Optically active trans-2-aminocyclopentanols: chemoenzymatic preparation and application as chiral ligands

Optically active trans-2-(N,N-dialkylamino)cyclopentanols and their acetates derivatives were obtained with very good chemical yields and enantiomeric excesses (95->/=99%), through a chemoenzymatic methodology based on the lipase-catalyzed acylation of the hydroxyl group. The utility of these compounds was shown by the preparation of the cyclopentylic analog of vesamicol and by their use as ligands in the enantioselective addition of diethylzinc to benzaldehyde.     

Enantioselective synthesis of (R)‐Cinacalcet via cobalt‐catalysed asymmetric Negishi cross‐coupling

A novel enantioselective synthesis of (R)‐cinacalcet with 99% enantiomeric excesses (ee) has been achieved. The main strategies of the approach include a gram‐scale cobalt‐catalysed asymmetric cross‐coupling of racemic ester with arylzinc reagent, Hoffman‐type rearrangement of acidamide, the amidation of chiral amine, and improving the ee of chiral amide from 87% to 99% via recrystallization.     

Asymmetric addition of phenylacetylene to aromatic ketones catalyzed by zinc or titanium complexes with chiral hydroxysulfonamide

Various new chiral hydroxysulfonamide ligands (3a-3n, 4a-4d) were prepared. Compounds 3a, 3g, 3i, 3k-3n, 4a-4d could accelerate the reaction and reduce reaction time, and 3a, 3g, 3i, 3k-3n catalyzed the reaction without titanium. The results obtained were promising in terms of yields and enantiomeric excesses (3k up to 85% ee, 4a up to 83% ee).     

Biotransformation of organic sulfides. Part 9. Formation of (S) para-substituted phenyl methyl sulfoxides by biotransformation usingHelminthosporium species NRRL 4671

Phenyl methyl sulfides substituted in thepara position with methyl, fluoro, chloro, bromo, cyano, nitro, amino, acyl, methoxy, thiomethyl and methylsulfinyl groups have been converted to (S) sulfoxides by biotransformation usingHelminthosporium species NRRL 4671. The highest yields and enantiomeric excesses were obtained with bromo, cyano, methoxy, thiomethyl and methylsulfinyl substituents and in two cases (para-Br and -CN) the products could be crystallized to give (S) sulfoxide of ≥ 96% ee.     

Microbial reduction of cyclohexanones

A Brazilian strain of the bacteria Serratia rubidaea CCT 5742 quantitatively reduced 4-tert-butylcyclohexanone and 4-methylcyclohexanone to the less thermodynamically stable diastereoisomeric alcohols cis-4-tert-butylcyclohexanol and cis-4-methylcyclohexanol with a diastereoisomeric excesses (de) of 96% and 44%, respectively. 2-Methylcyclohexanone was also totally reduced to the corresponding alcohols affording the trans-(+)-(1S, 2S)-2-methylcyclohexanol with 78% of de and an enantiomeric excess (ee) of 80%. The cis-(+)-(1S, 2R)-2-methylcyclohexanol was obtained in 98% ee.     

Chemoenzymatic synthesis of both enantiomers of alpha-tocotrienol

The stereoselective acylation of the achiral chromanedimethanol derivative 1 by vinyl acetate in the presence of Candida antarctica lipase B gave the (S)-monoester 2 in high enantiomeric purity (ee > or = 98%). Enzymatic hydrolysis of diesters of compound 1 failed to give (R)-monoester 2 in good yield and high ee. Thus, both enantiomers of alpha-tocotrienol were synthesized from the (S)-monoester 2.     

Stereoselective reduction of ketones by <Emphasis Type="Italic">Daucus carota</Emphasis> hairy root cultures

Reduction of acetophenone by Daucus carota hairy root cultures afforded (S)-phenylethanol in high yield (96%) and excellent enantiomeric excess (ee ≥ 98%). Aromatic ketones, keto esters, and a simple aliphatic ketone were reduced with good stereoselectivity (ee = 62–98%) and moderate to high chemical yields (25–90%).     

