Cycloaddition transition metal-catalysis

Padwa s group has not only developed highly efficient domino reactions using transition metal catalysis, but they are also well known for their unique combinations of a cycloaddition and a N-acyliminium ion cyclization. An example of this strategy, which is very suitable for the synthesis of heterocycles and alkaloids, is the reaction of 4-98 to give 4-101 via the intermediates 4-99 and 4-100 (Scheme 4.22). Furthermore, 4-101 was transformed into the alkaloid (+)-y-lycorane 4-102 [32]. 

Bicyclopropylidene (1) also reacts with activated alkenes under transition-metal catalysis. With electron-deficient alkenes under nickel(O) catalysis, the [2-1-2] cycloadduct 263 was the main component in the reaction mixture [2b, 150]. Under palladium(O) catalysis, formal [3-1-2] cycloaddition of electron-deficient (Scheme 60) as well as strained alkenes can be achieved exclusively... 

Pyridines and their benzo-derivatives have played an important role in the synthesis of biologically active synthetic and natural substances. As a result, the construction of this molecular architecture has attracted the attention of a diverse array of synthetic methodologies. Notably, transition metal catalysis, radical reactions and cycloaddition chemistry-based methods have been developed for the construction of this important ring system. Detailed herein is a summary of the methods developed for the synthesis of pyridines, quinolines, isoquinolines and piperidines that were disclosed in the literature in 2002. Rather than survey all existing methods for the construction of these compound classes, this review will serve as a supplement and update to the review published last year in this series. 

Because dienes have relatively high-energy HOMOs and low-energy LUMOs they should be able to take part in cycloadditions with themselves. And they do. What they cannot do is form an eight-membered ring in one step (though this is possible photo chemically or with transition metal catalysis as we shall see later). 

In contrast to the conventional methods of cycloaddition, capable of forming only one type of product, the reactions catalysed by metal complexes are fairly flexible. This versatility offers numerous possibilities for elaborating a number of methods for the preparation of structurally diverse structures. However, there is still no consistent theory for transition metal complex catalysis which enables one to predict which catalyst and/or conditions are to be employed for the desired transformation. Results are often achieved through intuition and not reasoning. However, who would dare to negate the usefulness of tools like intuition and mere luck if they produce spectacular results like those met in the area of transition metal catalysis "... 

Low-valent transition metal catalyzed versions of [2 + 2] cycloadditions. especially with nickel catalysts, were recognized early as useful alternatives to thermal and photochemical methods12-15. The observation of transition metal catalysis, active in [2 + 2]-cycloaddition reactions, originally caused considerable discussion of the mechanism as an inversion of symmetry rules, effected by the transition metal, may be assumed. Thus, it was suggested that, in the presence of the metal catalyst, a forbidden reaction becomes allowed 16,17. This interpretation, however, could not be verified for the overall process, since experimental investigations revealed a stepwise mechanism with metallacycle intermediates18-23. 

Due to their tendency to undergo side reactions and the lack of stereospecificity, free methylene or alkylcarbenes, as generated from diazoalkanes by photolysis or thermal nitrogen extrusion, are of minor synthetic importance for [2 4- 1] cycloadditions. However, transition metal catalysis, most commonly with copper or palladium compounds, offers a convenient solution to this problem (Vol. E19b. p 278)s. Probably the most active catalyst is copper(I) trifluoromcthanesulfonate9. The simple diastereoselectivity of these reactions is often negligible, as demonstrated by the copper(I) chloride or palladium(II) bis(benzonitrilo)dichloride promoted cyclopropanation of phenylethene with diazoethane10. 

This section is not concerned with transition metal catalysis. Catalytic activation of organic reactions by Lewis acids is a wide field of investigation [6]. It is usually preferred to other activation modes merely for commodity reasons. The idea of simultaneous use of pressure and traditional Lewis acid catalysts has been recognized for some time [7]. Curiously, the method was only developed in the last decade [8]. It was observed that coupling of both activation methods was beneficial in all [4 + 2] cycloadditions examined. However, most classical hard Lewis acids (AICI3, TiCU, SnCU, ZnCl2. ..) present a number of inherent problems such as... 

The title reaction exemplifies intriguing features of transition metal catalysis. In the absence of transition metal catalysts, reaction between bicyclo[2.1.0]pentane (11) and electron-poor olefins requires extremely forcing conditions and produces a very complex mixture. For example, because of the molecular orbital (MO) restrictions, tmns-l,2-dicyano-ethylene enters into the 2 + 2 cycloaddition across the central o- bond. 

