Π-acid Catalysis Research Articles

Merging Pd(0)-Catalyzed Selective Cacyl–O Bond Activation of Enol Esters with π-Acid Catalysis: Net Hydroxyacylation of Aliphatic Alkynes with Carboxylic Acids

Merging Pd(0)-Catalyzed Selective C_acyl–O Bond Activation of Enol Esters with π-Acid Catalysis: Net Hydroxyacylation of Aliphatic Alkynes with Carboxylic Acids

Sulfonium Cation in the Service of π-Acid Catalysis.

While still rare, cationic ligands offer much promise as tunable electron-withdrawing ligands for π-acid catalysis. Recently, we introduced pincer-type sulfonium cations into the list of available strongly π-acidic ancillary ligands. However, the M-S bond in sulfonium complexes of these ligands was found highly labile, precluding their catalytic applications. Herein we demonstrate that this obstacle can be overcome by increasing the rigidity of the sulfonium pincer scaffold. X-ray analyses confirm that despite bearing a formal positive charge, the sulfur atom of this newly designed sulfonium ligand maintains its coordination to the Pt(II)-center, while DFT calculations indicate that by doing so it strongly enhances the electrophilic character of the metal. Kinetic studies carried out on three model cycloisomerization reactions prove that such a tris-cationic sulfonium-Pt(II) complex is highly reactive, compared to its thioether-based analogue. This proof-of-concept study presents the first example of employing sulfonium-based ligands in homogeneous catalysis.

Sulfonium cations as versatile strongly π-acidic ligands.

More than a century old, sulfonium cations are still intriguing species in the landscape of organic chemistry. On one hand they have found broad applications in organic synthesis and materials science, but on the other hand, while isoelectronic to the ubiquitous tertiary phosphine ligands, their own coordination chemistry has been neglected for the last three decades. Here we report the synthesis and full characterization of the first Rh(i) and Pt(ii) complexes of sulfonium. Moreover, for the first time, coordination of an aromatic sulfonium has been established. A thorough computational analysis of the exceptionally short S–Rh bonds obtained attests to the strongly π-accepting nature of sulfonium cations and places them among the best π-acceptor ligands available today. Our calculations also show that embedding within a pincer framework enhances their π-acidity even further. Therefore, in addition to the stability and modularity that these frameworks offer, our pincer complexes might open the way for sulfonium cations to become powerful tools in π-acid catalysis.

Gold-Catalyzed Annulations with Nucleophilic Nitrenoids Enabled by Heteroatom-Substituted Alkynes.

The combination of a nucleophilic nitrene equivalent, a triple bond and a π-acid catalyst has underpinned numerous efficient transformations for the preparation of azacycles. This personal account details our efforts in developing an annulation strategy. Adding a nucleophilic nitrenoid to an activated alkyne can generate carbenoid character that is then quenched by a cyclisation onto the nitrenoid substituent. The use and development of N-acyl and N-heterocyclic pyridinium-N-aminides as 1,3-N,O and 1,3-N,N-dipole equivalents is discussed in the context of oxazole and heterocycle-fused imidazole formation, respectively. The resulting processes are highly efficient, practically straightforward, and tolerate considerable structural and functional group variation. Our use of heteroatom-substituted alkynes as enabling tools for reaction discovery is discussed. The reactivity accessed from the strong donor-like properties of ynamides is complemented by that obtained from alkynyl thioethers, which are emerging as interesting substrates for π-acid catalysis.

Gold(I)-Catalyzed Synthesis of 3-Sulfenyl Pyrroles and Indoles by a Regioselective Annulation of Alkynyl Thioethers.

The combination of nucleophilic nitrenoids and π-acid catalysis has emerged as a powerful tool in heterocycle synthesis. Accessing more varied heterocycle-substitution patterns by maintaining the same reaction pathways across different alkynes remains a challenge. Here we show that Au(I) catalysis of isoxazole-based nitrenoids with alkynyl thioethers provides controlled access to (3 + 2) annulation by a regioselective addition β to the sulfenyl group. The reaction with isoxazole-containing nitrenoids delivers sulfenylated pyrroles and indoles as single regioisomers bearing useful functional groups and structural variety.

