Oxidative Addition of (Hetero)aryl (Pseudo)halides at Palladium(0): Origin and Significance of Divergent Mechanisms
Year: 2024
Type: article
Abstract: Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and a nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited to a few specific combinations of substrate and ligand. Here, we computationally evaluated over 150 transition structures for oxidative addition in order to determine mechanistic trends based on substrate, ligand(s), and coordination number. Natural abundance 13C kinetic isotope effects provide experimental results consistent with computational predictions. Key findings include that (1) differences in HOMO symmetries dictate that, although 12e– PdL is strongly biased toward a 3-centered concerted mechanism, 14e– PdL2 often prefers a nucleophilic displacement mechanism; (2) ligand electronics and sterics, including ligand bite angle, influence the preferred mechanism of reaction at PdL2; (3) phenyl triflate always reacts through a displacement mechanism regardless of catalyst structure due to the stability of a triflate anion and the inability of oxygen to effectively donate electron density to Pd; and (4) the high reactivity of C—X bonds adjacent to nitrogen in pyridine substrates relates to stereoelectronic stabilization of a nucleophilic displacement transition state. This work has implications for controlling rate and selectivity in catalytic couplings, and we demonstrate application of the mechanistic insight toward chemodivergent cross-couplings of bromochloroheteroarenes.
DOI: 10.1021/jacs.4c04496
Institution: Montana State University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: G1555197637, G1787346651, Track 4: Advanced CI Coordination Ecosystem: Monitoring and Measurement Services, G338811424, G3749790172, G3902111948, Track 1: ACCESS Resource Allocations Marketplace and Platform Services (RAMPS), G4072547516, ACO: An Open CI Ecosystem to Advance Scientific Discovery (OpenCI), Track 3: COre National Ecosystem for CyberinfrasTructure (CONECT), G6648061574, G6662184586, G7916508619, MRI: Acquisition of a 400 MHz Nuclear Magnetic Resonance (NMR) Spectrometer, Track 2: Customized Multi-tier Assistance, Training, and Computational Help (MATCH) for End User ACCESS to CI, G8306589951, G8994211811, MT INBRE: A Multidisciplinary Research Network, CAREER: Combined Experimental and Computational Approach to Controlling Site Selectivity in Cross Coupling Chemical Reactions
OpenAlex ID: W4400280154