Synthesis of (R)-tembamide and (R)-aegeline via asymmetric transfer hydrogenation in water

The synthesis of (R)-tembamide and (R)-aegeline via asymmetric transfer hydrogenation involving enantioenriched monosulfonamide–RhCp¹ complex in aqueous sodium formate as hydride donor is described.     

Realistic modeling of ruthenium-catalyzed transfer hydrogenation

We report the first computational study of a fully atomistic model of the ruthenium-catalyzed transfer hydrogenation of formaldehyde and the reverse reaction in an explicit methanol solution. Using ab initio molecular dynamics techniques, we determined the thermodynamics, mechanism, and electronic structure along the reaction path. To assess the effect of the solvent quantitatively, we make a direct comparison with the gas-phase reaction. We find that the energy profile in solution bears little resemblance to the profile in the gas phase and a distinct solvation barrier is found: the activation barriers in both directions are lowered and the concerted hydride and proton transfer in the gas phase are converted into a sequential mechanism in solution with the substrate appearing as methoxide-like intermediate. Our results indicate that besides the metal-ligand bifunctional mechanism, as proposed by Noyori, also a concerted solvent-mediated mechanism is feasible. Our study gives a new perspective of the active role a solvent can have in transition-metal-catalyzed reactions.     

Synthesis of (+)-(S)-Streptenol A and Biomimetic Synthesis of (2R,4S)- and (2S,4S)-2-(Pent-3-enyl)piperidin-4-ol

(+)-(S)-Streptenol A is synthesized by coupling a 1,3-dithiane with an optically pure epoxide. The absolute configuration of (+)-(S)-streptenol A is thereby correlated with that of (S)-malic acid. Stereoselective reduction of an oxime that could easily be prepared from streptenol A gave the (3S,5R)- and (3S,5S)-aminostreptenols, and after cyclization, configurationally pure 2,4-functionalized piperidine alkaloids.     

Chemoenzymatic Synthesis of (R)- and (S)-4-Amino-3-Methylbutanoic Acids

(R)- and (S)-4-Amino-3-methylbutanoic acids were synthesized in high yields via initial enantioselective hydrolysis of dimethyl 3-methylglutarate to methyl (R)-3-methylglutarate with pig liver esterase. The ester group was converted to an amine to give (R)-4-amino-3-methylbutanoic acid; the carboxylic acid was converted to an amine to give (S)-4-amino-3-methylbutanoic acid.     

Synthesis of new mono-N-tosylated diamine ligands based on (R)-(+)-limonene and their application in asymmetric transfer hydrogenation of ketones and imines

A synthetic procedure leading to the preparation of a new family of enantiopure mono-N-tosylated-1,2-diamines derived from (R)-(+)-limonene is described. (+)-Limonene was transformed into the appropriate N-tosyl derivative using N-tosylaziridination based on chloramine-T trihydrate. Subsequent ring opening by sodium azide afforded the corresponding isomeric azides. Finally, reduction of the azide function gave enantiomerically pure mono-N-tosylated-1,2-diamines. The ligands obtained proved to be effective in the asymmetric transfer hydrogenation protocol on aromatic ketones and imines.     

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.     

Synthesis of antidepressant duloxetine via asymmetric transfer hydrogenation

Antidepressant duloxetine （1） was prepared via asymmetric transfer hydrogenation of 3-（dimethylamino）-1-（thiophen-2- yl）propan-1-one （3）. The Ru（Ⅱ）, Rh（Ⅲ） and Ir（Ⅲ） complexes of several chiral ligands were examined as the catalyst and （S,S）-N-tosyl-1,2-diphenyl ethylenediamine （TsDPEN）-Ru（Ⅱ） complex was found to provide good yield and excellent enantioselectivity. 2007 Ming Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Synthesis of (R)- and (S)-p-Mentha-1,8-dien-4-ols from (R)-Limonene

Synthesis of both enantiomers of p-mentha-1,8-dien-4-ol ( 1 ) from commercially available (+)-(R)-limonene ( 2 ) is described.     

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.     

