP. To check the practicality of the chiral bisthiourea/DMAP for enantiomeric determination, the ee values of mandelic acid (MA) samples over a wide ee range were determined by integration of the α-H signal of MA in 1H NMR. A discrimination mechanism is proposed, that the formation of two diasteromeric ternary complexes between the chiral bisthiourea and two in situ formed enantiomeric carboxylate-DMAPH+ ion pairs discriminates the enantiomers of carboxylic acids. Computational modeling studies show that the chemical shift value of α-H of (S)-MA is greater than that of (R)-MA in ternary complexes, which is consistent with experimental observation. 1D and 2D NOESY spectra demonstrate the intermolecular noncovalent interactions between the protons on the aromatic rings of chiral bisthiourea and α-H of the enantiomers of racemic α-methoxy phenylacetic acids in the complexes.

A mild, efficient, and transition-metal-free method for nucleophilic addition of arylacetylenes to diverse aromatic ketones, using catalytic amount of tetrabutylammonium chloride as a promoter and solid KOH as a base in THF, was developed to afford aromatic tertiary propargylic alcohols with high and excellent yields. Aliphatic ketones also gave satisfactory results.

Using the asymmetric addition reaction of diethylzinc with benzylaldehyde as a model, we have demonstrated that excellent correlations exist between steric reference parameters (Charton and Sterimol values) for appropriate sets of substituents present on chiral 1,2-amino-phosphoramide ligands and the enantiomeric ratios of alcohol products produced in this process.

On the basis of the investigation of the combinational effect of quaternary ammonium salts and organic bases, an added-metal-free catalytic system for nucleophilic addition reactions of a variety of Grignard reagents to diverse ketones in THF solvent has been developed to produce tertiary alcohols in good to excellent yields. By using tetrabutylammonium chloride (NBu4Cl) as a catalyst and diglyme (DGDE) as an additive, this system strongly enhances the efficiency of addition at the expense of enolization and reduction. NBu4Cl should help to shift the Schlenk equilibrium of Grignard reagents to the side of dimeric Grignard reagents to favor the additions of Grignard reagents to ketones via a favored six-membered transition state to form the desired tertiary alcohols, and DGDE should increase the nucleophilic reactivities of Grignard reagents by coordination. This catalytic system has been applied in the efficient synthesis of Citalopram, an effective U.S. FDA-approved antidepressant, and a recyclable version of this catalytic synthesis has also been devised.