Organophotochemical SNAr Reactions of Mildly Electron-Poor Fluoroarenes

Article abstract of DOI:10.1002/ejoc.202000337

C–F functionalization of arenes with a range of alcohol and pyrazole nucleophiles has been achieved without the need for metal catalysts or highly electron-poor substrates. Treatment of fluoroarenes with alcohols or pyrazoles and DDQ under irradiation by blue LED light provides the corresponding substituted products. The procedure is complementary to classical S_NAr chemistry which generally requires basic reaction conditions and high temperatures, and provides products under non-basic conditions at ≈ 40 °C.

Full text of DOI:10.1002/ejoc.202000337

Communication
doi.org/10.1002/ejoc.202000337
EurJOC
European Journal of Organic Chemistry
Photochemical SNAr
Organophotochemical SNAr Reactions of Mildly Electron-Poor
Fluoroarenes
Thomas Sheridan,[a] Hatice G. Yayla,[b] Yajing Lian,[b] Julien Genovino,[b] Nat Monck,[c] and
Jonathan W. Burton*[a]
Abstract: C–F functionalization of arenes with a range of alco- substituted products. The procedure is complementary to clas-
hol and pyrazole nucleophiles has been achieved without the sical SNAr chemistry which generally requires basic reaction
need for metal catalysts or highly electron-poor substrates. conditions and high temperatures, and provides products un-
Treatment of fluoroarenes with alcohols or pyrazoles and DDQ der non-basic conditions at ≈ 40 °C.
under irradiation by blue LED light provides the corresponding
Site selective functionalizations of arenes have long been
crucial in organic synthesis and are particularly pertinent to the
pharmaceutical, agrochemical and organic materials indus-
tries.[1–3] Classically, electrophilic aromatic substitution[4] and
nucleophilic aromatic substitution (SNAr)[5–7] have been key
methods to functionalize aromatic rings and are still widely
used along with the now ubiquitous transition metal catalyzed
cross-coupling reactions and C–H activation methodolo-
gies.[2,3,8–10] Despite the relevance of the SNAr reaction, the use
of this transformation is often prohibited by a stringent set of
requirements that includes basic reaction conditions, high tem-
peratures, and the presence of π-electron withdrawing groups
to stabilize the Misenheimer intermediate/transition state [Fig-
ure 1 (a)].[11,12] Recently, Nicewicz reported a photochemical
SNAr methodology, utilizing acridinium salts as photocatalysts
to activate anisoles for SNAr with loss of methanol [Figure 1
(b)].[13,14] This process likely occurs via initial single electron
oxidation of the anisole by the photoexcited acridinium cata-
lyst. The newly formed radical cation rapidly undergoes nucleo-
philic attack at the site of greatest partial positive charge (the
ipso carbon in most cases) followed by re-aromatization arising
from the reduction of the transient cyclohexadienyl radical with
loss of methanol [Figure 1 (c)].
Figure 1. Different SNAr approaches.
Given the greater ipso carbon polarization in fluoroarenes
relative to anisoles,[15] (see ESI) it would follow that fluoroarenes
are optimal substrates for such photochemical SNAr reactions.
[a] Department of Chemistry, University of Oxford, Chemistry Research
Nicewicz's method expands SNAr chemistry to electron-rich
anisoles, however, the high oxidation potential of mildly elec-
tron-poor fluoroarenes (oxidation potential for benzene in
acetonitrile = +2.48 V vs. SCE)[16] relative to that of the acridin-
ium photocatalyst ≈ +2.15 V vs. SCE (Figure S3, ESI),[17] results
in a large range of fluoroarenes being unamenable to either
classical SNAr methods or to modern photochemical efforts
with a number of photocatalysts (see Figure S3 for a compari-
son of the reduction potentials of a small group of photocata-
lysts). Here we extend photochemical SNAr to mildly electron-
poor fluoroarenes by utilizing photoexcited 2,3-dichloro-5,6-di-
Laboratory,
12 Mansfield Road, Oxford OX1 3TA, U.K.
E-mail: jonathan.burton@chem.ox.ac.uk
[b] Pfizer Worldwide Research and Development,
445 Eastern Point Road, Groton, Connecticut 06340, United States
[c] Evotec (UK) Ltd.,
114 Innovation Drive, Milton Park, Milton, Abingdon OX14 4RZ, U.K.
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.202000337.
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. ·
This is an open access article under the terms of the Creative Commons
Attribution License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
Eur. J. Org. Chem. 2020, 1–6
1
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
doi.org/10.1002/ejoc.202000337
EurJOC
European Journal of Organic Chemistry
cyano-p-benzoquinone (DDQ). DDQ is inexpensive, readily the fluoroarene as the limiting reagent, the nucleophile in ex-
available and has a well-founded pedigree as an organophoto- cess, with a focus on alcohols, and generally uses DDQ in either
catalyst.[14,18] Seminal work from Fukuzumi,[15] and further work stoichiometric or sub-stoichiometric quantities, without the re-
from König,[19] have utilized the impressive T1 excited state po- quirement for an electrochemical rig.
tential of DDQ (+3.18 V vs. SCE)[15] for interesting examples of
photooxidation reactions. These DDQ-mediated arene photo-
oxidation methodologies typically utilize tert-butyl nitrite (TBN)
as a re-oxidant.[20] Until recently, there were no general meth-
ods for the DDQ-mediated (arene) photosubstitution reactions
although the photosubstitution of a fluoroarene had been re-
ported as a by-product by both Fukuzumi [Figure 2 (a)][15] and
separately by Nicewicz[13] without further optimization. Such
reactions, which are redox neutral overall, obviate the need for
a reoxidant. Furthermore, regiochemical concerns are simplified,
as the position of the leaving group in the starting material
dictates the position at which the nucleophile is added. Under
oxidative conditions however, regioisomer mixtures are fre-
quently formed.[19]
As noted above, Fukuzumi[15] and Nicewicz[13] have both ob-
served SNAr reactions of fluoroarenes and we focused on opti-
mizing such reactions with DDQ as the photooxidant. We ini-
tially investigated the use of 2,4-dichloro-1-fluorobenzene 1 as
the arene substrate with methanol as the nucleophile. Thus,
irradiation (32 W blue LED Kessil lamp) of a solution of 2,4-
dichloro-1-fluorobenzene 1 (1 equiv.) and DDQ (1.2 equiv.) in
methanol for 48 h provided a 10 % isolated yield of 2,4-di-
chloro-1-methoxybenzene 1a with the mass balance attributed
to unreacted starting material 1 (Table 1, entry 1). This result,
while low yielding, was encouraging as the transformation was
completely selective. Changing the solvent to 1,2-dichloroeth-
ane (DCE), with ten equivalents of methanol (entry 2) gave the
desired product 1a in an increased 18 % yield and again unre-
acted starting material. With acetonitrile as solvent, desired
anisole 1a was isolated in an improved 44 % yield (entry 3);
2-chloro-1-fluoro-4-methoxybenzene was also formed in 12 %
yield a result of SNAr of the 4-chloro substituent in 1. It is known
that hexafluoroisopropanol (HFIP) stabilizes radical cations[22,23]
and can have a marked effect on the oxidation potential of the
single electron oxidant iodobenzenediacetate.[24,25] We rea-
soned that the use of polyfluorinated alcohols would increase
the lifetime of the radical cation intermediate and might affect
the oxidation potential of DDQ.[26] In the event, the use of HFIP
as solvent, with 10 equivalents of methanol, provided the de-
Table 1. Optimization of organophotochemical SNAr reaction.
Entry[a]
Solvent
DDQ
MeOH
Yield[b] [%]
[equiv.]
[equiv.]
1
2
3
4
5
6
7
8
MeOH
DCE
MeCN
HFIP
HFIP
HFIP
HFIP
TFE
1:1 DCE/TFE
1:1 DCE/TFE
HFIP
1:1 DCE/TFE
1:1 DCE/TFE
1:1 DCE/TFE
1:1 MeCN:TFE
control no light
control no DDQ
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
0.3
0.3
0.3[d]
0.3[e]
1.2
1.2
–
solvent
10
10
10
5
10
18
44[c]
92
53
18
11
93
94
93
24
81
74
91
85
0
2
Figure 2. Some photochemical approaches to nucleophilic.
1.2
10
10
2
10
10
10
10
10
10
10
Herein, we report the organophotochemical SNAr of various
fluoroarenes with alcohols and pyrazoles which occurs under
mild conditions (approximately 40 °C, blue LEDs, no added
base) to give the corresponding substituted products [Figure 2
(c)]. During the preparation of this manuscript Lambert and co-
workers published a very similar procedure to that reported
herein [Figure 2 (b)].[21] Their work uses both photochemistry
and electrochemistry to achieve the desired transformation.
Our procedure and the Lambert procedure, although closely
related, differ in that Lambert uses an electrochmeical rig, with
sub-stoichiometric quantities of DDQ (recycled electrochemi-
cally), with the fluoroarene substrate in excess, and a focus on
pyrazole nucleophiles as the limiting reagent. Our method uses
9
10
11
12
13
14
15
16
17
0
[a] Reactions conducted in a closed vessel with no precaution taken to ex-
clude oxygen unless otherwise indicated. A stream of nitrogen was passed
over the reaction flask during the irradiation which kept the temperature at
≈ 40 °C. [b] Isolated yield. [c] 12 % of 2-chloro-1-fluoro-4-methoxybenzene
was also formed. [d] Reaction mixture sparged with N2 prior to irradiation.
[e] Reaction mixture freeze-pump-thaw degassed × 3 prior to irradiation.
Eur. J. Org. Chem. 2020, 1–6
www.eurjoc.org
2
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
doi.org/10.1002/ejoc.202000337
EurJOC
European Journal of Organic Chemistry
sired product 1a in 92 % yield (entry 4). Reduction in the equiv- ence of DDQ, and both resulted in no conversion (entries 16
alents of methanol resulted in significantly lower yields of 1a and 17). Reducing the quantity of methanol to 2 equiv. gave
being formed (entries 5–7). Use of trifluoroethanol (TFE) as the the substituted product in 93 % yield (entry 10); however, with
solvent, which is significantly cheaper than HFIP, with 10 equiv-
alents of methanol, gave anisole 1a in 93 % yield with a re-
duced reaction time of 18 h (entry 8). The reaction was equally
efficient using a 1:1 mixture of DCE and TFE[27] as solvent (entry
9). With this solvent system, sub-stoichiometric quantities of
DDQ could be used although 1a was formed in highest yield
when the reaction mixture was thoroughly degassed (Table 1,
entries 11–14);[28] stoichiometric quantities of DDQ were re-
quired with the other fluoroarenes to achieve good yields of
products (see Table 2).
other substrates the use of 10 equiv. of methanol was optimal
(see Table 2). The optimized reaction procedure involved the
use of 1 equiv. of 2,4-dichloro-1-fluorobenzene 1, 1.2 equiv. of
DDQ and 10 equiv. of methanol in 1:1 DCE/TFE under blue LED
irradiation without precautions to exclude air (entry 9) and we
used these conditions to investigate the scope of the reaction
with respect to the arene substrate (Table 2). The photochemi-
cal SNAr was applicable to a range halogenated fluoroarenes.
The use of 4-bromo-2-chloro-1-fluorobenzene 2 gave the de-
sired SNAr product 2a in 85 % yield (Table 2, entry 2). The use
of 1-chloro-4-fluorobenzene 3 provided 1-chloro-4-methoxy-
benzene 3a in 62 % yield (entry 3), with the corresponding
bromide 5 providing 1-bromo-4-methoxybenzene 5a in 39 %
yield (entry 5). Use of the isomeric 1-chloro-2-fluorobenzene 6
gave the desired product 6a in 35 % yield (entry 6). With the
use of 4-bromo-1,2-difluorobenzene 7, 4-bromo-2-fluoro-1-
methoxybenzene 7a was formed in 64 % yield (entry 7). Like-
wise, 5-bromo-1,3-dichloro-2-fluorobenzene gave the anisole
4a in 59 % yield (entry 4). Exposure of a commercially available
mixture of a 1:1 mixture 1,3-dichloro-4-fluoro-2-methylbenzene
8 and 1,5-dichloro-2-fluoro-4-methylbenzene 9 to the opti-
mized reaction conditions provided the corresponding substi-
tuted products 8a and 9a as a 1:1 mixture of isomers in 65 %
yield (entry 8). It also proved possible to form methoxy-substi-
tuted sulfonamide 11a and cyanonaphthalene 10a using our
optimized procedure. The SNAr reaction of 2-halopyridines by
alcohols generally proceeds in the presence of base above
room temperature and is a reliable route to 2-functionalised
pyridines. Attempts to develop a photochemical and base-free
functionalization of 2-fluoropyridines met with limited success
with the desired products formed in low yields (Table 2, entries
11–13). Use of 2-fluoropyridine 13 under solvent-free condi-
tions, however, did provide 2-methoxyprydine 13a with 54 %
conversion and only trace amount of product formed in the
absence of light.