Scalable Synthesis of a Chiral Selenium π-Acid Catalyst and Its Use in Enantioselective Iminolactonization of β,γ-Unsaturated Amides

Chiral selenium π-acid catalysis has for a long time been lagging behind other areas of asymmetric catalysis due to a lack of highly enantioselective catalysts. In this regard, we recently developed the first chiral selenium π-acid catalyst which performs the oxidative cyclization of β,γ-unsaturated carboxylic acids with high enantioselectivities. We report herein our improved synthesis of this chiral selenium catalyst, which allows access to a large quantity of the catalyst as the diselenide. In addition, the catalyst is tested in the oxidative cyclization of N-methoxy β,γ-unsaturated amides to give iminolactones with high enantioselectivities.

Gold Catalysis for Heterocyclic Chemistry: A Representative Case Study on Pyrone Natural Products.

2-Pyrones and 4-pyrones are common structural motifs in bioactive natural products. However, traditional methods for their synthesis, which try to emulate the biosynthetic pathway of cyclization of a 1,3,5-tricarbonyl precursor, are often harsh and, therefore, not particularly suitable for applications to polyfunctionalized and/or sensitive target compounds. π-Acid catalysis, in contrast, has proved to be better for a systematic exploration of the pyrone estate. To this end, alkynes are used as stable ketone surrogates, which can be activated under exceedingly mild conditions due to the pronounced carbophilicity of [LAu]+ fragments (L=two electron donor ligand); attack of a tethered ester carbonyl group onto the transient alkyne-gold complex then forges the pyrone ring in a fully regiocontrolled manner.

Understanding the Effect of α-Cationic Phosphines and Group 15 Analogues on π-Acid Catalysis

The factors responsible for the experimentally observed acceleration of π-acid-catalyzed reactions induced by α-cationic phosphines and group 15 analogues have been computationally explored within the density functional theory framework. To this end, the gold(I)-catalyzed hydroarylation reactions of phenylacetylene and mesitylene involving both neutral and cationic ligands (L) have been quantitatively analyzed in detail using the combination of the activation strain model of reactivity and the energy decomposition analysis methods. It is found that the activating effect of the cationic ligand finds its origin in the much stronger interaction between the deformed reactants along the entire reaction coordinate, which in turn derives from the much higher π(acetylene) → σ*(Au–L) interaction in the initially formed acetylene-gold(I) π-complex.

Connected Community

Connected Community

Synthesis, Structure, and Applications of α-Cationic Phosphines.

In α-cationic phosphines, at least one of the three substituents on phosphorus corresponds to a cationic (normally, but not always heteroaromatic) group, which is attached without any spacer to the phosphorus atom by a relatively inert P-C bond. This unique architecture confers to the resulting ligand strong acceptor properties, which frequently surpass those of traditional acceptor ligands such as phosphites or polyfluorinated phosphines. In addition, the fine-tuning of the stereoelectronic properties of α-cationic phosphines is also possible by judicious selection of the number and nature of the cationic groups. The opportunities offered in catalysis by α-cationic ligands arise from this ability to deplete electron density from the metals they coordinate. Thus, if in a hypothetical catalytic cycle the step that determines the rate is facilitated by an increase of the Lewis acidity at the metal center, then an acceleration of the whole process is expected by their use as ancillary ligands. Interestingly, this situation is found more frequently than one might think; many common elementary steps involved in catalytic cycles, such as reductive eliminations, coordination of substrates to metals, or attack of nucleophiles to coordinated substrates, belong to this category and are often fostered by electron poor metal centers. In this regard, our group has observed remarkable ligand acceleration effects by the employment of α-cationic phosphines in Au(I)- and Pt(II)-promoted hydroarylation and cycloisomerization reactions. These results seem to be general in π-acid catalysis when the nucleophile used is not especially electron rich because then their attack to the activated alkene or alkyne is normally rate determining. On the other hand, the use of cationic phosphines also presents drawbacks that limit their range of application. As a general rule, the reduced σ-donation from the phosphine is not compensated by the increased π-back-donation from the metal making the resulting phosphorus-metal bond weaker, and the corresponding catalysts more prone to decomposition. This can be critical when di- or tricationic ancillary ligands are used. In addition, the positively charged groups occasionally participate in undesired side reactions, with either the metal or the substrate, which are not present when their neutral congeners are used. Stimulated by both the fundamental questions regarding bonding and their valuable applications in catalysis, the chemistry of α-cationic phosphines has experienced an enormous growth during the last years. This Account describes our group's efforts and those of others to understand their coordination behavior, study their reactivity, and further develop their range of applications in catalysis.

