Catalytic sequential reactions involving palladacycle-directed aryl coupling steps

Catalytic methods are important tools for the synthesis of C−C bonds under mild and ambient conditions. Palladium chemistry predominates in this area because it offers the opportunity to form several different types of bonds in one pot. Palladium can also tolerate a variety of functional groups. Among the many investigations of catalytic aryl−aryl couplings, the most successful technique has been the Suzuki reaction, which uses an arylboronic acid to attack an aryl−Pd bond. This Account reports our methodology, based on the cooperative action of Pd and norbornene, that achieves selective aryl−aryl coupling through C−halide and C−H activation. We are primarily interested in Pd-catalyzed sequential reactions. These reactions combine palladium as an inorganic catalyst and a strained olefin such as norbornene as an organic catalyst and can lead to biphenyl derivatives. While the palladium facilitates C−C bond formation through C−halide and C−H activation, the norbornene contributes to the construction of a palladacycle, an intermediate structure that controls and directs the subsequent reaction steps selectively. To achieve regioselective arylation at the carbon ortho to the original C−halide bond, palladacycles require an additional ortho substituent (R1). The palladacycle opens, giving rise to a biphenylylnorbornylpalladium complex. Because of the steric hindrance exerted by the two ortho groups, norbornene deinsertion readily occurs to form a biphenylylpalladium complex. Thus, norbornene acts as a removable scaffold. We used this biphenylylpalladium species to form C−C (with olefins, alkynes, or arylboronic acids) or C−H bonds (by hydrogenolysis). Using nonidentical aryl or heteroaryl halides, we also formed a biaryl-bonded Pd species able to undergo the final termination reaction (C−C, C−N, or C−O bond formation) either inter- or intramolecularly. We used this method to synthesize a variety of aromatic and heteroaromatic compounds. We also obtained the key metallacycle able to selectively direct the reactions by replacing norbornene with an aryl-bonded aminocarbonyl group. This method provided a diverse series of condensed heterocycles.