Expanding the Balz–Schiemann Reaction: Organotrifluoroborates Serve as Competent Sources of Fluoride Ion for Fluoro-Dediazoniation

Article abstract of DOI:10.1002/chem.201803575

The Balz–Schiemann reaction endures as a method for the preparation of (hetero)aryl fluorides yet is eschewed due to the need for harsh conditions or high temperatures along with the need to isolate potentially explosive diazonium salts. In a departure from these conditions, we show that various organotrifluoroborates (RBF₃^?s) may serve as fluoride ion sources for solution-phase fluoro-dediazoniation in organic solvents under mild conditions. This methodology was successfully extended to a one-pot process obviating aryl diazonium salt isolation. Sterically hindered (hetero)anilines are fluorinated under unprecedentedly mild conditions in good-to-excellent yields. Taken together, this work expands the repertoire of RBF₃^?s to act as fluorine ion sources in an update to the classic Balz–Schiemann reaction.

Full text of DOI:10.1002/chem.201803575

A Journal of
Accepted Article
Title: Expanding the Balz-Schiemann Reaction: organotrifluoroborates
serve as competent sources of fluoride ion for fluoro-
dediazoniation
Authors: Tharwat Mohy El Dine, Omar Sadek, Emmanuel Gras, and
David Perrin
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201803575
Link to VoR: http://dx.doi.org/10.1002/chem.201803575
Supported by

10.1002/chem.201803575
Chemistry - A European Journal
COMMUNICATION
Expanding the Balz-Schiemann Reaction: organotrifluoroborates
serve as competent sources of fluoride ion for fluoro-
dediazoniation
Tharwat Mohy El Dine†[a], Omar Sadek†[a,b], Emmanuel Gras*[b], David M. Perrin*[a]
† - these authors contributed equally to this work.
Abstract: The Balz-Schiemann reaction endures as a method for the
preparation of (hetero)aryl fluorides yet is eschewed due to the need
for harsh conditions or high temperatures along with the need to
isolate potentially explosive diazonium salts. In a departure from these
While yields remain variable and highly dependent on specific
conditions or a given substrate class,[12] no set of conditions has
emerged to be generally applicable for the Balz-Schiemann
reaction, a peculiarity typifying many fluorination methodologies
of variable scope often accompanied by significant limitations.[13]
–
conditions, we show that various organotrifluoroborates (RBF3 s) may
–
serve as fluoride ion sources for solution-phase fluoro-dediazoniation
in organic solvents under mild conditions. This methodology was
successfully extended to a one-pot process obviating aryl diazonium
salt isolation. Sterically hindered (hetero)anilines are fluorinated
under unprecedentedly mild conditions in good-to-excellent yields.
While organotrifluoroborates (RBF3 s) have been known since
1940, their use in fluoro-dediazoniation is limited to a single report
on the decomposition of 4-fluorophenyl-diazonium perfluoroalkyl-
–
BF3 salts at 140 °C.[14] Whereas the inductive effect of the
adjacent difluoromethylene group is known to greatly impede
–
–
–
Taken together, this work expands the repertoire of RBF3 s to act as
fluoride ion release from perfluoroalkyl-BF3 ,[15] other RBF3 s
solvolyze fluoride ion much more rapidly.[16] Here, we show that
fluorine ion sources in an update to the classic Balz-Schiemann
reaction.
–
commonly available RBF3 s serve as fluoride ion sources for
fluoro-dediazoniation under milder conditions (Scheme 1),
thereby identifying a new substrate class for this venerated
reaction. More importantly, we extend this application to a one-
An ever-increasing demand for fluorinated aromatics for use in
materials, pharmaceuticals, agrochemicals, and radiotracers
continues to drive innovation in forming aryl C-F bonds.[1]
Examples include new metal mediated processes,[2] deoxy-
fluorination reactions,[3] hypervalent iodine mediated oxidations,[4]
and halogen exchange processes.[5] Nevertheless, the canonical
Balz-Schiemann reaction, first reported in 1927[6] and featured in
all modern organic chemistry text books, is used to synthesize
fluorinated aromatics, including radiofluorinated ones.[7]
+
pot reaction where the ArN2 is generated in situ, thus avoiding
the need to isolate potentially explosive diazonium salts. Our
findings now expand the substrate scope of the historic Balz-
Schiemann reaction in its 91st year.
