Palladium-Catalyzed Electrooxidative Double C–H Arylation

Abstract

The electrochemical transition metal-catalyzed crossdehydrogenative reaction has emerged as a promising platform to achieve a sustainable and atom-economic organic synthesis that avoids hazardous oxidants and minimizes undesired byproducts and circuitous functional group operations. However, a poor mechanistic understanding still prevents the widespread adoption of this strategy. In this regard, we herein present an electrochemical palladium-catalyzed oxidative coupling strategy to access biaryls in the absence of a stoichiometric chemical oxidant. The robust palladaelectrocatalysis considerably suppresses the occurrence of homocoupling and oxygenation, being compatible even with electron-deficient arenes. Late-stage functionalization and Boscalid precursor synthesis further highlighted the practical importance of our electrolysis. Remarkably, mechanistic studies including the evaluation of the reaction order of each component by variable time normalization analysis (VTNA) and initial rate analysis, H/D exchange experiment, kinetic isotope effect, and stoichiometric organometallic experiments provided strong support for the involvement of transmetalation between two organopalladium complexes in the turnover limiting step. Therefore, matching the concentrations or lifetimes of two distinct organopalladium intermediates is revealed to be a pivot to the success of electrooxidative catalysis. Moreover, the presence of cationic copper(II) seems to contribute to the stabilization of the palladium(0) catalyst instead of playing a role in the oxidation of the catalyst.

Palladium-Catalyzed Annulations via Sequential C–H Activations of C(sp2)–H/C(sp3)–H or C(sp3)–H/C(sp3)–H Bonds

“…In the second possibility, the transformation occurs via two independent but sequential C–H activation events where the substrate reacts with a bifunctional electrophile to form the annulated products. While the first pathway has received considerable attention, especially in the direct coupling of two C­(sp 2 )–H bonds for the synthesis of biaryl compounds, reports of annulations proceeding through the activation of the more challenging C­(sp 3 )–H bonds have resisted development until recently.…”

Electrochemical Enantioselective C–H Annulation by Achiral Rhodium(III)/Chiral Brønsted Base Domino Catalysis

“…Within our continuous interest in metallaelectrocatalyzed C–H activation, − we questioned whether it would indeed be possible to introduce a domino catalytic system enabled by cooperative rhodium­(III) catalysis and asymmetric Brønsted base catalysis (Scheme C). Thus, an alkenylated intermediate would be generated via electrooxidative rhodium-catalyzed C–H olefination and would then participate in a chiral Brønsted base-catalyzed enantioselective oxa -Michael addition reaction, generating the chiral phthalide product.…”