The oxidative coupling of primary amines with internal alkynes catalyzed by Ru complexes is presented as a general atom-economy methodology with a broad scope of applications in the synthesis of N-heterocycles. Reactions proceed through regioselective C-H bond activation in 15 minutes under microwave irradiation or in 24 hours with conventional heating. The synthesis of 2,3,5-substituted pyridines, benzo[h]isoquinolines, benzo[g]isoquinolines, 8,9-dihydro-benzo[de]quinoline, 5,6,7,8-tetrahydroisoquinolines, pyrido[3,4g]isoquinolines, and pyrido[4,3g]isoquinolines is achievable depending on the starting primary amine used. DFT calculations on a benzylamine substrate support a reaction mechanism that consists of acetate-assisted C-H bond activation, migratory-insertion, and C-N bond formation steps that involve 28-30 kcal mol(-1) . The computational study is extended to additional substrates, namely, 1-naphthylmethyl-, 2-methylallyl-, and 2-thiophenemethylamines.
The Cu-mediated synthesis of tetrasubstituted olefins by the addition of an acetate group and a thiolate to an unactivated internal alkyne is described. The reaction is fully stereoselective, because only the E alkene is obtained. If the alkyne is asymmetric, the reaction also shows a very high degree of regioselectivity. The mechanism of the reaction is elucidated by DFT methods, which show that it takes place through Cu-stabilized radical species. Calculations highlight the crucial role of the dimeric copper(II) diacetate in the process, as it generates the active species in which the sulfur center has an incipient thiyl radical character and accepting, through a series of changes in the oxidation states of the two copper centers, the two electrons released in the addition of two nucleophiles to the alkyne.
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