Transition-Metal-Mediated Nucleophilic Aromatic Substitution with Acids

O’Reilly, Matthew E.; Johnson, Samantha I.; Nielsen, Robert J.; Goddard, William A.; Gunnoe, T. Brent

doi:10.1021/acs.organomet.6b00285

Transition-Metal-Mediated Nucleophilic Aromatic Substitution with Acids

Journal Article · Thu Jun 09 00:00:00 EDT 2016 · Organometallics

DOI:https://doi.org/10.1021/acs.organomet.6b00285· OSTI ID:1369726

O’Reilly, Matthew E. ^[1]; Johnson, Samantha I. ^[2]; Nielsen, Robert J. ^[2]; Goddard, William A. ^[2]; Gunnoe, T. Brent ^[1]

Univ. of Virginia, Charlottesville, VA (United States). Dept. of Chemistry
California Inst. of Technology (CalTech), Pasadena, CA (United States)

Transition-metal-mediated nucleophilic aromatic substitution (S_NAr) reactions prefer that a suitably strong nucleophile be in an aprotic medium. Usually, using protic nucleophile/medium requires high reaction temperatures (>180 °C) to overcome the attenuated nucleophilicity for attack on the arene π system. We demonstrate herein that surprisingly a Rh^III-mediated S_NAr reaction of a fluoroarene moiety with RCO₂H (R = CH₃, CF₃) in acid media that proceeds at moderate temperatures (<100 °C). We show both by experimental and with DFT calculations that the mechanism proceeds through an internal nucleophilic aromatic substitution (I-S_NAr), where the nucleophile coordinates to the metal ion prior to substitution, thereby mitigating the acid influence.

View Accepted Manuscript (DOE)

Research Organization:: Energy Frontier Research Centers (EFRC) (United States). Center for Catalytic Hydrocarbon Functionalization (CCHF); Univ. of Virginia, Charlottesville, VA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Science Foundation (NSF)

Grant/Contract Number:: SC0001298

OSTI ID:: 1369726

Journal Information:: Organometallics, Journal Name: Organometallics Journal Issue: 12 Vol. 35; ISSN 0276-7333

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

References (28)

