The asymmetric phospha-Michael addition of dialkyl phosphite to α,β-unsaturated carbonyl compounds by using an azetidine-derived dinuclear zinc catalyst was described. The catalyst was proved to be general and efficient for a broad spectrum of enones and α,β-unsaturated N-acylpyrroles. A series of phosphonate-containing compounds were generated with excellent enantioselectivities (up to 99% ee) and chemical yields (up to 99%) under mild conditions without using additives. The products were obtained with more than 95% ee for 23 examples of α,β-unsaturated carbonyl compounds. A positive nonlinear effect was observed and the possible mechanism was proposed.

A general AzePhenol dinuclear zinc catalytic system has been successfully developed and introduced into the asymmetric addition of dimethylzinc and alkynylzinc to aromatic aldehydes. In this system, an azetidine derived chiral ligand has proven to be an effective enantioselective promoter. Under the optimal reaction conditions, a series of chiral 1-hydroxyethyl (up to 99% ee) and secondary propargylic alcohols (up to 96% ee) were generated with good yields and enantioselectivities. Additionally, this novel catalytic system showed good functional group compatibility. Remarkably, the substituent's electronic nature alone is not sufficient to allow for exclusive enantioselectivity, an additional substituent's location also had an effect. We proposed that the formation of a stable and structural rigid transition state by the chelation of ortho substituted benzaldehydes to the zinc atom was responsible for the observed higher enantioselectivity. The possible catalytic cycles of both transformations accounting for the stereoselectivity were described accordingly.

A direct asymmetric Friedel–Crafts (F–C) alkylation reaction between a wide range of indoles and ethyl 2-(4-methoxyphenylimino)acetate catalyzed by Trost’s dinuclear complex is reported. A series of 3-indolylglycine derivatives were synthesized in enantioselectivity of up to >99% enantiomeric excess (ee) using 10 mol% catalyst loading under mild conditions. This atom economic reaction could be run on a gram scale without impacting its enantioselectivity. The absolute stereochemistry of catalytic products was determined by correlation with a known configuration compound. A possible mechanism was proposed for the asymmetric induction.

Optically active polycarbonates (PCs) are considered as candidates for new and valuable materials because of their well-defined chemical structures and special physical properties. Previous studies on asymmetric alternating copolymerization of cyclopentene oxide (CPO) and CO2 regarding chiral zinc catalysts provided poly(cyclopentene carbonate) (PCPC) with moderate enantioselectivity, and thus, the development of highly efficient catalysts for this enantioselective polymerization is highly desirable. This research work is enlightened by the DFT calculations. In this paper, we clearly describe the use of intramolecular dinuclear zinc–AzePhenol complex as a high performance catalyst for the asymmetric copolymerization of CPO and CO2, affording completely alternating PCPC under very mild conditions (1 atm CO2, 30 °C) in 98% yield with >99% enantioselectivity for (S,S)-configuration. The dinuclear catalyst is prepared in situ from the reaction of multidentate semiazecrown ether ligand and ZnEt2, followed by treatment with an alcohol additive. In addition, our previous studies indicated that this catalyst also showed excellent enantioselectivity in the asymmetric copolymerization of cyclohexene oxide (CHO) and CO2. In order to obtain more information on the mechanism of the catalytic copolymerization, the chemical structures of PCPC are characterized by 1H NMR and 13C NMR spectroscopy, and the nonlinear effect is also investigated in this copolymerization. A plausible catalytic cycle for the present reaction system is outlined. The reaction of chiral ligand with ZnEt2, followed by the ethyl group exchange with EtOH, affords the ethoxy-bridged dinuclear zinc complex. The copolymerization reaction is initiated by the insertion of CO2 into the Zn–OEt bond to give a carbonate–ester-bridged complex. The two zinc centers are situated sufficiently close to each other to allow a synergistic effect in the copolymerization, meaning that one zinc atom acts as Lewis acid to activate the epoxide, the other is responsible for carbonate propagation through the nucleophilic attack of carbonate ester at the back side of the cis-epoxide by a six-membered transition state. Furthermore, the dinuclear zinc structure of the catalyst remains intact throughout the catalytic copolymerization. The proposed mechanism implies that the intramolecular dinuclear zinc catalyst is very important for future research into the copolymerization of other epoxides with CO2.

