The synthesis of chiral tridentate ligands from l-proline and their application in the copper(II)-catalyzed enantioselective Henry reaction

A series of chiral tridentate ligands derived from readily available enantiopure l-proline were designed and synthesized. The ligands together with Cu(OAc)₂ were successfully used in asymmetric Henry reactions. Various structurally divergent aldehydes and nitromethane were converted into versatile β-nitro alcohols in MeOH at room temperature with very good yields (up to 85%) and enantioselectivities (up to 86%).     

Synthesis of novel chiral tetraaza ligands and their application in enantioselective transfer hydrogenation of ketones

Novel chiral tetraaza ligands(R)-N,N′-bis[2-(piperidin-1-yl)benzylidene]propane-l,2-diamine 6 and(S)-N-[2-(piperidin-l- yl)benzylidene]-3-{[2-(piperidin-1-yl)benzylidene]amino}-alanine sodium salt 7 have been synthesized and fully characterized by NMR,IR,MS and CD spectra.The catalytic property of the ligands was investigated in Ir-catalyzed enantioselective transfer hydrogenation of ketones.The corresponding optical active alcohols were obtained with high yields and moderate ees under mild reaction conditions.     

Synthesis of chiral hydantoin derivatives by homogeneous Pd-catalyzed asymmetric hydrogenation

5-Aryl substituted chiral hydantoin derivatives were synthesized via asymmetric hydrogenation of prochiral exocyclic alkenes using a Pd/BINAP catalyst. Moderate to good enantioselectivity were obtained (21–90% ee). A chiral Brönsted acid additive was found to be a key factor to obtain high enantioselectivity.     

Chiral terpene auxiliaries IV: new monoterpene PHOX ligands and their application in the catalytic asymmetric transfer hydrogenation of ketones

New PHOX ligands, derived in three steps from (1R,2S,3R,5R)-3-amino-apopinan-2-ol 1 and (1R,2R,3S,5R)-3-amino-pinan-2-ol 2 were applied as chiral ligands for the formation of ruthenium catalysts. The catalysts were used in asymmetric transfer hydrogenations of prochiral ketones producing the corresponding alcohols in moderate to high yields and enantioselectivity.     

Novel chiral tetraaza ligands: synthesis and application in asymmetric transfer hydrogenation of ketones

Novel chiral tetraaza ligands, N¹,N²-bis(2-(piperidin-1-yl)benzylidene)cyclohexane-1,2-diamine 1 and N¹,N²-bis(2-(piperidin-1-yl)benzyl)cyclohexane-1,2-diamine 2, have been synthesized and fully characterized by analytical and spectroscopic methods. The structure of (R,R)-1 has been established by X-ray crystallography. Asymmetric transfer hydrogenation of aromatic ketones with the catalysts prepared in situ from [IrHCl₂(COD)]₂ and the chiral tetraaza ligands in 2-propanol gave the corresponding optically active secondary alcohols in high conversions and good ees (up to 91%) under mild reaction conditions.     

Employing the structural diversity of nature: development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones

A library of novel dipeptide-analogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected alpha-amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [[RuCl(2)(p-cymene)](2)] and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2-propanol as the hydrogen donor. Excellent enantioselectivity of 1-phenylethanol (up to 98 % ee) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L-amino acids generated S-configured products, and catalysts based on D-amino acids favored the formation of the R-configured alcohol. The combination N-Boc-L-alanine and (R)-phenylglycinol (Boc-L-Ab) or its enantiomer (N-Boc-D-alanine and (S)-phenylglycinol, Boc-D-Aa) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee, was obtained.     

Synthesis and application of chiral phosphino-imidazoline ligands: Ir-catalyzed enantioselective hydrogenation

[reaction: see text] A series of chiral phosphino-imidazolines (PHIM ligands) 1a-j with different substituents at the stereogenic center, the nitrogen atom of the imidazoline ring, and at the phosphorus atom were synthesized. Iridium complexes derived from these ligands have been evaluated as catalysts for the enantioselective hydrogenation of unfunctionalized olefins. In several cases, higher enantiomeric excesses were observed than with analogous phosphino-oxazoline ligands.     