Computational Studies of Heteroatom-Assisted C—H Activation at Ru, Rh, Ir, and Pd as a Basis for Heterocycle Synthesis and Derivatization Carr, Kevin J. T.; Macgregor, Stuart A.; McMullin, Claire L. Transition Metal‐Catalyzed Heterocycle Synthesis via C—H Activation https://doi.org/10.1002/9783527691920.ch1	book	January 2016
tert-Butyl Ethers: Renaissance of an Alcohol Protecting Group. Facile Cleavage with Cerium(III) Chloride/Sodium Iodide Bartoli, Giuseppe; Bosco, Marcella; Carlone, Armando Advanced Synthesis & Catalysis, Vol. 348, Issue 7-8 https://doi.org/10.1002/adsc.200505469	journal	May 2006
An Expeditious and Metal-Free Synthetic Route towards Quinolones, Naphthyridones and Benzonaphthyridones Victor, Napoleon John; Muraleedharan, Kannoth Manheri Advanced Synthesis & Catalysis, Vol. 356, Issue 17 https://doi.org/10.1002/adsc.201300891	journal	November 2014
Rhodium Bis(quinolinyl)benzene Complexes for Methane Activation and Functionalization Fu, Ross; O'Reilly, Matthew E.; Nielsen, Robert J. Chemistry - A European Journal, Vol. 21, Issue 3 https://doi.org/10.1002/chem.201405460	journal	November 2014
Rhodium-Catalyzed C–H Bond Arylation of Arenes Bouffard, Jean; Itami, Kenichiro C-H Activation https://doi.org/10.1007/128_2009_12	book	January 2009
Transition Metal Arene π-Complexes in Organic Synthesis and Catalysis Kundig, E. Peter Topics in Organometallic Chemistry https://doi.org/10.1007/b76615	book	January 2004
Transition Metal Arene Complexes: Nucleophilic Addition Semmelhack, Martin F. Comprehensive Organometallic Chemistry II https://doi.org/10.1016/B978-008046519-7.00133-7	book	January 1995
Fluoride ion as a nucleophile and a leaving group in aromatic nucleophilic substitution reactions Vlasov, V. M. Journal of Fluorine Chemistry, Vol. 61, Issue 3 https://doi.org/10.1016/S0022-1139(00)80104-9	journal	April 1993
Practical synthesis of aromatic ethers by SNAr of fluorobenzenes with alkoxides Rodriguez, Juan R.; Agejas, Javier; Bueno, Ana B. Tetrahedron Letters, Vol. 47, Issue 32 https://doi.org/10.1016/j.tetlet.2006.06.029	journal	August 2006
Nucleophilic Aromatic Substitution Reactions in Water Enabled by Micellar Catalysis Isley, Nicholas A.; Linstadt, Roscoe T. H.; Kelly, Sean M. Organic Letters, Vol. 17, Issue 19 https://doi.org/10.1021/acs.orglett.5b02240	journal	September 2015
Rhodium Catalyzed Chelation-Assisted C–H Bond Functionalization Reactions Colby, Denise A.; Tsai, Andy S.; Bergman, Robert G. Accounts of Chemical Research, Vol. 45, Issue 6 https://doi.org/10.1021/ar200190g	journal	December 2011
Aromatic Nucleophilic Substitution Reactions. Bunnett, Joseph F.; Zahler, Roland E. Chemical Reviews, Vol. 49, Issue 2 https://doi.org/10.1021/cr60153a002	journal	October 1951
C−F Bond Activation in Organic Synthesis Amii, Hideki; Uneyama, Kenji Chemical Reviews, Vol. 109, Issue 5 https://doi.org/10.1021/cr800388c	journal	May 2009
Rhodium-Catalyzed C−C Bond Formation via Heteroatom-Directed C−H Bond Activation Colby, Denise A.; Bergman, Robert G.; Ellman, Jonathan A. Chemical Reviews, Vol. 110, Issue 2 https://doi.org/10.1021/cr900005n	journal	February 2010
Transition-Metal-Mediated Dearomatization Reactions Pape, Andrew R.; Kaliappan, Krishna P.; Kündig, E. Peter Chemical Reviews, Vol. 100, Issue 8 https://doi.org/10.1021/cr9902852	journal	July 2000
Activation of Carbon−Hydrogen Bonds via 1,2-Addition across M−X (X = OH or NH ₂ ) Bonds of d ⁶ Transition Metals as a Potential Key Step in Hydrocarbon Functionalization: A Computational Study Cundari, Thomas R.; Grimes, Thomas V.; Gunnoe, T. Brent Journal of the American Chemical Society, Vol. 129, Issue 43 https://doi.org/10.1021/ja074125g	journal	October 2007
Long-Range C–H Bond Activation by Rh ^III -Carboxylates O’Reilly, Matthew E.; Fu, Ross; Nielsen, Robert J. Journal of the American Chemical Society, Vol. 136, Issue 42 https://doi.org/10.1021/ja508367m	journal	October 2014
The Mechanism of Dimethyl Sulfoxide Catalysis in Nucleophilic Displacement Kingsbury, Charles A. The Journal of Organic Chemistry, Vol. 29, Issue 11 https://doi.org/10.1021/jo01034a032	journal	November 1964
Analysis of the Palladium-Catalyzed (Aromatic)C–H Bond Metalation–Deprotonation Mechanism Spanning the Entire Spectrum of Arenes Gorelsky, Serge I.; Lapointe, David; Fagnou, Keith The Journal of Organic Chemistry, Vol. 77, Issue 1 https://doi.org/10.1021/jo202342q	journal	December 2011
Mechanistic Analysis of Iridium Heteroatom C−H Activation: Evidence for an Internal Electrophilic Substitution Mechanism Oxgaard, Jonas; Tenn, William J.; Nielsen, Robert J. Organometallics, Vol. 26, Issue 7 https://doi.org/10.1021/om061189b	journal	March 2007
CatalyticSNAr reaction of non-activated fluoroarenes with amines viaRuη6-arene complexes Otsuka, Maiko; Endo, Kohei; Shibata, Takanori Chem. Commun., Vol. 46, Issue 2 https://doi.org/10.1039/B919413D	journal	January 2010
Mechanisms of C–H bond activation: rich synergy between computation and experiment Boutadla, Youcef; Davies, David L.; Macgregor, Stuart A. Dalton Transactions, Issue 30 https://doi.org/10.1039/b904967c	journal	January 2009
Reactions of co-ordinated ligands. Part 10. Rhodium-catalysed cyclisation of 3-(2-fluorophenyl)propanols to chromans Houghton, Roy P.; Voyle, Martyn; Price, Raymond Journal of the Chemical Society, Perkin Transactions 1 https://doi.org/10.1039/p19840000925	journal	January 1984
An Eco-Sustainable Erbium(III) Triflate Catalyzed Formation and Cleavage of tert-Butyl Ethers Procopio, Antonio; Costanzo, Paola; Curini, Massimo Synthesis, Vol. 2011, Issue 01 https://doi.org/10.1055/s-0030-1258332	journal	November 2010
Facile Catalytic SNAr Reaction of Nonactivated Fluoroarenes with Amines Using η6-Benzene Ruthenium(II) Complex Otsuka, Maiko; Yokoyama, Hiroya; Endo, Kohei Synlett, Vol. 2010, Issue 17 https://doi.org/10.1055/s-0030-1258774	journal	September 2010
Nucleophilic substitution of the nitro group, fluorine and chlorine in aromatic compounds Vlasov, Vladislav M. Russian Chemical Reviews, Vol. 72, Issue 8 https://doi.org/10.1070/RC2003v072n08ABEH000809	journal	August 2003
Overview of the Mechanistic Work on the Concerted Metallation–Deprotonation Pathway Lapointe, David; Fagnou, Keith Chemistry Letters, Vol. 39, Issue 11 https://doi.org/10.1246/cl.2010.1118	journal	November 2010
An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles Baumann, Marcus; Baxendale, Ian R. Beilstein Journal of Organic Chemistry, Vol. 9 https://doi.org/10.3762/bjoc.9.265	journal	January 2013

