Synthesis of enantiopure homoallylic ethers by reagent controlled facial selective allylation of chiral ketones

The stereoselective allylation of chiral methyl ketones to give tertiary homoallylic ethers, which can easily be transformed into homoallylic alcohols, is described. Reaction of the enantiopure ketones 8a-d and the racemic ketones 26a-d with the norpseudoephedrine derivative 2 or ent-2 and allylsilane in the presence of a catalytic amount of trifluoromethanesulfonic acid, led to a series of homoallylic ethers with good to excellent diastereoselectivity (85:15 to > 97:3). The allylation is reagent controlled and nearly independent from the stereogenic centers in the substrates. A partial kinetic resolution was observed using the racemic ketones 26a-d. In the reaction of the chiral ketones 8a-d with the achiral reagents ethoxytrimethylsilane and allylsilane only a low diastereoselectivity was observed.     

An efficient procedure for the synthesis of 2-N-Boc-amino-3,5-diols

We wish to describe here the diastereoselective reaction between chiral N-Boc-α-amino aldehydes with both achiral allyltrichlorostannanes leading to 1,2-syn-N-Boc-α-amino alcohols, which are easily converted to the corresponding 4-N-Boc-amino-3-hydroxy ketones after treatment with catalytic amounts of OsO₄ in the presence of NaIO₄. After reduction of the carbonyl function, these 4-N-Boc-amino-3-hydroxy ketones were converted to 1-deoxy-5-hydroxy sphingosine analogues.     

Asymmetric reduction of ketones with sodium aluminum hydride modified by various chiral diols

New stereoselective reducing reagents were preparedin situ by modification of NaAlH₄ with various chiral diols. The efficiency of 1,4- and 1,3-diols as chiral auxiliaries in the reactions of alkyl aryl ketones with modified NaAlH₄ was considerably higher than that of 1,2-diols. The effect of the nature of the achiral ligand additionally introduced into the chiral hydride reagent on the enantioselectivity of ketone reduction was studied. It was proposed that the sodium cation does not necessarily participate at the stage governing the reaction stereochemistry. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp 459–464, March, 2000.     

Cobalt-catalyzed asymmetric hydrogenation of ketones: A remarkable additive effect on enantioselectivity

A chiral cobalt pincer complex, when combined with an achiral electron-rich mono-phosphine ligand, catalyzes efficient asymmetric hydrogenation of a wide range of aryl ketones, affording chiral alcohols with high yields and moderate to excellent enantioselectivities (29 examples, up to 93% ee). Notably, the achiral mono-phosphine ligand shows a remarkable effect on the enantioselectivity of the reaction.     

L-selectride-mediated highly diastereoselective asymmetric reductive aldol reaction: access to an important subunit for bioactive molecules

L-selectride reduction of a chiral or achiral enone followed by reaction of the resulting enolate with optically active alpha-alkoxy aldehydes proceeded with excellent diastereoselectivity. The resulting alpha,alpha-dimethyl-beta-hydroxy ketones are inherent to a variety of biologically active natural products.     

Enantioselective reduction of trifluoromethyl ketones with chiral organomagnesium amides (COMAs)

Chiral organomagnesium amides (COMAs), readily prepared from dialkylmagnesiums and chiral secondary amines, can reduce trifluoromethyl ketones to form secondary alcohols with excellent enantioselectivities (up to 98:2 er) and chemical yields (typically >95% conversion, >85% isolated yields). These MPV-type reductions use an achiral hydride source, and the chiral amine is readily recovered. [reaction: see text]     

A Cinchona Alkaloid‐Functionalized Mesostructured Silica for Construction of Enriched Chiral β‐Trifluoromethyl‐β‐Hydroxy Ketones over An Epoxidation‐Relay Reduction Process

A cinchona alkaloid‐functionalized heterogeneous catalyst is prepared through a thiol‐ene click reaction of chiral N‐(3,5‐ditrifluoromethylbenzyl)quininium bromide and a mesostructured silica, which is obtained by co‐condensation of 1,2‐bis(triethoxysilyl)ethane and 3‐(triethoxysilyl)propane‐1‐thiol. Structural analyses and characterizations disclose its well‐defined chiral single‐site active center, and electron microscopy images reveal its monodisperse property. As a heterogenous catalyst, it enables an efficient asymmetric epoxidation of achiral β‐trifluoromethyl‐β,β‐disubstituted enones, the obtained chiral products can then be converted easily into enriched chiral β‐trifluoromethyl‐β‐hydroxy ketones through a sequential epoxidation‐relay reduction process. Furthermore, such a heterogeneous catalyst can be recovered conveniently and reused in asymmetric epoxidation of 4,4,4‐trifluoro‐1,3‐diphenylbut‐2‐enone, showing an attractive feature in a practical construction of enriched chiral β‐CF₃‐substituted molecules.     

