Catalytic Asymmetric Phase‐Transfer Michael Reaction and Mannich‐Type Reaction of Glycine Schiff Bases with Tartrate‐Derived Diammonium Salts

Catalytic asymmetric Michael and Mannich‐type reactions of glycine Schiff bases with chiral two‐center organocatalysts, tartrate‐derived diammonium salts (TaDiASs), are described. On the basis of conformational studies, optimized TaDiASs with a 2,6‐disubstituted cyclohexane spiroacetal were newly designed. These TaDiASs catalyzed the asymmetric Michael and Mannich‐type reactions of glycine Schiff bases with higher enantioselectivity than previous catalysts. In the Mannich‐type reaction, aromatic N‐Boc‐protected imines (Boc=tert‐butoxycarbonyl) as well as enolizable alkyl imines were applicable. As a synthetic application of the catalytic asymmetric Mannich‐type reaction with the optimized TaDiASs, we developed a catalytic asymmetric total synthesis of (+)‐nemonapride, which is an antipsychotic agent.     

Ferrocene‐Based Planar Chiral Imidazopyridinium Salts for Catalysis

Planar chirality remains an underutilized control element in asymmetric catalysis. Factors that have limited its broader application in catalysis include poor catalyst performance and difficulties associated with the economical production of enantiopure planar chiral compounds. The construction of planar chiral azolium salts that incorporate a sterically demanding iron sandwich complex is now reported. Applications of this new N‐heterocyclic carbene as both an organocatalyst and a ligand for transition‐metal catalysis demonstrate its unprecedented versatility and potential broad utility in asymmetric catalysis.     

Recent applications of chiral ferrocene ligands in asymmetric catalysis

Despite the impressive progress achieved in asymmetric catalysis during the last decade, an increasing number of new catalysts, ligands, and applications are reported every year to satisfy the need to embrace a wider range of reactions and to improve the efficiency of existing processes. Because of their availability, unique stereochemical aspects, and wide variety of coordination modes and possibilities for the fine-tuning of the steric and electronic properties, ferrocene-based ligands constitute one of the most versatile ligand architectures in the current scenario of asymmetric catalysis. Over the last few years ferrocene catalysts have been successfully applied in an amazing variety of enantioselective processes. This Review documents these recent advances, with special emphasis on the most innovative asymmetric processes and the development of novel, efficient types of ferrocene ligands.     

Direct Regiospecific and Highly Enantioselective Intermolecular α‐Allylic Alkylation of Aldehydes by a Combination of Transition‐Metal and Chiral Amine Catalysts

The first direct intermolecular regiospecific and highly enantioselective α‐allylic alkylation of linear aldehydes by a combination of achiral bench‐stable Pd⁰ complexes and simple chiral amines as co‐catalysts is disclosed. The co‐catalytic asymmetric chemoselective and regiospecific α‐allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2‐alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2‐alkyl substituted hemiacetals, 2‐alkyl‐butane‐1,4‐diols, and amines. The concise co‐catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.     

Catalytic asymmetric synthesis of chiral phosphanes

Chiral phosphanes, important ligands for metal-catalyzed asymmetric syntheses, are often prepared with compounds from the chiral pool, by using stoichiometric chiral auxiliaries, or by resolution. In some cases, this class of valuable compounds can be prepared more efficiently by catalytic asymmetric synthesis. This Concepts article presents an overview of these synthetic methods, including recent advances in catalysis by metal complexes, biocatalysis, organocatalysis, and ligand-accelerated catalysis.     

The combinatorial approach to asymmetric hydrogenation: phosphoramidite libraries, ruthenacycles, and artificial enzymes

For a more general implementation of asymmetric catalysis in the production of fine chemicals, the screening for new catalysts and ligands must be dramatically accelerated. This is possible with a high-throughput experimentation (HTE) approach. However, implementation of this technology requires the rapid preparation of libraries of ligands/catalysts and consequently dictates the use of simple ligands that can be readily synthesised in a robot. In this concept article, we describe how the development of new ligands based on monodentate phosphoramidites enabled the development of an integral HTE protocol for asymmetric hydrogenation. This "instant ligand library" protocol makes it possible to synthesise 96 ligands in one day and screen them the next day. Further diversity is possible by using mixtures of monodentate ligands. This concept has already led to an industrial application. Other concepts, still under development, are based on chiral ruthenacycles as new transfer hydrogenation catalysts and the use of enzymes as ligands for transition-metal complexes.     

