Chiral epoxides via borane reduction of 2-haloketones catalyzed by spiroborate ester: application to the synthesis of optically pure 1,2-hydroxy ethers and 1,2-azido alcohols

An enantioselective borane-mediated reduction of a variety of 2-haloketones with 10% spiroaminoborate ester 1 as catalyst is described. By a simple basic workup of 2-halohydrins, optically active epoxides are obtained in high yield and with excellent enantiopurity (up to 99% ee). Ring-opening of oxiranes with phenoxides or sodium azide is investigated under different reaction conditions affording nonracemic 1,2-hydroxy ethers and 1,2-azido alcohols with excellent enantioselectivity (99% ee) and in good to high chemical yield.     

Strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays based on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides: application to natural product synthesis

We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph(3)As[double bond]O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure alpha,beta-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/alpha-pyrone natural products, for example, cryptocaryolone diacetate.     

Catalytic Asymmetric Epoxidation of α,β‐Unsaturated Esters with Chiral Yttrium–Biaryldiol Complexes

The full details of the asymmetric epoxidation of α,β‐unsaturated esters catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium–biphenyldiol catalyst, generated from Y(OiPr)₃–biphenyldiol ligand–triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various α,β‐unsaturated esters. With this catalyst, β‐aryl α,β‐unsaturated esters gave high enantioselectivities and good yields (≤99 % ee). The reactivity of this catalyst is good, and the catalyst loading could be decreased to as little as 0.5–2 mol % (the turnover number was up to 116), while high enantiomeric excesses were maintained. For β‐alkyl α,β‐unsaturated esters, an yttrium–binol catalyst, generated from Y(OiPr)₃–binol ligand–triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (≤97 % ee). The utility of the epoxidation reaction was demonstrated in an efficient synthesis of (?)‐ragaglitazar, a potential antidiabetes agent.     

Novel chiral multidentate P3N4-type ligand for asymmetric transfer hydrogenation of aromatic ketones

Novel chiral multidentate P₃N₄-type ligand has been synthesized and characterized by NMR and HRMS. Using i-PrOH as solvent and hydrogen source, asymmetric transfer hydrogenation of various ketones was investigated. The catalyst generated in situ from chiral multidentate aminophosphine ligand (R,R,R,R)-3 and IrCl(CO)(PPh₃)₂ exhibited highly catalytic activity and excellent enantioselectivity under mild conditions, achieving the corresponding chiral alcohols with up to 99% yield and 99% ee.     

Catalytic asymmetric epoxidation of enones using La-BINOL-triphenylarsine oxide complex: structural determination of the asymmetric catalyst.

The catalytic asymmetric epoxidation of enones using the La-BINOL-Ph(3)As=O complex generated from La(O-i-Pr)(3), BINOL, and Ph(3)As=O in a ratio of 1:1:1 is described herein. Using 1-5 mol % of the asymmetric catalyst, a variety of enones, including a dienone and a cis-enone, were found to be epoxidized in a reasonable reaction time, providing the corresponding epoxy ketones in up to 99% yield and with more than 99% ee. The possible structure of the actual asymmetric catalyst has been clarified by various methods, including X-ray crystal structure analysis. This is the first X-ray analysis of an alkali-metal free lanthanoid-BINOL complex. Although La(binaphthoxide)(2)(Ph(3)As=O)(2) (7) was observed as the major complex in the complexes' solution, generated from La(O-i-Pr)(3), BINOL, and Ph(3)As=O in a ratio of 1:1:1, the possible active species turned out to be the La-BINOL-Ph(3)As=O complex in a ratio of 1:1:1. A probable reaction mechanism of the catalytic asymmetric epoxidation of enones is also proposed, suggesting that preferential formation of a heterochiral complex is the reason for asymmetric amplification. Moreover, the interesting role of La(O-i-Pr)(3) for accelerating the epoxidations while maintaining high ee's is discussed.     