Application of various ionic liquids as cosolvents for chloroperoxidase-catalysed biotransformations

Abstract  

Chloroperoxidase from Caldariomyces fumago catalyses oxidation of indole and thioanisole in reaction mixtures containing up to 40% (v/v) of different ionic liquids (ILs). Results indicate that ILs containing tosylate, trifluoroacetate, chloride, and methylsulfate anions are suitable cosolvents for these transformations, yielding high enantiomeric excess and good conversion rates.     

Brevibacterium epidermidis催化酮不对称还原胺化合成(S)-手性胺

光学纯手性胺是一类非常重要的手性化学品,作为手性砌块和手性拆分剂广泛用于医药、农业化学品、精细化学品等产品的合成中.据统计,美国FDA近年来批准的约40％药物中都含有一个或多个手性胺结构单元.胺脱氢酶(AmDH)是由氨基酸脱氢酶改造而来的一类催化酮不对称还原胺化的新酶,其在手性胺的合成中展现出较强的潜力,已引起国内外学术界和工业界的广泛关注.这是因为该酶能够利用廉价的无机铵为胺供体,且具有催化效率高、原子经济性好和环境友好等优点.迄今为止已经有数个高效的胺脱氢酶被成功开发和报道,但是这些通过蛋白质工程改造的胺脱氢酶均为(R)-选择性,因此只能合成(R)-选择性的手性胺,遗憾的是还未见有(S)-选择性胺脱氢酶的报道.因此,本文主要目的是期望从自然环境中鉴定能够不对称还原胺化酮合成(S)-手性胺的微生物,进而从中分离得到能够以无机铵作为胺供体合成(S)-手性胺的(S)-选择性酶.本文首先利用苯乙胺作为唯一氮源,从土壤中筛选能够利用苯乙胺生长的菌株,进而利用苯乙酮作为初筛底物对得到的菌株进行胺化能力筛选,再利用(4-氟苯基)丙酮作为模式底物进行进一步的筛选.幸运的是,我们获得了能够利用无机铵作为胺供体催化(4-氟苯基)丙酮不对称还原胺化合成(S)-4-氟-α-甲基苯乙胺的菌株,经过16S RNA鉴定为表皮短杆菌,命名为B.epidermidis ECU1015.接下来,我们对B.epidermidis ECU1015催化的胺化反应中的关键参数如胺基供体及其最适浓度、反应温度、pH值和底物浓度等进行了优化,确定最佳反应条件:胺供体为NH4Cl(1.25 mol/L),反应温度为30°C,KPB缓冲液(200 mmol/L,pH 7.5),底物浓度10 mmol/L.最后,在最适的反应条件下,我们对B.epidermidis ECU1015催化的底物谱进行了研究.结果表明,该微生物不能催化大位阻芳香酮和链状酮的胺化,对位阻较小的苯乙酮及(4-氟苯基)丙酮具有较好的还原胺化能力,而且对苯环上带有吸电子取代基的酮化合物具有更好的转化效果.经手性分析,所有生成的手性胺均为(S)-构型,产品的光学纯度均>99％.B.epidermidis催化酮不对称胺化所形成的产物构型均为(S)-选择性,这不同于已报道的(R)-选择性胺脱氢酶.该菌株的发现为(S)-选择性胺脱氢酶的进一步鉴定奠定了一定的研究基础,相关蛋白的分离纯化工作正在进行.     

Facile Access to Chiral Alcohols with Pharmaceutical Relevance Using a Ketoreductase Newly Mined from Pichia guilliermondii

Chiral secondary alcohols with additional functional groups are frequently required as important and valuable synthons for pharmaceuticals, agricultural and other fine chemicals. With the advantages of environmentally benign reaction conditions, broad reaction scope, and high stereoselectivity, biocatalytic reduction of prochiral ketones offers significant potential in the synthesis of optically active alcohols. A CmCR homologous carbonyl reductase from Pichia guilliermondii NRRL Y‐324 was successfully overexpressed. Substrate profile characterization revealed its broad substrate specificity, covering aryl ketones, aliphatic ketones and ketoesters. Furthermore, a variety of ketone substrates were asymmetrically reduced by the purified enzyme with an additionally NADPH regeneration system. The reduction system exhibited excellent enantioselectivity (>99% ee) in the reduction of all the aromatic ketones and ketoesters, except for 2‐bromoacetophenone (93.5% ee). Semi‐preparative reduction of six ketones was achieved with high enantioselectivity (>99% ee) and isolation yields (>80%) within 12 h. This study provides a useful guidance for further application of this enzyme in the asymmetric synthesis of chiral alcohol enantiomers.     

