A. Stephen K. Hashmi

Homogeneous Gold Catalysis Beyond Assumptions and Proposals—Characterized Intermediates

Gold catalysis is a very active area in the field of catalysis research. New reactions are published every week, amazing changes in the connectivity are often observed, the number of applications in total synthesis is increasing...--but what are the mechanisms of these reactions? Sound information can be provided by knowledge about the intermediates of these reactions.

Gold catalysis in total synthesis

In this tutorial review directed towards chemists interested in synthesis or catalysis, the application of gold catalysis in total synthesis is summarised and the mode of activation of the substrate by the gold catalyst is discussed.

Homogeneous gold catalysts and alkynes: A successful liaison

The use of the combination of homogeneous gold-catalysts and alkynes in organic synthesis is reviewed from its beginnings in C-N-bond formation to the newest developments in C-C-bond formation. The common basic principle of these reactions is discussed. Special attention is devoted to the question where the gold catalysts are superior to either other catalysts or more traditional synthetic approaches to the product molecules.

Simple Gold‐Catalyzed Synthesis of Benzofulvenes—gem‐Diaurated Species as “Instant Dual‐Activation” Precatalysts

In the field of homogeneous transition-metal chemistry, gold plays a major role in the discovery of new reactions. Most of the transformations are based on the electrophilic activation of a multiple bond. The decrease of electron density upon p coordination of a carbophilic gold center allows nucleophilic attack. Now, in independent and parallel work the group of Zhang and our team have discovered a different reactivity which was so far unprecedented in the field of gold chemistry. Initial activation of an alkyne by s coordination to gold increases the nucleophilicity of the b-carbon atom of this alkyne. This first alkyne combines with a second alkyne, which is activated by p coordination, and highly reactive gold vinylidene intermediates are formed by this dual s/p activation. The Zhang group s publication on the synthesis of benzofulvenes now prompts us to publish our additional findings on that specific reaction. Since alkyl-substituted alkynes are readily available, a new fascinating reaction pathway was opened for the gold vinylidene intermediates. The first two elementary steps of this reaction are identical to the previous reactions, which seem to be general for this new sector of gold catalysis. Herein we report on the use of tertiary alkyl groups, the isolation of gem-diaurated species which prove to be ideal precatalysts for this type of transformation, the dynamics of the equilibrium involving these diaurated species, and the catalyst transfer in the context of a detailed mechanistic discussion. We investigated several diyne systems 1 with a terminal alkynyl group and a tert-alkyl-substituted alkynyl group as potential substrates for the gold(I)-catalyzed intermolecular arene addition. A new reaction was observed, the clean formation of a benzofulvene derivative, a class of compounds that usually is not easily available. No incorporation of the solvent benzene was observed. To optimize the reaction, we performed reactions of substrate 1 a (Table 1) with different gold catalysts and different counterions (see the Supporting Information); the well-established catalyst [(IPr)AuCl], in combination with AgNTf2 gave the best results. To evaluate the substrate scope, a small library of substrates was transformed to the corresponding products under the optimized conditions (Table 1). One advantage of substrates 1 is their easy two-step synthesis (Sonogashira reaction, Seyferth–Gilbert homologation) from commercially available 2-bromobenzaldehydes. With our test substrate 1a,

Cyclization of Propargylic Amides: Mild Access to Oxazole Derivatives

The substrate scope, the mechanistic aspects of the gold-catalyzed oxazole synthesis, and substrates with different aliphatic, aromatic, and functional groups in the side chain were investigated. Even molecules with several propargyl amide groups could easily be converted, delivering di- and trioxazoles with interesting optical properties. Furthermore, the scope of the gold(I)-catalyzed alkylidene synthesis was investigated. Further functionalizations of these isolable intermediates of the oxazole synthesis were developed and chelate ligands can be obtained. The use of Barluengas reagent offers a new and mild access to the synthetically valuable iodoalkylideneoxazoles from propargylic amides, this reagent being superior to other sources of halogens.

