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Title: Oxidative Addition of (Hetero)aryl (Pseudo)halides at Palladium(0): Origin and Significance of Divergent Mechanisms
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 180 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 pro-vide 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.  more » « less
Award ID(s):
1848090 2400070
PAR ID:
10580318
Author(s) / Creator(s):
; ;
Publisher / Repository:
ACS
Date Published:
Journal Name:
Journal of the American Chemical Society
Volume:
146
Issue:
28
ISSN:
0002-7863
Page Range / eLocation ID:
19249 to 19260
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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