Direct Asymmetric Hydrogenation and Dynamic Kinetic Resolution of Aryl Ketones Catalyzed by an Iridium-NHC Exhibiting High Enantio- and Diastereoselectivity

A chiral iridium carbene-oxazoline catalyst is reported that is able to directly and efficiently hydrogenate a wide variety of ketones in excellent yields and good enantioselectivity (up to 93 % ee). Moreover, when using racemic α-substituted ketones, excellent diastereoselectivities were obtained (dr 99:1) by dynamic kinetic resolution of the in situ formed enolate. Overall, the herein described hydrogenation occurs under ambient conditions using low hydrogen pressures, providing a direct and atom efficient method towards chiral secondary alcohols.     

Characterization of the complex formed between samarium diiodide and the dehydro dimer of HMPA (diHMPA)

A new ligand that facilitates samarium diiodide-mediated reductions has been developed. Addition of a solution of samarium diiodide to the dehydro dimer of hexamethylphosphoramide results in a purple complex which is an excellent reductant for a variety of organic functionalities. The complex was characterized by the kinetics of reduction of 1-bromodecane, visible spectroscopy, and cyclic voltammetry.     

Efficient epoxidation reaction of terminal olefins with hydrogen peroxide catalyzed by an iron (II) complex

A highly active iron (II) complex that catalyzed epoxidation of terminal olefins with hydrogen peroxide was described. The catalytic system displayed excellent catalytic ability for the selective oxidation of terminal olefins to epoxides with high selectivity (up to 97.8%) in CH₃CN at 25?°C. The catalytic activity of three similarly structural iron (II) complexes was comparatively studied. The effect of various auxiliary ligands on epoxidation was investigated in detail.     

新型四氮锰配合物催化烯烃环氧化反应的研究

合成了一种新型四氮配体(1,3-bis(pyridin-2-ylmethyl)imidazolidine)及其相应的锰(MnⅡ)配合物,并将其应用于催化过氧乙酸氧化烯烃的环氧化反应中,考察了催化剂当量及氧化剂当量等一系列条件对反应结果的影响,并在优化条件下研究了各种底物的适用范围,最终取得了很好的化学选择性及85％～9...     

聚苯乙烯负载席夫碱Mo(Ⅵ)配合物合成、表征及其在环己烯环氧化反应中的催化活性

合成了聚苯乙烯负载乙二胺缩水杨醛席夫碱与Mo(Ⅵ)的配合物,并对其结构进行了表征.该配合物催化环己烯环氧化反应与小分子配合物MoO₂(acac)₂相比,具有更优良的催化活性和选择性;建立了催化剂中Mo分析和环氧环己烷气相色谱分析新方法;探讨了配合物及环氧环己烷合成过程诸因素的影响;优化了环氧环己烷合成条件,即以n(t-BuOOH)=0.1mol计,n(C₆H₁₀)∶n(t-BuOOH)=3∶1,溶剂5mL,反应温度80℃,时间60min.在该条件下,环氧环己烷收率(以t-BuOOH计)99.2%以上,质量分数约99.5%(GC检测).催化剂循环使用5次后,未见活性明显下降,环氧环己烷收率(以t-BuOOH计)仍接近99%.     

Cubic and doubly-fused cubic samarium clusters from Sm(II)-mediated reduction of organic azides and azobenzenes

A polynuclear samarium imido complex [(L)Sm(4)(μ(3)-NSiMe(3))(4)] (2) featuring a cubane-like cluster has been synthesized from the reaction of an organic azide and a samarium(II) complex [(L)SmI(2)Li(2)(THF)(Et(2)O)(2)] (1). In addition, this divalent samarium starting material (1) reacts with azobenzene to give the first example of a well-defined doubly-fused cubic imido-cluster [(L)Sm(6)(μ(3)-NPh)(4)(μ(4)-NPh)(2)I(2)(THF)(2)] (4) in addition to a major cubic complex [(L)Sm(4)(μ(3)-NPh)(4)] (3).     

