Highly enantioselective Michael addition of nitroalkanes to chalcones using chiral squaramides as hydrogen bonding organocatalysts

A series of squaramide-based organocatalysts were facilely synthesized and applied as hydrogen bonding organocatalysts in the enantioselective Michael addition of nitroalkanes to chalcones. These organocatalysts promoted the Michael addition with low catalyst loading under high temperature (80 °C), affording the desired R or S enantiomers of the products flexibly in high yields with excellent enantioselectivities (93-96% ee) by the appropriate choice of organocatalysts.     

Synthesis of axially chiral C10-BridgePHOS oxides and their use as organocatalysts in enantioselective allylations of aldehydes

A series of C₁₀-BridgePHOS oxides possessing different substituted groups on the diphenyl phosphine system were synthesized and tested as organocatalysts in the allylation of aldehydes with allyltrichlorosilane, providing chiral homoallylic alcohols. These types of organocatalysts showed high catalytic activity and only 2 mol% catalyst loading was required to induce short reaction times. Under optimal reaction conditions, excellent product yields and up to 92% ee were obtained for a variety of substrates.     

有机小分子催化不对称Henry反应的研究进展

综述了各类有机小分子催化剂(如金鸡纳碱衍生物、手性(硫)脲、手性二级胺、金鸡纳碱-硫脲衍生物、胍-硫脲衍生物等)在不对称Henry反应中的研究进展。参考文献18篇。     

Phosphinoyl-aziridines as a new class of chiral catalysts for enantioselective Michael addition

A series of new optically pure phosphine oxides containing chiral aziridine subunit were synthesized in good yields and applied as organocatalysts in asymmetric Michael reaction of various aliphatic aldehydes with β-nitrostyrene. The corresponding organocatalysts were synthesized starting from optically pure aziridines in a few simple efficient steps. The appropriate Michael adducts were obtained in most cases in very high chemical yield (up to 97%), excellent enantioselectivity (up to 98% of ee) and diastereoselectivity (up to 95:5 of dr).     

Silica-supported l-proline organocatalysts for asymmetric aldolisation

New heterogenised silica-based organocatalysts have been prepared via the sol–gel process from two silylated derivatives of l-proline, featuring either a carbamate or an ether linker. Co-gelification with variable amounts of TEOS was performed with and without porogen to yield high surface area solids. These materials were evaluated as heterogeneous phase organocatalysts for the asymmetric aldol reaction of p-nitrobenzaldehyde with acetone.     

Ionic-liquid tagged prolines as recyclable organocatalysts for enantioselective α-aminoxylations of carbonyl compounds

With the aim of improving catalytic performance and recyclability various ionic-liquid-tagged organocatalysts (ILTOCs) based on (S)-proline as organocatalysts and triazolium or guanidinium salts as ionic liquid tags were applied in the asymmetric α-aminoxylation of ketones and aldehydes with nitrosobenzene in IL as solvents. Amongst such ILTOC’s compounds were found which performed better (ee >99%, yield 97%) than (S)-proline in reported cases. Recycling and reusage of ILTOCs were easily possible and yields higher than 80% and ees higher than 90% were obtained until the fifth cycle. Important information about the crucial role of water in recycling of proline-derived organocatalysts in reactions with carbonyl compounds via enamine activation was found to prevent blockade of the organocatalyst by oxazolidinone formation.     

Design,synthesis, and application of chiral electron-poor guanidines as hydrogen-bonding catalysts for the Michael reaction

The first chiral electron-poor guanidine organocatalysts were synthesized. The presence of a tunable electron-withdrawing group on the guanidine moiety allows for the modulation of the catalysts’ activity. The application of this new class of organocatalysts to the Michael reaction is demonstrated.     

Solvent-effects tuning the catalytic reactivity of prolinamides in asymmetric aldol reactions

Novel prolinamides were prepared and applied as organocatalysts in the asymmetric aldol reaction. Stable imidazolidinones were formed between prolinamides and aromatic aldehydes in organic solvents. It was found that aqueous conditions can significantly suppress the formation of the unwanted imidazolidinone intermediate and improve the catalytic activity of the prolinamides. As a consequence, high chemical yields (up to 99%) and good diastereoselectivity (up to >20:1 dr) and enantioselectivity (up to 95% ee) were achieved in 2-Me-THF or brine. This strategy could serve as a general solution to enhance the performance of prolinamides as organocatalysts.     