The Balz-Schiemann reaction requires an aryl diazonium cation
+
(ArN2 ), which is usually isolated first and then reacted with fluoro-
“ate” anions that act as sources of fluoride ion. The BF4– anion is,
–
by far, the most commonly used fluoride ion source although PF6 ,
–
–
2–
AsF6 , SbF6 or SiF6
are known.[8] Fluoro-dediazoniation
typically proceeds at high temperature, either in the melt or in
high-boiling redox-inert solvents e.g. xylenes and para-
dichlorobenzene in which the salt is suspended.[6, 8b] Punctiliously
dry HF and pyridinium-fluoride-HF (prepared from dry HF) also
have been employed at lower temperatures with variable
outcomes.[8b]
Over the past 90 years, a considerable body of work on the
Balz-Schiemann and the related Wallach reactions has detailed
the use of different solvents including perfluorinated solvents and
ionic liquids,[9] one-pot reactions,[10] and flow reactors.[11] In nearly
all cases, high-temperature thermolysis (>100 °C) with inorganic
“ate” salts or demanding conditions (e.g. dry HF) are required.
Scheme 1. (1) and (2): previous developments in the Balz-Schiemann reaction.
(3): this work
We began this work by fluorinating 2,4,6-trimethylphenyl-
diazonium tosylate (1) with potassium phenyltrifluoroborate (2a)
in different solvents at various temperatures (Table S1, ESI). Thus,
low-boiling solvents promoted fluorination at 50 °C with THF
giving the highest yield (Scheme 2).
[a]
[b]
Dr. T. Mohy El Dine, O. Sadek, Prof. Dr. D. M. Perrin
Chemistry Department, University of British Columbia
2036 Main Mall, Vancouver, BC, V6T 1Z1 Canada
E-mail: dperrin@chem.ubc.ca
O. Sadek, Dr. E. Gras
LCC-CNRS, Université de Toulouse
205 route de Narbonne BP 44099 31077 Toulouse Cedex 4 France
E-mail: emmanuel.gras@lcc-toulouse.fr
Scheme 2. Fluorination of aryl diazonium tosylate in solution.
Supporting information is given via a link at the end of the document.
This article is protected by copyright. All rights reserved.

10.1002/chem.201803575
Chemistry - A European Journal
COMMUNICATION
Next, we extended this method to a one-pot reaction starting
with the corresponding aniline. We hypothesized that
diazotization would accompany diazonium-RBF3 ion pair
formation. Accordingly, the reaction between 2,4,6-
trimethylaniline (4a) and (2a) was subjected to diazotization in
several solvents (Table 1, also Table S2, ESI); t-BuOH provided
the best results producing 3a in 55% yield (Table 1, entry 3)
whereas THF and CH2Cl2 gave moderate yields (Table 1, entries
1 and 2, respectively).
(e.g. AcOH) further diminished yields (Table 2, entry 7), H3PO4
significantly increased yields to 76% (Table 2, entry 8). Similar
yields could be achieved with 0.5 eq. of H3PO4 at 45 °C (Table 2,
entry 10). Finally, degassing the solvent gave slightly improved
yields (Table 2, entry 11).
–
Table 2. Optimization of one-pot Balz-Schiemann type reaction.[a]
In contrast, protic solvents as MeOH furnished low yields (Table
1, entry 4), likely owing to preferential reaction of the solvent with
the diazonium cation to afford both the corresponding arene
(hydro-dediazoniation) and the arylmethyl-ether.[17] Poor yields
were also obtained in MeCN (Table 1, entry 5), due to
Entry
[NO]+ source
Isoamyl nitrite
Conc. acid
H2SO4
H2SO4
-
Temp. (°C)
Yield[b]
30
arylacetamide formation upon work-up via
a
Ritter-type
reaction.[11a, 18] Not unexpectedly, DMSO gave low yields (Table
1
95
95
95
95
95
95
95
95
95
45
45
25
+
1, entry 6) as it is well-known to reduce ArN2 s to the
2
55
corresponding arenes while also producing phenols and other by-
products.[19] Toluene and cyclohexane, two solvents wherein
ArN2 BF4– salts may be decomposed in suspension, provided low
3
26
+
yields (Table 1, entries 7 and 8, respectively), presumably owing
to differential solubility of starting materials in these two solvents.
