Biphilic Organophosphorus-Catalyzed Intramolecular C[subscript sp2]–H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations
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nihms939395.pdf
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Accepted version
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Author(s)
Nykaza, Trevor Vincent
Ramirez, Antonio
Harrison, Tyler S.
Luzung, Michael R.
Radosevich, Alexander T.
Date Issued
February 2018
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Nykaza, Trevor et al. "Biphilic Organophosphorus-Catalyzed Intramolecular C[subscript sp2]–H Amination: Evidence for a Nitrenoid in Catalytic Cadogan Cyclizations." Journal of the American Chemical Society 140, 8 (February 2018): 3103-3113 © 2018 American Chemical Society
Version
Author's final manuscript
Abstract
A small-ring phosphacycloalkane (1,2,2,3,4,4-hexamethylphosphetane, 3) catalyzes intramolecular C-N bond forming heterocyclization of o-nitrobiaryl and -styrenyl derivatives in the presence of a hydrosilane terminal reductant. The method provides scalable access to diverse carbazole and indole compounds under operationally trivial homogeneous organocatalytic conditions, as demonstrated by 17 examples conducted on 1 g scale. In situ NMR reaction monitoring studies support a mechanism involving catalytic P[superscript III]/P[superscript V] = O cycling, where tricoordinate phosphorus compound 3 represents the catalytic resting state. For the catalytic conversion of o-nitrobiphenyl to carbazole, the kinetic reaction order was determined for phosphetane catalyst 3 (first order), substrate (first order), and phenylsilane (zeroth order). For differentially 5-substituted 2-nitrobiphenyls, the transformation is accelerated by electron-withdrawing substituents (Hammett factor Ï = +1.5), consistent with the accrual of negative charge on the nitro substrate in the rate-determining step. DFT modeling of the turnover-limiting deoxygenation event implicates a rate-determining (3 + 1) cheletropic addition between the phosphetane catalyst 3 and 2-nitrobiphenyl substrate to form an unobserved pentacoordinate spiro-bicyclic dioxazaphosphetane, which decomposes via (2 + 2) cycloreversion giving 1 equiv of phosphetane P-oxide 3·[O] and 2-nitrosobiphenyl. Experimental and computational investigations into the C-N bond forming event suggest the involvement of an oxazaphosphirane (2 + 1) adduct between 3 and 2-nitrosobiphenyl, which evolves through loss of phosphetane P-oxide 3·[O] to give the observed carbazole product via C-H insertion in a nitrene-like fashion.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/jacs.7b13803
