Transition metals cycloaddition reactions

Keywords Bioorthogonal reaction Transition metal Cycloaddition reaction CuAAC reaction Unnatural amino acids... 

The transition metal-catalyzed reaction of diazoalkanes with acceptor-substituted alkenes is far more intricate than reaction with simple alkenes. With acceptor-substituted alkenes the diazoalkane can undergo (transition metal-catalyzed) 1,3-dipolar cycloaddition to the olefin [651-654]. The resulting 3//-pyrazolines can either be stable or can isomerize to l//-pyrazolines. 3//-Pyrazolines can also eliminate nitrogen and collapse to cyclopropanes, even at low temperatures. Despite these potential side-reactions, several examples of catalyzed cyclopropanations of acceptor-substituted alkenes with diazoalkanes have been reported [648,655]. Substituted 2-cyclohexenones or cinnamates [642,656] have been cyclopropanated in excellent yields by treatment with diazomethane/palladium(II) acetate. Maleates, fumarates, or acrylates [642,657], on the other hand, cannot, however, be cyclopropanated under these conditions. 

Photochemical or thermal extrusion of molecular nitrogen from ot-diazocarbonyl compounds generates a-carbonylcarbenes. These transient species possess a resonance contribution from a 1,3-dipolar (303, Scheme 8.74) or 1,3-diradical form, depending on their spin state. The three-atom moiety has been trapped in a [3 + 2] cycloaddition fashion, but this reaction is rare because of the predominance of a fast rearrangement of the ketocarbene into a ketene intermediate. There are a steadily increasing number of transition metal catalyzed reactions of diazocarbonyl compounds with carbon-carbon and carbon-heteroatom double bonds, that, instead of affording three-membered rings, furnish hve-membered heterocycles which... 

During the present decade, a wide variety of polycyclic carbacephem derivatives have been reported starting from readily available monocyclic /3-lactams, which after transformation in more functionalized compounds and further cyclization yielded different fused carbacephems. Several approaches for the preparation of fused carbacephem derivatives including cycloaddition reactions such as the [2+2], 1,3-dipolar, and Diels-Alder reactions, as well as transition metal-catalyzed reactions such as the Pauson-Khand and ring-closing metathesis (RCM) reactions have been reported in the literature. 

Abstract Major advances in transition-metal catalyzed reactions have taken place since the discovery of N-heterocydic carbenes (NHCs). This review provides a summery of recent M-NHC catalyzed reactions including cycloadditions, rearrangements, coupling reactions, polymerizations, and the additions of H-X. 

Tandem carbonyl ylide generation from the reaction of metallo carbenoids with carbonyl continues to be of great interest both mechanistically and synthetically. Effective carbonyl ylide formation in transition metal catalyzed reactions of diazo compounds depends on the catalyst, the diazo species, the nature of the interacting carbonyl group and competition with other processes. The many structurally diverse and highly successful examples of tetrahydrofuran formation cited in this mini-review clearly indicate that the tandem cyclization/cycloaddition cascade of metallo carbenoids has evolved as an important strategy in both carbo- and heterocyclic synthesis. 

The use of alkynes in transition metal catalyzed reactions is often complicated by their tendency to undergo cyclo-tiimerization and -tetramerization. Thus, it is useful to note that a phosphite-modified catalyst, Ni(COD)2Aris(o-phenylphenyl) phosphite (TOPP), promotes codimerization of alkynes with methylenecyclopropane and its a ylidene analogs. Both electron-rich and electron-poor alkynes participate in cycloaddition with moderate regioselectivity. Opposite regiochemistiy is sometimes observed widi disubstituted alkylidene systems (equations 97-99). 

The C,C-bond-forming reactions can be classified as polar reactions, in which an activated donor reacts selectively with an acceptor or vice versa radical reactions, which are increasingly applied in coupling or addition reactions because they do not interfere with polar groups in the molecule and thus save steps as no protections are needed [43] pericyclic reactions, especially cycloadditions, for the construction of ring compounds with high stereoselectivity [45] and transition metal-catalyzed reactions [46]. 