4
HCl
57
5
HNO3
p-TsOH
AcOH
H3PO4
64
Table 1. Solvent effect on one-pot Balz-Schiemann type reaction.[a]
6
40
7
t-BuONO
13
8
76
[c]
9
H3PO4
72
[c]
10
11[d]
12[d]
H3PO4
73
Entry
Solvent
THF
Temp. (°C)
Yield[b]
41
39
55
10
6
[c]
H3PO4
81[e]
33
1
2
3
4
5
6
7
8
75
[c]
H3PO4
CH2Cl2
t-BuOH
MeOH
50
[a] Reaction conditions similar to those in Table 1 using different acids and
[NO]+ sources. [b] Yields were determined as previously described. [c] 0.5
eq. of H3PO4. [d] Degassed t-BuOH. [e] 19F NMR yield for n=3.
95
75
Using optimized conditions (Table 2, entry 11) we investigated
the effect of various RBF3 s on fluoro-dediazoniation (Table 3,
also Table S3, ESI). Electron-rich/poor aromatic RBF3 s resulted
in lower yields irrespective of phenyl ring substitution (Table 3,
entries 1-4). Surprisingly, using extremely electron-poor
potassium perfluorophenyltrifluoroborate, 3a could still be
obtained in 50% yield (Table 3, entry 5). Interestingly, the
transformation works employing potassium alkyltrifluoroborates,
where similar yields were observed using vinyl or sec-butyl
trifluoroborate (Table 3, entries 7 and 8).
–
MeCN
92
–
DMSO
190
121
91
12
6
Toluene
Cyclohexane
4
[a] Reaction conditions: 4a (1 eq.), conc. H2SO4 (1 eq.), 2a (1.5 eq.), solvent,
t-BuONO (1.5 eq.), heated in a sealed tube at the indicated temperature for
2 h. [b] Due to the low b.p. of certain products, yields were determined by
19F NMR using 2,4-dinitrofluorobenzene as the internal standard (n=2).
Next, we sought to optimize other parameters relating to
diazotization. Of various diazotizing agents, t-BuONO was the
most efficient while aqueous HONO failed (Table 2, entries 2-12).
In the absence of acid, low yields were still obtained, likely due to
the presence of HNO3 in t-BuONO.[20] Hence, an acid is required
for adequate yields (Table 2, entry 3). Examination of various
acids revealed that HCl was efficient and HNO3 slightly improved
yields (Table 2, entries 4 and 5, respectively) while p-TsOH
lowered yields to 40% (Table 2, entry 6). Whereas weaker acids
This article is protected by copyright. All rights reserved.

10.1002/chem.201803575
Chemistry - A European Journal
COMMUNICATION
Table 3. Optimization of one-pot Balz-Schiemann type reaction.[a]
Entry
R
Yield[b]
34
1
2
3
4
5
6
7
8
p-methoxyphenyl (2b)
p-fluorophenyl (2c)
p-formylphenyl (2e)
o-hydroxyphenyl (2j)
Perfluorophenyl (2l)
m-acetamidephenyl (2m)
Vinyl
34
44
46
50
56
42
sec-butyl
44
[a] Reaction conditions: 4a (0.25 mmol), conc. H3PO4 (0.13 mmol), R-BF3K
(0.75 mmol), solvent (1.3 mL), Ar purge, then t-BuONO (0.38 mmol), rt for 20
min, heated in a sealed tube at 45-50 °C for 2 h. [b] Yields were determined
as previously described for n = 2.
Scheme 3. Substrate scope of the one-pot Balz-Schiemann reaction with 2a.
Yields were determined as previously described. ( ) Isolated yields. * = Conc.
H2SO4 in t-BuOH at 95 °C.