脯氨酸衍生的胺基吡啶四氮锰配合物催化双氧水参与的烯烃不对称环氧化反应（英文）

自然界中存在许多的金属酶,它们参与促进各种各样的氧化反应,例如羟化反应,环氧化反应等.金属酶催化的反应具有催化效率高、反应条件温和、选择性高等优点.受大自然中的金属酶结构及其性质的启发,人们提出了仿生催化氧化的理念,并开始对金属酶进行模拟,致力于发展清洁氧化的反应方式.在过去的几十年中,科学家们设计合成了一系列仿生金属配合物催化剂.例如,利用非手性的乙二胺骨架设计合成出四齿氮配体MEP(N,N'-dimethylN,N'-bis(2-pyridinylmethyl)ethane-1,2-diamine),将其制备成相应的铁配合物催化剂,该铁催化剂可以很好的实现脂肪族烯烃的环氧化,产率高达90%.2003年,Stack小组首次报道了利用手性N,N-二甲基环己二胺骨架衍生的四齿氮配体金属配合物Mn-MCP-(OTf)2(MCP=N,N-dimethyl-N,N-bis(2-pyridylmethyl)cyclohexane-trans-1,2-diamine)催化的不对称环氧化反应.该反应的对映选择性仅仅为10%.因此,发展新型手性四氮配体金属配合物,用于高产率、高对映选择性的不对称环氧化反应,值得进行深入研究.近年来发展的一些含手性二胺骨架的四齿氮配体,例如PDP(2-[[2-(1-(pyridin-2-ylmethyl)-pyrrolidin-2-yl)pyrrolidin-1-yl]methyl]pyridine),被应用到不对称环氧化反应中,但是其手性二胺骨架为联吡咯,价格昂贵,难以制备.这在很大程度上限制了其在不对称合成中的实际应用.因此,利用一些易于合成的手性二胺骨架,发展结构新颖、催化性能优良的四氮金属配合物,成为实现高效、高选择性不对称环氧化反应的关键.在之前的工作基础上,本文以简单易得、价格低廉的天然氨基酸——L-脯氨酸为起始原料,选取吡啶环和含取代基的吡啶环作为侧基氮供体,制备了三种手性四齿氮配体.随后,我们利用新发展的手性四齿氮配体,合成了相应的锰配合物,并且分别将其运用于烯烃不对称环氧化反应中,仔细评估了这些锰金属配合物的催化性能.建立了以0.2 mol%的锰配合物为催化剂,0.5当量的2,2-二甲基丁酸为添加剂,30%双氧水为氧化剂,反应温度为–30 oC,乙腈为溶剂的催化不对称环氧化反应体系.反应结果显示:该催化剂催化的不对称环氧化反应底物适用性广泛,其中苯乙烯、苯并吡喃、烯酰胺等化合物均可以被成功地转化为相应的环氧化物,得到中等至优异的对映选择性(产率最高可达95%,对映选择性最高可达99%).     

Total synthesis of α-1C-galactosylceramide, an immunostimulatory C-glycosphingolipid, and confirmation of the stereochemistry in the first-generation synthesis

A nonisosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, 1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to 1 and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of 1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.     

Asymmetric cyanohydrin formation from aldehydes catalyzed by manganese Schiff base complexes

The catalyst generated in situ from Mn(OAc)₂ and a chiral Schiff base ligand exhibited excellent catalytic abilities in asymmetric cyanohydrin formation from aldehydes with sodium cyanide in up to 99% enantioselectivity and good yield.     

Organocatalytic stereoselective epoxidation of trisubstituted acrylonitriles

The first diastereospecific and enantioselective epoxidation of trans-2-aroyl-3-arylacrylonitriles by means of the commercially available diaryl L-prolinol/tert-butyl hydroperoxide system has been developed. These diversely functionalized epoxides were obtained in excellent yield (up to 99%), complete diastereoselectivity for the trans-isomer, and good enantioselectivity (up to 84% ee). Highly enantioenriched epoxides can be easily obtained after a single crystallization (ee > 90%).     