The synthesis of cyclopropanes via cyclopropene ring opening with subsequent [1 +2] cycloaddition is restricted to thermolytically or photochemically initiated, and transition metal catalyzed reactions, and furthermore is only applicable to suitably substituted alkenes. 

As with other diazo compounds, cyclopropanation with 1 or 2 can proceed either via a photo-chemically or thermally generated carbene, in a transition-metal-catalyzed reaction, or by [3 -I- 2] cycloaddition of the diazo function to the C-C double bond followed by nitrogen extrusion from the thermally unstable cycloadduct. 

Obviously, the appropriate application of the Woodward-Hoffmann rules to transition metal complex reactions involving metal carbon bonds requires information about the mechanistic and stereochemical details which is not easy to come by and definitely not yet sufficiently available for photochemical cycloaddition reactions of complexed olefinic systems. 

In a preliminary chapter, entitled Introduction, the underlying principles of physical organic chemistry, as applied to stereoselective reactions, are succintly recalled. The three subsequent chapters describe the chiral auxiliaries, reagents, catalysts and ligands that are most commonly used in asymmetric synthesis. The remaining chapters are devoted to the description and delineation of the scope of the main classes of asymmetric organic reactions. These indude protonations and deprotonations alkylations and related reactions additions to C=0, C=N and C=C double bonds cycloadditions rearrangements and transition metal-catalyzed reactions. 

Alkene metathesis is a transition-metal-catalyzed reaction in which alkene bonds are cleaved and redistributed to form new alkenes [1-3]. The reaction proceeds through the formal [2 + 2] cycloaddition of an alkene and a metal alkylidene to yield a metallocyclobutane intermediate (Scheme 1). The productive retrocydoad-dition of this intermediate generates a new metal alkylidene and a new alkene product. These processes are generally reversible, and the reaction is under thermodynamic control. 

Stereochemical control of [2 + 2] cycloaddition is also achieved in transition metal catalyzed reactions of methylenecyclopropanes26 which, alternatively, can undergo [27t + 2a] cycloaddition, formally a [3 + 2] cycloaddition, leading to five-membered rings. These reactions are discussed in Sections 1.5.8.3.5.3. and D. 1.6.1.2.3. 

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. 

Unlike reactions with alkenes and alkynes, relatively few examples of intramolecular transition metal-cataly2ed reactions of allenes have been reported so far. Continuing our endeavor to extend the synthetic reach of transition-metal-catalyzed reactions, we have directed our attention at the use of an allene as the n-system. As with the alkene systems, two stereochemical outcomes are possible for the intramolecular [5+2] cycloaddition of allene-vinylcyclopropanes. The use of an allene moiety also presents an interesting opportunity to incorporate chirality into the substrate. Additionally, because ene-vinylcy-clopropane substrates substituted at the alkene terminus are not amenable to [5+2] cycloaddition, the use of an allene allows access to the same framework that would be obtained by cycloaddition of terminally substituted alkene substrates, thereby circumventing one of the few limitations encountered with ene-vinylcyclopropane cycloadditions. 

In 1953, Robert s experiments on the conversion of C-labeled chlorobenzene with KNH2 into aniline gave strong support to the intermediacy of ortho-benzyne in this and related reactions. Additional direct evidence for the existence of ortho-benzyne was provided by the observation of its IR spectrum, sohd-state dipolar NMR spectrum, and NMR in a molecular container, and by UV photoelectron spectroscopy. Even at low temperatures, arynes are extraordinary reactive. The reactions of arynes can be divided into three groups (i) pericyclic reactions, (ii) nucleophilic additions, and (iii) transition-metal catalyzed reactions. The pericyclic reactions can be divided into several categories such as Diels-Alder reactions, [2-f2] cycloadditions, 1,3- and l,4-dipolar cycloadditions, and the ene reactions. Arynes react with practically aU kinds of nucleophiles. More recently, the transition-metal catalyzed reactions of arynes have been studied, in particular those involving palladium. 

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