Notably, standard fluoride ion sources (e.g. KF, CsF, TBAF)
gave no detectable fluoro-arene while KBF4 afforded trace
amounts of product (<6%) (Table S4, ESI). Since BF4– may form
following protodeborylation we deliberately added BF4– to exclude
its role as a fluoride ion source under these conditions. Taken
In a preliminary study to probe the mechanism, various radical
scavengers/inducers were examined. Addition of TEMPO
(2,2,6,6-tetramethyl-1-piperidinyloxyl) had little effect on yields
while sodium ascorbate (0.5 or 1 eq.) provided inconsistent
results as yields were unaffected or greatly diminished. Ascorbate
is known to serve as a potent reductant in the case of homolytic
decomposition of the ArN2+ that is often initiated by contaminating
metal ions e.g. Cu2+ or light. As O2 may also intercept radical
intermediates, a lower yield in the presence of O2 often suggests
radical processes. Though degassing slightly improved yields
somewhat (Table 2, entries 10 and 11), such improvement is not
substantial enough to implicate a radical intermediate en route to
the fluoro-arene. Instead, O2 may serve to suppress other side-
reactions of a radical nature thereby increasing fluorination yields.
To further exclude the possibility of a radical mechanism, we
added cuprous ion (CuCO3 or Cu(MeCN)4PF6) or SnCl2 to the
reaction of 1 with 2a; all additives eroded fluorination yields (data
not shown). Hence, fluoro-dediazoniation likely proceeds by the
well-accepted heterolytic mechanism involving an ion pair, as little
evidence suggests a radical mechanism analogous to the
Sandmeyer reaction mechanism.[21]
–
together these results clearly demonstrate that RBF3 s release
fluoride ion under conditions under which standard Balz-
Schiemann reactions cannot be performed.
With optimized conditions in hand (Table 2, entry 11), we
applied this method to a variety of anilines (Scheme 3). Generally,
the desired fluoro-arenes were obtained in moderate to high
yields. Sterically hindered anilines were efficiently fluorinated (3b,
3c, 3f, 3g; Scheme 3). Interestingly, removing steric bulk from one
or both ortho positions of the aniline reduced yields. While 3b was
produced in 68% yield, ortho-t-butylaniline was fluorinated in 39%
yield (3g). Progressively moving the alkyl substituent to the meta
and then para positions further diminished yields to 26% (3h) and
14% (3i), respectively. The same trend holds for isopropyl
substituents with decreasing yields for 3f (78%), 3j (31%), and 3k
(14%). The effect of ortho steric bulk is evidenced by decreasing
yields between di- and mono-ortho substituted anilines; yields are
halved when comparing 3c (50%) to 3d (26%), and degrade
further when comparing 3f (78%) to 3j (31%). To address the role
of steric bulk at ortho positions, three anilines were synthesized
and fluorinated in good yields (3m-3o; Scheme 3) thus showing
tolerance of halogen and ether functionalities on the parent aniline.
The reaction conditions also allowed the fluorination of
heterocycle 3l in moderate yield. Heteroatom substituents at ortho
positions (e.g. Br, OH, OMe, OBn) gave only trace amounts of
product (3p-3r; Scheme 3). In all cases studied here, the by-
products are the corresponding phenols and small amounts of
biaryls as detected by GC-MS.
In light of these data, a brief discussion is warranted. While the
Balz-Schiemann reaction is thought to proceed via an SN1-like
mechanism, reactivity trends have been unpredictable. For
example, the reaction tolerates ortho steric hindrance to varying
12a]
degrees.[8b,
Yet strongly electron donating substituents at
ortho/para positions often give lower yields ~10%.[22] Our
observations with heteroatom-substituted anilines (3qi-iii;
Scheme 3) are generally consistent with past reports. Whereas
+
ortho-halogenated ArN2 s (except ortho-fluoro/nitro ones)[8b, 12a]
undergo efficient fluoro-dediazoniation,[8b] electron withdrawing
This article is protected by copyright. All rights reserved.

10.1002/chem.201803575
Chemistry - A European Journal
COMMUNICATION
ortho substituents give lower yields (3s; Scheme 3), consistent
with the reported destabilization of the aryl cation caused by such
substituents.
Finally, these results lead us to suggest that other organo-fluoro-
“ate” anions may also serve as soluble reservoirs of fluoride ion.
+
The higher yields for certain di-ortho substituted ArN2 s seen
herein corroborate the well-known effects of alkyl substituents
Acknowledgements
that stabilize the intermediate aryl cation complex BI; which has
+
been implicated in scrambling of 15N-14N labelled ArN2 ions
Support from the U. Paul Sabatier, French Canadian Research
Fund, and the Petroleum Research Fund is acknowledged.
