Visible-Light-Mediated Two Transient C(sp3) Radical-Selective Cross-Coupling via Nickel Catalyst Continuous Capture: Synthesis of Pyrroline Derivatives

Two C-(sp(3)) radicals cross-coupling as a straightforward method for constructing C-(sp(3))-C-(sp(3)) bonds has attracted extensive attention from chemists. Unfortunately, the strategy is challenging due to unexpected reactions of transient radicals, such as homocoupling and hydrogen atom transfer. In this regard, capturing open-shell radicals by metal catalysts can effectively enhance the selectivity of transient radical cross-coupling via the formation of more stable organometallic intermediates. Herein, we disclose a selective cross-coupling of two transient C-(sp(3)) radicals through the dual combination of iridium-catalyst-mediated decarboxylation and nickel-catalyst-mediated continuous capture of two radicals. This mild and atom-efficient Ni-catalyzed N-cyclization-alkylation protocol was employed to prepare various alkyl-alkyl cross-coupled products. The synthetic applications of this methodology are demonstrated by the late-stage functionalization of drugs, natural products, and biomolecules.

Automated summary

Cross-coupling of C-(sp(3)) radicals is an important method for constructing C-(sp(3))-C-(sp(3)) bonds. Capturing open-shell radicals with metal catalysts can enhance the selectivity. In this study, a selective cross-coupling method using iridium and nickel catalysts is disclosed, which is applied to the synthesis of alkyl-alkyl cross-coupled products. The method is also demonstrated for late-stage functionalization of drugs, natural products, and biomolecules.