Table 2. Arene scope in organophotochemical SNAr.[a,b]
Having investigated the variation of the arene substrate we
turned our attention to variation of the alcohol (Table 3). For
comparison the “standard” result of the formation of 2,4-di-
chloro-1-methoxybenzene 1a from 2,4-dichloro-1-fluorobenz-
ene 1 is shown in entry 1. Using ethanol or isopropanol also
gave the corresponding products 1b and 1c in good yield (87 %
and 89 % respectively, entries 2 and 3). Bulkier secondary alco-
hols such as cyclohexanol and menthol gave the desired prod-
ucts 1f and 1e in 64 % and 21 % yields respectively (entries 6
and 5). Increasing the steric hindrance of the alcohol with the
use of tert-butanol did not yield any 1-(tert-butoxy)-2,4-di-
chlorobenzene, however, a small amount (3 %) of 2,4-dichloro-
1-(2,2,2-trifluoroethoxy)benzene 1d was isolated (entry 4) aris-
ing from solvent participation in the photochemical SNAr reac-
tion. The use of cyclopropylmethanol or (R)-3-bromo-2-methyl-
propan-1-ol gave the corresponding alcohols 1g and 1h in
87 % and 36 % yields respectively (entries 7 and 8). Competition
[a] Isolated yields unless otherwise specified. [b] Starting material was a com-
mercial inseparable 1:1 mixture of 1,5-dichloro-2-fluoro-4-methylbenzene
and 1,3-dichloro-4-fluoro-2-methylbenzene and the products were isolated
as an inseparable mixture of 8a/9a. [c] Percentage conversion from GC analy-
sis. [d] Reaction conducted in the absence of solvents.
Interestingly, using a 1:1 mixture of acetonitrile and trifluoro-
ethanol resulted in an 85 % yield of 1a being formed as the
sole product with no substitution of either of the chlorides in
1 (entry 15). Control experiments used either the absence of between a secondary and primary alcohol using (R)-1,3-butane-
DDQ under irradiation or the absence of irradiation in the pres- diol gave a 3:1 inseparable mixture of substitution products
Eur. J. Org. Chem. 2020, 1–6
www.eurjoc.org
3
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
doi.org/10.1002/ejoc.202000337
EurJOC
European Journal of Organic Chemistry
(80 % combined yield) favoring substitution by the primary al- 1 to give the arylated pyrazole 3e in 34 % isolated yield (entry
cohol. Products 1a, 1b and 1c were also formed in decent yields 4). Use of a pyrazole ester gave arylated product 3g in 51 %
with 30 mol-% DDQ under degassed conditions (entries 1–3, yield (entry 6), however the use of pyrazole carrying the more
yields in parentheses); with other substrates these conditions electron withdrawing CF3 group gave the corresponding aryl-
gave the corresponding products in greatly reduced yields (en- ated product 3f in only 5 % yield (entry 5). With all of the reac-
tries 5–8, yields in parentheses).
tions involving pyrazole as the nucleophile, trace amounts of
the C–H substitution product were observed by GC-MS. These
C–H amination processes have been thoroughly studied by
König.[19]
Table 3. Alcohol scope in organophotochemical SNAr[a]
.
Table 4. Use of azoles in organophotochemical SNAr[a]
.
[a] Isolated yields. [b] Conversion by NMR – isolated yield is significantly lower
than the conversion due to partial decomposition during chromatographic
purification.
Based on the work of Fukuzumi,[15] Nicewicz,[13] König[19] and
Lambert,[21] the likely mechanism of the reaction of 1 with
methanol involves single electron oxidation of 1 by photoex-
cited DDQ (DDQ*) (Figure 3). The newly formed radical cation
1·+ then reacts with the methanol nucleophile to produce the
corresponding cyclohexadienyl radical 15. Back electron trans-
fer from the DDQ radical anion (DDQ·–) to the cyclohexadienyl
[a] Isolated yields. [b] Yields in parentheses are for reactions using 30 mol-%
DDQ under degassed conditions. [c] No product from substitution with
tBuOH was observed.