18, 23]
(Scheme 4).[17a,
Indeed, ortho substitution is known to
increase the rate of scrambling and nucleophilic trapping to give
P.[24] Our results with mono- and di-ortho substituted anilines (3d
vs. 3c and 3j vs. 3f respectively; Scheme 3) corroborate past
findings to support a heterolytic reaction mechanism involving a
solvated aryl cation-RBF3– ion pair.
Keywords: Balz-Schiemann Reaction
•
Diazonium
•
Organotrifluoroborate • Fluorinated arenes • Fluorination
[1]
a) M. G. Campbell, T. Ritter, Chem. Rev. 2015, 115, 612-633; b) S.
Preshlock, M. Tredwell, V. Gouverneur, Chem. Rev. 2016, 116, 719-
766; c) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnelly, N. A.
Meanwell, J. Med. Chem. 2015, 58, 8315-8359; d) F. Dollé, D.
Roeda, B. Kuhnast, M. C. Lasne, (Eds.: A. Tressaud, G. Haufe),
Elsevier, 2008, pp. 3-65; e) D. L. Orsi, R. A. Altman, Chem.
Commun. 2017, 53, 7168-7181; f) Y. Zhou, J. Wang, Z. Gu, S.
Wang, W. Zhu, J. L. Acena, V. A. Soloshonok, K. Izawa, H. Liu,
Chem. Rev. 2016, 116, 422-518; g) A. J. Cresswell, S. G. Davies,
P. M. Roberts, J. E. Thomson, Chem. Rev. 2015, 115, 566-611.
a) N. Ichiishi, A. J. Canty, B. F. Yates, M. S. Sanford, Org. Lett. 2013,
15, 5134-5137; b) Y. Ye, S. D. Schimler, P. S. Hanley, M. S.
Sanford, J. Am. Chem. Soc. 2013, 135, 16292-16295; c) H. Lee, J.
Borgel, T. Ritter, Angew. Chem. Int. Ed. 2017, 56, 6966-6969; d) A.
R. Mazzotti, M. G. Campbell, P. Tang, J. M. Murphy, T. Ritter, J. Am.
Chem. Soc. 2013, 135, 14012-14015; e) A. C. Sather, S. L.
Buchwald, Acc. Chem. Res. 2016, 49, 2146-2157; f) A. C. Sather,
H. G. Lee, V. Y. De La Rosa, Y. Yang, P. Muller, S. L. Buchwald, J.
Am. Chem. Soc. 2015, 137, 13433-13438.
[2]
[3]
[4]
C. N. Neumann, T. Ritter, Acc. Chem. Res. 2017, 50, 2822-2833.
a) M. A. Cortes Gonzalez, P. Nordeman, A. Bermejo Gomez, D. N.
Meyer, G. Antoni, M. Schou, K. J. Szabo, Chem. Commun. 2018,
54, 4286-4289; b) B. H. Rotstein, N. A. Stephenson, N. Vasdev, S.
H. Liang, Nat. Commun. 2014, 5, 4365.
Scheme 4. Abbreviated mechanism of the Balz-Schiemann reactions; BI has
been implicated as pseudo “ion pair” intermediate whereas BII is the fully
solvated aryl cation.
[5]
a) H. B. Gottlieb, J. Am. Chem. Soc. 1936, 58, 532-533; b) A.
Casitas, M. Canta, M. Sola, M. Costas, X. Ribas, J. Am. Chem. Soc.
2011, 133, 19386-19392; c) P. S. Fier, J. F. Hartwig, J. Am. Chem.
Soc. 2012, 134, 10795-10798.
G. Balz, G. Schiemann, Ber. Dtsch. Chem. Ges. 1927, 60, 1186-
1190.
Notwithstanding these mechanistic inferences, this report
expands the substrate scope of the Balz-Schiemann reaction by
establishing the use of RBF3 s as more soluble fluoride ion
–
[6]
[7]
sources that can be used in solvents that would normally be
–
a) C. Thibault, A. L'Heureux, R. S. Bhide, R. Ruel, Org. Lett. 2003,
5, 5023-5025; b) K. Søndergaard, J. Langgaard Kristensen, N.
Gillings, M. Begtrup, Eur. J. Org. Chem. 2005, 2005, 4428-4433; c)
A. A. Kiryanov, A. J. Seed, P. Sampson, Tetrahedron Lett. 2001, 42,
8797-8800; d) S. Abele, G. Schmidt, M. J. Fleming, H. Steiner, Org.
