Mechanistic Insight into Ligand-promoted Palladium-Catalyzed C-H Alkenylation of Simple Arenes with Internal Alkynes : A Computational Study
Weirong Wu,* a,b Hua Hou, b Yanzhen Li*a
Abstract The ligand-promoted palladium-catalyzed hydroarylation of alkynes with arenes without directing group is able to furnish alkenyl chlorides via a 1,4-chlorine migration or trisubstituted alkenes. This reaction is challenging due to bidentate N, N ligand and electron-neutral arenes have rarely been reported to afford good yields. We carried out density functional theory calculations to better understand the elementary steps of the reaction and unveil the ligand effects and origin of substituent-controlled chemoselectivity of challenging C-H activation. For the n-propyl-substituted substrate, CMD process is the rate-determining step of the catalytic reaction. And the chemoselectivity is controlled by oxidative addition with the C-Cl bond cleavage and protonation process. However, for the reaction with 3,5-dimethylphenyl-substituented substrate, the key step of the whole catalytic cycle is the protonation process. The stronger electrostatic attractions, repulsive force and aryl substituent effects result in reverse chemoselectivity. Bidentate ligand L1 (2-OH-1,10-phenanthroline) reacts with Pd(OAc)2 to form a most stable square-planer species, which is different from the one formed by ligand L2(1,10-phenanthroline). The steric repulsion are found to be mainly responsible for no product with L2 as the ligand, which is different from as proviously reported.
Keywords Ligand-promoted, Alkenylation, Vinyl Chlorides, Chemoselectivity, trisubstituted olefin
Introduction
Alkynes are widely used in the synthesis of various compounds of practical value, such as non-linear optical materials, liquid crystals, organic semiconductors and sensors. An important synthetic conversion of alkynes is alkenylation reaction with arenes and heteroarenes (Scheme 1), which may be also regarded as a hydro (or other group) -arylation of a acetylene bond1. Alkenyl insertion into aromatic and heteroaromatic rings by intermolecular or intramolecular methods provides a reaction route for the synthesis of substituted olefins, for example, styrene, stilbene.2-9 Substituted olefins are important intermediates for the preparation of valuable chemicals and have been extensively studied in the past decades. Currently, there are four main synthetic strategies for introducing alkenyl groups into (hetero) aromatic structures using alkynes 1. Among them, in the first synthesis strategy, various metal-catalyst-catalyzed carbonmetallation of internal alkynes is a direct and effective method for the synthesis of multisubstituted olefins (Scheme 1a). However, these reactions require pre-functionalized metal-organic reagents 10. In recent years, significant advances have been achieved by transition metal-catalyzed C-H activation for construction complex molecules from simple starting materials.11 Directing group (DG)-assisted C-H functionalization strategies have been extensively studied, and various arenes have reacted with alkynes and olefins to form functionalized olefins12.