1.1. General Reactivity of Alkyne-Gold(I) Complexes
For centuries, gold had been considered a precious, purely decorative inert metal. It was not until 1986 that Ito and Hayashi described the first application of gold(I) in homogeneous catalysis.1 More than one decade later, the first examples of gold(I) activation of alkynes were reported by Teles2 and Tanaka,3 revealing the potential of gold(I) in organic synthesis. Now, gold(I) complexes are the most effective catalysts for the electrophilic activation of alkynes under homogeneous conditions, and a broad range of versatile synthetic tools have been developed for the construction of carbon–carbon or carbon–heteroatom bonds.

Gold(I) complexes selectively activate π-bonds of alkynes in complex molecular settings,4−10 which has been attributed to relativistic effects.11−13 In general, no other electrophilic late transition metal shows the breadth of synthetic applications of homogeneous gold(I) catalysts, although in occasions less Lewis acidic Pt(II) or Ag(I) complexes can be used as an alternative,9,10,14,15 particularly in the context of the activation of alkenes.16,17 Highly electrophilic Ga(III)18−22 and In(III)23,24 salts can also be used as catalysts, although often higher catalyst loadings are required.

In general, the nucleophilic Markovnikov attack to η2-[AuL]+-activated alkynes 1 forms trans-alkenyl-gold complexes 2 as intermediates (Scheme 1).4,5a,9,10,12,25−29 This activation mode also occurs in gold-catalyzed cycloisomerizations of 1,n-enynes and in hydroarylation reactions, in which the alkene or the arene act as the nucleophile.



Scheme 1

Anti-Nucleophilic Attack to η2-[AuL]+-Activated Alkynes

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Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

A.L.-P. thanks CSIC for a contract under the JAE-doctor
program. Financial support by PLE2009 project from MCIINN
and Consolider-Ingenio 2010 (proyecto MULTICAT) are also
acknowledged.

Gold-catalyzed carbon-heteroatom bond-forming reactions.

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.

Homogeneous gold catalysis beyond assumptions and proposals--characterized intermediates.

Heterocycles constitute the largest and the most diverse family of organic compounds Among them, aromatic heterocycles represent structural motifs found in a great number of biologically active natural and synthetic compounds, drugs, and agrochemicals Moreover, aromatic heterocycles are widely used for synthesis of dyes and polymeric materials of high value 1 There are numerous reports on employment of aromatic heterocycles as intermediates in organic synthesis 2

Although, a variety of highly efficient methodologies for synthesis of aromatic heterocycles and their derivatives have been reported in the past, the development of novel methodologies is in cuntinious demand Particlularly, development of new synthetic approaches toward heterocycles, aiming at achieving greater levels of molecular complexity and better functional group compatibilities in a convergent and atom economical fashions from readily accessible starting materials and under mild reaction conditions, is one of a major research endeavor in modern synthetic organic chemistry Transition metal-catalyzed transformations, which often help to meet the above criteria, are among the most attractive synthetic tools

Several excellent reviews dealing with transition metal-catalyzed synthesis of heterocyclic compounds have been published in literature during recent years Many of them highlighted the use of a particular transition metal, such as gold,3 silver,4 palladium,5 copper,6 cobalt,7 ruthenium,8 iron,9 mercury,10 rare-earth metals,11 and others Another array of reviews described the use of a specific kind of transformation, for instance, intramolecular nucleophilic attack of heteroatom at multiple C–C bonds,12 Sonogashira reaction,13 cycloaddition reactions,14 cycloisomerization reactions,15 C–H bond activation processes,16 metathesis reactions,17 etc Reviews devoted to an application of a particular type of starting materials have also been published Thus, for example, applications of isocyanides,18 diazocompounds,19 or azides20 have been discussed In addition, a significant attention was given to transition metal-catalyzed multicomponent syntheses of heterocycles21 Finally, syntheses of heterocycles featuring formation of intermediates, such as nitrenes,22 vinylidenes,23 carbenes, and carbenoids24 have also been reviewed

