A chiral double-chain surfactant-type ligand was designed and synthesized. The rhodium catalyst formed from the ligand can self-assemble into chiral vesicular aggregates in water, which was applied to the ATH of a broad range of aromatic ketoesters in neat water and gave up to 99% yield and 99% ee. In addition, this double-chain surfactant-type catalyst could also be applied to the dynamic kinetic resolution (DKR) of bicyclic β-ketoesters in water.

A series of amphiphilic ligands were designed and synthesized. The rhodium complexes with the ligands were applied to the asymmetric transfer hydrogenation of broad range of long-chained aliphatic ketoesters in neat water. Quantitative conversion and excellent enantioselectivity (up to 99% ee) was observed for α-, β-, γ-, δ- and ε-ketoesters as well as for α- and β-acyloxyketone using chiral surfactant-type catalyst 2. The CH/π interaction and the strong hydrophobic interaction of long aliphatic chains between the catalyst and the substrate in the metallomicelle core played a key role in the catalytic transition state. Synergistic effects between the metal-catalyzed site and the hydrophobic microenvironment of the core in the micelle contributed to high stereoselectivity.

Water-soluble ligands (R,R)-2 were successfully prepared, in which the bis-meta-sulphonated ligand was definitely detected as the major product. The corresponding transition-metal complexes containing the ligands displayed excellent catalytic performance in asymmetric transfer hydrogenation (ATH) of aromatic ketones. Especially, the aromatic ketones with a bromine group in the α position could be smoothly reduced to the expected alcohol, keeping the bromine group intact with excellent enantioselectivities (up to 96% ee). The catalyst could be reused at least 21 times without erosion of the enantioselectivity in high conversion. Moreover, it was found that cationic surfactant and proper pH values were necessary for the maintenance of high reactivity.

A novel chiral surfactant-type catalyst is developed. Micelles formed in water by association of the catalysts themselves, and this was confirmed by TEM analyses. Asymmetric transfer hydrogenation of aliphatic ketones catalyzed by the chiral metallomicellar catalyst gave good to excellent conversions and remarkable stereoselectivities (up to 95% ee). Synergistic effects between the metal-catalyzed center and the hydrophobic microenvironment of the core in the metallomicelle led to high enantioselectivities.

A new flexible C1-symmetric tridentate ligand (S)-N-(2-(tert-butylsulfinyl)benzyl)-1-(pyridin-2-yl)methanamine sulfoxide (L1) was successfully prepared and utilized as a chiral ligand for Ir(I)-catalyzed ATH (asymmetric transfer hydrogenation) reactions. Without any cooperation of other chiral center, encouraging ee and conversion values have been achieved, which provide us a better understanding on these types of ligands and a new strategy to develop new high-efficiency chiral catalysts for asymmetric reaction.

As an efficient catalyst for asymmetric transfer hydrogenation reaction (ATH reaction) of α,β-unsaturated ketones, Rh-Cp∗–TsDPEN (Cp∗ = 1,2,3,4,5-pentamethylcyclopenta-1,3-diene, TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenyl- ethylenediamine) shows high chemoselectivity on CO and CC reduction. In our method, both CO and CC bonds in a variety of chromenone derivatives were reduced efficiently in aqueous media, resulting in at least 98% ee and up to 99% yields in a convenient way without further purification. The product was a useful intermediate for deriving chiral chroman-4-amine, which was reported as an effective agent against hypotension and inflammatory pain by inhibiting human bradykinin B1 receptor.

A chiral titanium complex, formed in situ from Ti(Oi-Pr)4, (S,S)-N,N′-dibenzyl tartramide and water was found to serve as an efficient catalyst for the asymmetric oxidations of 1H-benzimidazolyl pyridinylmethyl sulfides with cumene hydroperoxide (CHP) in the absence of a base. Several proton pump inhibitors (PPIs), such as esomeprazole, lansoprazole, rabeprazole and pantoprazole were obtained in high yield (up to 92%) and excellent enantiomeric excess (up to 96%).(S)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzo[d]imidazole (esomeprazole)C17H19N3O3S95% ee[α]D25=-152.0 (c 0.1, CHCl3)Absolute configuration: (S)Source of chirality: (S,S)-N,N′-Dibenzyl tartramide(S)-2-([3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole (lansoprazole)C16H14F3N3O2S94% ee[α]D25=-199.7 (c 1.0, acetone)Absolute configuration: (S)Source of chirality: (S,S)-N,N′-Dibenzyl tartramide(S)-2-([4-(3-Methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl)-1H-benzo[d]imidazole (rabeprazole)C18H21N3O3S94% ee[α]D25=-135.0 (c 0.05, CHCl3)Absolute configuration: (S)Source of chirality: (S,S)-N,N′-Dibenzyl tartramide(S)-6-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole (pantoprazole)C16H15F2N3O4S96% ee[α]D25=-95.5 (c 0.3, MeOH)Absolute configuration: (S)Source of chirality: (S,S)-N,N′-Dibenzyl tartramide

