Nickel-Catalyzed Highly Selective Radical C-C Coupling from Carboxylic Acids with Photoredox Catalysis.

Controlling the cross-coupling reaction between two different radicals is a long-standing challenge due to the process occurring statistically, which would lead to three products, including two homocoupling products and one cross-coupling product. Generally, the cross-coupling selectivity is achieved by the persistent radical effect (PRE) that requires the presence of a persistent radical and a transient radical, thus resulting in limited radical precursors. In this paper, a highly selective cross-coupling of alkyl radicals with acyl radicals to construct C(sp2)-C(sp3) bonds, or with alkyl radicals to construct C(sp3)-C(sp3) bonds have been achieved with the readily available carboxylic acids and their derivatives (NHPI ester) as coupling partners. The success originates from the use of tridentate ligand (2,2' : 6',2''-terpyridine) to enable radical cross-coupling process to Ni-mediated organometallic mechanism. This protocol offers a facile and flexible access to structurally diverse ketones (up to 90 % yield), and also a new solution for the challenging double decarboxylative C(sp3)-C(sp3) coupling. The broad utility and functional group tolerance are further illustrated by the late-stage functionalization of natural-occurring carboxylic acids and drugs.

Stereoselective benzylic C(sp3)-H alkenylation enabled by metallaphotoredox catalysis.

Selective activation of the benzylic C(sp3)-H bond is pivotal for the construction of complex organic frameworks. Achieving precise selectivity among C-H bonds with comparable energetic and steric profiles remains a profound synthetic challenge. Herein, we unveil a site- and stereoselective benzylic C(sp3)-H alkenylation utilizing metallaphotoredox catalysis. Various linear and cyclic (Z)-all-carbon tri- and tetrasubstituted olefins can be smoothly obtained. This strategy can be applied to complex substrates with multiple benzylic sites, previously deemed unsuitable due to the uncontrollable site-selectivity. In addition, sensitive functional groups such as terminal alkenyl and TMS groups are compatible under the mild conditions. The exceptional site-selectivity and broad substrate compatibility are attributed to the visible-light catalyzed relay electron transfer-proton transfer process. More importantly, we have extended this methodology to achieve enantioselective benzylic C(sp3)-H alkenylation, producing highly enantioenriched products. The applicability and scalability of our protocol are further validated through late-stage functionalization of complex structures and gram-scale operations, underscoring its practicality and robustness.