Nucleophilic Addition versus Migratory Insertion Pathways in the Gold-Catalyzed Heck Reaction: A Computational Study.

The initial reaction steps in the formation of Heck-type arylated alkenes catalyzed by P^N chelated Au(III) complexes have been studied computationally. Two mechanistic alternatives have been explored: (1) alkene coordination and insertion into a gold-carbon bond, and (2) nucleophilic attack on a gold(III) alkene adduct. The common starting point, the [(P^N)AuPh(alkene)] dication (alkene = CH, HC═CHEt, or HC═CEt), shows unequal bonding to the olefinic carbons of the 1-alkenes (P^N = 1,2-CHNMe(PR); R = H, Me, 1-adamantyl). This polarization increases with steric hindrance and with the inclusion of an OTf anion in the model. While the reaction pathways are strongly governed by the trans-influence of the ligand, the effects of steric hindrance in the ligand and alkene are remarkably small. In all cases the nucleophilic attack pathway is energetically favored. However, changing the ligand from a P^N to a P^P chelate, with a strongly electron-donating -PMe donor trans to Ph, sufficiently destabilizes the Au─Ph bond to make alkene insertion competitive. Alkene 1,2-insertion regiochemistry is always preferred, unlike Pd-catalyzed Heck reaction that requires a 2,1-insertion. Based on these results, an alkene insertion pathway en route to Heck-type olefins can therefore be ruled out.