A novel water-soluble cationic N-monosulfonated chiral diamine ligand diguanidinium 1c was easily prepared from (R,R)-DPEN and its rhodium complex and was successfully applied in the asymmetric transfer hydrogenation of prochiral ketones and imines in water by using sodium formate and formic acid as co-hydrogen donors. Various substrates were reduced with high yields and good to excellent enantioselectivities (up to >99% ee).(1R,2R)-1,2-Bis(3-nitrophenyl)ethylenediamineC14H14N4O4Ee >99%[α]D25=+109.3 (c 1.0, CH3OH)Source of chirality: (1R,2R)-1,2-diphenylethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-(p-Toluenesulfonyl)-1,2-bis(3-nitrophenyl)ethylenediamineC21H20N4O6SEe >99%[α]D28=+32.9 (c 0.98, CH3OH)Source of chirality: (1R,2R)-1,2-bis(3-nitrophenyl)ethylenediamineAbsolute configuration: (1R,2R)(1R,2R)-N-(p-Toluenesulfonyl)-N′-tert-butyloxycarbonyl-1,2-bis(3-nitrophenyl)-ethylenediamineC26H28N4O8SEe >99%[α]D20=+22.4 (c 0.51, CH3OH)Source of chirality: N-((1R,2R)-2-amino-1,2-bis(3-nitrophenyl)-ethyl)-4-methylbenzenesulfonamideAbsolute configuration: (1R,2R)(1R,2R)-N-(p-Toluenesulfonyl)-N′-tert-butyloxycarbonyl-1,2-bis(3-aminophenyl)ethylenediamineC26H32N4O4SEe >99%[α]D20=+47.1 (c 0.54, CH3OH)Source of chirality: tert-butyl-(1R,2R)-2-(4-methylphenylsulfonamido)-1,2-bis(3-nitrophenyl)ethylcarbamateAbsolute configuration: (1R,2R)(1R,2R)-N-(p-Toluenesulfonyl)-N′-tert-butyloxycarbonyl-1,2-bis(3-N,N′-di-tert-butyloxycarbonylguanidinophenyl)ethylenediamineC48H68N8O12SEe >99%[α]D20=+41.7 (c 0.7, CH3OH)Source of chirality: tert-butyl-(1R,2R)-1,2-bis(3-aminophenyl)-2-(4-methylphenylsulfonamido)ethylcarbamateAbsolute configuration: (1R,2R)(1R,2R)-N-(p-Toluenesulfonyl)-1,2-bis(3-guanidinophenyl)-1,2-ethylenediamine trifluoroacetic acid saltC29H31F9N8O8SEe >99%[α]D20=+19.8 (c 0.64, CH3OH)Source of chirality: N-(p-toluenesulfonyl)-N-tert-butyloxycarbonyl-1,2-bis(3-N,N′-di-tert-butyloxycarbonylguanidinophenyl)ethylenediamineAbsolute configuration: (1R,2R)

Asymmetric transfer hydrogenation of β,β-disubstituted nitroalkenes catalyzed by a chiral diamine–rhodium complex in combination with HCO2Na–HCO2H as a hydrogen source in water was successfully realized with high reactivity, excellent chemoselectivity and good enantioselectivity. The metal precursor and pH value of the aqueous solution have a large influence on the reactivity and chemoselectivity. The substituents on the benzene rings and the sulfonyl groups of TsDPEN have significant effects on the enantioselectivity. This catalytic asymmetric transformation is one of the most practical pathways to obtain optically active nitroalkanes.(1R,2R)-N-(p-Toluenesulfonyl)-1,2-bis(3-nitrophenyl)-1,2-ethylenediamineC21H20N4O6S[α]D28=+32.9 (c 0.98, MeOH)Source of chirality: (1R,2R)-1,2-bis(3-nitrophenyl)-1,2-ethylenediamineAbsolute configuration: (R,R)(1R,2R)-N-(3,5-Ditrifluoromethylbenzylsulfonyl)-1,2-bis(3-nitrophenyl)-1,2-ethylenediamineC22H16F6N4O6S[α]D20=+66.8 (c 0.5, MeOH)Source of chirality: (1R,2R)-1,2-bis(3-nitrophenyl)-1,2-ethylenediamineAbsolute configuration: (R,R)(1R,2R)-N-(3,5-Ditrifluoromethylbenzylsulfonyl)-1,2-bis(2-nitrophenyl)-1,2-ethylenediamineC22H16F6N4O6S[α]D20=-77.1 (c 0.5, MeOH)Source of chirality: (1R,2R)-1,2-bis(2-nitrophenyl)-1,2-ethylenediamineAbsolute configuration: (R,R)(1R,2R)-N-(3,5-Ditrifluoromethylbenzylsulfonyl)-1,2-bis(4-nitrophenyl)-1,2-ethylenediamineC22H16F6N4O6S[α]D20=+5.2 (c 0.5, MeOH)Source of chirality: (1R,2R)-1,2-bis(4-nitrophenyl)-1,2-ethylenediamineAbsolute configuration: (R,R)(1R,2R)-N-(3,5-Ditrifluoromethylbenzylsulfonyl)-1,2-bis(4-methoxyphenyl)-1,2-ethylenediamineC24H22F6N2O4S[α]D20=+129.2 (c 0.5, MeOH)Source of chirality: (1R,2R)-1,2-bis(4-methoxyphenyl)-1,2-ethylenediamineAbsolute configuration: (R,R)(1R,2R)-N-Trifluoromethanesulfonyl-1,2-bis(3-nitrophenyl)-1,2-ethylenediamineC15H13F3N4O6S[α]D20=+60.7 (c 0.5, MeOH)Source of chirality: (1R,2R)-1,2-bis(3-nitrophenyl)-1,2-ethylenediamineAbsolute configuration: (R,R)(S)-1,2-Dimethoxy-4-(1-nitropropan-2-yl)benzeneC11H15NO4Ee = 86%[α]D20=-52.0 (c 0.60, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

