Cycloadditions epoxide-azide

Synthesis of Triazoles A number of MCRs that use an epoxide-azide-alkyne Cu(I)-catalyzed cycloaddition sequence to provide substituted p-hydroxy-l,2,3-triazoles 70 (Scheme 3.36) have been recently developed. The azida-tion of an epoxide with sodium azide to give 2-azidoalcohols and subsequent reaction with a terminal alkyne have been carried out under mild conditions in environmentally friendly solvents, such as water, using the catalytic system CuSO sodium ascorbate [65] (see the example depicted in Scheme 3.36) [65a] or a porphyrinatocopper(II) complex... 

Wu and coworkers developed a Cu(I)-catalyzed three-component reaction of 2-(2-ethynylphenyl)oxiranes 111, sulfonyl azides 112, and ethyl a-isocyanoacetate (113) to afford 3 5 -dihydro-l//-spiro[benzo[d]oxepme-2,4 -imidazoles] 114 as a single diastereomer (Scheme 4.24) [44]. The reaction was initiated by a Cu(I)-catalyzed [3+2] cycloaddition between azide and alkyne to generate the intermediate 115. Subsequent release of nitrogen would provide the reactive ketenimine species 116. An intramolecular nucleophilic attack of epoxide to the ketenimine afforded the intermediate 117, which underwent fragmentation to provide 118. Finally, a [3+2] cycloaddition of 118 with a-isocyanoacetate 113 afforded the observed product 114. 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

It has been shown that allylic azides can be trapped, using either phenylacetylene cycloaddition to the azide, or alkene epoxidation, and that [3,3]-sigmatropic equilibration of the possible allylic azides is generally faster than the trapping reactions 42 Nucleoside-derived azide (46) has been shown to undergo reversible [3,3]-sigmatropic... 

Some of the important click reactions are (Kolb and Sharpless 2003 Adzima and Bowman 2012) azide-alkyne azide-sulfonyl cyanide benzyne-azide cycloaddition and hetero Diels-Alder reactions nucleophilic ring opening of strained molecules such as epoxides, aziridines, etc. non-aldol-type reactions and additions to carbon-carbon multiple bonds through oxidation-type reactions such as epoxidation, hydrox-ylation, etc. For more details, the reader is referred to a recent review by Adzima and Bowman (2012). 

A range of indolo(triazolo)-l,4-diazepine derivatives 104 were obtained by a microwave-heated three-component reaction involving tandem N-alkylation of indole 101 with epichlorohydrin 102, ring-opening of the epoxide with azide 103, and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions (13BJO401). Fused triazolodiazepinones were obtained via azide-alkyne 1,3-dipolar cycloaddition followed by lactamization (13JHC430). 

Tandem epoxide or aziridine ring opening by azide/copper catalyzed [3+2] cycloaddition efficient synthesis of 1,2,3-triazolo P-hydroxy or P-tosylamino functionality motif. 

The chemistry of l-methyl-truns-cyclo-octene has been studied. In particular it reacts with acidic methanol to give 1-methoxy-l-methylcyclo-octane, with bromine to give a complex mixture, and with peracid to give its epoxide. On warming in acetic acid it is isomerized to 1-methyl-cis-cyclo-octene, and it reacts with diazomethane and phenyl azide to give cycloaddition products. With 4-phenyl-1,2,4-triazine-3,5-dione, the ene product (121) is obtained. The major difference in reactivity between trans-cyclo-octene and its 1-methyl analogue was found for electrophilic addition reactions where the stability of the incipient 3° cation made the 1-methyl compound more reactive.Transannular products were obtained from the reaction between trans-... 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

Click chemistry is a chemical concept enunciated by Barry Sharpless, Scripps Research Institute, USA, in 2001, which highlights the importance of using a set of powerful, highly reliable, selective reactions under simple reaction conditions to join small molecular units together quickly for the rapid synthesis of new compounds via heteroatom links and create molecular diversity. Several types of reactions have been identified that fulfill the criteria- thermodynamically favored reactions that lead specifically to one product such as nucleophilic ring opening reactions of epoxides and aziridines, nonaldol type carbonyl reactions, additions to carbon-carbon multiple bonds, Michael additions, and cycloaddition reactions. The best-known cHck reactions are the copper-catalyzed reaction of azides and alkynes or the so-called CuAAC reaction and the thiol-ene reaction. 

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