Enantioselective Gold Catalysis Research Articles

Chiral Bifunctional Phosphine Ligand Enables Asymmetric Trapping of Catalytic Vinyl Gold Carbene Species.

Bifunctional ligand-enabled cooperative gold catalysis accelerates nucleophilic attacks and offers a versatile strategy to achieve asymmetric gold catalysis. Distinct from the prior studies employing alkyne/allene as the electrophilic site, this work engages an in situ-generated alkenyl/acyl gold carbene in a ligand-facilitated attack by an alcoholic nucleophile. With an amide-functionalized chiral binaphthylphosphine ligand, γ-alkoxy-α,β-unsaturated imides are formed with excellent enantiomeric excesses. The intermediacy of a carbene species is supported by its alternative access via dediazotization. The reaction tolerates a broad range of alcohols and can accommodate dienynamide substrates, in addition to arylenynamides. This work avails a versatile strategy to enrich gold chemistry and achieve challenging enantioselective gold catalysis via ligand-facilitated enantioselective trapping of reactive intermediates.

Chiral NHC Ligands for Enantioselective Gold(I) Catalysis Under Aerobic Conditions: the Importance of Conformational Flexibility and Steric Hindrance of NHC Ligand on Reactivity.

Gold(I) catalysis has been recognized as a valuable tool for the unique transformation of multiple carbon-carbon bonds. Enantioselective π-catalysis based on gold(I) complexes is, however, still underdeveloped due to lack of privileged ligands. Herein, we present an accessible method to a new family of stable yet catalytically active chiral NHC-Au(I)-Cl complexes. The key to preserving a simultaneous fine balance between reactivity and stability in this newly developed family appears to be sterically hindered, but conformationally flexible NHC ligands. These could be easily accessed on a multigram scale by merging sterically hindered anilines with commercially available amino alcohols and amines via a four-steps synthetic sequence without the need for chromatographic purification. Further investigations of the catalytic activity of NHC-Au-Cl complexes identified the OH functionality incorporated into the NHC core as crucial for the level of enantioselectivity as well as the TsO- anion responsible for the activation of NHC-Au(I)-Cl. Finally, NMR studies and X-ray investigations revealed for the first time that the widely accepted ion metathesis (NHC-Au-Cl to NHC-Au-OSO2 R) responsible for the activation of NHC-Au-Cl complexes does not take place (or it is very slow) in commonly used MeNO2 in contrast to DCM.

Desymmetrization and Parallel Kinetic Resolution of 1-Ethynylcyclobutanols via Asymmetric Cooperative Gold Catalysis.

Enantioselective gold catalysis remains a challenging area of research. By harnessing gold-ligand cooperation in the presence of a chiral bifunctional phosphine ligand featuring a novel 3'-phosphine oxide moiety, highly enantioselective desymmetrization of 1-ethynylcyclobutanols is achieved, permitting access to chiral α-methylenecyclopentanones featuring a diverse array of chiral quaternary and tertiary centers. This cooperative gold catalysis also enables parallel kinetic resolution in gold catalysis, delivering cyclopentanone regioisomers with excellent enantiomeric excesses. DFT calculations of the transition states support the distinct mechanism of asymmetric induction via controlling the conformation of the bound substrate and hence dictating the ring bond undergoing migration.

Advances in Versatile Chiral Ligands for Asymmetric Gold Catalysis

The formation of valuable chiral skeletons through asymmetric gold catalysis has made considerable progress due to the unrivaled affinity of gold complexes with multiple carbon–carbon bonds. The renaissance of chiral ligands in recent decades has enabled the elaborate design of chiral gold complexes, which are of great significance to control chiral formation in these catalytic reactions. Therefore, this review intends to highlight the design and central role of versatile chiral ligands in asymmetric gold catalysis. Specifically, the seminal applications of various chiral ligands with representative examples in various gold-catalyzed asymmetric reactions are comprehensively explored. In addition, the reaction mechanisms are mentioned when the crucial interactions between ligands and activated substrates are introduced. Furthermore, the applications of enantioselective gold catalysis in the construction of chiral functional organic materials and drug molecules are also presented.