ChemInform Abstract: Nucleophilic Nitrenoids Through π‐Acid Catalysis: Providing a Common Basis for Rapid Access into Diverse Nitrogen Heterocycles

AbstractReview: [48 refs.

ChemInform Abstract: New Procedures for Catalytic Carbophilic Activation by Gold and Gallium π‐Acids

AbstractReview: [51 refs.

New Procedures for Catalytic Carbophilic Activation by Gold and Gallium π-Acids

Cationic gold(I) complexes are soft Lewis acids that are able to trigger numerous types of nucleophilic attack onto alkenes, allenes, and alkynes (π-acid catalysis). In this account, we initially summarize the novel methods that we have developed to generate such catalysts by silver-free activation of ligated gold(I) chlorides. The advantages of this approach are the use of lower quantities of gold and the ability to scale-up transformations during which the standard gold/silver catalytic system is rapidly decomposed. In the second part, the synthesis and catalytic activity of original organogallium compounds is described. We have shown that (NHC)GaCl2 +-type complexes display a high affinity for alkenes and alkynes, and trigger tandem C–C/C–C or C–C/C–H bond formation processes. Thus, they also behave as π-acids. Practical applications of these different gold- and gallium-based catalytic systems for the synthesis of cyclic compounds are presented. 1 Introduction 2 Silver-Free Two-Component Approaches in Gold Catalysis 2.1 The Gold/Copper Catalytic System 2.2 Other Applications with Gold/Lewis Acid Systems 3 Gallium Catalysis 3.1 Cationic Gallium Complexes Supported by N-Heterocyclic Car­bene Ligands 3.2 Catalytic Applications 4 Conclusions

Structure of a Reactive Gold Carbenoid

A formal gold-for-chromium transmetalation allowed the gold carbenoid species [Cy3 PAuCAr2 ]NTf2 (11) (Ar=pMeOC6 H4 -) to be obtained in crystalline form. The structure in the solid state suggests that there is only little back donation of electron density from gold to the carbene center of 11 and hence very modest AuC double-bond character; rather, it is the organic ligand framework that is responsible for stabilizing this species by resonance delocalization of the accumulated positive charge. Because 11 is capable of cyclopropanating p-methoxystyrene even at low temperature, the discussion of its structure is deemed relevant for a better understanding of the mechanisms of π-acid catalysis in general.

Selective synthesis of indazoles and indoles via triazene–alkyne cyclization switched by different metals

We described two orthogonal heterocycle syntheses, where an arene bearing both an alkyne and a triazene functionality underwent two distinct cyclization pathways mediated by different transition metals. Starting from the same substrates, a synthesis of 2H-indazole was accomplished by a Cu(II) salt promoted oxidative cyclization, while 2-substituted indoles could be accessed via a Ag(I) salt mediated N-N bond cleavage. This method represents the first synthesis of indoles from alkynyl triazenes. Computational analysis was performed for both reaction pathways, supporting a Lewis acid role for Cu and a π-acid catalysis for Ag.

Gold Carbenoids: Lessons Learnt from a Transmetalation Approach

Carbophilic catalysts that are based on Au(I) allow a host of different nucleophiles to be added across various π systems. Although many of these reactions are thought to proceed via gold carbenoids, the challenge to observe and characterize these putative intermediates has basically been unmet. The current mechanistic interpretation therefore largely relies on indirect evidence and computational data, some of which are subject to debate. In an attempt to fill this gap, we pursued a potential route to gold carbenoids by formal transmetalation of chromium or tungsten Fischer carbene complexes with [LAu](+). Whereas this transformation proceeds with exceptional ease as long as a stabilizing heteroelement is present on the carbene center, it stops half-way in its absence. Rather unusual bimetallic arrays are formed, which allow the charge density to delocalize over several positions. The obvious difficulty of releasing an "unstabilized" gold carbenoid has potential mechanistic implications for the understanding of π-acid catalysis in general.

