Noncarbon Cumulenes

The [3+2] cycloaddition reaction of azides to numerous dipolarophiles is a standard Huis-gen type cycloaddition reaction. The reaction usually proceeds via a concerted reaction of the HOMO orbitals of the 1,3-dipole with the LUMO orbitals of the dipolarophile. However, switter ionic intermediates are observed in the cycloaddition reaction of ketene-Af acetals with nitroarylazides. In the reaction of picrylazide with one of the ketene-AAf-acetals a 90 % yield of the stable switterionic linear adduct is obtained. Electron withdrawing groups on the dipolarophile normally favor the concerted formation of cycloadducts, while electron donating groups on the dipolarophile favor the formation of switterionic intermediates. 

The dipolar character of the azides is demonstrated by their mesomeric structures. 

The [3+2] cycloaddition reaction of azides with terminal olefins is of considerable interest in the modification of biomolecules, because the azide group is abiotic in animals. Especially, the Cu(i) catalyzed cycloaddition reaction of azides with terminal alkynes achieves regioselective formation of 1,4-disubstituted 1,2,3-triazoles and this reaction is currently referred to as click chemistry . In the thermal reaction of azides with terminal alkynes, about 1 1 mixtures of 1,4- and 1,5-disubstituted 1,2,3-triazoles are obtained. Likewise, disubstituted alkynes afford mixtures of the stereoisomers. In order to avoid the cellular toxicity caused by the copper catalyst, Cu-free click chemistry is of considerable interest. The use of strained cyclooctyne derivatives as dipolarophiles was proposed recently. In this manner a novel 6,7-dimethoxyazacyclooct-4-yne was constructed from a glucose analogue s. The disadvantage of this reaction is its significantly slower reaction rate but introduction of fluoro groups adjacent to the triple bond achieves some rate enhancement.  

Cumulenes in Click Reactions Henri Ulrich 2009 John Wiley Sons, Ltd 

3-dipolarophiles participating in the [3+2] cycloaddition reaction with azides include carbon-carbon multiple bonds, such as alkynes, olefins, vinyl ethers and ketene acetals, but addition across C=N multiple bonds, such as in nitriles and isocyanates, C=S and P=C bonds is also observed. The yields observed for many of these reactions approach quantitative. 

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A relatively unknown class of noncarbon cumulenes are the highly colored thionitroso 5-sulfides, RN=S=S. They are also 1,3-dipolar species, which undergo [3+2] cycloaddition reactions. Huisgen and Peng have studied the reaction of 2-methyM,6-di-t-butyl-phenylthionitroso 5-sulfide with cyclooctene and obtained the [3+2] cycloadduct in 50 % yield. In a similar manner, reaction with cyclooctadiene afforded the mono cycloadduct in 83 % yield. 

The cumulenes discussed in this book are subdivided into carbon- and noncarbon cumulenes, and the 1-carbon cumulenes (sulfines, sulfenes, thiocarbonyl S -imides and thiocar-bonyl S -sulfides) are excellent dipolar species. The 2-carbon or the center-carbon cumulenes (carbon dioxide and carbon sulfides) are less reactive but their imides (isocyanates, isothiocyantes and carbodiimides) readily participate in many of the discussed reactions. The 1,2-dicarbon cumulenes (ketenes, thioketenes and ketenimenes) similarly participate in cycloaddition reactions, as well as the more exotic 1,2-dicarbon cumulenes (1-silaalene, 1-phosphaallene and other metal allenes). In contrast, 1,3-dicarbon cumulenes are only... 

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