N-Benzyl-norephedrine derivatives as new,efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones

Significant catalytic activities (up to 600 h⁻¹ at 20°C) and enantiomeric excesses ranging from 56 to 89% for the asymmetric transfer hydrogenation of β-ketoesters, methoxyacetone and 2-acetylpyridine to the corresponding alcohols are achieved in the presence of catalytic combinations of [RuCl₂(η⁶-arene)]₂ and N-substituted derivatives of (1S,2R)-norephedrine such as N-benzyl-norephedrine and N-(4-biphenyl)methyl-norephedrine.     

2-Azanorbornyl alcohols: very efficient ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic ketones

2-Azanorbornyl-derived amino alcohols were prepared and evaluated as ligands in the Ru(II)-catalyzed asymmetric transfer hydrogenation of aromatic ketones. To improve selectivity and rate, the structure of the ligand was optimized. Acetophenone was reduced using 0.5 mol % catalyst in 40 min in 94% ee. This system was also able to reduce a wide range of aromatic ketones to the corresponding alcohols, while maintaining high enantioselectivities and yields. The effects of catalyst loading and the presence of cosolvents in the reaction vessel were examined, and a linearity study was also done.     

Highly enantioselective ruthenium-catalyzed reduction of ketones employing readily available Peptide ligands

Highly efficient and selective catalysts for the asymmetric reduction of aryl alkyl ketones under hydrogen-transfer conditions (2-propanol) were obtained by combining a novel class of pseudo-dipeptide ligands with [[RuCl(2)(p-cymene)](2)]. A library of 36 dipeptide-like ligands was prepared from N-Boc-protected alpha-amino acids and the enantiomers of 2-amino-1-phenylethanol and 1-amino-2-propanol. The catalyst library was evaluated with the reduction of acetophenone and excellent enantioselectivity of 1-phenylethanol was obtained with several of the novel catalysts. A ligand based on the combination of N-Boc-L-alanine and (S)-1-amino-2-propanol (ligand A-(S)-4) was found to be particular effective. When the situ formed ruthenium complex of this ligand was employed as the catalyst in the hydrogen-transfer reaction of various aryl alkyl ketones, the corresponding alcohol products were achieved in excellent enantioselectivity (up to 98 % ee).     

Highly enantioselective transfer hydrogenation of fluoroalkyl ketones

[Structure: see text] The asymmetric transfer hydrogenation of fluoroalkyl ketones mediated by [Ru(eta6-arene)((S,S)-R2NSO2DPEN)] catalysts using HCO2H-Et3N afforded the corresponding alcohols with high ee's and in excellent yields.     

Synthesis and application of chiral N-heterocyclic carbene-oxazoline ligands: iridium-catalyzed enantioselective hydrogenation

Two libraries of enantiomerically pure imidazolium salts bearing an oxazoline unit were synthesized. Deprotonation of the imidazolium salts and complexation of the resulting oxazoline-carbene ligands to iridium(I) was achieved in one step by mixing the imidazolium salts with NaOtBu and [(eta(4)-cod)IrCl](2) in THF at room temperature. The air-stable complexes were purified by flash chromatography. All complexes were analyzed by two-dimensional (2D) NMR methods and one compound from each family was characterized by X-ray structure analysis. The two libraries of iridium complexes were successfully tested in the asymmetric hydrogenation of unfunctionalized and functionalized olefins. Enantioselectivities of up to 90 % ee were obtained with trans-alpha-methylstilbene. Upon complexation of imidazolium salt 15 p with R(1) = phenyl, C-H bond activation of the phenyl ring gave rise to iridium(III) complex 17, which was fully characterized by NMR spectroscopy and X-ray structure analysis. Complex 17 proved to be catalytically inactive in the hydrogenation.     

Synthesis of a novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid and application to the asymmetric catalytic Biginelli reaction

A novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid was designed and synthesized based on highly regioselective cyclosulfitation of chiral 1,1,4,4-tetraphenylbutanetetraol. The asymmetric Biginelli reaction catalyzed by this newly synthesized chiral phosphoric acid was examined, and enantioselectivities up to 99% ee was obtained.     

