Beyond Directed ortho Metalation: Ru-Catalyzed CAr–O Activation/Cross-Coupling Reaction by Amide Chelation

Disclosed is a new, catalytic, and general methodology for the chemical synthesis of biaryl, hetero­biaryl, and polyaryl molecules by the cross-coupling of o-methoxy­benzamides with aryl boroneo­pentylates. The reaction is based on the activation of the unreactive C–OMe bond by the proximate amide directing group using catalytic RuH2(CO)­(PPh3)3 conditions. A one-step, base-free coupling process is thereby established that has the potential to supersede the useful two-step directed ortho metalation/​cross-coupling reaction involving cryogenic temperature and strong base conditions. High regio­selectivity, orthogonality with the Suzuki–Miyaura reaction, operational simplicity, minimum waste, and convenient scale-up make these reactions suitable for industrial applications.