Journal of the American Chemical Society
Communication
D.; Davies, I. W. Oxyfunctionalization of the Remote C−H Bonds of
Aliphatic Amines by Decatungstate Photocatalysis. Angew. Chem., Int.
Ed. 2017, 56, 15274. (d) Ravelli, D.; Fagnoni, M.; Fukuyama, T.;
Nishikawa, T.; Ryu, I. Site-Selective C−H Functionalization by
Decatungstate Anion Photocatalysis: Synergistic Control by Polar and
Steric Effects Expands the Reaction Scope. ACS Catal. 2018, 8, 701.
(e) Salamone, M.; Bietti, M. Tuning Reactivity and Selectivity in
Hydrogen Atom Transfer from Aliphatic C−H Bonds to Alkoxyl
Radicals: Role of Structural and Medium Effects. Acc. Chem. Res.
2015, 48, 2895.
alkylation of aryl bromides and chlorides. J. Am. Chem. Soc. 2012, 134,
6146−6159.
́
́
(16) Sommer, H.; Julia-Hernandez, F.; Martin, R.; Marek, I. Walking
metals for remote functionalizations. ACS Cent. Sci. 2018, 4, 153−
165.
(7) (a) Tellis, J. C.; Primer, D. N.; Molander, G. A. Single-Electron
Transmetalation in Organoboron Cross-Coupling by Photoredox/
Nickel Dual Catalysis. Science 2014, 345, 433. (b) Zuo, Z.; Ahneman,
D. T.; Chu, L.; Terrett, J. A.; Doyle, A. G.; MacMillan, D. W. C.
Merging Photoredox with Nickel Catalysis: Coupling of α-Carboxyl
Sp3-Carbons with Aryl Halides. Science 2014, 345, 437.
(8) (a) Shaw, M. H.; Shurtleff, V. W.; Terrett, J. A.; Cuthbertson, J.
D.; MacMillan, D. W. C. Native Functionality in Triple Catalytic
Cross-Coupling: Sp3 C−H Bonds as Latent Nucleophiles. Science
2016, 352, 1304. (b) Shields, B. J.; Doyle, A. G. Direct C(Sp3)-H
Cross Coupling Enabled by Catalytic Generation of Chlorine
Radicals. J. Am. Chem. Soc. 2016, 138, 12719. (c) Heitz, D. R.;
Tellis, J. C.; Molander, G. A. Photochemical Nickel-Catalyzed C-H
Arylation: Synthetic Scope and Mechanistic Investigations. J. Am.
Chem. Soc. 2016, 138, 12715. (d) Shen, Y.; Gu, Y.; Martin, R. Sp3 C−
H Arylation and Alkylation Enabled by the Synergy of Triplet Excited
Ketones and Nickel Catalysts. J. Am. Chem. Soc. 2018, 140, 12200.
(e) Dauncey, E.; Dighe, S. U.; Douglas, J. J.; Leonori, D. A Dual
Photoredox-Nickel Strategy for Remote Functionalization via Iminyl
Radicals: Radical Ring-Opening−Arylation, − Vinylation and −
Alkylation Cascades. Chem. Sci. 2019, 10, 7728.
(9) (a) Perry, I. B.; Brewer, T. F.; Sarver, P. J.; Schultz, D. M.;
DiRocco, D. A.; MacMillan, D. W. C. Direct Arylation of Strong
Aliphatic C−H Bonds. Nature 2018, 560, 70. (b) Ackerman, L. K. G.;
Martinez Alvarado, J. I.; Doyle, A. G. Direct C−C Bond Formation
from Alkanes Using Ni-Photoredox Catalysis. J. Am. Chem. Soc. 2018,
140, 14059.
(10) (a) Chu, J. C. K.; Rovis, T. Amide-Directed Photoredox-
Catalysed C−C Bond Formation at Unactivated Sp3 C−H Bonds.
Nature 2016, 539, 272. (b) Choi, G. J.; Zhu, Q.; Miller, D. C.; Gu, C.
J.; Knowles, R. R. Catalytic Alkylation of Remote C−H Bonds
Enabled by Proton-Coupled Electron Transfer. Nature 2016, 539,
268.
(11) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.;
MacMillan, D. W. C. The Merger of Transition Metal and
Photocatalysis. Nature Reviews Chemistry 2017, 1, 52.
(12) Similar strategies have been implemented for remote arylation
from a homolytically cleaved N−F bond; see: (a) Li, Z.; Wang, Q.;
Zhu, J. Copper-Catalyzed Arylation of Remote C(Sp3)−H Bonds in
Carboxamides and Sulfonamides. Angew. Chem. 2018, 130, 13472.
(b) Zhang, Z.; Stateman, L. M.; Nagib, D. A. δ C−H (Hetero)-
Arylation via Cu-Catalyzed Radical Relay. Chem. Sci. 2019, 10, 1207.
(13) (a) Morcillo, S. P.; Dauncey, E. M.; Kim, J. H.; Douglas, J. J.;
Sheikh, N. S.; Leonori, D. Photoinduced Remote Functionalization of
Amides and Amines Using Electrophilic Nitrogen Radicals. Angew.
Chem., Int. Ed. 2018, 57, 12945. (b) Xia, Y.; Wang, L.; Studer, A. Site-
Selective Remote Radical C−H Functionalization of Unactivated C−
H Bonds in Amides Using Sulfone Reagents. Angew. Chem., Int. Ed.
2018, 57, 12940. (c) Chen, D.-F.; Chu, J. C. K.; Rovis, T. Directed γ-
C(Sp3)−H Alkylation of Carboxylic Acid Derivatives through Visible
Light Photoredox Catalysis. J. Am. Chem. Soc. 2017, 139, 14897.
(14) Secondary alkyl bromides have also been explored. The model
secondary alkyl bromide, cyclohexyl bromide, usually generates
desired product in 5−15% yield. Efforts to mitigate this through
ligand substitution and excess alkyl bromide has thus far proven
unproductive.
(15) Everson, D. A.; Jones, B. A.; Weix, D. J. Replacing conventional
carbon nucleophiles with electrophiles: Nickel-catalyzed reductive
F
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX