Merging Electrosynthesis and Bifunctional Squaramide Catalysis in the Asymmetric Detrifluoroacetylative Alkylation Reactions

An enantioselective bifunctional squaramide-catalyzed detrifluoroacetylative alkylation reaction has been developed under electrochemical conditions. The unified strategy based on this key tandem methodology has been divergently explored for the asymmetric synthesis of fluorine-containing target molecules with good stereocontrol (up to 95 % ee). Furthermore, this asymmetric catalytic reaction combines the benefits of electrosynthesis and organocatalysis for the preparation of biologically relevant products containing C-F tertiary stereogenic centers.     

手性亚磷酰胺配体及其在不对称催化中的应用

由于结构稳定、合成简便、修饰容易、效果独特等优点,手性亚磷酰胺配体在近十几年得到了迅速的发展,大量基于不同骨架的配体被开发出来,并被成功地应用于多种不对称催化反应中.主要综述了该类配体在不对称共轭加成和烯丙基取代反应中的研究进展,同时也简单介绍了该类配体在其它不对称催化反应中的最新应用.     

Catalytic Asymmetric Construction of Axially Chiral Indole-Based Frameworks: An Emerging Area

Axially chiral indole-based frameworks have been recognized as a class of important five-membered heterobiaryls and developing catalytic asymmetric approaches for constructing these frameworks in an enantioselective manner is highly desirable. In recent years, synthetic chemists have paid much attention to this research field, and rapid developments have occurred. At this point, a range of axially chiral indole-based scaffolds have been constructed via various catalytic asymmetric reactions based on different strategies. Thus, the catalytic asymmetric construction of axially chiral indole-based frameworks has become an emerging area. This minireview summarizes the rapid advances in this field and gives some insights into future developments, which will help this research field to thrive.     

Asymmetric Ion‐Pairing Catalysis

Charged intermediates and reagents are ubiquitous in organic transformations. The interaction of these ionic species with chiral neutral, anionic, or cationic small molecules has emerged as a powerful strategy for catalytic, enantioselective synthesis. This review describes developments in the burgeoning field of asymmetric ion‐pairing catalysis with an emphasis on the insights that have been gleaned into the structural and mechanistic features that contribute to high asymmetric induction.     

对映选择性亲电氟化反应研究进展

含氟有机化合物, 特别是手性氟化物在医药、农药及功能性材料等相关领域的作用备受注目. 尽管在分子中有立体选择性地引入一个氟原子一直是有机化学家面临的一个挑战性问题, 近年来在化学家们的不断努力下, 对映选择性氟化反应研究取得重要进展. 高光学活性的手性氟化物可通过手性亲电氟化试剂诱导的立体选择性氟化反应, 基于底物的手性氟化反应以及手性催化剂诱导的不对称催化氟化反应等来制备. 特别是, 手性金属配合物和有机催化剂诱导的不对称催化氟化反应被广泛应用于各类手性氟化物的合成, 已成为不对称氟化反应研究的热点. 全面介绍对映选择性亲电氟化反应研究概况和最新进展, 讨论各种不对称氟化反应的特点及应用范围.     

手性双官能硫族化合物催化烯烃的不对称亲电硫化反应

手性含硫化合物在药物化学和不对称合成领域中应用广泛,发展这类化合物的新合成方法是有机合成化学的重要任务.烯烃的不对称亲电硫化反应为手性含硫化合物的合成提供了一条方便的途径,通过这种方式不仅可以在烯烃母体分子上引入一个含硫基团,同时也能够引入另外一个重要的官能团.我们课题组设计、合成了一系列手性双官能硒醚/硫醚催化剂,并成功将其应用在不同种类烯烃的分子内和分子间的不对称三氟甲硫基化、烷硫基化和芳硫基化反应,高对映选择性地合成了各种手性含硫化合物.总结了我们课题组在手性双官能硒醚/硫醚催化的烯烃不对称亲电硫化反应中的研究进展,并对该领域的发展进行展望.     