Asymmetric transfer hydrogenation of aromatic ketones catalyzed by the iridium hydride complex under ambient conditions

The chiral Ir catalytic system generated in situ from iridium hydride complex and chiral diaminodiphosphine ligand was employed in asymmetric transfer hydrogenation of aromatic ketones to give the corresponding optically active alcohols, with up to 99% ee in high yield were obtained even when the substrate-to-catalyst molar ratio reached 10000:1.     

Assembling a Hybrid Pd Catalyst from a Chiral Anionic CoIII Complex and Ligand for Asymmetric C(sp3)–H Functionalization

An unusual hybrid palladium catalyst containing an anionic chiral Co^III complex and a chiral phosphoramidite ligand shows a high capacity for catalyzing asymmetric thioamide‐directed C(sp³)?H arylation and delivers excellent yield and enantioselectivity (up to 99 % yield, 99 % ee). Significant synergy between the chiral ligand and the anion in terms of stereochemical control was observed. Mechanistic investigations have revealed both the nature of the C?H activation and the origin of the enantioselectivity.     

Synthesis of a new chiral N,N,N-tridentate pyridinebisimidazoline ligand library and its application in Ru-catalyzed asymmetric epoxidation

A small ligand library of chiral tridentate N,N,N-pyridinebisimidazolines have been synthesized for the first time. This new class of ligands can be easily tuned and synthesized on multi g-scale. The usefulness of the ligands is shown in the ruthenium-catalyzed asymmetric epoxidation with hydrogen peroxide as oxidant. Excellent yields (>99%) and good enantioselectivities (up to 71% ee) have been obtained for the epoxidation of aromatic olefins. [reaction: see text]     

Catalytic asymmetric 1,4-addition reactions using alpha,beta-unsaturated N-acylpyrroles as highly reactive monodentate alpha,beta-unsaturated ester surrogates

Synthesis and application of alpha,beta-unsaturated N-acylpyrroles as highly reactive, monodentate ester surrogates in the catalytic asymmetric epoxidation and Michael reactions are described. alpha,beta-Unsaturated N-acylpyrroles with various functional groups were synthesized by the Wittig reaction using ylide 2. A Sm(O-i-Pr)(3)/H(8)-BINOL complex was the most effective catalyst for the epoxidation to afford pyrrolyl epoxides in up to 100% yield and >99% ee. Catalyst loading was successfully reduced to as little as 0.02 mol % (substrate/catalyst = 5000). The high turnover frequency and high volumetric productivity of the present reaction are also noteworthy. In addition, a sequential Wittig olefination-catalytic asymmetric epoxidation reaction was developed, providing efficient one-pot access to optically active epoxides from various aldehydes in high yield and ee (96-->99%). In a direct catalytic asymmetric Michael reaction of hydroxyketone promoted by the Et(2)Zn/linked-BINOL complex, Michael adducts were obtained in good yield (74-97%), dr (69/31-95/5), and ee (73-95%). This represents the first direct catalytic asymmetric Michael reaction of unmodified ketone to an alpha,beta-unsaturated carboxylic acid derivative. The properties of alpha,beta-unsaturated N-acylpyrrole are also discussed. Finally, the utility of the N-acylpyrrole unit for further transformations is demonstrated.     

Remarkable effect of tris(4-fluorophenyl)phosphine oxide on the stabilization of chiral lanthanum complex catalysts. A new and practical protocol for the highly enantioselective epoxidation of conjugated enones

A new and efficient chiral catalyst system, lanthanum-chiral BINOL-tris(4-fluorophenyl)phosphine oxide-cumene hydroperoxide, was developed for the epoxidation of alpha, beta-unsaturated ketones thus providing the corresponding epoxy ketones with excellent enantioselectivities (up to >99% ee) in good to excellent yields at room temperature.