Copper(I)-catalyzed cycloaddition of organic azides and 1-iodoalkynes.
Copper(I)-catalyzed cycloaddition of organic azides and 1-iodoalkynes.
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DOI：
10.1002/anie.200903558
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发表时间：
2009
影响因子：
16.6
通讯作者：
Fokin, Valery V.
中科院分区：
文献类型：
--
作者：
Hein, Jason E.;Tripp, Jonathan C.;Krasnova, Larissa B.;Sharpless, K. Barry;Fokin, Valery V.
The copper-catalyzed azide-alkyne cycloaddition reaction [1](CuAAC)(Scheme 1, a) is known for its high fidelity in the presence of many functional groups and under demanding reaction conditions.[2] Experimental simplicity and high selectivity of this process have been exploited in many applications in synthetic and medicinal chemistry,[3] bioconjugations,[4] materials science,[5] and polymer chemistry.[6] The efficiency and selectivity of this transformation are a direct consequence of the reactivity of in situgenerated copper (I) acetylides. Coordination of the organic azide to the copper center of the acetylide increases the nucleophilicity of the triple bond and initiates a sequence of steps which ultimately results in the formation of the new C—N bond between the nucleophilic βcarbon atom of the acetylide and the terminal, electrophilic nitrogen atom of the azide (Scheme 2). Naturally, internal alkynes are devoid of such reactivity, and therefore CuAAC is limited to terminal acetylenes, producing only 1, 4-disubstituted triazoles. Although the ruthenium-catalyzed azide-alkyne cycloaddition reaction (Scheme 1, b)[7] and methods of functionalization of the triazole heterocycle itself [8] partially address these deficiencies, a general method for the regiocontrolled synthesis of differently substituted 1, 2, 3-triazoles would be a valuable addition to the family of catalytic cycloaddition reactions.In this communication we report that 1-iodoalkynes, stable and readily accessible (vide infra) internal acetylenes, exhibit exceptional reactivity in the copper-catalyzed annulation reaction with organic azides (Scheme 1, c). Indeed, their reactivity appears to surpass that of terminal alkynes. As an added benefit, the products of the reaction, 5-iodo-1, 2, 3-triazoles, are versatile synthetic intermediates amenable for further functionalization. Although several syntheses of iodotriazoles are known, the reactions require stoichiometric amounts of copper catalysts and employ reactive electrophilic halogenating reagents (eg, iodine monochloride, N-iodosuccinimide).[9] In addition, some procedures require extended reaction times and generate mixtures of 5-H and 5-iodo-triazoles.[10]
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影响因子：
2.6
作者：
Deng, J;Wu, YM;Chen, QY
通讯作者：
Chen, QY
影响因子：
2.1
作者：
Gerard, Baudouin;Ryan, Jamie;Porco, John A., Jr.
通讯作者：
Porco, John A., Jr.
影响因子：
15
作者：
Wang, Q;Chan, TR;Finn, MG
通讯作者：
Finn, MG
影响因子：
15
作者：
Himo, F;Lovell, T;Fokin, VV
通讯作者：
Fokin, VV
影响因子：
15
作者：
Boren, Brant C.;Narayan, Sridhar;Fokin, Valery V.
通讯作者：
Fokin, Valery V.