Synthesis of methyl N-Boc-(2S,4R)-4-methylpipecolate

An efficient stereoselective synthesis of fully protected (2S,4R)-4-methylpipecolic acid has been developed. The synthesis was achieved by initial asymmetric α-alkylation of glycine with a chiral iodide, affording the linear precursor as a single stereoisomer. Subsequent aldehyde formation using OsO(4)/NaIO(4) followed by immediate intramolecular cyclization afforded an enamine that was then subjected to hydrogenation to give the final compound in 23% yield over 10 steps.     

Synthesis of (2S,4S)- and (2S,4R)-5-fluoroleucine and (2S,4S)-[5,5-2H2]-5-fluoroleucine

Syntheses of (2S,4S)- and (2S,4R)-5-fluoroleucine, and, and of (2S,4S)-[5,5-(2)H(2)]-5-fluoroleucine, have been completed. The methodology allows these compounds to be prepared in sufficient quantities for incorporation by solid-state protein synthesis into strategic sites in proteins for folding studies. X-ray structures of the epimers and have been obtained and show the presence of conformational isomerism. The torsion angles between the F-C bond and the main chain are compared with values found in a mutant of the protein ubiquitin in which (2S,4S)-5-fluoroleucine replaces leucine residues 50 and 67 in the native protein.     

Synthesis of (−)-(5R,6S)-6-acetoxyhexadecan-5-olide by l-proline-catalyzed asymmetric aldol reactions

The natural mosquito attractant pheromone, (−)-(5R,6S)-6-acetoxyhexadecan-5-olide 1, was synthesized from readily available aldehyde 3 and cyclopentanone 4 using l-proline catalyzed asymmetric aldol reactions as the key step.     

Rhodium complexes of (R)-Me-CATPHOS and (R)-(S)-JOSIPHOS: highly enantioselective catalysts for the asymmetric hydrogenation of (E)- and (Z)-β-aryl-β-(enamido)phosphonates

Rhodium complexes of (R)-Me-CATPHOS and (R)-(S)-JOSIPHOS form a complementary pair of catalysts for the highly efficient asymmetric hydrogenation of a selection of (E)- and (Z)-β-aryl-β-(enamido)phosphonates, respectively, in the majority of cases giving excellent yields and ee’s in excess of 99%; the highest to be reported for this class of substrate.     

Synthesis of (4S, 5R)-1,4,5-Hexanetriol and D-Amicetose

Starting from L-glutamic acid the synthesis of (4S, 5R),-1,4,5-hexanetriol and D-amicetose is described.     

Synthesis of (R)- and (S)-Oxymethylmorpholine Derivatives

(S)-N-benzyl-3-tert-butyldiphenylsilyloxymethylmorpholine and (R)-N-benzyl-3-benzyloxymethylmorpholine are synthesized starting from (R)-1-benzylglycerol.     

(4S)-4-羧基杂氮硅三环的合成

利用L-N,N-双(β-羟乙基)丝氨酸及L-N,N-双(β-羟乙基)苏氨酸与三乙氧基硅烷或氯烷基三乙氧基硅烷反应合成了具有手性的(4S)-4-羧基杂氮硅三环(1～5),并运用IR、~1HNMR、EI-MS等手段表征了结构。证据显示存在着贯穿笼状结构的N→Si配键。     

Synthesis of dendritic catalysts and application in asymmetric transfer hydrogenation

Frechet-type core-functionalized chiral diamine-based dendritic ligands and hybrid dendritic ligands condensed from polyether wedge and Newkome-type poly(ether-amide) supported multiple ligands were designed and synthesized. The solubility of hybrid dendrimers was found to be finely controlled by the polyether dendron. The catalytic efficiency and recovery use of dendritic ruthenium complexes were compared in the transfer hydrogenation of acetophenone. The core-functionalized dendritic catalysts demonstrated much better recyclability, which verified the stabilizing effects of the bulky polyether wedge on the catalytically active complex. Moreover, the dendritic catalysts were applied in the asymmetric transfer hydrogenation of ketones, enones, imine, and activated olefin, and moderate to excellent enantioselectivitiy was achieved comparable to that of monomeric catalysts.     

An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.