Cited By (3)

How difficult are anion-molecule SNAr reactions of unactivated arenes in the gas phase, dimethyl sulfoxide, and methanol solvents? Silva, Daniela R.; Pliego, Josefredo R. Structural Chemistry, Vol. 30, Issue 1 https://doi.org/10.1007/s11224-018-1172-7	journal	August 2018
Defluorosilylation of fluoroarenes and fluoroalkanes Cui, Benqiang; Jia, Shichong; Tokunaga, Etsuko Nature Communications, Vol. 9, Issue 1 https://doi.org/10.1038/s41467-018-06830-w	journal	October 2018
Product inhibition in nucleophilic aromatic substitution through DPPPent-supported π-arene catalysis Mueller, Benjamin R. J.; Schley, Nathan D. Dalton Transactions https://doi.org/10.1039/d0dt00786b	journal	January 2020

Similar Records

Cation Radical-Accelerated Nucleophilic Aromatic Substitution for Amination of Alkoxyarenes

Journal Article · Tue Jun 02 00:00:00 EDT 2020 · Organic Letters · OSTI ID:1801388

Surprising effect of leaving group on the nucleophilic aromatic substitution reaction catalyzed by 4-chlorobenzoyl-CoA dehalogenase

Journal Article · Wed Jul 14 00:00:00 EDT 1993 · Journal of the American Chemical Society; (United States) · OSTI ID:5712582

Aromatic nucleophilic substitution reactions in high temperature, high pressure water

Conference · Thu Nov 30 23:00:00 EST 1995 · OSTI ID:126732

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Aromatic compounds
Chemical structure
Hydrocarbons
Substitution reactions
Transition states

Transition-Metal-Mediated Nucleophilic Aromatic Substitution with Acids

Citation Formats

References (28)

Cited By (3)

Similar Records

Related Subjects