Organocatalysis mediated by (thio)urea derivatives

Over the last decade the potential for N,N-dialkyl(thio)urea derivatives to serve as active metal-free organocatalysts for a wide range of synthetically useful reactions susceptible to the influence of general acid catalysis has begun to be realised. This article charts the development of these catalysts (with emphasis on the design principles involved), from early "proof-of-concept" materials to contemporary active chiral (bifunctional) promoters of highly selective asymmetric transformations.     

Recent topics in dual hydrogen bonding catalysis

Dual hydrogen bonding donors have received much attention in the area of organocatalysis after the discovery of chiral thiourea derivatives that act as asymmetric catalysts. This digest focuses on recent advances in this area categorized in the following three topics: 1) enhanced hydrogen bonding donor catalysis; new scaffolds with improved reactivity and selectivity are introduced and compared with established catalysts; 2) anion binding catalysis; recent advances in terms of catalysts and their applications is addressed; 3) multiple catalysis involving dual hydrogen bonding catalysts; a relatively new field of dual hydrogen bonding donor catalysis combined with other catalysis is introduced.     

"Asymmetric" catalysis by lanthanide complexes

Catalysis with lanthanide (Ln) complexes has been underestimated for long time, although Ln(III) complexes have great advantages as Lewis acid catalysts for "asymmetric" carbon-carbon bond-forming reactions. Lanthanide complexes are highly active in ligand-substitution reactions, especially with hard ligands. The association with substrates and dissociation of products are achieved fast enough for high catalyst efficiency. The asymmetric catalysis of organic reactions can be greatly advanced by the use of Ln complexes with chiral ligands such as binaphthol (binol). Ln(II) complexes are good reducing agents, which can be used in a wide variety of synthetically important reactions; when chiral ligands are used, many of these reactions are highly stereoselective. In the context of "green chemistry", the development of asymmetric Ln catalysts, and their recyclable use, is of increasing importance. This review gives an overview of the most recent developments in catalysis with lanthanide(II) and lanthanide(III) complexes.     

Asymmetric catalysis of metal complexes with non-planar ONNO ligands: salen, salalen and salan

Chiral metal (M)-salen complexes are one of the most versatile asymmetric catalysts and the catalysis of trans-M(salen) complexes has been well cultivated. On the other hand, non-planar cis-beta M(salen) complexes were recently found to show unique asymmetric catalysis that cannot be attained by trans-M(salen) complexes. Moreover, related non-planar M(salalen) and M(salan) complexes were also found to exert unprecedented asymmetric catalysis. This Feature Article summarizes the seminal studies on asymmetric catalysis of non-planar M(ONNO) complexes, full utilization of which will provide marked improvement in asymmetric synthesis.     

Asymmetric activation of tropos species in the achievement of chiral inducers for enantioselective catalysis

The use of chiral derivatives embedding flexible chiral moieties in enantioselective catalysis is reported and the compounds are classified as chiral ligands for metal catalysis, on the basis of the coordinating atom and phase transfer catalysts. The use of phosphorus, nitrogen, and oxygen ligands as well as the development of organocatalysts, with these structural features, outlines the wide applicability of this approach to asymmetric catalysis.     

Ligand and substrate π-stacking interaction controlled enantioselectivity in the asymmetric aziridination

Both the steric hindrance and the electronic effect are important factors for controlling the enantioselectivity in asymmetric catalysis. The substituent-dependent enantioselectivity in the asymmetric aziridination of chalcones catalyzed by 1,8-anthracene-linked bis-oxazoline (AnBOX) was rationalized to the π-stacking interaction between the ligand backbone and substrates and primarily confirmed by the use of bulky substrates and catalysts without aromatic backbones. The results provide important information for designing novel ligands and for understanding the influence of the electronic effect in asymmetric catalysis.     

Enantioselective Synthesis of Isoquinolines: Merging Chiral‐Phosphine and Gold Catalysis

The highly enantioselective synthesis of dihydroisoquinoline derivatives from aromatic sulfonated imines tethered with an alkyne moiety, through a one‐pot asymmetric relay catalysis of chiral‐phosphine and gold catalysts, is reported. Enantiomerically enriched dihydroisoquinoline derivatives were afforded in good yields and good‐to‐excellent ee values under mild conditions, based on the asymmetric aza‐Morita‐Baylis–Hillman reaction. Dihydroisoquinoline derivatives containing two chiral centers were also synthesized through further transformations.     