A highly enantioselective Friedel–Crafts (F–C) alkylation of pyrrole with a wide range of simple nonchelating chalcone derivatives catalyzed by a chiral (Zn2EtL)n (L = (S,S)-1) complex has been developed. The catalyst (Zn2EtL)n complex was prepared in situ by reacting the chiral ligand (S,S)-1 with 2 equiv of diethylzinc. A series of β-pyrrole-substituted dihydrochalcones were usually formed mostly in excellent yields (up to 99%) and excellent enantioselectivity [up to 99% enantiomeric excess (ee)] by using 15 mol % catalyst loading under mild conditions. The absolute stereochemistry of the products was determined to be the S-configuration by X-ray crystallographic analysis of 13g. Meanwhile, a weak negative nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible mechanism was proposed to explain the origin of the asymmetric induction.

The diastereomeric aziridine carbinols are applied, respectively, as efficient chiral ligand in the catalysis of asymmetric arylation and sequential arylation-lactonization cascade. The two diastereomers, which are facilely synthesized from the same chiral source, function as pseudo enantiomers in arylation of aromatic aldehydes providing the different enantiomers of the diarylmethanols with almost the same excellent enantioselectivities. The arylation method is also carried out in tandem with lactonization process to afford a concise synthetic approach to both enantiomers of optically active 3-aryl phthalide.

A kinetic system correlating the enantioselectivity with a catalyst’s conformational equilibrium, as a theoretical basis for the evaluation, design, and prediction of chiral ligand, is described for the addition of diethylzinc to benzaldehyde, and more importantly, a quantitative relationship between the conformations and the enantioselectivity is derived from this catalytic asymmetric kinetic system, which interprets that the observed enantioselectivity is not a weighted average of the enantioselectivity of the individual conformers.

A mathematical expression for the enantioselectivity and thermodynamic factors is presented in the conformational equilibrium of a flexible chiral catalyst for the asymmetric addition of diethylzinc to aldehydes. The results show that the total enantioselectivity of the catalyzed reaction is not only governed by the free energy difference of two ground-state conformers, as well as the free energies of activation for the major enantiomeric product formed from each of the catalyst’s conformations, but also by the difference in the transition state energies of the formation of the (S)- and (R)-enantiomers from the individual conformers of the catalyst.

A new electronically deficient atropisomeric diphosphine ligand (S)-CF3O-BiPhep was synthesized from 1-bromo-3-(trifluoromethoxy)benzene in high yield. The key steps included oxidative coupling with anhydrous ferric chloride and optical resolution by (+)-DMTA. The ligand afforded high performance for Ir-catalyzed asymmetric hydrogenation of quinolines with ee up to 92% and TON up to 25,000. It was also successfully applied to the Pd-catalyzed asymmetric hydrogenation of simple indoles with ee up to 87% and Rh-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone with 97% ee.A new electronically deficient atropisomeric diphosphine ligand (S)-CF3O-BiPhep was synthesized from 1-bromo-3-(trifluoromethoxy)benzene in high yield. The key steps included oxidative coupling with anhydrous ferric chloride and optical resolution by (+)-DMTA. The ligand afforded high performance for Ir-catalyzed asymmetric hydrogenation of quinolines with ee up to 92% and TON up to 25,000. It was also successfully applied to the Pd-catalyzed asymmetric hydrogenation of simple indoles with ee up to 87% and Rh-catalyzed asymmetric 1,4-addition of phenylboronic acid to 2-cyclohexenone with 97% ee.