Enzymatic and chromatographic chiral discrimination of racemic (thio)glycidyl esters: Part I. A chemoenzymatic approach to both enantiomers of thioglycidyl esters

Both hitherto unknown (+)-(R)- and (?)-(S)-thioglycidyl esters, (R)-( 2 ) and (S)-( 2 ), have been synthesized with different high enantiomeric excesses (ee) by two routes from the corresponding rac-glycidyl esters rac-( 1 ). The first includes a porcine pancreatic lipase (PPL)-mediated kinetic resolution of these esters followed by sulfuration with practically complete inversion to the (+)-(R)-enantiomer (+)-(R)-( 2 ) (36–86% ee). (?)-(S)-Thioglycidyl esters (?)-(S)-( 2 ) are obtained by the reverse reaction sequence (43–80% ee). In the latter case the hydrolysis rate is lower than that of analogous glycidyl esters. Moreover, the dependence of enantiomeric excess on the size of the acyl-group is of the opposite tendency. Therefore, in both cases suitable selection of the acid residue gives rise to maximum enantioselectivity. The irreversible lipase-catalyzed acylation of rac-glycidol and rac-thioglycidol, however, was found to be a less suitable alternative. The enantiomeric excess of recovered homochiral esters was determined by chiral chromatography using modified cellulose stationary phases (OB, OD). © 1993 Wiley-Liss, Inc.     

Photobiocatalyzed asymmetric reduction of ketones using Chlorella sp. MK201

Aromatic ketones were reduced using suspension culture of Chlorella sp. MK201 under fluorescent light illumination producing the corresponding chiral alcohols in high yields with excellent enantiomeric excess (ee). For example, 2′,3′,4′,5′,6′-pentafluoroacetophenone at 0.25?mg/ml was converted to the corresponding (S)-alcohol in 80?% yield with?>99?% ee by 1?mg dry wt of Chlorella/ml in 12?h illumination (2,000 lux).     

产碱杆菌ECU0401催化拆分扁桃酸及其衍生物

从土壤中分离的1株产碱杆菌Alcaligenes sp.ECU0401具有扁桃酸脱氢酶活性,可以以扁桃酸、苯甲酰甲酸或苯甲酸为唯一C源生长,并且具有较高的脱氢酶活力。以外消旋扁桃酸为C源,采用分批补料策略培养（或反应）99h,扁桃酸累计投入量为30.4g/L,（S）-（＋）-扁桃酸被完全降解,（R）-（-）-扁桃酸回收产率为32.8%,对映体过量值（e.e.）〉99.9%。利用静息细胞作为催化剂不对称降解外消旋扁桃酸的氯代衍生物,制备获得光学活性的（R）-（-）-邻氯扁桃酸、（S）-（＋）-间氯扁桃酸和（S）-（＋）-对氯扁桃酸,光学纯度均超过99.9%e.e.。     

Preparation of optically pure chiral amines by lipase-catalyzed enantioselective hydrolysis of N-acyl-amines

Summary A new and effective method using lipase from Candida antarctica (native or Novozym SP-435) for the preparation of enantiopure primary R-amines is reported. Hydrolysis of rac-N-acetyl-amines resulted in high conversion > 40% (168 hrs) and > 48% (> 240 hrs) and enantiomeric excesses (> 99% ee) for both the product and the remaining substrate.     

A concise summary of experimental facts about the Soai reaction

The Soai reaction amplifies small enantiomeric excesses in a spectacular manner. Being known for 20 years, it has drawn the attention of many scientists in different fields as it is to date the only chemical reaction offering the chance to study the phenomenon of asymmetric autocatalysis in conjunction with high amplification of enantiomeric excess (ee). This mini-review comprises an introduction to the discovery of asymmetric autocatalysis with amplification of ee and a concise summary of published experimental results showing which starting materials and reaction parameters play an important role in this reaction and which influences are understood. It is addressed especially to scientists entering the field of the Soai reaction to get a quick overview of important aspects.     

Sugar-derived 2-S-substituted-2H-pyran-3(6H)-ones: synthesis and reactivity

A practical procedure for the preparation of chiral 2-S-substituted-2H-pyran-3(6H)-ones is described. According to the reaction conditions, 1,5-anhydro-2,3,4-tri-O-acetyl-D-threo-pent-1-enitol (1) reacted with thiophenol under Lewis acid catalysis to afford the polysubstitution product 1,5-anhydro-2,3,4-tri-S-phenyl-2,3,4-trithio-D,L-threo-pent-1-enitol (2) or phenyl 2,4-di-O-acetyl-3-deoxy-1-thio-alpha- and beta-D-glycero-pent-2-enopyranoside (3 and 4, respectively). The iodine-promoted addition of thiophenol or alpha-toluenethiol to 1 gave (2S)-2-phenylthio-2H-pyran-3(6H)-one (5) or its 2-benzylthio analogue 6, but these products showed low enantiomeric excesses (ee approximately 40-60%). However, dihydropyranone 5 with high optical purity (ee>94%) was successfully obtained by treatment of 4 with iodine in acetonitrile. On the other hand, it was established that the benzylthio group of 5 exerts high stereocontrol in reduction and cycloaddition reactions performed on the alpha,beta-unsaturated carbonyl system.     