Chiral Ligands for Au(I), Au(III), and Au(I)/Au(III) Redox Catalysis

AbstractGold catalysis has emerged as an efficient tool for the selective functionalisation of C−C multiple bonds. Despite significant progress in this field, the potential of asymmetric gold catalysis has not been fully explored to date. A historical retrospect on the progress in this area reveals that enantioselective gold catalysis is based on three pillars: Au(I) catalysis, Au(III) catalysis, and Au(I)/Au(III) redox catalysis. Irrespective of the mode of catalysis being operative, the design of new ligands is crucial for the development of gold‐catalysed organic transformations. This minireview summarizes the progress made in the development of ligand design for enantioselective Au(I) catalysis, Au(III) catalysis, and Au(I)/Au(III) redox catalysis focusing on the ligands which were specially designed for gold catalysis.

Helical Chiral N-Heterocyclic Carbene Ligands in Enantioselective Gold Catalysis.

The first chiral helicene-NHC gold(I) complexes efficient in enantioselective catalysis were prepared. The L-shaped chiral ligand is composed of an imidazo[1,5-a]pyridin-3-ylidene (IPy) scaffold laterally substituted by a configurationally stable [5]-helicenoid unit. The chiral information was introduced in a key post-functionalization step of a NHC-gold(I) complex bearing a symmetrical anionic fluoreno[5]helicene substituent, leading to a racemic mixture of complexes featuring three correlated elements of chirality, namely central, axial and helical chirality. After HPLC enantiomeric resolution, X-ray crystallography and theoretical calculations enabled structural and stereochemical characterization of these configurationally stable NHC-gold(I) complexes. The high potential in asymmetric catalysis is demonstrated in the benchmark cycloisomerization of N-tethered 1,6-enynes with up to 95 : 5 er.

Tethered Counterion-Directed Catalysis: Merging the Chiral Ion-Pairing and Bifunctional Ligand Strategies in Enantioselective Gold(I) Catalysis.

Tethering a metal complex to its phosphate counterion via a phosphine ligand enables a new strategy in asymmetric counteranion-directed catalysis (ACDC). A straightforward, scalable synthetic route gives access to the gold(I) complex of aphosphine displaying a chiralphosphoric acid function. The complex generates a catalytically active species with an unprecedented intramolecular relationship between the cationic Au(I) center and the phosphate counterion. The benefits of tethering the two functions of the catalyst are demonstrated here in a tandem cycloisomerization/nucleophilic addition reaction, by attaining high enantioselectivity levels (up to 97% ee) at an unusually low 0.2 mol % catalyst loading. Remarkably, the method is also compatible with a silver-free protocol.

Gold-catalyzed enantioselective functionalization of indoles.

Gold catalysis and indole chemistry are two mature and prolific fields. The gold-catalyzed functionalization of indoles has produced numerous results and paved the way for novel strategies in the building of molecular complexity. However - and curiously - though enantioselective gold catalysis is now a well-established field, it has been relatively little applied to the modification of indoles. This review highlights most of the enantioselective gold-catalyzed examples of the functionalization of indoles in order to emphasize the strengths and limitations of the method.

ChemInform Abstract: Recent Advances in Enantioselective Gold Catalysis

AbstractReview: [advances in enantioselective gold catalysis over the past five years; 109 refs.

Recent advances in enantioselective gold catalysis.

Interest in homogeneous gold catalysis has undergone a marked increase. As strong yet air- and moisture-tolerant π-acids, cationic gold(i) complexes have been shown to catalyze diverse transformations of alkenes, alkynes and allenes, opening new opportunities for chemical synthesis. The development of efficient asymmetric variants is required in order to take full advantage of the preparative potential of these transformations. During the last few years, the chemical community has achieved tremendous success in the area. This review highlights the updated progress (2011-2015) in enantioselective gold catalysis. The discussion is classified according to the π-bonds activated by gold(i), in an order of alkynes, allenes and alkenes. Other gold activation modes, such as σ-Lewis acid catalyzed reactions and transformations of diazo compounds are also discussed.

The synthesis of substituted phosphathiahelicenes via regioselective bromination of a preformed helical scaffold: a new approach to modular ligands for enantioselective gold-catalysis.

Substituted phosphathiahelicenes have been prepared via a straightforward two-step procedure involving the regioselective bromination of a preformed helical scaffold, followed by palladium catalyzed coupling reactions. The new helicenes have been used as ligands in gold(i)-catalyzed [4+2] cyclizations of 1,6-enynes. The resulting dihydro-cyclopenta[b]naphthalene derivative was obtained in excellent yields and with up to 91% ee.

