Search

A novel Pd0 -catalyzed asymmetric [4+3] annulation reaction of two readily accessible starting materials has been developed for building seven-membered heterocyclic architectures. The potential [3+2] side pathway could be suppressed though fine tuning of the conditions. A broad scope of cycloaddition donors and acceptors participated in the transformation with excellent chemo-, regio-, diastereo-, and enantioselectivtities, leading to valuable tetrahydroazepines and benzo[b]oxepines.

A general method for asymmetric synthesis of heteroaryl-containing cycles via palladium-catalyzed cyclization is reported. Most classes of nitrogen-containing aromatics, including pyridines, quinolines, pyrimidines, various azoles and the derivatives of nucleobases are compatible substrates, offering various heteroaryl-substituted cyclopentane, pyrrolidine, furanidine and bicyclo[4.3.1]decadiene derivatives with good to excellent enantioselectivity and diastereoselectivity.

We describe the development of a Pd-catalyzed decarboxylative asymmetric allylic alkylation of α-nitro allyl esters to afford acyclic tetrasubstituted nitroalkanes. Optimization of the reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo- and enantioselective C-alkylation of electronically challenging benzylic nitronates and sterically encumbered 2-allyl esters. Substrates were efficiently accessed in a combinatorial fashion by a cross-Claisen/ α-arylation sequence. The method provides functional group orthogonality that complements nucleophilic imine allylation strategies for α-tertiary amine synthesis.

A novel Pd0 -catalyzed highly regio- and enantioselective [3+2] spiroannulation reaction has been developed for rapid assembly of a new class of [5,5] spirocyclic carbo- and heterocycles. Notably, the regioselectivity could be dominated by fine-tuning of the Pd-π-allyl intermediate. An array of coupling partners could be well-tolerated with excellent regio-, and enantioselectivities. Moreover, the potential application of this reaction was exemplified by several further transformations.

Enolate chemistry is one of the most fundamental strategies for the formation of carbon-carbon and carbon-heteroatom bonds. Classically, this has been accomplished through the use of stoichiometric quantities of strong base and cryogenic reaction temperatures. However, these techniques present issues related to enolate regioselectivity and functional group tolerance. While more modern methods utilizing stoichiometric activating agents have overcome some of these limitations, these processes add additional steps and suffer from poor atom economy. While certain classes of highly acidic nucleophiles have enabled the development of elegant and general catalytic solutions to address all of these limitations, functionalizing less acidic nucleophiles remains difficult.To overcome these challenges, we developed an alternative general approach for the formation and subsequent functionalization of metal enolates that leverages catalytic amounts of Lewis acid and entirely avoids the need for exogenous base or stoichiometric additives. To do so, we re-engineered the classical Meyer-Schuster rearrangement, which normally converts propargylic alcohols into α,β-unsaturated carbonyl compounds. By careful control of reaction conditions and by selection of an appropriate vanadium-oxo catalyst, the transient metal enolates formed via the 1,3-transposition of propargylic or allenylic alcohols can be guided away from simple protonation reaction pathways and toward more synthetically productive carbon-carbon, carbon-halogen, and carbon-nitrogen bond-forming processes.By utilizing readily available propargylic and allenylic alcohols as our starting materials and relying on a catalytic 1,3-transposition to generate metal enolates