A library consisting of a series of O,O′-diaryzoyl-L-(-)-tartaric acids (2) was designed and synthesized. The substituent on the aromatic ring of 2 significantly affects the diastereomeric excess and efficiency of the resolution of racemic albuterol (1). Excellent resolving reagent 2a was selected for the resolution of rac-1 via the parallel approach. However, a family of three resolving reagents failed to improve the resolution efficiency of rac-1.

The highly enantioselective Michael addition of malononitrile to acyclic and cyclic α,β-unsaturated ketones has been developed. The Michael reaction catalyzed by a primary amine derived from quinidine proceeded smoothly and provided the desired adducts with excellent enantioselectivities (83–97% ee).

A novel water-soluble rhodium(III)catalyst prepared from o,o′-aminated N-tosyl-1,2-diphenylethylenediamine(S,S)-3 and [Cp*RhCl2]2, which was efficient for the asymmetric transfer hydrogenation of ketones and imines in neat water with high reactivity and excellent enantioselectivity, has been developed.

The first highly regio-, chemo-, diastereo- and enantioselective direct vinylogous Michael addition of α,α-dicyanoolefins to α,β-unsaturated aldehydes is described, employing readily available chiral α,α-diarylprolinol salts as iminium organocatalysts.

The first asymmetric transfer hydrogenation of cyclic imines and iminiums in water was successfully performed in high yields and enantioselectivities with sodium formate as the hydrogen source and CTAB as an additive catalyzed by a water-soluble and recyclable ruthenium(II) complex of the ligand (R,R)-2.

Hydrophobic Fréchet-type dendritic chiral 1,2-diaminocyclohexane–Rh(III) complexes have been applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen source. The catalysts were found to be finely dissolved in the liquid substrates in the aqueous mixture and exhibited high catalytic activity and enantioselectivity (52–97% ee). The catalytic loading could be decreased to 0.01 mol% and good conversion was still obtained with excellent enantioselectivity. Moreover, the catalyst could be easily precipitated from the mixture by adding hexane and reused several times without affecting the high enantioselectivity.

Herein we present a new example of coordination-mediated resolution of racemic acids by a chiral acid. The reaction of copper(II) acetate monohydrate, optically pure O,O′-dibenzoyltartaric acid (DBTA) and racemic α-bromo-2-chlorophenylacetic acid (HL1) in acetonitrile solution afforded a binuclear copper(II) complex with D-DBTA dianion, α-bromo-2-chlorophenylacetate and acetate as ligands. After decomposition of the complex with acid, the optically active acid ((R)–HL1) was obtained. Similarly, α-bromo-2-fluorophenylacetic acid (HL2), α-bromo-2-bromophenylacetic acid (HL3), α-chloro-2-chlorophenylacetic acid (HL4), α-chloro-2-fluorophenylacetic acid (HL5), α-bromophenylacetic acid (HL6), α-bromo-4-chlorophenylacetic acid (HL7), 2-bromopropionic acid (HL8) and 2-chloropropionic acid (HL9) were resolved by the same method. Satisfactory results were obtained for HL2 to HL5. For HL6 and HL7, only racemic acids were obtained. For the two α-halo aliphatic acids (HL8 and HL9), poor enantioselectivity was obtained. It is more interesting that three acids (HL1, HL2 and HL3) could spontaneously racemize in acetonitrile solution, which resulted in crystallization-induced dynamic resolution (CIDR) with greater than 50% yield.