水相不对称转移氢化*

手性醇和胺是重要的精细化学品,不对称转移氢化是获得这类手性化合物有效、实用的途径之一。在众多的催化剂中,Noyori等发展的手性二胺与过渡金属钌TsDPEN-Ru（TsDPEN = 1,2-二苯基乙二胺）络合物是最有效的催化剂。近年来,随着化学家对绿色化学的日益重视,水作为绿色溶剂被广泛地用作为不对称催化转移氢化的反应介质,具有很高的反应活性、对映选择性和化学选择性。本文综述近年来应用未经修饰和修饰的手性二胺配体与过渡金属钌[(cymene)RuCl₂]₂、铑[(Cp*)RhCl₂]₂和铱[(Cp*)IrCl_2]2的络合物催化的水相中酮、亚胺和活化烯烃的不对称转移氢化的研究进展。     

Palladium-catalysed α-allylation of chiral sulfinimines derived from symmetric cyclic ketones

A diastereoselective mono-allylation reaction at the α-position of symmetric cyclic ketones by using tert-butanesulfinamide as a chiral auxiliary is explored. Excellent yields and high diastereomeric ratios were achieved under palladium(0) catalysis in the presence of a readily available achiral phosphine ligand.     

Asymmetric borane reduction of achiral ketones mediated by a chiral oxazaborolidine derived from (−)-ephedrine

Asymmetric borane reduction of achiral ketones in the presence of a chiral oxazaborolidine derived from (−)-ephedrine yielded the corresponding alcohols in optical yields of 41 – 83 % ee.     

Cooperative Catalysis: Combining an Achiral Metal Catalyst with a Chiral Brønsted Acid Enables Highly Enantioselective Hydrogenation of Imines

Asymmetric hydrogenation of imines leads directly to chiral amines, one of the most important structural units in chemical products, from pharmaceuticals to materials. However, highly effective catalysts are rare. This article reveals that combining an achiral pentamethylcyclopentadienyl (Cp*)–iridium complex with a chiral phosphoric acid affords a catalyst that allows for highly enantioselective hydrogenation of imines derived from aryl ketones, as well as those derived from aliphatic ones, with ee values varying from 81 to 98 %. A range of achiral iridium complexes containing diamine ligands were examined, for which the ligands were shown to have a profound effect on the reaction rate, enantioselectivity and catalyst deactivation. The chiral phosphoric acid is no less important, inducing enantioselection in the hydrogenation. The induction occurs, however, at the expense of the reaction rate.     

Intramolecular vs. intermolecular induction in the diastereoselective catalytic reduction of enantiomerically pure ketones with borane in the presence of cyclic β-amino alcohols

Asymmetric reduction of various enantiomerically pure ketones was carried out by using oxazaborolidine catalysts with a variety of achiral and chiral ligands. The efficiency of chiral 1,2-amino alcohols as well as the effect of the stereogenic centers in the substrate on the catalytic asymmetric reduction were studied. It was found that the corresponding secondary alcohols were obtained with extremely high stereoselectivities with the proper choice of chiral ligands although a considerably large double asymmetric induction was observed in some cases.     

Addition of allyltrichlorostannanes to aldehydes: application in the synthesis of 4-N-Boc-amino-3-hydroxy ketones

We wish to describe here the diastereoselective reaction between chiral N-Boc-α-amino aldehydes and achiral allyltrichlorostannanes leading to 1,2-syn-N-Boc-α-amino alcohols, which are treated with catalytic amounts of OsO₄ in the presence of NaIO₄ to provide the corresponding 4-N-Boc-amino-3-hydroxy ketones.     

Nanocrystalline aluminium oxide: a mild and efficient reusable catalyst for the one-pot synthesis of poly-substituted quinolines via Friedlander hetero-annulation

Abstract  

o-Aminoaryl ketones undergo smooth condensation with α-methylene ketones in the presence of nanocrystalline aluminium oxide under mild reaction conditions to afford the corresponding poly-substituted quinolines in excellent yields. The catalyst can be recovered by simple filtration and can be recycled in subsequent reactions.     

Small amounts of achiral beta-amino alcohols reverse the enantioselectivity of chiral catalysts in cooperative asymmetric autocatalysis

An asymmetric autocatalytic reaction has been catalyzed by a mixture of chiral and achiral beta-amino alcohols. The absolute configuration of the highly enantioenriched obtained product (>98% ee) was shown to depend not only on the absolute configuration of the chiral catalyst but also on the structure and the amount of achiral catalyst. Even in default versus the chiral catalyst, achiral catalysts were shown to be able to reverse the enantioselectivity of the reaction.     

Synthesis of 6-chloroquinolines using benzyltrimethylammonium tetrachloroiodate as a selective chlorinating agent and an efficient generator of HCl

Abstract  

A simple and efficient one-pot synthesis of 6-chloroquinolines was achieved in good yields via the three-component reaction of 2-aminoaryl ketones, α-methylene carbonyl compounds, and BTMA ICl₄ in AcOH.     

Pyrrolidine-based chiral pyridinium ionic liquids (ILs) as recyclable and highly efficient organocatalysts for the asymmetric Michael addition reactions

A novel series of pyrrolidine-based chiral pyridinium ionic liquids (ILs) have been developed by using commercially available (S)-(2-aminomethyl)-1-N-Boc-pyrrolidine. These chiral ILs have been found to be recyclable and efficient organocatalysts for the asymmetric catalytic Michael addition reactions of ketones to nitroolefins with high yields, high enantioselectivies, and diastereoselectivies.