The catalytic asymmetric synthesis of complex molecules has been the focus of our research program for several decades because such strategies have significant utility for the construction of chiral building blocks for drug development as well as the total synthesis of natural products. Cycloaddition reactions are very powerful transformations in organic synthesis providing access to highly functionalized motifs from simple starting materials. In concert with this central interest, four decades ago, we reported the palladium-catalyzed trimethylenemethane (TMM) cycloaddition for forging odd-membered ring systems. In recent years, we focused our attention on the development of powerful ligand scaffolds which enable the preparation of valuable products with complete control of chemo-, regio-, diastereo-, and enantioselectivity, thereby addressing several limitations in the field of palladium-catalyzed asymmetric cycloadditions. The first section of this Account will outline the discovery of a new class of highly modular pyrrolidine-based phosphoramidite and diamidophosphite chiral ligands which facilitate [3 + 2] cycloadditions of TMM donors, opening a new area in asymmetric construction of five-membered rings.The formation of the Pd-TMM zwitterionic intermediates is driven by the unique charge distribution of the cationic π-allyl motif, in which the most electropositive central carbon stabilizes the neighboring carbanion generated by either desilylation or deprotonation. The second section of this Account summarizes the scope of cycloadditions between Pd-TMM zwitterionic intermediates generated via desilylation and a variety of electron-deficient acceptors to access cyclopentanes, pyrrolidines and tetrahydrofurans. This section also includes the use of nitrile-, vinyl-, alkynyl- and allene-substituted TMM donors to rapidly generate cycloadducts with high molecular complexity. The extension of this strategy to include [6 + 3] cycloadditions and dearomative processes will also be presented. The third section will discuss a new generation of TMM donors substituted with electron-withdrawing groups such as nitrile, benzophenone imine, trifluoromethyl, and phosphonate, where the Pd-TMM zwitterionic intermediates are generated via deprotonation of the acidic C-H bond adjacent to the π-allyl motif. This new strategy has enabled the synthesis of heterocycles with increased numbers of functional groups in highly asymmetric and atom-economic fashion.Throughout this Account, we will describe the implementation of these transformations toward the rapid assembly of drug candidates and the total synthesis of natural products such as (-)-marcfortine C. We will also give details of mechanistic studies regarding relevant intermediates within the catalytic cycles of the different strategies, which allowed us to better understand the origin of selectivity with various donors.

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium-catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio-, enantio-, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.

The first realization of the amino-trimethylenemethane chemistry is reported using a deprotonation strategy to simplify the synthesis of the amino-trimethylenemethane donor in two steps from commercial and inexpensive materials. A broad scope of cycloaddition acceptors (seven different classes) participated in the chemistry, chemo-, regio-, diastereo-, and enantioselectively generating various types of highly valuable complex amino cycles. Multiple derivatization reactions that further elaborated the initial amino cycles were performed without isolation of the crude product. Ultimately, we applied the amino-trimethylenemethane chemistry to synthesize a potential pharmaceutical in 8 linear steps and 7.5 % overall yield, which previously was achieved in 18 linear steps and 0.6 % overall yield.

The enantioselective N-alkylation of indole and its derivatives with aldimines is efficiently catalyzed by a zinc-ProPhenol dinuclear complex under mild conditions to afford N-alkylated indole derivatives in good yield (up to 86 %) and excellent enantiomeric ratio (up to 99.5:0.5 e.r.). This method tolerates a wide array of indoles, as well as pyrrole and carbazole, to afford the corresponding N-alkylation products. The reaction can be run on a gram scale with reduced catalyst loading without impacting the efficiency. The chiral aminals were further elaborated into various chiral polyheterocyclic derivatives. The surprising stability of the chiral N-alkylation products will open new windows for asymmetric catalysis and medicinal chemistry.

Herein, we report a Zn-ProPhenol catalyzed aza-Darzens reaction using chlorinated aromatic ketones as nucleophilic partners for the efficient and enantioselective construction of complex trisubstituted aziridines. The α-chloro-β-aminoketone intermediates featuring a chlorinated tetrasubstituted stereocenter can be isolated in high yields and selectivities for further derivatization. Alternatively, they can be directly transformed to the corresponding aziridines in a one pot fashion. Of note, the reaction can be run on gram-scale with low catalyst loading without impacting its efficiency. Moreover, this methodology was extended to α-bromoketones which are scarcely used in enantioselective catalysis because of their sensitivity and lack of accessibility.

We describe the design and application of tailored aminoallyl precursors for catalytic (3+2) cycloaddition with conjugated dienes via a Pd-aminoallyl intermediate. The new cycloaddition reactions override the conventional (4+3) selectivity of aminoallyl cation cycloaddition through a sequence of Pd-allyl transfer and ring closure. A variety of highly substituted or fused pyrrolidine rings were synthesized using the cycloaddition, and can further undergo [1,3] N-to-C rearrangement to five-membered carbocycles with a different palladium catalyst. The utility of the (3+2) cycloaddition is also demonstrated by the preparation of various derivatives from the bicyclic pyrrolidine products.

The synthesis of vinyl boronates and vinyl silanes was achieved by employing a Ru-catalyzed alkene-alkyne coupling reaction of allyl boronates or allyl silanes with various alkynes. The double bond geometry in the generated vinyl boronates can be remotely controlled by the juxtaposing boron- and silicon groups on the alkyne substrate. The synthetic utility of the coupling products has been demonstrated in a variety of synthetic transformations, including iterative cross-coupling reactions, and a Chan-Lam-type allyloxylation followed by a Claisen rearrangement. A sequential one-pot alkene-alkyne-coupling/allylation-sequence with an aldehyde to deliver a highly complex α-silyl-β-hydroxy olefin with a handle for further functionalization was also realized.

We report a Zn-ProPhenol catalyzed asymmetric Mannich reaction between butenolides and polyfluorinated alkynyl ketimines to obtain vinylogous products featuring two contiguous tetrasubstituted stereogenic centers. Notably, this is the first successful use of ketimines in the ProPhenol Mannich process, and the reaction offers a new approach for the preparation of pharmaceutically relevant products possessing trifluoromethylated tetrasubstituted alkylamines. The reaction can be performed on large scale with reduced catalyst loading without impacting its efficiency. Moreover, the acetylene moiety can be further elaborated using various methods.

Stickstoff-, Sauerstoff- und Phosphorliganden mit chiralen Grundgerusten sind die historischen Arbeitspferde fur asymmetrische ubergangsmetallkatalysierte Reaktionen. Dagegen wurden am Schwefelatom chirale Sulfoxide uberwiegend als chirale Auxiliare fur diastereoselektive Reaktionen verwendet. Obwohl diese Verbindungen gegenuber den ublichen Ligandengerusten mehrere deutliche Vorteile bieten, z. B. die Nahe der chiralen Information zum Metallzentrum und die Fahigkeit, zwischen S- und O-Koordinierung zu wechseln, entwickelten sie sich erst in jungster Zeit zu einer vielseitigen Klasse chiraler Liganden. In diesem Aufsatz wird die Geschichte der Entwicklung chiraler Sulfoxidliganden fur die asymmetrische Katalyse eingehend besprochen. Daruber hinaus geben wir kurze Beschreibungen der Metall-Sulfoxid-Bindung und der Synthesestrategien fur enantiomerenreine Sulfoxide. Abschliesend werden Einblicke in die kunftige Entwicklung dieser nur wenig genutzten Ligandenklasse gegeben.

Conspectus The development of catalytic enantioselective transformations has been the focus of many research groups over the past half century and is of paramount importance to the pharmaceutical and agrochemical industries. Since the award of the Nobel Prize in 2001, the field of enantioselective transition metal catalysis has soared to new heights, with the development of more efficient catalysts and new catalytic transformations at increasing frequency. Furthermore, catalytic reactions that allow higher levels of redox- and step-economy are being developed. Thus, alternatives to asymmetric alkene dihydroxylation and the enantioselective reduction of α,β-unsaturated ketones can invoke more strategic C–C bond forming reactions, such as asymmetric aldol reactions of an aldehyde with α-hydroxyketone donors or enantioselective alkynylation of an aldehyde, respectively. To facilitate catalytic enantioselective addition reactions, including the aforementioned aldol and alkynylation reactions, our lab has developed the ProPhenol ligand. In this Account, we describe the development and application of the ProPhenol ligand for asymmetric additions of both carbon- and heteroatom-based nucleophiles to various electrophiles. The ProPhenol ligand spontaneously forms chiral dinuclear metal complexes when treated with an alkyl metal reagent, such as Et2Zn or Bu2Mg. The resulting complex contains both a Lewis acidic site to activate an electrophile and a Brønsted basic site to deprotonate a pronucleophile. Initially, our research focused on the use of Zn-ProPhenol complexes to facilitate the direct aldol reaction. Fine tuning of the reaction through ligand modification and the use of additives enabled the direct aldol reaction to proceed in high yields and stereoselectivities with a broad range of donor substrates, including acetophenones, methyl ynones, methyl vinyl ketone, acetone, α-hydroxy carbonyl compounds, and glycine Schiff bases. Additionally, an analogous magnesium ProPhenol complex was used to facilitate enantioselective diazoacetate aldol reactions with aryl, α,β-unsaturated, and aliphatic aldehydes. The utility of bimetallic ProPhenol catalysts was extended to asymmetric additions with a wide range of substrate combinations. Effective pronucleophiles include oxazolones, 2-furanone, nitroalkanes, pyrroles, 3-hydroxyoxindoles, alkynes, meso-1,3-diols, and dialkyl phosphine oxides. These substrates were found to be effective with a number of electrophiles, including aldehydes, imines, nitroalkenes, acyl silanes, vinyl benzoates, and α,β-unsaturated carbonyls. A truly diverse range of enantioenriched compounds have been prepared using the ProPhenol ligand, and the commercial availability of both ligand enantiomers makes it ideally suited for the synthesis of complex molecules. To date, enantioselective ProPhenol-catalyzed reactions have been used in the synthesis of more than 20 natural products.