From Understanding to Prediction: Gold- and Platinum-Based π-Acid Catalysis for Target Oriented Synthesis

During the last century, conceptual advances in organometallic chemistry were often rapidly embraced by target oriented synthesis. Feedback provided by such preparative scrutiny has greatly benefitted method development; particularly prominent are examples from the entire cross coupling arena, as well as olefin metathesis. Seen against this backdrop, it is somewhat surprising that the explosive growth of research into π-acid catalysis has not yet yielded a matching number of implementations into the synthesis of structurally complex targets of biological significance. In contrast to the massive output of methodological and mechanistic investigations, few studies illustrate the strategic use of gold, silver, or platinum catalysis in late stages of such multistep endeavors. These elaborate and highly precious compounds demand utmost confidence in the reliability and robustness of the method to be applied. In this Account, we analyze the possible reasons for this imbalance, after a short summary of the conceptual basis of carbophilic activation of π-bonds with the aid of soft transition metal cations or complexes. We pinpoint mechanistic subtleties, which, at least in part, produce a great deal of structural diversity but can jeopardize predictive power. With the advances in the understanding of π-acid catalyzed processes in general, however, this uncertainty is gradually vanishing and the entire field is transitioning from comprehension to prediction. This is expected to foster advanced applications, while recent progress in asymmetric gold catalysis further improves the preparative significance. The presented work in this Account illustrates our own commitment to the field as well as our growing confidence in the maturity of platinum and gold catalysis. The carbophilic activation of π-bonds, particularly of alkynes, provides a method to manipulate functional groups that is orthogonal to traditional carbonyl chemistry. We illustrate this notion by presenting a new approach to hydroxypyrone derivatives that has enabled the total synthesis of the fragile polyunsaturated cyclophane derivative neurymenolide A. The synthesis of the pyrrole alkaloid streptorubin by an enyne cycloisomerization is equally instructive. In addition, different manifestations of transannular hydroxyl addition reactions across alkyne partners mark the late stages of our conquests of amphidinolide F, polycavernoside A, and spirastrellolide F. Together with a few model studies and a personal selection of recent highlights from other groups, these examples augur well for future applications of π-acid catalysts in the realm of target oriented synthesis.

ChemInform Abstract: π‐Acid Mediated Insertion of Alkynes into Carbon—Heteroatom σ‐Bonds

AbstractReview: about 100 refs.

π-Acid Mediated Insertion of Alkynes into Carbon–Heteroatom σ-Bonds

The rapidly expanding field of gold and platinum π-acid catalysis has led to the discovery of diverse transformations that are initiated with nucleophilic attack onto a metal-activated alkyne. This review brings together those reactions which employ a heteroatom nucleophile bearing a functional group that can subsequently migrate to effect a formal insertion of the alkyne into a carbon–heteroatom­ σ-bond. This reactivity profile is encountered in a range of efficient and powerful cycloisomerisations for the preparation of carbo- and heterocycles. 1 Introduction 2 1,2-Addition of Carbon–Heteroatom Bonds across Alkynes 2.1 Heteroatom-to-Carbon Allyl Migrations 2.2 Accessing Sigmatropic Rearrangements 2.3 Related Palladium-Catalysed 1,2-Carboalkoxylations and Carboaminations 2.4 Beyond Allyl Migration in the 1,2-Carbofunctionalisation of Alkynes 2.5 Oxonium Ion Migration 2.6 Migrating Centres at Higher Oxidation Levels 2.7 Migration of Heteroatoms 3 1,5 Heteroatom-to-Carbon Migrations 3.1 Alkynyl Benzoates as Alkylating Agents 4 Internal versus External Migrations 4.1 Internal Migrations of Oxonium Species 5 1,1-Carbofunctionalisations 6 Application in Natural Products 7 Summary and Conclusions

Synthesis of (-)-Berkelic Acid

Key words Suzuki–Miyaura cross-coupling - π-acid catalysis - multicomponent reaction - (–)-berkelic acid