Energy Decomposition Analyses Reveal the Origins of Catalyst and Nucleophile Effects on Regioselectivity in Nucleopalladation of Alkenes

• DOI: 10.1021/jacs.9b02893
• Publication Date: 2019-06-21T08:47:07Z
• Authors: Xiaotian Qi; Daniel G. Kohler; Kami L. Hull; Peng Liu
• Keywords: Markovnikov's rule; Alkene; Electronic effect

Nucleopalladation is one of the most common mechanisms for Pd-catalyzed hydro- and oxidative functionalization alkenes. Due to electronic bias π-alkene-palladium complexes, nucleopalladations with terminal aliphatic alkenes typically deliver nucleophile more substituted sp2 carbon form Markovnikov-selective products. The selective formation anti-Markovnikov nucleopalladation products requires inherent effects be overridden, which still a significant challenge reactions simple Because interactions between alkene substrate are influenced by complex combination multiple types steric effects, thorough understanding interplay these underlying needed rationalize predict regioselectivity. Here, we employ an energy decomposition approach quantitatively separate different nucleophile-substrate interactions, including steric, electrostatic, orbital dispersion impacts each factor on We demonstrate use this origins catalyst-controlled anti-Markovnikov-selectivity in Hull's amination reactions. In addition, evaluated regioselectivity series neutral anionic Pd catalysts N- O-nucleophiles properties. On basis computational analyses, generalized scheme established identify dominant interaction affecting nucleophiles.