We then moved briefly to investigate pyrazole substrates radical 15 may occur, with expulsion of fluoride to give the
(Table 4) which have found utility in the work of Nicewicz[13] desired substitution product 1a and DDQ.[29] This mechanism
and König,[19] and latterly in the work of Lambert.[21] We found is likely operative under anaerobic conditions with substoichio-
that to achieve reasonable yields of substitution products it was metric quantities of DDQ and may be operative with other
necessary to add the azole slowly over the course of the reac- arenes and alcohols using stoichiometric DDQ although it is
tion (syringe pump) which may be necessary to avoid reaction known that the DDQ radical anion is a poor reducing agent
of the pyrazole with DDQ.[19] In the event, use of the preferred and hence the cycle would be inefficient.[14,15,30,31] With arene
arene substrate, namely 2,4-dichloro-1-fluorobenzene 1, with substrates and a range of alcohols, moderate to excellent yields
pyrazole gave desired product 1k in 20 % yield whereas using of substitution products are produced. While it is easier to gen-
4-chloro-1-fluorobenzene 3 gave desired product 3b in 62 % erate the arene radical cation from the more electron-rich
yield. Use of a small set of functionalized pyrazoles gave the arenes, the subsequent attack on the radical cation by the
corresponding arylated products with a range of yields. Using nucleophile is competitive with back electron transfer from the
4-chloro or 4-bromo-1H-pyrazole gave the corresponding aryl- DDQ radical anion (DDQ·–).[15,21] Conversely, the radical cations
ated pyrazoles 3c and 3d in 45 % and 54 % yields respectively of more electron-deficient arenes undergo facile attack by nu-
(Table 4, entries 2 and 3). Interestingly, 4-pyrazoleboronic acid cleophiles but are themselves less readily formed by oxidation.
pinacol ester could be coupled with 4-chloro-1-fluorobenzene Furthermore, the efficiency of reduction of the intermediate
Eur. J. Org. Chem. 2020, 1–6
www.eurjoc.org
4
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
doi.org/10.1002/ejoc.202000337
EurJOC
European Journal of Organic Chemistry
[3] F. Zhang, D. R. Spring, Chem. Soc. Rev. 2014, 43, 6906–6919.
[4] R. Taylor, Electrophilic Aromatic Substitution, Wiley-VCH, Weinheim, Ger-
many, 1990.
[5] J. F. Bunnett, R. E. Zahler, Chem. Rev. 1951, 49, 273–412.
[6] H. Amii, K. Uneyama, Chem. Rev. 2009, 109, 2119–2183.
[7] F. Terrier, Modern Nucleophilic Aromatic Substitution, Wiley-VCH, Wein-
heim, Germany, 2013.
[8] D. G. Brown, J. Bostrom, J. Med. Chem. 2016, 59, 4443–4458.
[9] For example Chapters 1 and 7, in Palladium-Catalyzed Coupling Reactions:
Practical Aspects and Future Developments (Ed.: A. Molnár), Wiley-VCH,
Weinheim, Germany, 2013.
[10] For example Chapters 2–9, 13, 17, 18 and 19, in Metal-Catalyzed Cross-
Coupling Reactions and More, 1, 2 and 3 (Eds.: A. de Meijere, S. Bräse, M.
Oestreich), Wiley-VCH, Weinheim, Germany, 2013.
cyclohexadienyl radical (e.g. 15) by the DDQ radical anion will
be dependent on the electronics of each substrate. All of the
above result in the requirement for mildly electron-poor arene
substrates. The balance of these factors accounts, in part, for
the range of yields for the photochemical SNAr.[21] For arene
substrate 7 where regioisomeric substitution products can be
formed, the regioselectivity is dictated by the charge density in
the first formed radical cation (see ESI). In line with the results
from Fukuzumi[15] and Lambert[21] further substitution of the
original SNAr products is not observed.[32]
[11] E. E. Kwan, Y. Zeng, H. A. Besser, E. N. Jacobsen, Nat. Chem. 2018, 10,
917–923.
[12] A. J. Blacker, G. Moran-Malagon, L. Powell, W. Reynolds, R. Stones, M. R.
Chapman, Org. Process Res. Dev. 2018, 22, 1086–1091.
[13] N. E. S. Tay, D. A. Nicewicz, J. Am. Chem. Soc. 2017, 139, 16100–16104.
[14] N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016, 116, 10075–10166.
[15] K. Ohkubo, A. Fujimoto, S. Fukuzumi, J. Am. Chem. Soc. 2013, 135, 5368–
5371.
[16] P. B. Merkel, P. Luo, J. P. Dinnocenzo, S. Farid, J. Org. Chem. 2009, 74,
5163–5173.
[17] N. A. Romero, K. A. Margrey, N. E. Tay, D. A. Nicewicz, Science 2015, 349,
1326–1330.
[18] L. Marzo, S. K. Pagire, O. Reiser, B. König, Angew. Chem. Int. Ed. 2018, 57,
10034–10072; Angew. Chem. 2018, 130, 10188.