Die Koordination von Ubergangsmetallen an organische Einheiten kann zu Komplexen mit faszinierenden und unerwarteten Bindungsmustern fuhren. Untersuchungen von Benzylmetall-Komplexen haben die Moglichkeit einer η3-Koordination ergeben, die zu einem desaromatisierten Ring fuhrt. Als Zwischenstufen in Katalysezyklen bieten diese Komplexe zudem Einblicke in Reaktionsmechanismen. In diesem Aufsatz werden die Synthese und Charakterisierung dieser Komplexe mit spaten Ubergangsmetallen sowie die nachfolgende Entwicklung katalytischer Methoden zur Funktionalisierung der Benzylposition einschlieslich asymmetrischer Varianten besprochen.

An approach to 2,2-disubstituted 4-methylenetetrahydrofurans has been developed utilizing a cycloaddition of trimethylenemethane with aryl ketones, with formation of the products in up to 96% yield and 95% ee. The reaction is catalyzed by palladium in the presence of a phosphoramidite ligand possessing a stereogenic phosphorus, where only a single epimer at phosphorus yields the active catalyst. The identity of this epimer and the origin of its effect on reactivity are discussed.

Asymmetric allylic alkylation (AAA)[1] is a powerful and versatile method for the catalytic, asymmetric construction of quaternary stereocenters.[2] In the Mo- and Pd-AAA in particular, a broad range of functionalized electrophiles has been utilized, enabling the rapid synthesis of complex molecules in an atom- and step-economical manner.[3,4] Geminal dicarboxylates (e.g., allylidene dicarboxylates) constitute an under-explored set of electrophiles in this area.[5]

This is the first catalytic enantioselective allylic C—H alkylation, accomplished by the use of a new class of phosphoramidite ligands.

The nature of the leaving group in the first half of the tandem process is essential for the success of the second half.

Allylic chlorides prepared from commercially available trans-1,4-dichloro-2-butene were converted to trans-disubstituted 5- and 6-membered ring systems with perfect diastereoselectivity and high enantioselectivity under chiral ruthenium catalysis. These products contain stereodefined secondary and tertiary alcohols that originate from the trapping of an alkylruthenium intermediate with adventitious water. Key to the success of this transformation was the development of a new BINOL-based phosphoramidite ligand containing bulky substitution at its 3- and 3′-positions. As a demonstration of product utility, diastereoselective Friedel–Crafts reactions were performed on the chiral benzylic alcohols in high yield and stereoselectivity.

The first direct asymmetric Mannich reaction by using α-branched ketones as nucleophilic partners is presented and gives an enantio- and diastereoselective access to various β-amino ketones.

The synthesis of densly functionized α-silyl-β-hydroxyl vinylsilanes via ruthenium-catalyzed multicomponent reaction (MCR) is reported herein. Exceptionally high regio- and diastereoselectivity was achieved by employing an unprecedented hydrosilylation of bifunctional silyl-propargyl boronates. The simple protocol, mild reaction conditions, and unique tolerability of this method make it a valuable tool for the synthesis of highly elaborated building blocks. The one-pot synthesis of stereodefined olefins, the generation of a valuable cyclohexene building block through a four-component MCR, and further functionalization in an abundance of diastereoselective reactions is disclosed herein.

Alkynyl ketones are attractive but challenging nucleophiles in enolate chemistry. Their susceptibility to other reactions such as Michael additions and the difficulty of controlling the enolate geometry make them difficult substrates. Mannich-type reactions, which previously have not been reported using N-carbamoyl-imines with simple ketone enolates, became our objective. In this report, we describe the first direct catalytic Mannich-type reaction between various ynones and N-Boc imines, whose stereocontrol presumably derives from catalyst control of enolate geometry. This method produces α-substituted β-amino ynones with excellent chemo-, diastereo-, and enantioselectivity. The products can be readily transformed into a broad range of molecular scaffolds upon further one-step transformations, demonstrating the utility of ynones as masked synthetic equivalents for a variety of unsymmetrically substituted acyclic ketones. In particular, alkynyl alkyl ketones resolve the long-standing problem of the inability to use the enolates of unsymmetrical dialkyl ketones lacking α-branching for regio- and stereoselective reactions.

