An Improved P III /P V ═O-Catalyzed Reductive C–N Coupling of Nitroaromatics and Boronic Acids by Mechanistic Differentiation of Rate- and Product-Determining Steps
Name
jacs.0c01666.pdf
Description
Published version
Size
3.01 MB
Format
Adobe PDF
Checksum (MD5)
338994d97b6c1e95793adb02f3c471d3
Author(s)
Li, Gen
Nykaza, Trevor V
Cooper, Julian C
Ramirez, Antonio
Luzung, Michael R
Radosevich, Alexander T
Date Issued
2020
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Version
Final published version
Abstract
© 2020 American Chemical Society. Experimental, spectroscopic, and computational studies are reported that provide an evidence-based mechanistic description of an intermolecular reductive C-N coupling of nitroarenes and arylboronic acids catalyzed by a redox-active main-group catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide, i.e., 1·[O]). The central observations include the following: (1) catalytic reduction of 1·[O] to PIII phosphetane 1 is kinetically fast under conditions of catalysis; (2) phosphetane 1 represents the catalytic resting state as observed by 31P NMR spectroscopy; (3) there are no long-lived nitroarene partial-reduction intermediates observable by 15N NMR spectroscopy; (4) the reaction is sensitive to solvent dielectric, performing best in moderately polar solvents (viz. cyclopentylmethyl ether); and (5) the reaction is largely insensitive with respect to common hydrosilane reductants. On the basis of the foregoing studies, new modified catalytic conditions are described that expand the reaction scope and provide for mild temperatures (T ≥ 60 °C), low catalyst loadings (≥2 mol%), and innocuous terminal reductants (polymethylhydrosiloxane). DFT calculations define a two-stage deoxygenation sequence for the reductive C-N coupling. The initial deoxygenation involves a rate-determining step that consists of a (3+1) cheletropic addition between the nitroarene substrate and phosphetane 1; energy decomposition techniques highlight the biphilic character of the phosphetane in this step. Although kinetically invisible, the second deoxygenation stage is implicated as the critical C-N product-forming event, in which a postulated oxazaphosphirane intermediate is diverted from arylnitrene dissociation toward heterolytic ring opening with the arylboronic acid; the resulting dipolar intermediate evolves by antiperiplanar 1,2-migration of the organoboron residue to nitrogen, resulting in displacement of 1·[O] and formation of the target C-N coupling product upon in situ hydrolysis. The method thus described constitutes a mechanistically well-defined and operationally robust main-group complement to the current workhorse transition-metal-based methods for catalytic intermolecular C-N coupling.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1021/jacs.0c01666
