Gold salts and complexes have emerged in the past few years as the most powerful catalysts for electrophilic activation of alkynes toward a variety of nucleophiles under homogeneous conditions. In a simplified form, nucleophilic attack on the [AuL]-activated alkyne proceeds via π complexes 1 to give trans-alkenyl gold complexes of type 2 as intermediates (Scheme 1). This type of coordination is also a common theme in gold-catalyzed cycloisomerizations of enynes, in which the alkene function acts as the nucleophile. In the reaction of enynes with complexes of other transition metals, an Alder-ene cycloisomerization can take place by simultaneous coordination of the alkyne and the alkene to the metal followed by an oxidative cyclometalation. In contrast, this process does not occur for gold(I) since oxidative addition processes are not facile for this metal. 6 In addition, the [AuL] fragment, which is isolobal to H and HgL, adopts a linear coordination and binds to either the alkene or the alkyne. Thus, cycloisomerizations of enynes catalyzed by gold proceed by an initial coordination of the metal to the alkyne, and as illustrated in Scheme 2, the resulting complex 3 reacts with the alkene by either the 5-exo-dig or 6-endo-dig pathway to form the exoor endocyclopropyl gold carbene 4 or 5, respectively, as has been established with other electrophilic transition-metal complexes or halides MXn as catalysts. The proposed involvement of cyclopropyl metal carbenes of type 4 in the electrophilic activation of enynes by transition metals was first substantiated in reactions catalyzed by Pd(II), in which the initially formed cyclopropyl palladium carbenes undergo [4 + 2] cycloaddition with the double bond of the conjugate enyne. Strong evidence for the existence of cyclopropyl metal carbenes as intermediates was also obtained in the reaction of enynes bearing additional double bonds at the alkenyl chain with Ru(II) and Pt(II) catalysts. In these reactions, the cyclopropyl metal carbenes are trapped intramolecularly by the terminal alkene to give tetracycles containing two cyclopropanes. Gold(I) complexes usually surpass the reactivity shown by Pt(II) and other electrophilic metal salts and complexes for the activation of enynes. They are highly reactive yet uniquely selective Lewis acids that have a high affinity for π bonds. This high π-acidity is linked to relativistic effects, which reach a maximum in the periodic table with gold. However, on occasion, the stronger Lewis acidity of gold complexes can be detrimental in terms of selectivity and because of their low tolerance to certain functional groups. In these instances, the less-strongly Lewis acidic Pt(II) complexes could be the catalysts of choice. * To whom correspondence should be addressed. E-mail: aechavarren@ iciq.es. † Additional affiliation: Departamento de Quı́mica Orgánica, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Scheme 1 Chem. Rev. 2008, 108, 3326–3350 3326

Gold-catalyzed cycloisomerizations of enynes: a mechanistic perspective.

5.7. [32π + 32σ] Cycloadditions 74 5.8. [44π + 22π] Cycloadditions 75 6. Seven-Membered Ring Formation 78 6.1. [44π + 32σ] Cycloadditions 78 6.2. [52π+2σ + 22π] Cycloadditions 79 7. Eight-Membered Ring Formation 79 7.1. [22π + 22π + 22π + 22π] Cycloadditions 80 7.2. [44π + 22π + 22π] Cycloadditions 80 7.3. [44π + 44π] Cycloadditions 81 7.4. [66π + 22π] Cycloadditions 83 8. Ten-Membered Ring Formation 85 9. Conclusion and Remarks 87

Transition Metal-Mediated Cycloaddition Reactions

Transition metal chemistry of cyclopropenes and cyclopropanes.

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

Cascade Processes of Metallo Carbenoids

Rhodium-catalyzed ring-opening reaction of cyclopropenes. Control of regioselectivity by the oxidation state of the metal

Rearrangement of 4-alkynylcyclobutenones: a new synthesis of 1,4-benzoquinones

o-Alkynyl-substituted α-diazoacetophenones undergo facile cyclization to indenone derivatives upon treatmcnt with catalytic quantities of Rh(II) carboxylates. The cyclization reaction involves addition of a rhodium stabilized α-keto carbenoid onto the neighboring acetylenic π-bond to give a cyclized vinyl carbenoid. When an alkene is tethered to the alkynyl group, the vinyl carbenoid complex undergoes further cyclization to produce a cyclopropenyl-substituted indenone. Different enyl substituents resulted in a significant variation in the behavioral pattern of the reactive cyclopropene ring

Rearrangement of alkynyl and vinyl carbenoids via the rhodium(II)-catalyzed cyclization reaction of .alpha.-diazo ketones

A new phenol synthesis from the rhodium (I) catalyzed reaction of cyclopropenes and alkynes

Chemoselectivity in the rhodium(II) catalyzed reaction of an acetylenic α-diazo ketone was found to be markedly influenced by the solvent used. Cyclopropenyl indenones are formed in pentane whereas alkenyl-substituted indenones are produced when CH 2 Cl 2 is used as the solvent

Simon L. Xu

Papers

Rhodium-catalyzed ring-opening reaction of cyclopropenes. Control of regioselectivity by the oxidation state of the metal

Rearrangement of 4-alkynylcyclobutenones: a new synthesis of 1,4-benzoquinones

Rearrangement of alkynyl and vinyl carbenoids via the rhodium(II)-catalyzed cyclization reaction of .alpha.-diazo ketones

A new phenol synthesis from the rhodium (I) catalyzed reaction of cyclopropenes and alkynes

Control of chemoselectivity in the rhodium(II)-catalyzed alkyne insertion reaction of .alpha.-diazo ketones