Metal-catalyzed Asymmetric Reactions Research Articles

P(III)-Directed Asymmetric C-H Arylation toward Planar Chiral Ferrocenes by Palladium Catalysis.

Planar chiral ferrocenyl phosphines have been employed as highly valuable ligands in metal-catalyzed asymmetric reactions. However, their preparation remains a formidable challenge due to the requirement for intricate, multistep synthetic sequences. In addressing this issue, we have developed a groundbreaking enantioselective C-H activation strategy facilitated by P(III) directing groups, enabling the efficient construction of planar chiral ferrocenyl phosphines in a single step. Our innovative approach entails the combination of a palladium catalyst, a parent ferrocenyl phosphine, and a chiral phosphoramidite ligand, leading to exceptional reactivity and enantioselectivity. Remarkably, these novel ligands exhibit remarkable efficacy in silver-catalyzed asymmetric 1,3-dipolar cycloadditions. We carried out a combination of experimental and computational studies to obtain a more comprehensive understanding of the reaction pathway and the factors contributing to enantioselectivity.

Recent advances in Pd-catalyzed asymmetric cyclization reactions.

Over the past few decades, there have been major developments in transition metal-catalyzed asymmetric cyclization reactions, enabling the convenient access to a wide spectrum of structurally diverse chiral carbo- and hetero-cycles, common skeletons found in fine chemicals, natural products, pharmaceuticals, agrochemicals, and materials. In particular, a plethora of enantioselective cyclization reactions have been promoted by chiral palladium catalysts owing to their outstanding features. This review aims to collect the latest advancements in enantioselective palladium-catalyzed cyclization reactions over the past eleven years, and it is organized into thirteen sections depending on the different types of transformations involved.

Metal-catalyzed asymmetric reactions enabled by organic peroxides.

As a class of multifunctional reagents, organic peroxides play vital roles in the chemical industry, pharmaceutical synthesis and polymerization reactions. Metal-catalyzed asymmetric catalysis has emerged as one of the most straightforward and efficient strategies to construct enantioenriched molecules, and an increasing number of metal-catalyzed asymmetric reactions enabled by organic peroxides have been disclosed by researchers in recent years. Despite remarkable progress, the types of asymmetric reactions facilitated by organic peroxides remain limited and the catalysis systems need to be further broadened. To the best of our knowledge, there is still no review devoted to summarizing the reactions from this perspective. In this review, we will endeavor to highlight the advances in metal-catalyzed asymmetric reactions enabled by organic peroxides. We hope that this survey will summarize the functions of organic peroxides in catalytic reactions, improve the understanding of these compounds and inspire future developments in this area.

P(III)-Chirogenic Phosphinite Building Blocks by Stereospecific N→O Phosphinyl Migration.

In the recent past, the chirality borne by a phosphorus center has aroused growing interest in many fields, and the development of new methodologies, notably using inexpensive reagents and simple experimental conditions, has become topical. An efficient stereoselective synthesis of P-chirogenic phosphinites useful as chiral phosphorus building blocks is herein described thanks to a new intramolecular phosphorus rearrangement based on P*(III)-phosphinyl N→O migration. This rearrangement was performed by heating at 50 °C aminophosphine-boranes, easily prepared from chiral amino alcohols, with DABCO in toluene overnight. Twenty-seven P-chirogenic phosphinites and borane complexes were thus prepared in yields up to 89%. The crude P*(III)-phosphinites were in situ used in stereoselective synthesis of P-chirogenic aminophosphine-phosphinites, phosphinothioates, sec- and tert-phosphine-oxides, and mono- and diphosphines in overall yields ranging from 28 to 89% and with e.e. up to 99%. Twenty-one X-ray structures of P-chirogenic compounds were established, allowing us to attribute undoubtedly their absolute configuration and the stereochemistry of the reactions. Finally, new ferrocenyl-bridged diphosphine ligands synthesized from P*(III)-chirogenic diphosphinites were tested in asymmetric metal-catalyzed reactions, providing enantioselectivities up to 95% e.e. in allylation of α-naphthylmethylamine at room temperature. To conclude, this rearrangement opens up an efficient new way for the stereoselective synthesis of numerous classes of P-chirogenic phosphorus compounds, notably bearing bulky substituents.

Coinage Metal-Catalyzed Asymmetric Reactions of ortho-Alkynylaryl and Heteroaryl Aldehydes and Ketones.

Coinage metals have become the metal of choice due to their excellent catalytic activity in organic transformation processes. Combining various chiral ligands and coinage metals became a productive area of research and access to heterocyclic derivatives according to an efficient and sustainable manner. This review was devoted to the various recently developed coinage metal-catalyzed domino processes of ortho-alkynylaryl and heteroaryl aldehydes and ketones leading to functionalized heterocycles. Various gold chiral complexes were presented, and methods of preparations of chromenes along with indoles were covered. Ag-chiral complexes are also prone to interesting activities such as cyclization followed by reduction and functionalization with enolizable ketones or (diazomethyl)phosphonate. Asymmetric Cu-catalyzed domino cyclization and asymmetric transfer hydrogenation reactions efficiently led to functionalized chromenes. Some remarkable examples involving copper associated with ruthenium in the context of a cyclization and asymmetric hydrogenation process were also presented.