NHC-containing chiral bidentate ligands: synthesis and evaluation in enantioselective copper-catalyzed conjugate addition

New chiral phosphine-, thiolate-, mesylate-, and tosylate-containing N-heterocyclic carbene ligands have been synthesized in fair to excellent yield. These bidentate ligands have been evaluated in enantioselective copper-catalyzed conjugate addition to both cyclic and acyclic enones and displayed good catalytic activities and poor to good enantiomeric excesses (up to 80%).     

Microbiological Reduction Ofcarbonyl Groupings: Preparation of Stereoisomers Acyclic Chiral α-Diols

Enantiogenic microbiological reduction of acyclic 2,3-diketones readily yields enantiomeric or diastereoisomeric chiral diols with high enantiomeric excesses. Some α-hydroxyketones can also be isolated. Regardless of the substituents certain microorganisms always produce compounds with the same absolute configuration. Preliminary results concerning the mechanism of these reductions are presented.     

Tetranuclear titanium 7,7'-modified binaphtholate cluster as a novel chiral Lewis acid catalyst

Chiral tetranuclear Ti cluster, a cubic structure constituted of four Ti atoms and OHs, and six (R)-binaphthols (BINOL) bridged two Ti atoms as ligands, is shown to be a novel chiral Lewis acid catalyst for the [2+3] cycloaddition reaction with nitrones. The chiral Ti clusters with 7,7'-substituted (R)-BINOL ligands was synthesized to give enhanced enantiomeric excesses up to 78% ee.     

Synthesis of new pryridyl alcohols and their use as catalysts in the asymmetric addition of diethylzinc to aldehydes.

Optically active new pyridyl alcohols 1-4, which can be easily synthesized by the reaction of (+)-camphor or (-)-menthone with lithiated pyridine derivatives, were applied as chiral ligands in the asymmetric addition of diethylzinc to aldehydes. Good yields with up to 94.0% enantiomeric excesses were observed in these reactions.     

Mass balancing in kinetic resolution: calculating yield and enantiomeric excess using chiral balance

When kinetic resolution is applied for the production of enantiomerically pure compounds, process options may be used which involve more than one chiral substrate and one chiral product, such as sequential or parallel enzymatic kinetic resolutions or hydrolysis of diastereomers. Although the relation between the yields (y) of the chiral compounds is straightforward in these cases, the relation between their enantiomeric excess (ee) values is not. Combining mass balances into a so-called chiral balance (Sigma y . ee(R) = 0) provides the relation between enantiomeric excess values in a useful manner. This chiral balance easily shows which nonmeasured enantiomeric excess values and yields can be calculated from measured values. The chiral balance is only valid when configurations at chiral centers are conserved. (c) 1995 John Wiley & Sons, Inc.     

Organocatalytic synthesis of 5-hydroxyisoxazolidine catalyzed by camphor sulfonyl hydrazines through aza-Michael addition/cyclization

A series of chiral 5-hydroxy isoxazolidines has been successfully synthesized through camphor sulfonyl hydrazine-catalyzed asymmetric aza-Michael addition reaction between N,O-protected hydroxyamines and enals. Moderate yields with moderate to good enantioselectivities (up to 96% enantiomeric excess [ee]) were achieved. It provides an alternative asymmetric approach to preparing isoxazolidine derivatives.     

Preparation of arylzinc reagents and their use in the rhodium-catalyzed asymmetric 1,4-addition for the synthesis of 2-aryl-4-piperidones

A protocol for the catalytic asymmetric synthesis of 2-aryl-4-piperidones with high enantiomeric excess (ee) (typically > or = 99% ee) has been described here. The preparation of arylzinc reagents, which are used as nucleophiles in catalysis, is also included. The whole protocol can be completed in 10-20 h, starting from the preparation of the arylzinc reagents, depending on the reaction time of the rhodium-catalyzed process. A detailed protocol is described using the preparation of 4-fluorophenylzinc chloride and its addition to benzyl 3,4-dihydro-4-oxo-1(2H)-pyridinecarboxylate in the presence of [RhCl((R)-binap)]2 as an example.