Efficient Asymmetric Hydrogenation of α‐Acetamidocinnamates through a Simple,Readily Available Monodentate Chiral H‐Phosphinate

An air‐stable, simple (R_P)‐mentylbenzylphosphinate, readily available in large quantities, can efficiently induce the rhodium‐catalyzed asymmetric hydrogenation of α‐acetamidocinnamates with high enantioselectivity (up to 99.6 % ee). Intramolecular hydrogen bonding plays an important role in this asymmetric induction.     

Catalytic Asymmetric Synthesis of trans‐Configured β‐Lactones: Cooperation of Lewis Acid and Ion Pair Catalysis

The development of the first trans‐selective catalytic asymmetric [2+2] cyclocondensation of acyl halides with aliphatic aldehydes furnishing 3,4‐disubstituted β‐lactones is described. This work made use of a new strategy within the context of asymmetric dual activation catalysis: it combines the concepts of Lewis acid and organic aprotic ion pair catalysis in a single catalyst system. The methodology could also be applied to aromatic aldehydes and offers broad applicability (29 examples). The utility was further demonstrated by nucleophilic ring‐opening reactions that provide highly enantiomerically enriched anti‐aldol products.     

Asymmetric Catalysis with Heterobimetallic Compounds

This review focuses on a new concept in catalytic asymmetric reactions that was first realized for the use of heterobimetallic complexes. As these heterobimetallic complexes function as both a Brønsted base and as a Lewis acid, just like an enzyme, they make possible a variety of efficient catalytic asymmetric reactions. This heterobimetallic concept should prove to be applicable to a variety of new asymmetric catalyses. The first part of this review describes the development of rare-earth–alkali metal complexes such as LnM₃tris(binaphthoxide) complexes (LnMB, Ln = rare-earth metal, M = alkali metal), which are readily prepared from the corresponding rare-earth trichlorides or rare-earth isopropoxides, and their application to catalytic asymmetric synthesis. By using a catalytic amount of LnMB complexes several asymmetric reactions proceed efficiently to give the corresponding desired products in up to 98% ee: LnLB-catalyzed asymmetric nitroaldol reactions (L = Li), LnSB-catalyzed asymmetric Michael reactions (S ? Na), and LnPB-catalyzed asymmetric hydrophosphonylations of either imines or aldehydes (P ? K). Applications of these heterobimetallic catalysts to the syntheses of several biologically and medicinally important compounds are also described. Spectral analyses and computational simulations of the asymmetric reactions catalyzed by the heterobimetallic complexes reveal that the two different metals play different roles to enhance the reactivity of both reaction partners and to position them. From mechanistic considerations, a useful activation of the heterobimetallic catalyses was realized by addition of alkali metal reagents. The second part describes the development of another type of heterobimetallic catalysts featuring Group 13 elements such as Al and Ga as the central metal. Among them, the AlLibis(binaphthoxide) complex (ALB) is an effective catalyst for asymmetric Michael reactions, tandem Michael–aldol reactions, and hydrophosphonylation of aldehydes.     

Chiral Anion Phase Transfer of Aryldiazonium Cations: An Enantioselective Synthesis of C3‐Diazenated Pyrroloindolines

Herein is reported the first asymmetric utilization of aryldiazonium cations as a source of electrophilic nitrogen. This is achieved through a chiral anion phase‐transfer pyrroloindolinization reaction that forms C3‐diazenated pyrroloindolines from simple tryptamines and aryldiazonium tetrafluoroborates. The title compounds are obtained in up to 99 % yield and 96 % ee. The air‐ and water‐tolerant reaction allows electronic and steric diversity of the aryldiazonium electrophile and the tryptamine core.     

Catalytic Asymmetric Synthesis of 3,3′‐Diaryloxindoles as Triarylmethanes with a Chiral All‐Carbon Quaternary Center: Phase‐Transfer‐Catalyzed SNAr Reaction

Catalytic asymmetric synthesis of unsymmetrical triarylmethanes with a chiral all‐carbon quaternary center was achieved by using a chiral bifunctional quaternary phosphonium bromide catalyst in the S_NAr reaction of 3‐aryloxindoles under phase‐transfer conditions. The presence of a urea moiety in the chiral phase‐transfer catalyst was important for obtaining high enantioselectivity in this reaction.     