Electrochemical Asymmetric Diacetoxylation of Styrenes Mediated by Chiral Iodoarene Catalyst**

Organocatalysis with chiral iodoarenes has emerged as a powerful approach for performing enantioselective transformations. However, it suffers from the need to utilize stoichiometric amounts of peroxy acids or similar high energy oxidants. Electrosynthesis enables eliminating stoichiometric redox reagents by replacing them with electric stimuli. In this context, an electrochemically-promoted variant of the chiral iodoarene-catalyzed asymmetric diacetoxylation of styrenes was evaluated. The screening of reaction parameters established a set of conditions under which, for the first time, an enantioselective electrochemical oxidation mediated by a chiral iodoarene achieving a catalytic turnover has been accomplished. The reaction was applied for the synthesis of an array of products in 15–60 % yields and 0–84 % ee. The modest efficiency of the electrocatalysis was traced to a partial direct oxidation of styrene substrates leading to racemic products and undesired dimeric side-products. Cyclic voltammetry measurements demonstrated that such outcome originates from a somewhat difficult electrochemical oxidation of the applied iodoarene catalyst. Present work provides important insights and implications for the design of more efficient electrocatalytic systems employing chiral iodoarenes as mediators.     

Heterogeneous Enantioselective Catalysis with Chiral Encoded Mesoporous Pt−Ir Films Supported on Ni Foam

The development of heterogeneous catalysts for asymmetric synthesis is one of the most challenging topics in chemistry, as it allows obtaining enantiomerically pure compounds. Recently, metal layers incorporating molecular chiral cavities, obtained by electroreduction of a metal source in the simultaneous presence of a non-ionic surfactant and asymmetric molecules, have been proposed for a wide range of applications, including enantioselective electroanalysis and electrosynthesis, as well as chiral separation. In contrast to this previous work, solely based on electrochemical phenomena, herein we designed and employed nanostructured chiral encoded Pt−Ir alloys, supported on high surface area nickel foams, as heterogeneous catalysts for the asymmetric hydrogenation of aromatic ketones. Fine-tuning the experimental conditions allows achieving very high enantioselectivity (>80%), combined with improved catalyst stability.     

Enantioselective divergent approaches to both (−)-platensimycin and (−)-platencin

Enantioselective divergent approaches to (−)-platencin and (−)-platensimycin have been developed. A rationally designed chiral synthetic intermediate, possessing a useful α,β-unsaturated sulfone functionality, which served as a masked ketone as well as a good Michael acceptor, was successfully prepared via the highly enantioselective catalytic asymmetric intramolecular cyclopropanation (CAIMCP) developed in our laboratory.     

Catalytic Asymmetric [2+3] Cyclizations of Azlactones with Azonaphthalenes

The first catalytic asymmetric [2+3] cyclization of azlactones with azonaphthalenes has been established. This strategy allowed the synthesis of a variety of chiral isatin derivatives in generally good yields and excellent enantioselectivities (up to 99 % yield, 98 % ee). The developed reaction has not only established a catalytic enantioselective [2+3] cyclization using azlactones as two‐carbon building blocks, but also enriches the chemistry of catalytic asymmetric cyclizations of azonaphthalenes. In addition, this protocol will provide a useful method for constructing enantioenriched 3,3′‐disubstituted isatin‐type frameworks.     

Catalytic Enantioselective Amination of Alcohols by the Use of Borrowing Hydrogen Methodology: Cooperative Catalysis by Iridium and a Chiral Phosphoric Acid

The catalytic asymmetric reduction of ketimines has been explored extensively for the synthesis of chiral amines, with reductants ranging from Hantzsch esters, silanes, and formic acid to H₂ gas. Alternatively, the amination of alcohols by the use of borrowing hydrogen methodology has proven a highly atom economical and green method for the production of amines without an external reductant, as the alcohol substrate serves as the H₂ donor. A catalytic enantioselective variant of this process for the synthesis of chiral amines, however, was not known. We have examined various transition‐metal complexes supported by chiral ligands known for asymmetric hydrogenation reactions, in combination with chiral Brønsted acids, which proved essential for the formation of the imine intermediate and the transfer‐hydrogenation step. Our studies led to an asymmetric amination of alcohols to provide access to a wide range of chiral amines with good to excellent enantioselectivity.     

Catalytic Kinetic Resolution of Biaryl Compounds

Biaryl compounds with axial chirality are very common in synthetic chemistry, especially in catalysis. Axially chiral biaryls are important due to their biological activities and extensive applications in asymmetric catalysis. Thus the development of efficient enantioselective methods for their synthesis has attracted considerable attention. This Minireview discusses the progress made in catalytic kinetic resolution of biaryl compounds and chronicles significant advances made recently in catalytic kinetic resolution of biaryl scaffolds.     

Catalytic Enantioselective Aza-pinacol Rearrangement

The first catalytic enantioselective asymmetric aza-pinacol rearrangement is reported. The reactions are catalyzed by a chiral phosphoric acid and proceed via a highly organized transition state involving a cyclic aza-ortho-xylylene intermediate to afford the indoline structures with good to excellent enantioselectivity. The synthetic utility of this method is demonstrated by the asymmetric synthesis of a key intermediate to the natural product minfiensine and the identification of a chiral lead compound to repress antibiotic resistance.     