高效多羟胺有机催化剂选择性催化分子氧氧化研究进展

基于氧气(空气)为氧源的选择性催化分子氧氧化技术在制备含氧精细化学品或食品添加剂与医药等的重要中间体方面一直受到科学界的广泛关注.由于碳氢化合物中碳氢键的反应惰性和分子氧的自旋禁阻作用,设计与开发高效催化剂或催化体系以实现碳氢化合物的选择性氧化是当前催化氧化领域的研究热点.在已发展的过渡金属盐、仿生催化剂、有机催化剂、酶、碳材料和卤化物等众多催化剂中,以N-羟基邻苯二甲酰亚胺(NHPI)为代表的羟胺有机催化剂由于在温和条件下的卓越催化性能而备受瞩目.尽管基于羟胺有机催化剂的催化体系具有良好的工业应用前景,但仍存在催化剂高温易分解、使用量较大和可回收性较差等缺点.近年来,许多实验与理论工作围绕改进这些缺点展开,设计了一系列羟胺有机催化剂及其协同催化体系,如在NHPI结构中修饰疏水链基团、吸电子基团、N-烷氧基团和离子液体,或固载金属-有机框架材料、无机物和聚合物,或组合光催化剂.尽管已有大量综述总结了相关研究进展,但尚未见到有关近年来发展的多羟胺有机催化剂及其高效催化氧化性能的综述报道.本文综述了近15年来多羟胺有机催化剂选择性催化分子氧氧化碳氢化合物的研究进展.首先,简要概述了N,N-二羟基邻苯二甲酰亚胺(NDHPI)和N,N',N"-三羟基异氰基尿酸(THICA)两种多羟胺有机催化剂的合成方法,系统介绍了它们在各类碳氢化合物氧化中的高效催化性能,并与普遍应用的NHPI的催化性能进行对比.由于NDHPI与THICA具有多羟胺的独特结构,它们只需要比NHPI更少的用量便可获得比NHPI更高的催化氧化效率,可以直接利用高压空气实现对碳氢化合物的选择性催化氧化,并且在较高温度下依然具有较好的催化效果.在此基础上,介绍了联系实验与理论之间的重要工作,总结了多羟胺有机催化剂的合理设计策略.理论计算研究揭示了NDHPI与THICA的催化性能优于NHPI的主要原因是具有类似于吸电子效应的多羟胺与多氮氧自由基结构能显著增强催化剂的夺氢活性.通过对NDHPI结构的进一步修饰和夺氢活性研究,提出了该类催化剂的合理设计策略:在芳环体系中增加共轭的羟胺基团数量,或在NDHPI苯环中掺杂N原子或引入离子对基团都能提高催化剂的夺氢活性;增大芳环共轭体系对催化剂的夺氢活性影响较小,但该活性仍高于NHPI.这也为基于碳材料的非均相共轭多羟胺有机催化剂的开发提供了理论依据.最后,结合羟胺有机催化剂的发展现状和上述设计策略,设计了基于金属卟啉/席夫碱等仿生催化剂、(含离子对结构)聚合物、非均相碳材料和多N-烷氧基团等几种具有潜在发展前景的模型多羟胺有机催化剂,分别讨论了这些催化剂的优点和局限性,并展望了多羟胺有机催化剂的可能应用及其在催化氧化过程中仍需系统研究的方向.     

Highly diastereo- and enantioselective direct aldol reactions promoted by water-compatible organocatalysts bearing a pyrrolidinyl-camphor structural scaffold

Efficient synthetic routes have been developed for the synthesis of a series of pyrrolidinyl-camphor containing organocatalysts (1-10). Structural modifications were made by varying the stereo- and electronic properties of the camphor scaffold and the aromatic substituents. These readily tunable and amphiphilic organocatalysts were evaluated for the direct asymmetric aldol reaction of various aromatic aldehydes and cyclohexanone either in organic solvents or in the presence of water. The aldol reaction proceeded smoothly with excellent chemical yields (up to 99%), enantioselectivities (up to 99% ee), and anti-diastereoselectivities (up to 99:1) with a catalytical amount of the bifunctional organocatalysts (20 mol %) under optimal reaction conditions. Mechanistic transition models are proposed and the stereochemical bias of the asymmetric aldol reaction is presented.     

Threonine-surfactant organocatalysts for the highly diastereo- and enantioselective direct anti-Mannich reactions of hydroxyacetone

In this work, several new l-threonine derivatives as organocatalysts were synthesized in one step for the first time by the reaction of threonine with acyl chlorides at room temperature in trifluoroacetic acid on a large-scale without protecting groups involved or chromatographic techniques, and those threonine-surfactant organocatalysts mediated the direct asymmetric anti-Mannich reactions of hydroxyacetone and anilines with aldehydes to synthesize anti-1,2-amino alcohols in good yields (75-93%) and highly enantioselectivities (up to 99% ee).     

The Resurgence of the Highly Ylidic N‐Heterocyclic Olefins as a New Class of Organocatalysts

In recent decades, N‐heterocyclic carbenes have become established as a prevalent family of organocatalysts. N‐Heterocyclic olefins, the alkylidene derivatives of N‐heterocyclic carbenes, have recently also emerged as efficient promoters for CO₂ fixation and polymerization reactions. Their extraordinarily strong Lewis/Brønsted basicity suggests great potential as a new class of organocatalysts for a broad range of reactions in synthetic chemistry.     

Evolution of pyrrolidine-type asymmetric organocatalysts by "click" chemistry

Click chemistry has been employed to construct a library of the pyrrolidine-type asymmetric organocatalysts. The clicked organocatalysts were evaluated in asymmetric Michael addition of ketones to nitroolefins, showing good catalytic activity and stereoselectivity (up to 100% yield, syn:anti = 99:1, 96% ee).     

