Computational Clarification of Synergetic RuII/CuI-Metallaphotoredox Catalysis in C(sp3)-N Cross-Coupling Reactions of Alkyl Redox-Active Esters with Anilines

The C-N coupling of alkyl electrophiles for amine synthesis is a less-developed area in comparison with that of aryl electrophiles largely because of the difficulty in product-generating C(sp(3))-N reductive elimination. The recent work by Hu et al. (Nat. Catal. 2018, 1, 120-126) developed an effective strategy for the C-N coupling of alkyl redox-active esters with anilines by merging photoredox catalysis and copper catalysis with an oxoacetic acid ligand (LH2). Here, we present a DFT-based computational study to understand how the special dual catalysis works in a cooperative fashion with the assistance of the ligand. Photoredox catalysis is found to occur most possibly through an oxidative quenching mechanism (Ru-II/*Ru-II/Ru-III/Ru-II) with Et3N as the quencher rather than with the experimentally proposed copper complex. Copper catalytic cycle (Cu-I/Cu-II/Cu-III/Cu-I) is predicted to proceed via a Cu-I-oxidation-first pathway instead of the hypothetical aniline-deprotonation-first pathway in the experiment, and the most likely catalytic active species is identified as the (CuLH)-L-I complex. With the Ru-II/Cu-I - metallaphotoredox catalysis, the most feasible mechanism for the C(sp(3))-N cross-coupling involves six steps: (i) generation of cyclohexyl radical (Cy-center dot) via the single electron transfer (SET) from photoexcited *Ru(II )to the complex of redox-active ester with Cu-I, (ii) coordination of aniline to Cu-I center, (iii) Cy-center dot radical addition to Cu-II-center, (iv) SET between Cu-II-cyclohexyl aniline complex and generated Et3N center dot+, (v) deprotonation of aniline, and (vi) reductive elimination of the Cu-III-cyclohexyl amido intermediate to produce the C(sp(3))-N coupling product. The Cu-I-complex is identified to play a dual role in the title reaction, which acts as the promoter in oxidative quenching process and as the catalyst in the copper catalytic cycle.