The metal-catalyzed coupling of alkynes is a powerful method for the preparation of 1,3-enynes, compounds that are of broad interest in organic synthesis. Numerous strategies have been developed for the homo- and cross coupling of alkynes to enynes via transition metal catalysis. In such reactions, a major issue is the control of regio-, stereo-, and, where applicable, chemoselectivity. Herein, we highlight prominent methods for the selective synthesis of these valuable compounds. Further, we illustrate the utility of these processes through specific examples of their application in carbocycle, heterocycle, and natural product syntheses.

The synthesis of vinyl boronates and vinyl silanes was achieved by employing a Ru-catalyzed alkene-alkyne coupling reaction of allyl boronates or allyl silanes with various alkynes. The double bond geometry in the generated vinyl boronates can be remotely controlled by the juxtaposing boron- and silicon groups on the alkyne substrate. The synthetic utility of the coupling products has been demonstrated in a variety of synthetic transformations, including iterative cross-coupling reactions, and a Chan-Lam-type allyloxylation followed by a Claisen rearrangement. A sequential one-pot alkene-alkyne-coupling/allylation-sequence with an aldehyde to deliver a highly complex α-silyl-β-hydroxy olefin with a handle for further functionalization was also realized.

Reported herein is a Zn/Prophenol-catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio- and diastereoselective construction of β-fluoroamine motifs featuring a fluorinated tetrasubstituted carbon. The reaction can be run on a gram scale with a low catalyst loading without impacting its efficiency. Moreover, a related aldol reaction was also developed. Together, these reactions provide a new approach for the preparation of pharmaceutically relevant products possessing tetrasubstituted C-F centers.

The aldol reaction represents an important class of atom-economic carbon-carbon bond-forming reactions vital to modern organic synthesis. Despite the attention this reaction has received, issues related to chemo- and regioselectivity as well as reactivity of readily enolizable electrophiles remain. To help overcome these limitations, a new direct approach toward aldol products that does not rely upon carbonyl substrates is described. This approach employs room-temperature contemporaneous lanthanum/vanadium dual catalysis, whereby a vanadium-catalyzed 1,3-transposition of allenols is coupled with a lanthanum-catalyzed Meinwald rearrangement of epoxides in situ to directly form aldol products.

α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique σ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism.

The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed.

Aiming high: The title reaction for the synthesis of tertiary a hydroxyketones is reported. Protected 12 enediol carbonates the starting materials were accessed from simple and readily available enol carbonates. Highly functionalized tertiary a hydroxyketones can be obtained in high yield with excellent enantioselectivity using this method (see scheme).

By controlling the kinetics of alkynylation over aldolisation (by slowing adding the acceptor), the challenging asymmetric catalytic alkynylation of acetaldehyde has been realized. This protocol yields the corresponding attractive synthons in good to excellent enantiocontrol and shows broad tolerance and applicability. This was highlighted by its application to the synthesis of several natural products such as the rapid construction of the macrocyclic diolide (+)-tetrahydropyrenophorol.

A dinuclear zinc-ProPhenol catalyst enables highly enantioselective nitro-Michael reactions with oxazol-4(5H)-ones as nucleophilic substrates (see scheme, Nap = 2-naphthyl). This work highlights the utility of the ProPhenol family of ligands. The modular nature of these ligands proved crucial in the optimization of reaction conditions to achieve excellent stereoselectivities.

Activated: the title reaction proceeds with a broad range of nucleophiles and variously substituted 1,4-dienes under mild conditions, and provides direct access to the corresponding 1,3-diene-containing products with high regio- and stereocontrol (see scheme; 2,6-DMBQ=2,6-dimethylbenzoquinone, EWG=electron-withdrawing group). This is the first catalytic allylic C-H alkylation that proceeds in the absence of sulfoxide ligands.

