Abstract
Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. A theoretical study was performed to reveal the mechanism and selectivity of the copper-catalyzed C–N radical–radical cross-coupling reaction. The concerted coupling pathway, in which a C–N bond is formed through the direct nucleophilic addition of a carbon radical to the nitrogen atom of the Cu(II)–N species, is demonstrated to be kinetically unfavorable. The stepwise coupling pathway, which involves the combination of a carbon radical with a Cu(II)–N species before C–N bond formation, is shown to be probable. Both the Mulliken atomic spin density distribution and frontier molecular orbital analysis on the Cu(II)–N intermediate show that the Cu site is more reactive than that of N; thus, the carbon radical preferentially react with the metal center. The chemoselectivity of the cross-coupling is also explained by the differences in electron compatibility of the carbon radical, the nitrogen radical and the Cu(II)–N intermediate. The higher activation free energy for N–N radical–radical homo-coupling is attributed to the mismatch of Cu(II)–N species with the nitrogen radical because the electrophilicity for both is strong.
Highlights
Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction
The energy barrier could be represented by the minimum energy crossing point (MECP)[36,37,38], the energy of which plays a significant role in determining the reaction mechanism and selectivity[38,39,40,41,42]
In the selected copper-catalyzed C–N coupling reaction, di-tert-butyl peroxide (DTBP), which could decompose to tert-butoxyl radicals, was used as the radical initiator[21]
Summary
Transition metal-catalyzed radical–radical cross-coupling reactions provide innovative methods for C–C and C–heteroatom bond construction. For transition metal-catalyzed radical–radical cross-coupling, the stability and reactivity of radicals would be changed in the presence of metals, which probably does not meet the criteria of the persistent radical effect[16,35] On another hand, the direct combination of two radicals might pass through www.nature.com/scientificreports/. A spin-crossover process with energy barrier when the spin state of the reactants is a triplet and the coupling product is a singlet (Fig. 2) In this case, the energy barrier could be represented by the minimum energy crossing point (MECP)[36,37,38], the energy of which plays a significant role in determining the reaction mechanism and selectivity[38,39,40,41,42]. More effort should be devoted to reveal the detailed reaction pathway and the origin of the cross-combination selectivity
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