Mechanism of Pd/Senphos-Catalyzed trans-Hydroboration of 1,3-Enynes: Experimental and Computational Evidence in Support of the Unusual Outer-Sphere Oxidative Addition Pathway

• Published in: Journal of organic chemistry Vol. 88; no. 4; pp. 2415 - 2424
• Main Authors: Zhang, Yuanzhe, Wang, Ziyong, Lamine, Walid, Xu, Senmiao, Li, Bo, Chrostowska, Anna, Miqueu, Karinne, Liu, Shih-Yuan
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17-02-2023
• Subjects: Chemical Sciences; or physical chemistry; Theoretical and
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c02841

The reaction mechanism of the Pd/Senphos-catalyzed trans-hydroboration reaction of 1,3-enynes was investigated using various experimental techniques, including deuterium and double crossover labeling experiments, X-ray crystallographic characterization of model reaction intermediates, and reaction progress kinetic analysis. Our experimental data are in support of an unusual outer-sphere oxidative addition mechanism where the catecholborane serves as a suitable electrophile to activate the Pd0-bound 1,3-enyne substrate to form a Pd-η3-π-allyl species, which has been determined to be the likely resting state of the catalytic cycle. Double crossover labeling of the catecholborane points toward a second role played by the borane as a hydride delivery shuttle. Density functional theory calculations reveal that the rate-limiting transition state of the reaction is the hydride abstraction by the catecholborane shuttle, which is consistent with the experimentally determined rate law: rate = k[enyne]0[borane]1[catalyst]1. The computed activation free energy ΔG ‡ = 17.7 kcal/mol and KIE (k H/k D = 1.3) are also in line with experimental observations. Overall, this work experimentally establishes Lewis acids such as catecholborane as viable electrophilic activators to engage in an outer-sphere oxidative addition reaction and points toward this underutilized mechanism as a general approach to activate unsaturated substrates.