A DFT Study of the Ambiphilic Nature of Arylpalladium Species in Intramolecular Cyclization Reactions

作者：Fernandez Israel^*; Sole Daniel; Sierra Miguel A

来源：Journal of Organic Chemistry, 2011, 76(6): 1592-1598.

DOI：10.1021/jo1020954

The remarkable structure-dependent reactivity observed in the cyclization of (2-haloanilino)-ketones with Pd-catalysts has been studied computationally within the density functional theory framework. The experimental reaction products ratio may be explained through the formation of a common palladaaminocyclobutane intermediate which can undergo a nucleophilic addition reaction and/or an enolate alpha-arilation process. The evolution of this metallacycle to the final products depends on two factors, the length of the tether joining the amino and the carbonyl groups, and the electronic nature of the substituent directly attached to the nitrogen atom. Thus, shorter chains (2 CH(2)) facilitate the nucleophic addition reaction by approximating the reactive aryl and Pd-coordinated carbonyl groups whereas longer chains (3 CH(2)) favor the enolate alpha-arylation procces. For electron-withdrawing groups attached to the aniline nitrogen atom, the nucleophilic addition pathway becomes slightly disfavored, mainly due to the electron-withdrawing effect of the CO(2)Me group which avoids the delocation of the LP in the pi-system, thus decreasing the nucleophilicity of the reactive arylic carbon atom. In contrast, the enolate alpha-arylation reaction is facilitated by the CO(2)Me group. This is translated into a small computed barrier energy difference of these competitive reaction pathways which should lead to a mixture of reaction products as experimentally found.

• 出版日期2011-3-18