Mechanistic Switch in Dual Gold Catalysis of Diynes: C(sp3)–H Activation through Bifurcation—Vinylidene versus Carbene Pathways

The other side of the mountain: Changing the framework of diyne systems opens up new cyclization modes for dual gold catalysis. Instead of a 5-endo cyclization and gold vinylidenes a 6-endo cyclization gives rise to gold-stabilized carbenes as key intermediates for selective C-H insertions.

Mechanistic insights into the gold chemistry of allenes

Although most mechanistic studies on gold-catalysed reactions focused on alkynes as substrates, some knowledge about gold-catalysed conversions of allenic substrates has been obtained. This contribution summarises these insights into the reaction mechanisms of gold-catalysed transformations of allenes which are based on computational studies, labelling studies, the detection of intermediates, chirality transfer and diastereoselective product formation.

A New Insight into Gold(I)‐Catalyzed Hydration of Alkynes: Proton Transfer

Hydration and alkoxylation of alkynes are important reactions in organic synthesis, for which mercury(II) salts initially served as catalysts. Due to substantial practical aspects, such as the requirement of strongly acidic reaction media, the quick denaturation of the Hg catalyst and environmental concerns, alternative catalysts were sought for quite some time. In particular, for the addition of water and methanol to unactivated alkynes, Au3] and Pt-containing catalysts 5] were investigated as an alternative but turned out to be less efficient. In 1998, Teles et al. reported a very efficient method for the alkoxylation of alkynes using cationic Au complexes of the type [(PR3)Au] + . In dry methanol, acetals D and E were obtained, whereas in the presence of water, ketones B and C were the only products (Scheme 1). In the case of terminal alkynes, the Markovnikov products were formed with very high selectivity whereas internal alkynes led to product mixtures. Subsequent work by Tanaka et al. and Nolan et al. even further improved that reaction.

Gold Vinylidene Complexes: Intermolecular C(sp3)H Insertions and Cyclopropanations Pathways

Highly reactive gold vinylidene species are used for intermolecular C(sp(3))-H insertions into unactivated alkanes (see scheme). In addition, they can be regarded as synthons for alkylidene carbenes. Initiated by cyclopropanation of the vinylidene species/alkylidene carbenoide, cyclobutene derivatives are formed in a diastereoselective fashion by a ring-enlargement cascade in only one step.

Gold and Palladium Combined for Cross-Coupling†

The use of gold catalysts as highly active tools for efficient and atom-economic transformations continues to grow exponentially. In contrast to other transition metals, the most significant limitation of homogeneous gold catalysts seems to be the inferior ability of gold to change oxidation states during catalytic cycles. Of the few reported homogeneous gold-catalyzed coupling reactions in which changes in oxidation states in catalytic cycles are presumed, they are all accomplished at elevated temperatures wherein heterogeneous catalysis should at least be considered. One approach to broadening the scope of gold-catalyzed coupling reactions was accomplished by the use of external stoichiometric oxidants instead of oxidation by the substrate. 4] Whereas recently only symmetric molecules could be synthesized by the oxidative dimerization of gold(III) intermediates, Zhang and co-workers reported an impressive oxidative crosscoupling reaction using Selectfluor as reoxidizing reagent. In our opinion, there is another option to extend the scope of homogeneous gold chemistry: the transmetalation of the in situ generated organogold species A to other transition metals such as palladium species B (Scheme 1). In these reactions strong stoichiometric oxidizing reagents could be avoided, and the reluctance of the gold species to undergo an oxidation state change could become an advantage as the orthogonal reactivity of the two metals could guarantee highly selective reactions. Our initial experiments to achieve a double catalytic conversion gave only low yields, potentially caused by the ligand exchange processes between the two different metal centers. Therefore we decided to turn to transmetalation experiments using stoichiometric amounts organogold compounds to simplify the reaction conditions. To the best of our knowledge, a general study of the transmetalation abilities of organogold compounds with catalytic amounts of palladium is lacking. So far there are only few examples for transmetalation and gold. Herein we present a study of the gold/palladium system by using stoichiometric amounts of organogold compounds and catalytic amounts of palladium complexes in cross-coupling reactions. Our initial foray into the cross-coupling of organogold intermediates began with an assessment of palladium catalysts 1–7 (Figure 1) for the model reaction of iodobenzene and triphenylphosphine vinyl gold 8a. Of the different