ChemInform Abstract: When Gold Meets Chiral Broensted Acid Catalysts: Extending the Boundaries of Enantioselective Gold Catalysis

AbstractReview: 47 refs.+ subrefs.

Phosphathiahelicenes: synthesis and uses in enantioselective gold catalysis.

Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine-Au(I) complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee).

ChemInform Abstract: Enantioselective Gold(I) Catalysis with Chiral Monodentate Ligands

AbstractReview: gold‐catalyzed asymmetric cycloaddition/cycloisomerization reactions; 37 refs.+ subrefs.

ChemInform Abstract: Helicenes with Embedded Phosphole Units in Enantioselective Gold Catalysis.

AbstractThe use of phosphahelicenes as chiral ligands in transition‐metal catalysis is described for the first time.

ChemInform Abstract: Development of Catalysts and Ligands for Enantioselective Gold Catalysis

AbstractReview: 55 refs.

When gold meets chiral Brønsted acid catalysts: extending the boundaries of enantioselective gold catalysis.

This review describes the development in the use of Au(I)/Brønsted acid binary catalytic systems to enable an enantioselective transformation in one-pot that cannot be achieved by gold catalysts alone. The examples discussed herein are promising since apart from using chiral ligands there exists a possibility of using chiral Brønsted acids. Clearly, the horizon for enantioselective gold catalysis has been expanded as more options to make the gold-catalyzed reactions enantioselective have become available.

Helicenes with Embedded Phosphole Units in Enantioselective Gold Catalysis

This paper discloses the first uses of phosphahelicenes as chiral ligands in transition-metal catalysis. Unlike all known helical phosphines used so far in catalysis, the phosphorus function of phosphahelicenes is embedded in the helical structure itself. This crucial structural feature originates unprecedented catalytic behaviors and efficiency. An appropriate design and fine tuning allowed both high catalytic activity and good enantiomeric excesses to be attained in the gold promoted cycloisomerizations of N-tethered 1,6-enynes and dien-ynes.

Helicenes with Embedded Phosphole Units in Enantioselective Gold Catalysis

This paper discloses the first uses of phosphahelicenes as chiral ligands in transition-metal catalysis. Unlike all known helical phosphines used so far in catalysis, the phosphorus function of phosphahelicenes is embedded in the helical structure itself. This crucial structural feature originates unprecedented catalytic behaviors and efficiency. An appropriate design and fine tuning allowed both high catalytic activity and good enantiomeric excesses to be attained in the gold promoted cycloisomerizations of N-tethered 1,6-enynes and dien-ynes.

Development of Catalysts and Ligands for Enantioselective Gold Catalysis

During the past decade, the use of Au(I) complexes for the catalytic activation of C-C π-bonds has been investigated intensely. Over this time period, the development of homogeneous gold catalysis has been extraordinarily rapid and has yielded a host of mild and selective methods for the formation of carbon-carbon and carbon-heteroatom bonds. The facile formation of new bonds facilitated by gold naturally led to efforts toward rendering these transformations enantioselective. In this Account, we survey the development of catalysts and ligands for enantioselective gold catalysis by our research group as well as related work by others. We also discuss some of our strategies to address the challenges of enantioselective gold(I) catalysis. Early on, our work with enantioselective gold-catalyzed transformations focused on bis(phosphinegold) complexes derived from axially chiral scaffolds. Although these complexes were highly successful in some reactions like cyclopropanation, the careful choice of the weakly coordinating ligand (or counterion) was necessary to obtain high levels of enantioselectivity for the case of allene hydroamination. These counterion effects led us to use the anion itself as a source of chirality, which was successful in the case of allene hydroalkoxylation. In general, these tactics enhance the steric influence around the reactive gold center beyond the two-coordinate ligand environment. The use of binuclear complexes allowed us to use the second gold center and its associated ligand (or counterion) to exert a further steric influence. In a similar vein, we employed a chiral anion (in place of or in addition to a chiral ligand) to move the chiral information closer to the reactive center. In order to expand the scope of reactions amenable to enantioselective gold catalysis to cycloadditions and other carbocyclization processes, we also developed a new class of mononuclear phosphite and phosphoramidite ligands to supplement the previously widely utilized phosphines. However, we needed to judiciously design the steric environment to create "walls" that enclose the gold center. We also successfully applied these same considerations to the development of binuclear carbene ligands for gold. Finally, we describe the design of bifunctional urea-monophosphine ligands used in a gold-catalyzed three-component coupling.