Tuning the Reactivity of Radical through a Triplet Diradical Cu(II) Intermediate in Radical Oxidative Cross-Coupling

Abstract

Highly selective radical/radical cross-coupling is paid more attention in bond formations. However, due to their intrinsic active properties, radical species are apt to achieve homo-coupling instead of cross-coupling, which makes the selective cross-coupling as a great challenge and almost untouched. Herein a notable strategy to accomplish direct radical/radical oxidative cross-coupling has been demonstrated, that is metal tuning a transient radical to a persistent radical intermediate followed by coupling with another transient radical. Here, a transient nitrogen-centered radical is tuned to a persistent radical complex by copper catalyst, followed by coupling with a transient allylic carbon-centered radical. Firstly, nitrogen-centered radical generated from N-methoxybenzamide stabilized by copper catalyst was successfully observed by EPR. Then DFT calculations revealed that a triplet diradical Cu(II) complex formed from the chelation N-methoxybenzamide nitrogen-centered radical to Cu(II) is a persistent radical species. Moreover, conceivable nitrogen-centered radical Cu(II) complex was observed by high-resolution electrospray ionization mass spectrometry (ESI-MS). Ultimately, various allylic amides derivatives were obtained in good yields by adopting this strategy, which might inspire a novel and promising landscape in radical chemistry.

The Persistent Radical Effect in Organic Synthesis

“…Calculations supported the suggested combination of the alkyl radical with the amine ligand, which is referred to as “ radical capture ” and can be considered as a formal homolytic substitution at nitrogen . Based on this seminal work, other radical Cu‐catalyzed C−N bond formations at activated C−H sites with amides, sulfonamides, imides, carbamates, sulfoximines, and Weinreb amides as the nucleophilic N sources have been developed. Recently, carboxylic acids in combination with alkyl chlorides and hypervalent iodine were established in such couplings.…”

Tuning radical reactivity for selective radical/radical cross-coupling

“…Commonly, tuning Å R t into Å R-M n via metal chelation is another method to enhance the stability of Å R t by conjugation. In 2016, we have achieved the synthesis of allylic amine by another novel strategy that metal (M n ) tunes Å R t (nitrogen-centered radical) into Å R-M n (persistent radical complex) via metal chelation [25]. The key to this reaction is that nitrogen-centered radical is stabilized through a triplet diradical Cu(II) complex (Scheme 3).…”

Stabilization of Two Radicals with One Metal: A Stepwise Coupling Model for Copper-Catalyzed Radical–Radical Cross-Coupling

“…For transition metal-catalyzed radical–radical cross-coupling, however, 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 effect1635. On another hand, the direct combination of two radicals might pass through 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.…”