Palladium-Catalyzed Benzene Arylation:  Incorporation of Catalytic Pivalic Acid as a Proton Shuttle and a Key Element in Catalyst Design

2006-12-27T00:00:00Z (GMT) by Marc Lafrance Keith Fagnou
A palladium−pivalic acid cocatalyst system has been developed that exhibits unprecedented reactivity in direct arylation. This reactivity is illustrated with the first examples of high yielding direct metalation−arylation reactions of a completely unactivated arene, benzene. Experimental and computational evidence indicates that the pivalate anion is a key component in the palladation/C−H bond breaking event, that it lowers the energy of C−H bond cleavage and acts as a catalytic proton shuttle from benzene to the stoichiometric carbonate base. Eight examples of substituted aryl bromides are included which undergo direct arylation with benzene in 55−85% yield.