For representative reviews on metal-catalyzed MCRs, see (a) D. M. D Souza, T. J. J. Muller, Chem. Soc. Rev. 2007, 36, 1095-1108. Multi-component syntheses of heterocycles by transition-metal catalysis, (b) J. A. Varela, C. Saa, Synlett 2008, 2571-2578. Recent advances in the synthesis of pyri-dines by transition-metal-catalyzed [2+2+2] cycloaddition, (c) H. Clavier, H. PeUissier, Adv. Synth. Catal. 2012, 354, 3347-3403. Recent developments in enantioselective metal-catalyzed domino reactions. 

Vinylcyclopropane (VCP) can be viewed as the homologue of 1,3-butadiene, which is supported by theoretical computations and spectroscopy analysis [1], However, it s the experimental fact that VCP can participate in cycloadditiOTis as does 1,3-butadiene that may make the viewpoint more convincing. The vinyl substituent of VCP is usually essential to activate or direct the cyclopropane opening, but it does not have to participate in cycloadditions. As a result, VCP can act as either a five-carlxMi synthon or a three-carbon synthon. Combination of many other components with VCP (as a five- or three-carbon synthon) under transition metal catalysis or mediation has led to development of numerous new cycloaddition patterns. The cycloadditions of VCP introduced will be classified according to its role as a five- or three-carbon synthon. Under each category, further elaboratifMi is arranged by different cycloaddition patterns and transition metals. 

As predicted by retrosynthesis, a number of pyridine syntheses utilize cycloaddition reactions, which often are mediated by transition metal catalysis. 

The present state of knowledge concerning homogeneous catalysis of ethylene polymerization by vanadium and by chromium compounds has been reviewed. The relevance of orbital symmetry rules to transition-metal catalysis of [2 + 2] cycloaddition reactions has been discussed. Examples of oligomerization reactions, catalysed by transition-metal complexes, are given in Table 3,105-m... 

Heterocyclic compounds are indispensable in recent far-reaching developments in the material and biological sciences because they can be used as a substructure in functional materials, agrochemicals, and pharmaceuticals. Transition-metal catalysis continues to be a fruitful source of new methods for the synthesis of heterocyclic compounds, since transition-metal catalysts can be used to construct complex structures directly from easily accessible starting materials under neutral and mild reaction conditions. The cycloaddition of unsaturated molecules is one of the most straightforward and atom-economical reactions for constructing substituted heterocyclic compounds [20]. 

Catalytic transformation of arynes [1] and o-quinodimethanes (o-QDMs) [2] has proven in the past decade to be a potent and unique method for constructing aromatic skeletons, since Pena, Romero, Alonso, and co-workers reported the direct synthesis of triphenylene derivatives by the palladium-catalyzed [2 -b 2 -t- 2] cycloaddition of arynes in 1998 [3], demonstrating that their high reactivity was controllable precisely under transition-metal catalysis (Scheme 28.1). 

Although in principle the thermal [2-I-2-I-2] cycloaddition process is allowed by orbital symmetry rules, there are problems with the entropy component, which may be overcome by using transition metal catalysis. This approach (Scheme 2.35) is one of the most convenient for the synthesis of pyridines 2.100. Metal-induced cycloaddition of two alkyne and one nitrile molecules has been described in general reviews of cycloaddition reactions [3,4]. However in some reviews on heterocycles the nitriles are considered as equivalent to alkyne in the [2+2+2] cyclotrimerization reaction [76], in particular, for the synthesis of pyridines and pyridinones in the reactions catalyzed by cobalt, ruthenium, titanium, and zirconium. 

The development of new routes for the synthesis of phosphines is crucial for the synthesis of organophosphorus ligands for use in transition metal catalysis. Chemical transformations involving triple C-C bonds, such as nucleophilic addition and cycloaddition, are widely used for the synthesis of a diverse range of phosphines, which cannot be synthesized by other means [100], On the other hand, the [2- -2- -2] cycloaddition of alkynes catalyzed by transition metals are attracting much attention due to their use in the synthesis of various substituted aryl phosphines. This methodology can also be applied with other methods to synthesize various aryl phosphines [100, 101]. 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Cycloaddition catalyzed by transition metal complexes. Advances in Synthesis Catalysis, 348, 2307-2327 (b) Varela, J.A. and Saa, C. (2008) Recent advances in the synthesis of pyridines by transition-metal-catalyzed [2 + 2 + 2] cycloaddition. Synthesis, 2571-2578. 

Keywords Catalysis Cycloaddition Cyclopentenones Pauson-Khand reaction Transition metal complexes... 

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