Progress in Transition Metal-Catalyzed Asymmetric Ring-Opening Reactions of Epoxides and Aziridines

Progress in Transition Metal-Catalyzed Asymmetric Ring-Opening Reactions of Epoxides and Aziridines

Organosilanes in Metal-Catalyzed, Enantioselective Reductions

The growth and development of an extensive range of metals complexed with chiral ligands for the purpose of catalyzing a variety of reactions in an enantioselective manner has been impressive for its scope, chemical yields and high ee values. Chief among the classes of synthetic transformations has been that of the asymmetric reduction of prochiral substrates. These include the asymmetric reduction of prochiral ketones, imines, unsaturated aldehydes, ketones, esters, nitriles and olefins, as well as a number of asymmetric coupling reactions. In concert with these efficient catalyst systems, organosilanes have the ability to carry out any number of organic reductions under a variety of conditions. In these reactions, which in reality are hydrosilylations (hydrosilylation and reduction are considered interchangeable herein) in which the initially resulting silylated product is hydrolyzed to the ultimate desired functionality, the ability to sterically and electronically alter the organosilane reductant can contribute to the overall success of the transformation. In this review, we present a thorough compilation of the literature covering the use of organosilanes in metal-catalyzed asymmetric reductions (hydrosilylations) and coupling reactions.

Low-Temperature Nickel-Catalyzed C-N Cross-Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N-Heterocyclic Carbene Ligand.

The transition-metal-catalyzed C-N cross-coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low-temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low-temperature (as low as -50 °C), enantioselective Ni-catalyzed C-N cross-coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N-heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ-bonds on the C2 -symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal-catalyzed asymmetric cross-coupling reactions.

Transition metal catalyzed asymmetric multicomponent reactions of unsaturated compounds using organoboron reagents.

Asymmetric multicomponent reactions allow stitching several functional groups in an enantioselective and atom economical manner. The introduction of boron-based reagents as a multicomponent coupling partner has its own merits. In addition to being non-toxic and highly stable, organoboron compounds can be easily converted to other functional groups in a stereoselective manner. In the last decade several transition metal catalyzed asymmetric multicomponent strategies have been evolved using boron based reagents. This review will discuss the merits and scope of multicomponent strategies based on their difference in the reaction mechanism and transition metals involved.

Chiral <italic>N</italic>,<italic>N</italic>ʹ-dioxide and their metal complexes in asymmetric catalysis

Chirality is a fundamental property of nature. Chiral compounds are closely related to life science, human health, material science, and so on. Asymmetric catalysis is one of the most efficient and important synthetic methodologies to obtain chiral compounds, which meets the requirement of green chemistry. Metal-catalyzed asymmetric reactions attract much attention in the past few years, and thousands of chiral ligands have been synthesized, however, widely applicable, so-called privileged chiral ligands are still very limited. Therefore, the design and synthesis of highly efficient and selective chiral ligands becomes the most important and challenging goal. Our group is committed to asymmetric catalysis and develope a novel type of C 2-symmetric chiral ligand of N , N ʹ-dioxide amide compounds which is easily synthesized from cheap chiral amino acids and amines. Such conformationally flexible privileged ligands break through the notion of the rigid feature of previously privileged ligands. Naturally, it would guide the creation of new ideal chiral ligands and catalysts. N , N ʹ-dioxides are not only used as bifunctional organocatalysts, but also provide an arsenal of chiral metal complexes upon coordination with a variety of metal salts, such as alkaline-earth metal salts, transition metal salts and rare-earth metal salts. This powerful catalyst system has been proved to be highly effective for more than fifty types of asymmetric reactions with wide substrate generality under mild conditions, including carbon-carbon bond formation, and carbon-heteroatom bond formation reactions. The concerns of controlling chemo-, regio-, and stereoselectivity of involved reactions are well addressed. Some new and challengling asymmetric reactions are realized, for intances, the first asymmetric Roskamp reaction is achieved with a N , N ʹ-dioxide/Sc(III) complex at low catalyst loading, which updates the comment about β-keto esters in text of Organic Chemistry , Oxford, and the reaction is amended as “Roskamp-Feng reaction” in Elsevier’s Organic Synthesis Based on Name Reactions . The asymmetric amination of ketones with α-diazoesters shed light on the diversity of diazo chemistry. N , N ʹ-dioxide/La(III) complex catalyzed sulfa-Michael reaction exhibits very strong chiral amplification effect. N , N ʹ-dioxide/Ni(II) complex acts as both chiral Lewis catalyst and metal-carbene promotor in Doyle-Kirmse reaction, [ 2 , 3 ] -Stevens rearrangement and Sommelet-Hauser rearrangement of a new type of designed α-diazo pyrazoleamides. Such the creation of catalytic systems and catalytic asymmetric methods provide simple, efficient, precise, green access to several biologically active drug molecules and natural products, such as Paroxetine, Pregabalin, Thiazesim, KAE609 and so on. Now, N , N ʹ-dioxides have become commercially available chiral ligands and have been successfully applied by many research groups and companies. The above original and systematic research achievements make important contribution to the chirality science.

