Palladium-Mediated 6-endo-trig Intramolecular Cyclization of N-Acryloyl-7-bromoindolines. A Regiochemical Variant of the Intramolecular Heck Reaction

摘要

The palladium-catalyzed coupling of haloarenes and haloalkenes with olefms, known as the Heck reaction, has proved to be a general reaction for carbon-carbon bond formation. The utility of this reaction in both inter-and intramolecular variations forthe synthesis of car-bocyclic and heterocyclic systems is well documented. However, the regiochemical outcome of this intramolecular palladium-catalyzed cyclization nearly always favors the 5-exo-trig pathway in those cases where competition between 6-endo- and 5-exo-trig closures is possible. In an attempt to favor ring closure through a 6-endo-trig pathway by increasing the steric hindrance at the a position, Heck and Terpko studied the cyclization of a-substituted N-acryloyl-o-bromoanilines.3 It wasfound that 2-quinolones were in fact produced from these cyclization reactions; however, the products apparently arose from a 5-exo-trig closure followed by an aminocar-bonyl rearrangement and palladium hydride elimination. Grigg and co-workers cyclized2-bromo 1,6-dienes using various palladium catalysts to yield products arising from either the 5-exo- or 6-endo-trig mode of cyclization. Although these reactions generally gave mixtures favoring 5-exo-trig closure, in one case a 10:1 ratio favoring theproduct of 6-endo-trig cyclization was observed. Several other examples have been documented where the 6-endo-trig pathway is the preferred mode of cyclization; however, in these cases the elimination of palladium hydride cannot occur if the 5-exo-trig cyclization results.