The development and application of a new generation of non-C2-symmetric ProPhenol ligands is reported herein. Rational design of the ProPhenol ligand paved the way to the first catalytic and asymmetric vinylation of N-Boc imines via hydrozirconation giving rise to valuable allylic amines in excellent yields and enantioselectivities. The utility of this method was demonstrated by developing the shortest reported asymmetric synthesis of the selective serotonine reuptake inhibitor (SSRI) (−)-dapoxetine.

Reported herein is a Zn/Prophenol catalyzed Mannich reaction using fluorinated aromatic ketones as nucleophilic partners for the direct enantio and diastereoselective construction of beta fluoroamine motifs featuring a fluorinated tetrasubstituted carbon. The reaction can be run on a gram scale with a low catalyst loading without impacting its efficiency. Moreover a related aldol reaction was also developed. Together these reactions provide a new approach for the preparation of pharmaceutically relevant products possessing tetrasubstituted C F centers.

I am highly honored to be the co-recipient of the Tetrahedron Prize for 2014 with Professor Jiro Tsuji for our work on metal catalyzed allylic alkylation, notably that using palladium. In the context of this award, this report deals only with the evolution of our work. Nevertheless, it is important to note that innumerable groups around the world have and are playing essential roles metal catalyzed allylic alkylations. The reader can find citations to such work in the references to our work that appears in this report. My involvement with this field derived from work in my laboratory dealing with the structure determination and synthesis of the insect juvenile hormone.1 The juvenile hormone is one of three hormones that control the stages of insect development from the pupae to the larvae and finally to the adult. Thus, these hormones, most notably the juvenile hormone that prevented molting was targeted as a potentially more environmentally benign insecticide. The structural relationship of the insect juvenile hormone and methyl farnesoate suggests a possible biosynthetic pathway may be involving the homologation of two of the olefinic methyl groups to ethyl groups. Such an approach, if feasible, would be very attractive, short, and potentially very practical. Unfortunately, such a synthetic protocol did not exist – a fact that intrigued me. While the reactions of the oxygen analog wherein alkylation at the carbon adjacent to the π-unsaturated carbonyl group is one of the most important synthetic reactions, the inability of the all carbon analog to undergo a similar transformation was very attractive.

The oxidative addition of cyano substituted esters (II) and (IV) to allylic imines proceeds at the imine carbon to yield 1-aza-1,3-dienes (III) and (V).

Starting from protected propargyl imines an efficient one-pot approach to 1,2-dihydropyridines is elaborated.

Nitrogen-, phosphorus-, and oxygen-based ligands with chiral backbones have been the historic workhorses of asymmetric transition-metal-catalyzed reactions. On the contrary, sulfoxides containing chirality at the sulfur atom have mainly been used as chiral auxiliaries for diastereoselective reactions. Despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between S and O coordination, these compounds have only recently emerged as a versatile class of chiral ligands. In this Review, we detail the history of the development of chiral sulfoxide ligands for asymmetric catalysis. We also provide brief descriptions of metal–sulfoxide bonding and strategies for the synthesis of enantiopure sulfoxides. Finally, insights into the future development of this underutilized ligand class are discussed.

Carbamates are investigated as directing groups in the title process and -NH-Boc is found to be the optimal one.

The asymmetric key step of the new protocol is the molybdenum-catalyzed allylic alkylation of the oxindole (II) to give (III) with high enantioselectivity.

Enantiomerically enriched [3.1.0] bicycles containing vicinal quaternary centers are synthesized from [1,6]-enynes using a ruthenium catalyst with a tethered chiral sulfoxide.

ConspectusThe development of catalytic enantioselective transformations has been the focus of many research groups over the past half century and is of paramount importance to the pharmaceutical and agrochemical industries. Since the award of the Nobel Prize in 2001, the field of enantioselective transition metal catalysis has soared to new heights, with the development of more efficient catalysts and new catalytic transformations at increasing frequency. Furthermore, catalytic reactions that allow higher levels of redox- and step-economy are being developed. Thus, alternatives to asymmetric alkene dihydroxylation and the enantioselective reduction of α,β-unsaturated ketones can invoke more strategic C–C bond forming reactions, such as asymmetric aldol reactions of an aldehyde with α-hydroxyketone donors or enantioselective alkynylation of an aldehyde, respectively. To facilitate catalytic enantioselective addition reactions, including the aforementioned aldol and alkynylation reactions, our lab has devel...