Catalytic enantioselective domino oxa-michael/aldol condensations: asymmetric synthesis of benzopyran derivatives

The first direct organocatalytic asymmetric domino oxa-Michael/aldol condensation reaction is presented. The unprecedentedly simple, chiral, pyrrolidine-catalyzed asymmetric domino reactions between salicylic aldehyde derivatives and alpha,beta-unsaturated aldehydes proceed with high chemo- and enantioselectivities to give the corresponding chromene-3-carbaldehyde derivatives in high yields and with ee values of 83-98%.     

Chiral olefins as steering ligands in asymmetric catalysis

Metal-catalyzed asymmetric processes offer one of the most straightforward ways to introduce stereogenic centers. Hence, the development of novel chiral ligands that can effectively induce asymmetry in reactions is crucial in modern organic synthesis. While many established chiral ligands bind to a metal through heteroatoms, structures that coordinate to metals through carbon atoms have received little attention so far. Here, we highlight the increasing number of such chiral chelating olefin ligands as well as their application in a variety of metal-catalyzed transformations.     

Asymmetric Triple Relay Catalysis: Enantioselective Synthesis of Spirocyclic Indolines through a One‐Pot Process Featuring an Asymmetric 6π Electrocyclization

A rare example of a one‐pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two‐step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one‐pot process gave the desired products in good yields and with excellent enantioselectivity.     

微通道反应器在不对称催化中的应用

不对称催化是合成手性化合物的重要手段,针对该领域已开展了大量的研究工作并获得了引人瞩目的研究成果。相比于传统的釜式反应器,微通道反应器具有传质/传热效率高、反应时间短、易于自动化和提高安全性等优势。因此,将微通道反应器应用于不对称催化领域已成为当前的研究热点,并且在耦合在线分析、多相催化和光催化等领域已展现出良好的应用前景。本文对近年来微通道反应器在不对称催化领域中的最新研究进展进行总结和综述,并对未来的发展方向进行展望。     

Phase‐Transfer‐Catalyzed Asymmetric SNAr Reaction of α‐Amino Acid Derivatives with Arene Chromium Complexes

Although phase‐transfer‐catalyzed asymmetric S_NAr reactions provide unique contribution to the catalytic asymmetric α‐arylations of carbonyl compounds to produce biologically active α‐aryl carbonyl compounds, the electrophiles were limited to arenes bearing strong electron‐withdrawing groups, such as a nitro group. To overcome this limitation, we examined the asymmetric S_NAr reactions of α‐amino acid derivatives with arene chromium complexes derived from fluoroarenes, including those containing electron‐donating substituents. The arylation was efficiently promoted by binaphthyl‐modified chiral phase‐transfer catalysts to give the corresponding α,α‐disubstituted α‐amino acids containing various aromatic substituents with high enantioselectivities.     

Nickel‐Catalyzed Enantioselective CC Bond Formation through CO Cleavage in Aryl Esters

We report the first enantioselective C? C bond formation through C? O bond cleavage using aryl ester counterparts. This method is characterized by its wide substrate scope and results in the formation of quaternary stereogenic centers with high yields and asymmetric induction.     

Synthesis of the Novel Chiral Catalysts by Click Chemistry and Their Application

Novel cinchonine ammonium salt derivatives have been prepared by 1,3‐dipolar cycloaddition. Their chiral catalytic efficacy was investigated in the asymmetric alkylation of N‐diphenylmethyleneglycine t‐butyl ester in the water phase. As the special structure of the catalyst, its asymmetric alkylation catalytic behavior both in organic solvents and in water is satisfactory, which is environmentally friendly.     

Versatile In Situ Generated N‐Boc‐Imines: Application to Phase‐Transfer‐Catalyzed Asymmetric Mannich‐Type Reactions

The efficient construction of nitrogen‐containing organic compounds is a major challenge in chemical synthesis. Imines are one of the most important classes of electrophiles for this transformation. However, both the available imines and applicable nucleophiles for them are quite limited given the existing preparative methods. Described herein are imine precursors which generate reactive imines with a wide variety of substituents under mild basic conditions. This approach enables the construction of various nitrogen‐containing molecules which cannot be accessed by the traditional approach. The utility of the novel imine precursor was demonstrated in the asymmetric Mannich‐type reaction under phase‐transfer conditions.     

光学活性沙丁胺醇的不对称合成研究进展

综述了不对称反应合成光学活性沙丁胺醇的研究进展。其中包括手性辅基诱导、不对称硼氢化、不对称催化氢化、不对称转移氢化、不对称双羟基化反应、酶催化的不对称氰醇化反应等。