Self-supported chiral catalysts for heterogeneous enantioselective reactions

The development of heterogeneous chiral catalysts for enantioselective reactions is highly desirable in order to overcome some drawbacks of homogeneous catalysts. Different from the conventional approaches by using various types of supports or biphasic systems for the recovery and reuse of homogeneous catalysts, a conceptually new strategy for heterogenization of homogeneous chiral catalysts, that is, a "self-supporting" approach, has been developed to use homochiral metal-organic coordination polymers generated by the self-assembly of chiral multitopic ligands with metal ions, and thus obviates the use of any support. In this concept article, the success of this "self-supporting" strategy will be exemplified in heterogeneous catalysis of asymmetric carbonyl-ene, sulfoxidation, epoxidation, and asymmetric hydrogenation reactions.     

Enantioselective organo-cascade catalysis

A new strategy for organocatalysis based on the biochemical blueprints of biosynthesis has enabled a new laboratory approach to cascade catalysis. Imidazolidinone-based catalytic cycles, involving iminium and enamine activation, have been successfully combined to allow a large diversity of nucleophiles (furans, thiophenes, indoles, butenolides, hydride sources, tertiary amino lactone equivalents) and electrophiles (fluorinating and chlorinating reagents) to undergo sequential addition with a wide array of alpha,beta-unsaturated aldehydes. These new cascade catalysis protocols allow the invention of enantioselective transformations that were previously unknown, including the asymmetric catalytic addition of the elements of HF across a trisubstituted olefin. Importantly, these domino catalysis protocols can be mediated by a single imidazolidinone catalyst or using cycle-specific amine catalysts. In the latter case, cascade catalysis pathways can be readily modulated to provide a required diastereo- and enantioselective outcome via the judicious selection of the enantiomeric series of the amine catalysts. A central benefit of combining multiple asymmetric organocatalytic events into one sequence is the intrinsic requirement for enantioenrichment in the second induction cycle, as demonstrated by the enantioselectivities obtained throughout this study (>/=99% ee in all cases).     

手性氨基酚催化二乙基锌对芳香醛的不对称加成反应

用易得的原料合成了4个手性氨基酚，这些化合物成功地催化了二乙基锌对醛 的不对称加成反应．其中1a催化间氯苯甲醛和二乙基锌的加成反应获得了较高的化 学产率(95％)和较好的ee值(57％)．     

Asymmetric Catalysis with Bis(hydroxyphenyl)diamides/Rare‐Earth Metal Complexes

A series of asymmetric catalysts composed of conformationally flexible amide‐based chiral ligands and rare‐earth metals was developed for proton‐transfer catalysis. These ligands derived from amino acids provide an intriguing chiral platform for the formation of asymmetric catalysts upon complexation with rare‐earth metals. The scope of this arsenal of catalysts was further broadened by the development of heterobimetallic catalytic systems. The cooperative function of hydrogen bonding and metal coordination resulted in intriguing substrate specificity and stereocontrol, and the dynamic nature of the catalysts led to a switch of their function. Herein, we summarize our recent exploration of this class of catalysts.     

Engineering Chiral Catalysts through Asymmetric Activation and Super High Throughput Screening (SHTS)

A conceptually new strategy for asymmetric catalysis, namely asymmetric activation, in which a chiral activator selectively activates one enantiomer of a racemic chiral catalyst, and a highly efficient screening system for finding the most effective catalysts, namely super high throughput screening (SHTS), by which the reaction can be conducted in parallel and the ee% of the product is allowed to determine within minutes, are summarized in the present account. It is reasonable to believe that SHTS technique combined with asymmetric activation or deactivation principle will provide a very powerful methodology for finding the new catalysts and the best catalyst tuning for asymmetric reactions.     

Chiral Frustrated Lewis Pair@Metal-Organic Framework as a New Platform for Heterogeneous Asymmetric Hydrogenation

Asymmetric hydrogenation, a seminal strategy for the synthesis of chiral molecules, remains largely unmet in terms of activation by non-metal sites of heterogeneous catalysts. Herein, as demonstrated by combined computational and experimental studies, we present a general strategy for integrating rationally designed molecular chiral frustrated Lewis pair (CFLP) with porous metal–organic framework (MOF) to construct the catalyst CFLP@MOF that can efficiently promote the asymmetric hydrogenation in a heterogeneous manner, which for the first time extends the concept of chiral frustrated Lewis pair from homogeneous system to heterogeneous catalysis. Significantly, the developed CFLP@MOF, inherits the merits of both homogeneous and heterogeneous catalysts, with high activity/enantio-selectivity and excellent recyclability/regenerability. Our work not only advances CFLP@MOF as a new platform for heterogeneous asymmetric hydrogenation, but also opens a new avenue for the design and preparation of advanced catalysts for asymmetric catalysis.     