A pair of diastereomers 7 and 8 were easily synthesized in only two steps from a single common chiral source according to the concept of conformation design. The efficiency of these chiral ligands was evaluated by their application to the asymmetric addition of diethylzinc to aldehydes. This catalytic asymmetric process afforded the a most efficient access to the (R)- and (S)-enantiomers of a given secondary alcohol with similarly outstanding enantioselectivities and high yields. Our results also showed that the control of the desired conformer’s population by conformation design is a new and practical strategy for the rational and precise design of highly enantioselective chiral ligands for metal-catalyzed reactions. The mechanism and possible transition states for the catalytic asymmetric addition have been proposed on the basis of previous studies as well as the crystal structure of the chiral ligands 7 and 8.Diphenyl-(l-((1S)-phenylethyl)aziridin-(2R)-yl)-methanolC23H23NO[α]D20=-50.4 (c 0.660, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (S,2R)Diphenyl-(l-((1S)-phenylethyl)aziridin-(2S)-yl)-methanolC23H23NO[α]D20=-49.0 (c 0.502, CHCl3)Source of chirality: (S)-phenylethylamineAbsolute configuration: (S,2S)

Asymmetric addition of dimethylzinc to a wide variety of aromatic aldehydes is described in the presence of a catalytic amount of chiral β-amino alcohol [(2S)-1-ferrocenyl- methylaziridin-2-yl(diphenyl)methanol], and a reaction enantioselectivity of up to 97.5% ee was achieved in this transformation in the absence of additional metals such as Ti or Ni. The results showed that this particular addition reaction, characterized by the lower reactivity of dimethylzinc with aldehydes, was more sensitive to structural variations in substrate aldehydes than the corresponding diethylzinc addition. A possible transition state for the catalytic asymmetric addition has been proposed on the basis of previous studies.(S)-1-m-Phenoxyphenyl-1-ethanolC14H14O2[α]D20=-28.0 (c 0.26, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(S)-1-[3,4-(Methylenedioxy)phenyl]-1-ethanolC9H10O3[α]D20=-42.0 (c 0.61, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(S)-1-p-Dimethylaminophenyl-1-ethanolC10H15NO[α]D20=-8.9 (c 0.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Chiral azetidino amino alcohol ligands bearing an additional stereogenic center were readily prepared and used as catalysts for the asymmetric addition of alkynylzinc to aromatic aldehydes with enantioselectivities of up to 87% ee. The relationship between the reaction enantioselectivity and the structure of the chiral ligands was also evaluated in this reaction. The experimental results showed that the enantioselectivity level of the reaction was greatly influenced by the second stereogenic center attached to azetidine ring, but the stereochemical sense was only determined by the configuration of the azetidine ring. A possible transition structure for the catalytic asymmetric addition was also proposed.Diphenyl-(l-((1R)-phenylethyl)azetidin-(2S)-yl)-methanolC24H25NO[α]D20=+63.6 (c 1.00, CHCl3)Source of chirality: (R)-phenylethylamineAbsolute configuration: (R,2S)Diphenyl-(l-((1R)-phenylethyl)azetidin-(2R)-yl)-methanolC24H25NO[α]D20=+22.4 (c 1.00, CHCl3)Source of chirality: (R)-phenylethylamineAbsolute configuration: (R,2R)