手性炔丙醇的不对称催化合成研究进展

手性炔丙醇是一种重要中间体化合物,作为合成多种光学活性化合物的重要合成前体受到学者们广泛关注。目前通过酮的不对称催化反应合成手性炔丙醇的研究开发具有极大发展前景,因此本文围绕酮类化合物的不对称催化反应来进行综述,结合相关反应最新研究进展,全面总结并分类了不对称催化还原、催化不对称加成等反应类型,介绍了合成不同结构手性炔丙醇的新思路,并对酮的不对称催化反应在未来能成为工业化重要生产途径作出展望。     

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost‐effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo‐ and organometal‐catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles.     

Catalytic,Enantioselective Synthesis of 1,2‐anti‐Diols by Asymmetric Ring‐Opening/Cross‐Metathesis

An enantioselective method for the synthesis of 1,2‐anti‐diols has been developed. A cyclometalated chiral‐at‐ruthenium complex catalyzes the asymmetric ring‐opening/cross‐metathesis of dioxygenated cyclobutenes, thus resulting in functionally rich synthetic building blocks. Syntheses of the insect pheromone (+)‐endo‐brevicomin and monosaccharide ribose demonstrate the synthetic utility of the 1,2‐anti‐diol fragments generated in the title reaction.     

Construction of All-Carbon Chiral Quaternary Centers through CuI-Catalyzed Enantioselective Reductive Hydroxymethylation of 1,1-Disubstituted Allenes with CO2

A catalytic enantioselective construction of all-carbon chiral quaternary centers through reductive hydroxymethylation of 1,1-disubstituted allenes with CO₂ has been developed. In the presence of a copper/Mandyphos catalyst, CO₂ is transformed into an alcohol oxidation level by an asymmetric reductive C−C bond formation with allenes by using hydrosilane (HSi(OMe)₂Me) as a reductant. The resulting chiral homoallylic alcohols are versatile synthetic intermediates and can be conveniently converted into a variety of useful chiral chemicals.     

Recent Developments in Asymmetric Phase‐Transfer Reactions

Phase‐transfer catalysis has been recognized as a powerful method for establishing practical protocols for organic synthesis, because it offers several advantages, such as operational simplicity, mild reaction conditions, suitability for large‐scale synthesis, and the environmentally benign nature of the reaction system. Since the pioneering studies on highly enantioselective alkylations promoted by chiral phase‐transfer catalysts, this research field has served as an attractive area for the pursuit of “green” sustainable chemistry. A wide variety of asymmetric transformations catalyzed by chiral onium salts and crown ethers have been developed for the synthesis of valuable organic compounds in the past several decades, especially in recent years.     

Axially Chiral Aryl‐Alkene‐Indole Framework: A Nascent Member of the Atropisomeric Family and Its Catalytic Asymmetric Construction

A new class of axially chiral aryl‐alkene‐indole frameworks have been designed, and the first catalytic asymmetric construction of such scaffolds has been established by the strategy of organocatalytic (Z/E)‐selective and enantioselective (4+3) cyclization of 3‐alkynyl‐2‐indolylmethanols with 2‐naphthols or phenols (all >95 : 5 E/Z, up to 98% yield, 97% ee). This reaction also represents the first catalytic asymmetric construction of axially chiral alkene‐heteroaryl scaffolds, which will add a new member to the atropisomeric family. This approach has not only confronted the great challenges in constructing axially chiral alkene‐heteroaryl scaffolds but also provided a powerful strategy for the enantioselective construction of axially chiral aryl‐alkene‐indole frameworks.     

Catalytic enantioselective peroxidation of alpha,beta-unsaturated ketones

Despite the potential of chiral peroxides as biologically interesting or even clinically important compounds, no catalytic enantioselective peroxidation has been reported. With a chiral catalyst not only to induce enantioselectivity but also to convert a well established epoxidation pathway into a peroxidation pathway, the first efficient catalytic peroxidation has been successfully developed. Employing readily available alpha,beta-unsaturated ketones and hydroperoxides and an easily accessible cinchona alkaloid catalyst, this novel reaction will open new possibilities in the asymmetric synthesis of chiral peroxides. Under different conditions a highly enantioselective epoxidation with the same starting materials, reagents, and catalyst has was also established.