Directing Effects on the Copper-Catalyzed Site-Selective Arylation of Indoles.

Different site selectivities have been reported for indoles with different directing groups in copper-catalyzed site-selective C-H arylations. Computational and mass spectrometric studies have been conducted in an effort to understand the origin of site selectivity and the effects of the directing groups. A Heck-like mechanism involving a four-membered ring is found in all three of the cases studied. For N-acetyl indole with a weak directing group, a neutral Heck-like mechanism is controlled by an electronic effect resulting in C2 site selectivity. In contrast, indole with a N-P(O) Bu group and N-benzyl-3-pivaloyl indole prefer a cationic Heck-like reaction in which a favorable six-membered chelation between the directing group and the Cu center determines the C6 and C5 site selectivities.