The copper-catalyzed enantioselective 1,4-conjugate addition of diethylzinc to chalcones was investigated in the presence of a catalytic amount of N,P-ferrocenyl ligands with central and planar chirality under mild conditions (0 °C→rt). It was found that chalcones with ortho-substituents (from ortho-substituted benzaldehydes and acetophenone/substituted acetophenones) led to a dramatic improvement in the enantioselectivities. The (R)- and (S)-antipodes of the addition reaction were obtained with up to 92% ee after this transformation.(+)-3-(3-Chlorophenyl)-1-phenyl-1-pentanoneC17H17ClOEe = 46%[α]D20=+39.3(c0.23,CHCl3)(−)-3-(2-Chlorophenyl)-1-phenyl-1-pentanoneC17H17ClOEe = 92%[α]D20=-33.8(c0.13,CHCl3)(−)-1-(4-Chlorophenyl)-3-(2-chlorophenyl)-1-pentanoneC17H16Cl2OEe = 85%[α]D20=-28.6(c0.56,CHCl3)(+)-3-(2-Chlorophenyl)-1-(4-methoxyphenyl)-1-pentanoneC18H19ClO2Ee = 81%[α]D20=+21.5(c0.53,CHCl3)(−)-3-(2-Methoxyphenyl)-1-phenyl-1-pentanoneC18H20O2Ee = 88%[α]D20=-28.7(c0.72,CHCl3)(+)-1-(4-Chlorophenyl)-3-(2-methoxyphenyl)-1-pentanoneC18H19ClO2Ee = 87%[α]D20=+18.0(c0.93,CHCl3)(−)-3-(2-Methoxyphenyl)-1-(4-nitrophenyl)-1-pentanoneC18H19NO4Ee = 82%[α]D20=-11.8(c0.71,CHCl3)(−)-1-Ferrocenyl-3-(2-methoxyphenyl)-1-pentanoneC22H24FeO2Ee = 92%[α]D20=-54.4(c0.45,CHCl3)(−)-3-(2-Bromophenyl)-1-ferrocenyl-1-pentanoneC21H21BrFeOEe = 91%[α]D20=-84.1(c0.24,CHCl3)(−)-1-Ferrocenyl-3-(2-methylphenyl)-1-pentanoneC22H24FeOEe = 20%[α]D20=-2.7(c0.41,CHCl3)

The direct strong steric interaction between substrate substituents and ligand substituents was first discovered in asymmetric addition of diethylzinc to aldehydes catalyzed by sterically congested ferrocenyl aziridino alcohol derivatives. In addition, this nonbonded steric repulsion influenced significantly enantioselectivities of this reaction, and even led to inversion of the absolute configuration. This fact was further confirmed by the theoretical calculations and the design of a new chiral ferrocenyl aziridino alcohol ligand. A plausible mechanism for this asymmetric reaction was also proposed.Methyl (2S,3S)-N-ferrocenylmethyl-allo-l-threomine esterC16H21FeNO3[α]D20=-40.8 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3S)Methyl (2S,3R)-1-ferrocenylmethyl-3-methylaziridine-2-carboxylateC16H19FeNO2[α]D20=-86.6 (c 0.77, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)(2S,3R)-1-Ferrocenylmethyl-3-methylaziridin-2-yl(diphenyl)methanolC27H27FeNO[α]D20=-10.0 (c 0.46, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2S,3R)

A new type of chiral copper complexes of N,P-ferrocenyl ligands with central and planar chirality as efficient catalyst was applied to the enantioselective addition of diethylzinc to N-diphenylphosphinoylimines. The (R)- and (S)-enantiomers of the addition reaction were obtained for this transformation. In the presence of 6 mol % of bidentate ligand 1 and 12 mol % of Cu(OTf)2, the asymmetric addition process affords N-diphenylphosphinoylamides in up to 97% ee and 95% yields.

A series of novel chiral ferrocenyl aziridino alcohols 5a–i were conveniently synthesized from l-serine and ferrocenecarboxaldehyde. These compounds have been used as chiral catalysts in the asymmetric addition of diethylzinc to aldehydes and the effects of the ligand structures on the enantioselectivity was studied. Enantioselectivities up to 98.8% have been obtained.(S)-Methyl N-ferrocenylmethyl-l-serine esterC15H19FeNO3[α]D20=-32.6 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-ylmethanolC14H17FeNO[α]D20=-0.8 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(dimethyl)methanolC16H21FeNO[α]D20=-42.3 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(diethyl)methanolC18H25FeNO[α]D20=-35.4 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(di-n-propyl)methanolC20H29FeNO[α]D20=-28.4 (c 1.10, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(di-n-butyl)methanolC22H33FeNO[α]D20=-27.1 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(di-i-butyl)methanolC22H33FeNO[α]D20=-30.7 (c 1.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(di-n-pentyl)methanolC24H37FeNO[α]D20=-24.2 (c 1.0, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)(2S)-1-Ferrocenylmethylaziridin-2-yl(di-i-pentyl)methanolC24H37FeNO[α]D20=-23.6 (c 0.96, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)