Proc. Res. Dev. 2014, 18, 993-1001; e) T. Fukuhara, N. Yoneda, K.
Takamura, A. Suzuki, J. Fluor. Chem. 1991, 51, 299-304; f) R.
Pasceri, H. E. Bartrum, C. J. Hayes, C. J. Moody, Chem. Commun.
2012, 48, 12077-12079; g) T. Fukuhara, N. Yoneda, A. Suzuki, J.
Fluor. Chem. 1988, 38, 435-438.
a) H. Zollinger, Diazo Chemistry I: Aromatic and Heteroaromatic
Compounds, Wiley VCH, 1994; b) B. Langlois, in Houben-Weyl
Methods Org. Chem. Vol. E10 - Organo-Fluorine Compounds, Vol.
E10 (Eds.: B. Baasner, H. Hagemann, J. C. Tatlow), Thieme,
Stuttgart, New York, Delhi, Rio, 1998, pp. 686-740; c) C. Sellers, H.
Suschitzky, J. Chem. Soc. C 1968, 2317.
a) C. K. Chu, J. H. Kim, D. W. Kim, K. H. Chung, J. A.
Katzenellenbogen, D. Y. Chi, Bull. Korean Chem. Soc. 2005, 26,
599-602; b) J. Heredia-Moya, K. L. Kirk, J. Fluor. Chem. 2007, 128,
674-678; c) A. Hubbard, T. Okazaki, K. K. Laali, J Org Chem 2008,
73, 316-319; d) K. K. Laali, V. J. Gettwert, J. Fluor. Chem. 2001,
107, 31-34; e) M. Dobele, S. Vanderheiden, N. Jung, S. Brase,
Angew. Chem. Int. Ed. 2010, 49, 5986-5988.
L. Garel, L. Saint-Jalmes, Tetrahedron Lett. 2006, 47, 5705-5708.
a) N. H. Park, T. J. Senter, S. L. Buchwald, Angew. Chem. Int. Ed.
2016, 55, 11907-11911; b) Z. Yu, Y. Lv, C. Yu, Org. Proc. Res. Dev.
2012, 16, 1669-1672; c) Z.-q. Yu, Y.-w. Lv, C.-m. Yu, W.-k. Su,
Tetrahedron Lett. 2013, 54, 1261-1263.
incompatible with inorganic “ate” salts e.g. BF4 . Moreover, this
work provides facile access to aryl fluorides, particularly those
with a significant degree of ortho steric hindrance as fluorination
yields for these substrates were particularly high. Such fluoro-
arenes are considered challenging to obtain as sterically hindered
+
ArN2 s are known to detonate.[7a, 25]
In conclusion, the salient points of this work are as follows:
herein we demonstrate the viability of readily accessible
organotrifluoroborates as fluoride ion sources for a Balz-
Schiemann type reaction that proceeds in various organic
solvents under remarkably mild conditions. In stark contrast to
typical Balz-Schiemann reactions that demand dry conditions,
[8]
[9]
–
RBF3 s afford the use of an aqueous acid with enhanced
tolerance for some water. Furthermore, the low temperature at
which fluoro-dediazoniation occurs (45 °C) is unprecedented in
Balz-Schiemann type reactions using standard “fluoro-ate” anions.
This feature affords a milder route to fluoro-arenes while avoiding
[10]
[11]
+
the potentially hazardous handling of isolated ArN2 s or forcing
their decomposition at much higher temperatures. Given the facile
–
synthetic access to a diverse array of RBF3 s, further tuning of the
–
RBF3– substituents along with the use of solid-supported RBF3 s
[12]
[13]
a) A. Roe, in Organic Reactions, Vol. 5, 1949, pp. 193-228; b) T.
Furuya, A. S. Kamlet, T. Ritter, Nature 2011, 473, 470-477.
L. J. Allen, S. H. Lee, Y. Cheng, P. S. Hanley, J. M. Muhuhi, E. Kane,
S. L. Powers, J. E. Anderson, B. M. Bell, G. A. Roth, M. S. Sanford,
D. C. Bland, Org. Proc. Res. Dev. 2014, 18, 1045-1054.
–
in-flow are expected to improve these yields. As RBF3 s can be
radiofluorinated at very high molar activities,[26] this mild one-pot
method, may present distinct advantages for radiofluorination.
