Gold-catalyzed reactions

Gold catalyzed reactions are currently enjoying considerable interest, and have also found applications in thiophene ring synthesis. A series of (a-alkoxyalkyl)(o-alkynylphenyl) sulfides 14 was subjected to treatment with catalytic amounts of AuCl, giving the benzo[fe]thiophenes 15 in excellent yields. Some additional, more complex examples were also provided <06AG(E)4473>. 

It has been known from the earliest observations in gold chemistry that olefins form very weak 7r-complexes with gold in any of its oxidation states.1-3 Therefore, only a very few stable complexes of this type have been isolated. However, unstable 7r-complexes of olefins with gold compounds are believed to be important intermediates or transient species in gold-catalyzed reactions of unsaturated organic compounds.122-125,131,286-288,307-312... 

Most gold-catalyzed reactions involve this pattern of reactivity that has been studied since the eighties. The first examples were found with allenes as substrates and subsequently alkenes and alkynes started to be used, the latter being the most popular in the last five years. 

Alkynes are by far the most popular and studied functional group in gold catalyzed reactions since Thomas et al. chose them for their research in 1976 [53, 84]. 

Silver and gold-catalyzed reactions have recently been exploited in approaches to various kinds of heterocycles, including thiophenes. For example, a gold-catalyzed annulation has been utilized in the conversion of the substrate 20 into the benzo[Z>]thiophene 21, involving an interesting silyl migration <070L4081>. 

Albeit no examples of a stable bicyclo[3.2.0]hept-5-ene obtained by a metal-catalyzed reaction from a 1,6-enyne have been observed, interestingly, following earlier work done with PtCl2 as catalyst,it was found that the gold-catalyzed reaction of 1,6-ene-ynamides gives cyclobutanones (equation 42), in a process that probably proceeds through unstable bicyclic enamines. 

It is interesting to note that although this was one of the first gold-catalyzed reactions, and despite the great boost in the last few years, gold asymmetric catalysis is stiU an underdeveloped field. 

The last of the nncleophiles discussed in this section is hydride. Aldehyde (equation 127) and aldimine (equation 128) hydrosilylations have been shown to be gold-catalyzed reactions and selective over ketones. 

Yet the reaction that attracted more interest has been the conjngate addition of arenes. It was first described by Hashmi in 2000 that enones and furans could react in the presence of AuCb. In the reported cases, furans were also formed by a gold-catalyzed reaction of allenones (equation 133). Electron-rich substituted benzenes also underwent 1,4-addition with Michael acceptors. Later, 7-azamdoles (equation 134) 28 ere shown to provide 3-aUcylated derivatives. On the other hand, indoles (equation 135) reacted selectively... 

Gold-catalyzed reactions of oxo-alk3mes in preparation of O-heterocycles 07ARK(5)6. 

In a relatively short time span, gold-catalyzed reactions have blossomed into a powerful new methodology in organic synthesis. Given several reviews in the period 2011 throngh 2014 on gold-catalyzed indole synthesis [1-4], this chapter focuses on a few seminal papers and then very recent work. 

Improvement of Catalyst Stability During Gold-Catalyzed Reactions Due to the Use of NHC Ligands... 

A further example of a gold-catalyzed reaction where a strong influence of the electronic properties of the ligand used is observed is the gold-catalyzed cycliza-tion of the allene diene 19. In the presence of gold complexes bearing tt-accept-ing phosphite ligands, the [4-f 2]-cycloadduct 20 is formed almost exclusively. 

Nitrogen nucleophiles have also proven to be suitable nucleophiles in a series of gold-catalyzed reactions, as exemplified by the transformations shown below (Scheme 16.14) [18, 17c]. The great majority of the reactions deal with the formation of nitrogen-containing heterocycles. 

Besides alkenes, several other carbon nucleophiles, as for instance, diketones and aryl groups, can participate in gold-catalyzed reactions. Selected examples of intermolecular reactions are displayed in Scheme 16.17 [17c, 21],... 

The use of gold-catalyzed reactions in the total synthesis of natural products or biologically active molecules remains so far relatively limited. One can explain such a situation by the fact that the interest in gold catalysis is rather recent, and that most of the efforts carried out in this area have concerned the exploration of the reactivity of gold species and the development of new synthetic methods. The applications of gold catalysis in total synthesis that have been reported so far are however highly characteristic of its synthetic potential, more especially in terms of efficiency, selectivity, and compatibility with various... 

The success of homogeneous gold catalysis [1] was accompanied by intensive efforts to understand the mechanisms of the new conversions [2]. None of the many new gold-catalyzed reactions proceeds through only one transition state, we always deal with multistep mechanisms. Many of the reactions have the first steps in common, and then diverge at a later stage of the sequence of elementary steps of the catalytic cycles, which ultimately leads to the manifold of different products that can be obtained. 

As the most important finding of the computational study, it was revealed that there is a pathway for the fi-H elimination, but the overall barrier is so high that this reaction should proceed only at temperatures of about 220 C, which means that this step indeed should be irrelevant for all homogeneous gold-catalyzed reactions published so far. 

The continuously growing family of gold-catalyzed reactions, which still is allowing the development of new reaction possibihties for the different types of intermediates, will add new elementary reactions and new modes of activation of the organic substrates to the toolbox of the synthetic chemist. In the years to come, we will see more exciting new results of this type. 

First gold-catalyzed reaction of aiienes, ketones as nucleophiles and step-wise two-fold hydroarylation... 

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