Tunable dendritic N-mono-sulfonyl ligands have been designed and synthesized via direct N-mono-sulfonylization of the chiral dendritic vicinal diamines and their ruthenium complexes demonstrated high catalytic and recyclable activities with comparable enantioselectivities to Noyori–Ikariya’s TsDPEN-Ru in the asymmetric transfer hydrogenation of an extended range of substrates, such as ketones, keto esters, and olefins.(1R,2R)-N-[2-Amino-1,2-bis-(4-methoxyphenyl)ethyl]-4-methylbenzenesulfonamideC23H26N2O4S[α]D22=+121.8 (c 0.67, CHCl3)Source of chirality: (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1R,2R(1R,2R)-N-[2-Amino-1,2-bis-(4-benzyloxyphenyl)ethyl]-4-methylbenzenesulfonamideC35H34N2O4S[α]D22=+65.7 (c 0.55, CHCl3)Source of chirality: (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1R,2R(1R,2R)-N-{2-Amino-1,2-bis-[4-(3,5-bisbenzyloxybenzyloxy)phenyl]ethyl}-4-methylbenzenesulfonamideC63H58N2O8S[α]D22=+3.0 (c 1.2, CHCl3)Source of chirality: (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1R,2R(1R,2R)-N-{2-Amino-1,2-bis-[4-[3,5-bis(3,5-bisbenzyloxybenzyloxy)benzyloxy]phenyl]ethyl}-4-methylbenzenesulfonamideC119H106N2O16S[α]D22=+7.9 (c 1.2, CHCl3)Source of chirality: (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1R,2R(1R,2R)-N-{2-Amino-1,2-bis-[4-[3,5-bis[3,5-bis(3,5-bis-benzyloxybenzyloxy)benzyloxy]benzyloxy]phenyl]ethyl}-4-methylbenzenesulfonamideC231H202N2O32S[α]D22=+0.3 (c 2.24, CHCl3)Source of chirality: (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1R,2R(1S,2S)-N-{2-Amino-1,2-bis-[4-[3,5-bis(3,5-bisbenzyloxybenzyloxy)benzyloxy]phenyl]ethyl}-2,4,6-triethylbenzenesulfonamideC124H116N2O16S[α]D25=-16.7 (c 1.0, CHCl3)Source of chirality: (S,S)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1S,2S(1S,2S)-N-{2-Amino-1,2-bis-[4-[3,5-bis(3,5-bisbenzyloxybenzyloxy)benzyloxy]phenyl]ethyl}-2,4,6-triisopropylbenzenesulfonamideC127H122N2O16S[α]D25=-23.0 (c 3.0, CHCl3)Source of chirality: (S,S)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1S,2S(1S,2S)-N-2-Amino-1,2-bis-[4-[3,5-bis(3,5-bisbenzyloxybenzyloxy)benzyloxy]phenyl]ethyl naphthalene-1-sulfonamideC122H106N2O16S[α]D25=-44.6 (c 1.15, CHCl3)Source of chirality: (S,S)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamineAbsolute configuration: 1S,2S

An effective resolving agent, (2S,3S)-di-O-(p-toluoyl) tartaric acid (4), was screened using a ‘family’ approach to yield direct resolution of (R)-terbutaline (1) with high optical purity and yield. Molecular recognition was studied by X-ray crystallographic analyses of the single crystals of the pair of diastereomeric salts. The more-soluble salt formed a sheet supramolecular structure, and the less-soluble salt formed a columnar supramolecular structure by enantiodifferentiating self-assembly. The water molecule plays an important role during optical resolution, and makes the supramolecular structure of the less-soluble salt more thermodynamically stable than that of the more-soluble salt. Solvent system has little influence on the resolution.

The chiral spirobiindane ligand, 1,1′-spirobiindane-7,7′-diol has been resolved efficiently by inclusion complexation with commercially available N-benzylcinchonidinium chloride. The resolved complex was studied by X-ray crystallography in order to characterize the intermolecular interactions and recognition nature.Graphic(S)-(−)-1,1′-Spirobiindane-7,7′-diolC17H16O2E.e. >99%[α]D20=−38.8 (c 0.6, CHCl3)Source of chirality: resolutionAbsolute configuration: S

The synthesis of chiral diamine based dendritic ligands andtheir ruthenium complex catalysed asymmetric transfer hydrogenation isdescribed.

The highly enantioselective Michael addition of malononitrile to acyclic and cyclic α,β-unsaturated ketones has been developed. The Michael reaction catalyzed by a primary amine derived from quinidine proceeded smoothly and provided the desired adducts with excellent enantioselectivities (83–97% ee).