[14]
V. V. Bardin, H.-J. Frohn, J. Fluor. Chem. 2013, 156, 333-338.
This article is protected by copyright. All rights reserved.

10.1002/chem.201803575
Chemistry - A European Journal
COMMUNICATION
[15]
a) A. J. Lennox, G. C. Lloyd-Jones, J. Am. Chem. Soc. 2012, 134,
7431-7441; b) Z. Liu, D. Chao, Y. Li, R. Ting, J. Oh, D. M. Perrin,
Chem. Eur. J. 2015, 21, 3924-3928.
[16]
[17]
R. Ting, C. W. Harwig, J. Lo, Y. Li, M. J. Adam, T. J. Ruth, D. M.
Perrin, J. Org. Chem. 2008, 73, 4662-4670.
a) C. G. Swain, J. E. Sheats, K. G. Harbison, J. Am. Chem. Soc.
1975, 97, 783-790; b) A. Fernandez-Alonso, C. Bravo-Diaz, Org.
Biomol. Chem. 2008, 6, 4004-4011.
[18]
K. Laali, I. Szele, H. Zollinger, Helv. Chim. Acta 1983, 66, 1737-
1747.
[19]
[20]
H. Zollinger, Angew. Chem. Int. Ed. 1978, 17, 141-150.
M. P. Doyle, J. W. Terpstra, R. A. Pickering, D. M. LePoire, J. Org.
Chem. 1983, 48, 3379-3382.
[21]
[22]
J. K. Kochi, J. Am. Chem. Soc. 1957, 79, 2942-2948.
P. C. Bélanger, C. K. Lau, H. W. R. Williams, C. Dufresne, J.
Scheigetz, Can. J. Chem. 1988, 66, 1479-1482.
[23]
a) B. R. Ussing, D. A. Singleton, J. Am. Chem. Soc. 2005, 127,
2888-2899; b) K. Laali, I. Szele, K. Yoshida, Helv. Chim. Acta 1983,
66, 1710-1720; c) H. G. O. Becker, G. Israel, J. Prakt. Chem. 1979,
321, 579-586; d) C. G. Swain, R. J. Rogers, J. Am. Chem. Soc.
1975, 97, 799-800; e) H. Nakazumi, T. Kitao, H. Zollinger, J. Org.
Chem. 1987, 52, 2825-2830; f) P. Burri, H. Loewenschuss, H.
Zollinger, G. K. Zwolinski, Helv. Chim. Acta 1974, 57, 395-402; g)
R. G. Bergstrom, R. G. M. Landells, G. H. Wahl, H. Zollinger, J. Am.
Chem. Soc. 1976, 98, 3301-3305; h) I. Szele, H. Zollinger, J. Am.
Chem. Soc. 1978, 100, 2811-2815; i) I. Szele, H. Zollinger, Helv.
Chim. Acta 1981, 64, 2728-2732.
[24]
[25]
H. Maskill, K. McCrudden, Croat. Chem. Acta 1992, 65, 567-574.
a) P. C. Myhre, J. W. Edmonds, J. D. Kruger, J. Am. Chem. Soc.
1966, 88, 2459-2466; b) H. Zollinger, Acc. Chem. Res. 1973, 6, 335-
341.
[26]
D. M. Perrin, Acc. Chem. Res. 2016, 49, 1333-1343.
This article is protected by copyright. All rights reserved.

10.1002/chem.201803575
Chemistry - A European Journal
COMMUNICATION
COMMUNICATION
Tharwat Mohy El Dine, Omar Sadek,
Emmanuel Gras*, David M. Perrin*
Page No. – Page No.
Expanding the Balz-Schiemann
Reaction: Organotrifluoroborates
serve as competent sources of
fluoride
ion
for
fluoro-
dediazoniation
Smoothing the BS: Organotrifluoroborates cool down the Balz-Schiemann. The
involvement of organotrifluoroborates in a one-pot Balz-Schiemann reaction allows
access to sterically hindered aryl fluorides under user-friendly conditions. The scope of
the reaction is generally consistent with the parameters governing the decomposition of
diazonium salts.
This article is protected by copyright. All rights reserved.