Synthesis of threo- and erythro-configured trihydroxy open chain lipophilic ketones as possible anti-mycobacterial agents

A series of threo- and erythro-configured open-chain trihydroxy ketones was synthesized starting from l- and d-ascorbic acid respectively as the starting material, through the use of Grignard reactions for the requisite CC bond formations. The lipophilic ketones were screened against Mycobacteriumtuberculosis for anti-proliferative activity. The lipophilic ketones with tetradecyl alkyl side chains were found to be moderately active against cell proliferation.     

手性双胺双膦-铱体系催化芳香酮的高对映选择性氢转移氢化

在异丙醇溶液中,从[Ir(COD)Cl]2和C2-对称的手性双胺双膦配体原位制备了手性能-Ir(Ⅰ)配合物,并直接用于催化几种芳香酮的不对称氢转移氢化。结果表明,该配合物是异丙基苯基酮不对称转移氢化的优秀催化剂,当底物酮与催化剂的摩尔比(S/C)为1200:1时,在室温下反应4h后,得到相应的手性芳香醇的转化率和对映选择性分别高达98%和98%ee.     

Screening of chiral ferrocenyl amino alcohols as ligands for ruthenium-catalysed transfer hydrogenation of ketones

A variety of ferrocenyl amino alcohols possessing central chirality have been screened as ligands for ruthenium(II)-catalysed transfer hydrogenation of acetophenone using 2-propanol in the presence of KOH as the hydrogen source. Enantiomerically enriched 1-phenylethanol was obtained in high yield and 70% e.e. using ligand 9. This ligand was employed in the asymmetric reduction of different arylalkyl ketones and the corresponding alcohols were obtained in up to 80% e.e. A comparison of the catalytic properties of ferrocenyl amino alcohols and their phenyl analogues is discussed briefly.     

S-Substituted-2-mercaptobenzthiazolium-based chiral ionic liquids: efficient organocatalysts for enantioselective sodium borohydride reductions of prochiral ketones

Novel chiral ionic liquids having chirality in their cationic part have been synthesized for evaluation of their catalytic potential as organocatalysts in sodium borohydride reduction of prochiral ketones to yield optically active secondary alcohols. The chiral ionic liquids have been synthesized from the reaction of (?)-menthol or (?)-borneol, chloroacetic acid and S-methyl/benzyl-2-mercaptobenzthiazole. The synthesized chiral ionic liquids have been characterized by ¹H, ¹³C NMR and Mass spectrometry. Moderate to excellent enantiomeric excess (ee > 99%) has been obtained in asymmetric sodium borohydride reduction of prochiral ketones using these salts as chiral catalysts.     

Highly enantioselective transfer hydrogenation of alpha,beta-unsaturated ketones

We describe an efficient and highly enantioselective conjugate transfer hydrogenation of alpha,beta-unsaturated ketones that is catalyzed by a salt made from tert-butyl valinate and a recently introduced powerful chiral phosphoric acid catalyst (TRIP).     

New class of chiral ligands derived from isosorbide: first application in asymmetric transfer hydrogenation

A new class of β-amino alcohol and diamine ligands was prepared from isosorbide as a chiral renewable resource. The original wedge-shaped structure of isosorbide offers an interesting chiral pocket to promote the metal-catalyzed enantioselective reduction of ketones by transfer hydrogenation.     

New monoterpene-derived phosphinopyridine ligands and their application in the enantioselective iridium-catalyzed hydrogenation

Pyridine derivatives with a phosphine or phosphinite pendant (1-11) have been synthesized from (+)-α-pinene, (−)-isopinocampheol, and/or (+)-camphor via Kröhnke annulation or another annulation method as the key step for the construction of the pyridine nucleus. The iridium complex of 6 proved to catalyze hydrogenation of the prochiral unfunctionalized alkene 44 with 94% ee, whereas the complex of 2 was most efficient in the hydrogenation of the cinnamyl-type ester 45 (83% ee).