[19] S. Das, P. Natarajan, B. König, Chem. Eur. J. 2017, 23, 18161–18165.
[20] A. Dahiya, A. K. Sahoo, T. Alam, B. K. Patel, Chem. Asian J. 2019, 14, 4454–
4492.
[21] H. Huang, T. H. Lambert, Angew. Chem. Int. Ed. 2020, 59, 658–662; Angew.
Chem. 2020, 132, 668–672.
[22] Nicewicz proposed stabilization of radical cations with trifluoroethanol
as solvent see ref 13.
Figure 3. Potential mechanism for photochemical SNAr reaction.
In summary, we have developed a mild method for the C–F
functionalization of fluoroarenes by a photochemical SNAr reac-
tion using DDQ. The method is operationally simple to conduct
and complements the closely-related photoelectrochemical
method reported recently by Lambert and co-worker.
[23] L. Eberson, M. P. Hartshorn, O. Persson, F. Radner, Chem. Commun. 1996,
2105–2112.
[24] I. Colomer, R. C. Barcelos, K. E. Christensen, T. J. Donohoe, Org. Lett. 2016,
18, 5880–5883.
[25] I. Colomer, A. E. R. Chamberlain, M. B. Haughey, T. J. Donohoe, Nat. Rev.
Chem. 2017, 1, 0088.
[26] For the importance of hydrogen bonding with hexafluoro2-propanol in
alkene expoxidation with hydrogen peroxide see: A. Berkessel, J. A.
Adrio, D. Hüttenhain, J. M. Neudörfl, J. Am. Chem. Soc. 2006, 128, 8421–
8426.
[27] K. A. Margrey, J. B. McManus, S. Bonazzi, F. Zecri, D. A. Nicewicz, J. Am.
Chem. Soc. 2017, 139, 11288–11299.
Acknowledgments
THS is grateful to the EPSRC Centre for Doctoral Training in
Synthesis for Biology and Medicine (EP/L015838/1) for a stu-
dentship, generously supported by AstraZeneca, Diamond Light
Source, Defence Science and Technology Laboratory, Evotec,
GlaxoSmithKline, Janssen, Novartis, Pfizer, Syngenta, Takeda,
UCB and Vertex. The authors would like to acknowledge the
use of the University of Oxford Advanced Research Computing
(ARC) facility in carrying out this work. https://doi.org/10.5281/
zenodo.22558.
[28] C. Grewer, H.-D. Brauer, J. Phys. Chem. 1994, 98, 4230–4235.
[29] Other mechanistic scenarios are possible including the potential loss of
fluroide from 15 to give the radical cation of 1a which then accepts an
electron to give product.
[30] D. Walker, J. D. Hiebert, Chem. Rev. 1967, 67, 153–195.
[31] A. E. Wendlandt, S. S. Stahl, Angew. Chem. Int. Ed. 2015, 54, 14638–14658;
Angew. Chem. 2015, 127, 14848.
Keywords: Photochemistry · SNAr · DDQ · C–F activation
[32] Exposure of 1a to the same reaction conditions as Table 1, entry 9, with
10 equiv. of ethanol in place of 10 equiv. of methanol resulted in com-
plete recovery of 1a after irradiation in the presence of DDQ for 48 h.
[1] For example see Chapters 3, 4 and 10, in Modern Arene Chemistry (Ed.:
D. Astruc), Wiley-VCH, Weinheim, Germany, 2013.
[2] T. Cernak, K. D. Dykstra, S. Tyagarajan, P. Vachal, S. W. Krska, Chem. Soc.
Rev. 2016, 45, 546–576.
Received: March 13, 2020
Eur. J. Org. Chem. 2020, 1–6
www.eurjoc.org
5
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
doi.org/10.1002/ejoc.202000337
EurJOC
European Journal of Organic Chemistry
Photochemical SNAr
T. Sheridan, H. G. Yayla, Y. Lian,
J. Genovino, N. Monck,
J. W. Burton* ....................................... 1–6
Organophotochemical SNAr Reac-
tions of Mildly Electron-Poor Fluoro-
arenes
C–F functionalization of arenes with a fluoroarenes with alcohols or pyrazoles
range of alcohol and pyrazole nucleo- and DDQ under irradiation by blue
philes has been achieved without the LED light provides the corresponding
need for metal catalysts or highly elec- substituted products.
tron-poor substrates. Treatment of
doi.org/10.1002/ejoc.202000337
Eur. J. Org. Chem. 2020, 1–6
www.eurjoc.org
6
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim