Copper catalysis cycloaddition

Ethyl diazopyruvate, under copper catalysis, reacts with alkynes to give furane-2-carboxylates rather than cyclopropenes u3) (Scheme 30). What looks like a [3 + 2] cycloaddition product of a ketocarbenoid, may actually have arisen from a primarily formed cyclopropene by subsequent copper-catalyzed ring enlargement. Such a sequence has been established for the reaction of diazoacetic esters with acetylenes in the presence of certain copper catalysts, but metallic copper, in these cases, was not able to bring about the ring enlargement14). Conversely, no cyclopropene derivative was detected in the diazopyruvate reaction. 

Evans et al. (219, 220) examined the use of electron-poor heterodienes as partners in cycloadditions with electron-rich alkenes under copper catalysis. In particular, a,p-unsaturated acylphosphonates and keto-esters afford hetero-Diels-Alder adducts in high selectivities when treated with enol ethers in the presence of catalysts 269c and 269d. 

The discovery of copper catalysis in 1,3-dipolar cycloadditions of terminal alkynes to azides (click chemistry) in 2002 <2002AGE2596, 2002JOC3057> has revolutionized the field . It is not only that the catalyzed reactions proceed faster under mild conditions, but full regioselectivity of the products is also achieved. Terminal alkynes generate only 1,4-disubstituted triazoles. A brief outline of the reaction mechanism is given in Scheme 253 . Some aspects of this new methodology are discussed in a review <2007ALD7>. 

It is now usual to promote these cycloadditions by catalysts for example, reaction with A -tosyl-ynamides, using ruthenium or copper catalysts, giving 1-substituted 5- and 4-amino triazoles, respectively the formation of the 1,4-substitution pattern with copper catalysis and 1,5-pattem with ruthenium catalysis seems to be general. The latter metal will also promote addition to internal alkynes. ... 

S.2.2.4. Triazoles from Azides. Cycloadditions of this type constitute a valuable synthetic route to the triazole ring system. This is shown in Scheme 5.30. This combination dates back to the early work of Huis-gen, but in more recent times it was discovered to be subject to catalysis by Cu(I) compounds. The reactions are fast under mild conditions, have high regiospecificity, and occur in a variety of solvents including water. In addition, reaction products are easily isolated. Reactions with these characteristics have become known as comprising click chemistry this term was coined by K. B. Sharpless. The first and most commonly used reaction referred to by this name is indeed the azide-alkyne cycloaddition, and new interest has developed in triazole hemistry since the discoveiy of the copper catalysis. In addition to its use in organic... 

In the last decade, the combination of CRP techniques and newly found or reinvented highly effective and selective organic reactions termed as the click chemistry has been demonstrated to be a versatile tool for the specific constmction of novel functional macromolecules [28]. In 2001, Sharpless et al. [29] introduced the term click chemistry with its famous representative, the cycloaddition of azides with alkynes under copper catalysis. He defined a click reaction with a set of criteria The reaction must be modular, wide in scope, give very high yields, generate only inoffensive byproducts that can be removed by nonchromatographic methods, and be stereospecific (but not... 

In the last two decades, copper catalysis has been intensively utilized for numerous useful transformations including oxidation (Diaz-Requejo et al., 2000 Kantam et al., 2009a), cycloaddition (Reymond and Cossy, 2008 Hein and Fokin, 2010), crosscoupling (Ma and Cai, 2008), C-H activation (Daugulis et al., 2009 Wendlandt et al., 2011), domino reactions (Liu and Wan, 2011, 2012), and so on. These Cu-mediated reactions are also involved in many valuable synthetic applications such as the assembly of biologically and medicinally useful molecules. 

Triazoles are an interesting class of heterocyclic units widely used in the discovery and modulation of drug candidates, development of new materials, supramolecular chemistry, design of new supported organocatalysts, and biotechnology area [55], Therefore, several elegant methods for the synthesis of this classic nitrogen heterocyclic compounds have been reported by 1,3-dipolar cycloaddition of azides with alkynes under thermal [56] conditions as well as copper catalysis. 

Scheme 8.3 Tandem reduction-ring-closure-ring-opening-l,3-dipolar cycloaddition reaction catalysed by whole-ceU catatysis and copper catalysis.

Phenylthiomethyl)trimethylsilyl carbene (10) has been generated via two independent methods, either from the diazo compound through copper catalysis (eq 14), or from the chloro-(phenylthiomethyl)silane by base-induced o -elimination. The generation of carbene 10 was verified by [2 +1] cycloadditions with olefins affording cyclopropanes (eq 15) in low to moderate yields (12-61%). ... 

The Huisgen 1,3-dipolar cycloaddition to triazoles can be performed under copper-catalysis and is then known as Copper-Catalyzed Azide-Alkyne Cycloaddition... 

Fig. 7.19 Phenyl azide and phenyl acetylene are coencapsulated to give a Michaelis complex with high molarity and effective molarity. The cycloaddition (click) reaction takes place without copper catalysis...

Cp = pentamethylcyclopentadienyl) catalyzed the Huisgen 1,3-dipolar cycloaddition interestingly, the observed regioselectivity was reversed when compared with related copper catalysis [71, 72]. 

The thermal [1] or photochemical [5] isomerization of N-silylated allylamine in the presence of Fe(CO)5 provides the corresponding N-silylated enamines 7a and 7b. Z-enamine 7b does not react in any of the examined cycloadditions. The cyclopropanation of E-enamine 7a with methyl diazoacetate under copper(I) catalysis provides the donor-acceptor-substituted cyclopropane 9 [1], which can be converted in good yield into the interesting dipeptide 10 [6]. 

The [3+2] cycloaddition of azides to double and triple bond systems has found considerable interest over the last couple of years. The reaction can either be performed under thermal conditions or by copper(i) catalysis <2001AG(E)2004, 2002AG(E)2596>. In an attempt to broaden the chemistry of such cycloaddition processes, Sharpless et al. reported the generation of tetrazole derivatives 61 by an intramolecular process (Scheme 12). In... 

This chapter will begin with a discussion of the role of chiral copper(I) and (II) complexes in group-transfer processes with an emphasis on alkene cyclo-propanation and aziridination. This discussion will be followed by a survey of enantioselective variants of the Kharasch-Sosnovsky reaction, an allylic oxidation process. Section II will review the extensive efforts that have been directed toward the development of enantioselective, Cu(I) catalyzed conjugate addition reactions and related processes. The discussion will finish with a survey of the recent advances that have been achieved by the use of cationic, chiral Cu(II) complexes as chiral Lewis acids for the catalysis of cycloaddition, aldol, Michael, and ene reactions. 

The reaction of a-diazocarbonyl compounds with nitriles produces 1,3-oxazoles under thermal (362,363) and photochemical (363) conditions. Catalysis by Lewis acids (364,365), or copper salts (366), and rhodium complexes (367) is usually much more effective. This latter transformation can be regarded as a formal [3 + 2] cycloaddition of the ketocarbene dipole across the C=N bond. More than likely, the reaction occurs in a stepwise manner. A nitrilium ylide (319) (Scheme 8.79) that undergoes 1,5-cyclization to form the 1,3-oxazole ring has been proposed as the key intermediate. 

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