Copper-catalyzed aerobic oxidative coupling of arylboronic acid derivatives and heteroatom nucleophiles is a highly useful method for the formation of aryl-heteroatom bonds, Mechanistic studies reveal that this reaction proceeds via an "oxidase"-style mechanism. Kinetic and spectroscopic studies establish that transmetalation of the aryl group from boron to Cu-II is the turnover-limiting step and reoxidation of the reduced catalyst by O-2 is rapid. Further mechanistic analysis implicates the involvement of an aryl-copper(III) intermediate that undergoes facile C-O bond formation.