Aminocatalytic asymmetric Diels–Alder reaction of phosphorus dienophiles and 2,4-dienals

Chiral compounds bearing a phosphorus functional group are valuable because of their wide application in biological studies and asymmetric catalysis. Here we present an asymmetric Diels–Alder cycloaddition between phosphor-containing dienophiles and 2,4-dienals under the catalysis of chiral amine 1 via the intermediacy of trienamine species (trienamine catalysis). A spectrum of densely functionalized phosphonocyclohexene derivatives was efficiently constructed in excellent enantioselectivity (up to 99% ee) and with good to high diastereoselectivity (up to >19:1).     

Catalysts Based on Amino Acids for Asymmetric Reactions in Water

Wet and wild : Water is a powerful force in nature, as evident in the painting “ES” by Zdzislaw Beksinski (1985, oil, 92 cm×90 cm; reproduced with permission from Piotr Dmochowski), as well as a promising medium for asymmetric reactions. As catalysts, natural amino acids are ideal candidates. This Minireview summarizes recent advances in asymmetric catalysis in water, with amino acids and their derivatives as effective catalysts or essential components.

     

Stereogenic‐Only‐at‐Metal Asymmetric Catalysts

Chirality is an essential feature of asymmetric catalysts. This review summarizes asymmetric catalysts that derive their chirality exclusively from stereogenic metal centers. Reported chiral‐at‐metal catalysts can be divided into two classes, namely, inert metal complexes, in which the metal fulfills a purely structural role, so catalysis is mediated entirely through the ligand sphere, and reactive metal complexes. The latter are particularly appealing because structural simplicity (only achiral ligands) is combined with the prospect of particularly effective asymmetric induction (direct contact of the substrate with the chiral metal center). Challenges and solutions for the design of such reactive stereogenic‐only‐at‐metal asymmetric catalysts are discussed.     

Asymmetric cooperative catalysis in the conjugate addition of pyrazolones to nitroolefins and subsequent dearomative chlorination

Over the past decade many bifunctional amine-thioureas have been developed as active metal-free organocatalysts.Cooperative catalysis of these amino-thioureas allows high reaction rates and excellent transfer of stereochemical information.Despite these impressive advances,the design of new high-performance catalysts for applications in asymmetric catalytic reactions is of ongoing interest in organic chemistry.Herein we describe a cooperative catalyst system consisting of a chiral aminethiourea and an achiral organic acid that promotes the conjugate addition of 4-nonsubstituted pyrazolones to nitroolefins and subsequent dearomative chlorination.The corresponding adducts and the subsequent products were obtained in high to excellent yields(up to 99%)and high stereoselectivities(up to 99/1 dr,98%ee)under mild reaction conditions.These transformations provide an easy access to enantio-enriched pyrazole derivatives,which could possess potential pharmaceutical activity.     

Recent advances in gold-complex and chiral organocatalyst cooperative catalysis for asymmetric alkyne functionalization

Homogeneous gold catalysis has demonstrated the preponderant capability of realizing a broad range of synthetically versatile alkyne functionalization over the last two decades. Though catalytic asymmetric alkyne transformation has focused on the principle of using gold catalysts either associated with chiral phosphine ligand or combined with chiral counterion, a variety of breakthroughs have been reported with the application of gold-complex and chiral organocatalyst cooperative catalysis strategy, which could enable the challenging transformations that cannot be realized by mono-catalysis with excellent stereoselectivity. This review will cover two general protocols in this field, including relay catalysis and synergistic catalysis, with emphasis on the detailed cooperative catalysts models to illustrate the roles of the two catalysts and highlight the potential synthetic opportunities offered by asymmetric cooperative catalysis.     

Catalytic asymmetric synthesis of piperidine derivatives through the [4 + 2] annulation of imines with allenes

Although tertiary phosphines have emerged as remarkably versatile nucleophilic catalysts, there has been only very limited progress in achieving asymmetric catalysis with chiral phosphines. In this report, the first highly enantioselective variant of the Kwon annulation of imines with allenes is described. Thus, C2-symmetric chiral phosphepine 1 serves as an effective catalyst for this powerful process, furnishing an array of functionalized piperidine derivatives with very good stereoselectivity.     

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.