Novel chiral diamidophosphites for asymmetric metal-catalyzed reactions

Chiral diamidophosphites with 1,3,2-diazaphospholidine cycles were prepared. A study of these chiral inducers showed them to provide up to 97% ee in the Pd-catalyzed allylic alkylation of (E)-1,3-diphenylallyl acetate with dimethyl malonate.

Diamidophosphites with P*-stereocentres and their performance in metal-catalyzed enantioselective reactions

In this mini-review, the application of P*-chiral diamidophosphites in metal-catalyzed asymmetric reactions. These ligands demonstrate moderate to high levels of asymmetric induction in Pd-catalyzed enantioselective allylations of (E)-1,3-diphenylallyl acetate, desymmetrizations of N,N’-ditosyl-meso-cyclopent-4-ene-1,3-diol bis-carbamate, in the asymmetric construction of quaternary carbon stereocenters and Rh-catalyzed hydrogenation of (Z)-methyl 2-acetamido-3-phenylacrylate.

Recent advances in chiral imino-containing ligands for metal-catalyzed asymmetric transformations.

In this review, the recent applications of a variety of chiral imino-containing ligands classified by different types of metal-catalyzed asymmetric reactions are summarized. The progress made in this area would encourage us to design and synthesize more novel chiral imino-containing ligands, and explore their applications in metal-catalyzed asymmetric transformations.

ChemInform Abstract: Applications and Stereoselective Syntheses of P‐Chirogenic Phosphorus Compounds

AbstractReview: [183 refs.

Chiral Bidentate NHC Ligands Based on the 1,1'-Binaphthyl Scaffold: Synthesis and Application in Transition-Metal-Catalyzed Asymmetric Reactions.

The use of the chiral 1,1'-binaphthyl scaffold to construct chiral ligands can be traced back for a long time. However, the development of bidentate NHC ligands based on the same backbone has only appeared recently. In this account, we describe the design and synthesis of a new family of chiral NHC ligands based on the 1,1'-binaphthyl scaffold and demonstrate the applications of these chiral NHC-metal complexes in the catalyzed oxidative kinetic resolution of secondary alcohols, asymmetric carbon-carbon bond formations, hydrosilylations, and cyclizations of 1,6-enynes. The chiral NHC ligands containing the 1,1'-binaphthyl backbone can be synthesized in good yields from enantiomerically pure 1,1'-binaphthyl-2,2'-diamine. These transition metals coordinated with chiral bidentate NHC ligands exhibit high catalytic activities and good enantioselectivities for a wide range of metal-catalyzed asymmetric reactions.

Progress in Transition Metal-Catalyzed Asymmetric Ring-Opening Reactions of Oxa(Aza)bicyclic Alkenes with Carbanion Nucleophiles

The recent progress in transition metal-catalyzed asymmetric ring-opening reactions of oxa(aza)bicyclic alkenes with carbanion nucleophiles was reviewed focused on the influence of the types of transition metal catalysts, carbanion nucleophiles, ligands, the structures of oxa(aza)bicyclic alkenes, solvents and additives on the asymmetric ring-opening reactions. Moreover, the parties of possible mechanisms for the asymmetric ring-opening reactions were also discussed.

ChemInform Abstract: Recent Applications of Chiral N‐tert‐Butanesulfinyl Imines, Chiral Diene Ligands and Chiral Sulfur‐Olefin Ligands in Asymmetric Synthesis

AbstractReview: 104 refs.

P(O)R2-directed Pd-catalyzed C-H functionalization of biaryl derivatives to synthesize chiral phosphorous ligands.

Chiral phosphorus ligands have been widely used in transition metal-catalyzed asymmetric reactions. Herein, we report a new synthesis approach of chiral biaryls containing a phosphorus moiety using P(O)R2-directed Pd-catalyzed C–H activation; the functionalized products are produced with good enantioselectivity.

ChemInform Abstract: DIFLUORPHOS and SYNPHOS in Asymmetric Catalysis: Synthetic Applications

AbstractReview: 58 refs.

Metalloporphyrin Symmetry in Chiral Recognition and Enantioselective Catalysis

Symmetry plays a fundamental role in chiral recognition and enantioselective catalysis. Porphyrins possess a number of structural features that make them attractive for the stereocontrol of chiral recognition and metal-catalyzed asymmetric reactions. This article is a brief account of our studies on chiral recognition and enantioselective catalysis by optically active metalloporphyrins. Some of the studies on chiral recognition and asymmetric catalysis by metalloporphyrins performed by others have also been included when useful.