The main focus of the present review is a transition metal-catalyzed synthesis of aromatic monocyclic heterocycles The organization of the review is rather classical and is based on a heterocycle, categorized in the following order: (a) ring size of heterocycle, (b) number of heteroatoms, (c) type of heterocycle, and (d) a class of transformation involved A brief mechanistic discussion is given to provide information about a possible reaction pathway when necessary The review mostly discusses recent literature, starting from 200425 until the end of 2011, however, some earlier parent transformations are discussed when needed

Transition Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles

Die Gold-Katalyse ist ein sehr aktives Gebiet im Feld der Katalyseforschung. Wochentlich werden neue Reaktionen publiziert, oft werden erstaunliche Konnektivitatsanderungen beobachtet, die Zahl der Anwendungen in der Totalsynthese steigt … – aber was sind die Mechanismen dieser Reaktionen? Fundierte Informationen konnen aus dem Wissen uber Zwischenstufen dieser Reaktionen erhalten werden.

Homogene Gold‐Katalyse jenseits von Vermutungen und Annahmen – charakterisierte Intermediate

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 Barluenga's reagent offers a new and mild access to the synthetically valuable iodoalkylideneoxazoles from propargylic amides, this reagent being superior to other sources of halogens.

Cyclization of Propargylic Amides: Mild Access to Oxazole Derivatives

Homogeneous gold catalysis has made a major contribution to organic synthesis in the past decade and, apart from significant methodology work in the meantime, it has become an efficient tool in total synthesis. It has almost been forgotten that enantioselective gold catalysis was the origin of homogenous gold catalysis. After significant initial success, stereoselective gold catalysis was neglected for some time. As recently predicted, enantioselective gold catalysis revived in the last years and significant success has been achieved with a number of different enantiomerically pure gold complexes and even enantiomerically pure counterions. Common for these enantioselective reactions is that the new stereocenters are formed by the transformation of a sp center of a C=C double bond (in an allene or alkene 1, Scheme 1) to a chiral center with sp hybridization in the product 2. Alternatively, a C=O double bond (in an aldehyde) is transformed. So far only an enantiofacial selection in the selectivity determining step has been exploited for enantioselective homogeneous gold catalysis. With mono-alkynes, such a facial selection is not possible—the typical addition reactions initially form alkenes that do not possess a stereocenter. Dialkynes 3 with symmetry equivalent, enantiotopic alkynyl groups would allow stereoselective conversions. If, after the coordination (an intermolecular process) of the alkyne to the enantiomerically pure gold catalyst, the subsequent intramolecular addition is fast for both diastereomeric p complexes (leading to the two enantiomeric products 4 and ent-4 ; in general, gold-catalyzed reactions are fast compared to other catalysts). The stereoselection would be quite difficult, as the p coordination of one of the two alkynes to the gold catalyst would become the selectivity determining step (in general, the subsequent addition reactions are not reversible). Here we report our findings with regard to this concept in the gold-catalyzed phenol synthesis. As the test substrate for this investigation, we used the furyldialkyne 8. It was easily prepared from 5-methylfurfural (5) by an aldol condensation with tert-butyl acetate to deliver the furylacrylate 6, followed by chemoselective transfer hydrogenation to give 7 and twofold addition of propargyl magnesium bromide to the ester group (Scheme 2). With 5 mol % AuCl3 this substrate 8 readily and chemoselectively underwent cycloisomerization to the phenol rac-9

Gold catalysis: enantiotopos selection.

A gold-catalyzed phenol synthesis was successfully used in the synthesis of dihydroisocoumarins for the first time. A large number of gold(i) complexes were prepared and tested; only complexes based on the biarylphosphine motif were successful.

Melissa Hamzic

Papers

Cyclization of Propargylic Amides: Mild Access to Oxazole Derivatives

Gold catalysis: enantiotopos selection.

Gold Catalysis: Biarylphosphine Ligands as Key for the Synthesis of Dihydroisocoumarins

Gold‐Katalyse: Umlenken des Reaktionspfades der Furan‐Alkin‐ Cyclisierung