Click反应和多氮化合物手性催化剂

Click化学涉及一系列能够在温和条件下高产率进行的有机反应, 已经被用来构建一些手性有机催化剂. 一些多氮化合物作为手性有机催化剂, 在反应过程中形成多重氢键使反应过渡态得以稳定, 显示出非常好的立体选择性.     

Enantioselective Michael reaction of β-keto esters organocatalyzed by recoverable Cinchona-derived dimeric ammonium salts

Dimeric anthracenyldimethyl-derived Cinchona ammonium salts are used as chiral organocatalysts in 1–10 mol % for the enantioselective conjugate addition of 2-alkoxycarbonyl-1-indanones to β-unsubstituted Michael acceptors. The corresponding adducts bearing a new all-carbon quaternary center were usually obtained in high yield and with up to 94% ee when using ammonium salts derived from quinidine and its pseudoenantiomer quinine as organocatalysts. These catalysts can be almost recovered quantitatively by precipitation in ether and reused.     

Linking Conformational Flexibility and Kinetics: Catalytic 1,4‐Type Friedel–Crafts Reactions of Phenols Utilizing 1,3‐Diamine‐Tethered Guanidine/Bisthiourea Organocatalysts

Herein, we present details of our conformationally flexible, 1,3‐diamine‐tethered guanidine/bisthiourea organocatalysts for chemo‐, regio‐, and enantioselective 1,4‐type Friedel–Crafts reactions of phenols. These organocatalysts show a unique stereo‐discrimination governed by the differential activation entropy (ΔΔS^≠), rather than by the differential activation enthalpy (ΔΔH^≠). Extensive kinetic analyses using Eyring plots for a series of guanidine/bisthiourea organocatalysts revealed the key structural motif in the catalysts associated with a large magnitude of differential activation entropy (ΔΔS^≠). A plausible guanidine–thiourea cooperative mechanism for the enantioselective Friedel–Crafts reaction is proposed.     

Asymmetric direct vinylogous carbon-carbon bond formation catalyzed by bifunctional organocatalysts

The bifunctional chiral thiourea-tertiary amine organocatalysts have been applied to a direct asymmetric vinylogous Michael addition of α,α-dicyanoolefins to nitroolefins with 2-10 mol % catalyst loadings. The electronic properties of the thiourea-based catalysts have significant influences on this reaction. Moderate to excellent enantioselectivities (57-95% ee) have been achieved with low to good isolated yields through fine tuning the structures of the bifunctional organocatalysts. Much better ees were obtained for some α,α-dicyanoolefinic substrates compared with that catalyzed by modified cinchona alkaloids.     

Synthesis of novel carbohydrate-based valine-derived formamide organocatalysts by CuAAC click chemistry and their application in asymmetric reduction of imines with trichlorosilane

Novel organocatalysts combining carbohydrate and N-formyl-l-valine derivatives were prepared by Cu^II-catalyzed diazo transfer and Cu^I-catalyzed azide–alkyne 1,3-dipolar cycloaddition CuAAC click chemistry. It was found that the carbohydrate-based valine-derived formamide organocatalyst had high catalytic activity for the asymmetric reduction of imines with trichlorosilane. The reduction can proceed at room temperature in toluene in high yield (up to 98%) and with excellent enantioselectivity (up to 94%). ‘CuAAC’ click chemistry is a bridge to link N-formyl-l-valine derived organocatalysts with carbohydrates.     

Synthesis of polyhydroquinoline derivatives through unsymmetric Hantzsch reaction using organocatalysts

A novel and green approach for efficient and rapid synthesis of polyhydroquinoline derivatives via unsymmetric Hantzsch reaction using organocatalysts at room temperature was reported. The process is a simple, environmentally friendly, rapid, and high yielding reaction for the synthesis of polyhydroquinoline derivatives. The catalytic efficiency of various small organocatalysts such as l-proline, trans-4-hydroxy-l-proline, l-thiaproline, dl-phenylglycine, and (−)-cinchonidine was studied under aqueous, organic, and solvent free conditions.     

New thiourea organocatalysts and their application for the synthesis of 5-(1H-indol-3-yl)methyl-2,2-dimethyl-1,3-dioxane-4,6-diones a source of chiral 3-indoylmethyl ketenes

The stereoselective properties of modified thiourea organocatalysts were tested in the Friedel–Crafts alkylation of indole with 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones, which produces chiral 5-((1H-indol-3-yl)(aryl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-diones. Based on a tentative reaction mechanism for ((S)-N-benzyl-2-(3-(3,5-bis(trifluoromethyl)phenyl)thioureido)-N,3,3-trimethylbutanamide organocatalysts, modifications were applied in four selected regions. Systematic structure-stereoselectivity relationship study allowed designing the best efficient organocatalyst for the investigated Friedel–Crafts alkylation of indole with 5-arylidene-2,2-dimethyl-1,3-dioxane-4,6-diones.