Synthesis of fluorinated heteroaromatics through formal substitution of a nitro group by fluorine under transition-metal-free conditions

Article abstract of DOI:10.1002/chem.201402282

An efficient and transition-metal-free approach was developed to access a series of fluorinated heteroaromatics in moderate to excellent yields. This one-pot procedure features a triple-relay transformation of rapid dearomatization, fluorination, and rearomatization processes, which represents a conceptually novel strategy of combining partial hydrogenation and electrophilic fluorination.

Full text of DOI:10.1002/chem.201402282

DOI: 10.1002/chem.201402282
Communication
&
Synthetic Methods
Synthesis of Fluorinated Heteroaromatics through Formal
Substitution of a Nitro Group by Fluorine under Transition-Metal-
Free Conditions
Ran-Ning Guo,[a, b] Xian-Feng Cai,[a] Lei Shi,*[a] Zhang-Pei Chen,[a] and Yong-Gui Zhou*[a]
compounds,[9,10] 3-nitroquinolines have been studied
(Scheme 2a).[11] Due to the high electron-withdrawing and con-
Abstract: An efficient and transition-metal-free approach
was developed to access a series of fluorinated heteroaro-
matics in moderate to excellent yields. This one-pot proce-
dure features a triple-relay transformation of rapid dearo-
matization, fluorination, and rearomatization processes,
which represents a conceptually novel strategy of combin-
ing partial hydrogenation and electrophilic fluorination.
jugative effect of the nitro group, the 1,4-reduction intermedi-
ate 3 was relatively stable in the asymmetric transfer hydroge-
nation (ATH) process; thus, it was isolated and used in further
transformations to give more insights on the mechanism. The
key-intermediate enamine 3[12] also inspired us to investigate
the possibility of combining the partial reduction process with
other transformations. We envisioned that electrophilic fluorine
could be introduced into the C3-position of 3 to yield the fluo-
rinated intermediate 4, and, driven by the strong force of rear-
omatization, nitrous acid would then subsequently be eliminat-
ed to yield the desired 3-fluoroquinoline (Scheme 2b). To ach-
ieve this sequential transformation, the reactivity of the enam-
Fluorinated molecules are of remarkable significance in phar-
maceuticals, agrochemicals, tracers for positron emission to-
mography and new materials due to their improved properties
of lipophilicity, bioavailability, metabolic stability, etc.[1] To date,
great achievements have been made in the construction of
carbon–fluorine bonds, while the fluorination of aromatic com-
pounds is still challenging.[2] Fluorination of medicinally rele-
vant heteroaromatics, for example, mainly relies on classic fluo-
rination methods,[3] such as the Halex (halogen exchange) pro-
cess, the Balz–Schiemann reaction, and recently emerged tran-
sition-metal-mediated fluorination reactions.[2b,c,4–6] Transition
metal-catalyzed fluorinations using palladium or silver have
been proven to be highly efficient and encompass a broad
substrate scope compared to traditional reactions; however, di-
recting groups and high catalyst loading are unavoidable.
Therefore, new and efficient fluorination methodologies are
highly desirable in response to the ever-growing need of fluo-
rinated aromatics in organic fluorine chemistry. Herein, we
present a conceptually novel and transition-metal-free route to
fluorinated heteroaromatics (Scheme 1).
Scheme 1. Different approaches to fluorinated heteroaromatics.
In organic synthesis, the nitro group is viewed as a syntheti-
cally important functional group owing to its easy availability
and transformation into a variety of diverse functionalities.[7,8]
Very recently, as part of our ongoing efforts to promote the
development of asymmetric hydrogenations of heteroaromatic
[a] R.-N. Guo, X.-F. Cai, L. Shi, Z.-P. Chen, Prof. Y.-G. Zhou
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics
Chinese Academy of Sciences, Dalian 116023 (P. R. China)
Fax: (+86)411-84379220
E-mail: ygzhou@dicp.ac.cn
[b] R.-N. Guo
Department of Chemistry, Dalian University of Technology
Dalian 116012 (P. R. China)
Scheme 2. a) ATH process of 3-nitroquinolines with Hantzsch ester. b) Syn-
thesis of 3-fluoroquinolines through the partial reduction, fluorination, and
elimination of nitrous acid.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402282.
Chem. Eur. J. 2014, 20, 1 – 5
1
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
ine intermediate 3 with an electrophilic fluorine reagent and
the selectivity of the elimination of nitrous acid or hydrogen
fluoride are key considerations.
agent, a sequential transformation of 1a to 2a was conducted,
as depicted in Table 2. A high conversion of 96% was obtained
in CH3CN, but other solvents diminished the first 1,4-reduction
step and reduced the fluorination and elimination rate drasti-
cally (Table 2, entries 1–5). Strong acids such as l-CSA or p-
TsOH·H2O could replace 1,1’-binaphthyl-2,2’-diylhydrogenphos-
phate (BPA) perfectly (Table 2, entries 8–9), while weaker acids
such as o-nitrobenzoic acid or acetic acid failed (Table 2, en-
tries 6–7). Therefore, p-TsOH·H2O was chosen as the alternative
hydrogenation catalyst in consideration of its cost and availa-
bility. The optimized conditions for this mild and metal-free flu-
orination reaction were finally established as: HEH (1.1 equiv),
p-TsOH·H2O (5 mol%); Selectfluor (1.3 equiv); KOtBu (2.0 equiv),
CH3CN.
Following above hypothesis, the important step is how to
trap the 1,4-reduction intermediate 3 by electrophilic fluorina-
tion. An original survey on common fluorine sources showed
that both Selectfluor and N-fluorobenzenesulfonimide (NFSI)
performed well in trapping the in situ generated 3-nitro-2-
phenyl-1,4-dihydroquinoline (3a) in CH3CN. In addition, the
electrophilic attack by Selectfluor quantitatively converted 3a
to 3-fluoro-3-nitro-2-phenyl-3,4-dihydro-quinoline (4a) within
5 min.[13] With isolated 4a in hand, further research focused on
screening the conditions for the selective elimination of nitrous
acid.[14] Preliminary trials revealed that a base could accelerate
the eliminative rearomatization of 4a, while acids, oxidants, or
heating could not (Table 1, entries 1–3); a promising result (full
conversion, 86% selectivity to 2a) was obtained in the pres-
ence of Et3N (Table 1, entry 4). Further evaluation of different
bases illustrated that complete rearomatization could be ach-
ieved by a series of common bases, with inorganic bases per-
forming better than organic bases in terms of selectivity and
yield, and the best result was obtained with KOtBu (Table 1,
entries 6–9,). Notably, no deterioration of conversion or selec-
tivity was observed when half amount of the base was used
(Table 1, entry 10). With KOtBu (2.0 equiv) as the optimized
base, increasing or lowering the temperature only had a mar-
ginal influence on the selectivity and conversion (Table 1, en-
tries 11–12).
With this newly developed triple-relay transformation strat-
egy in hand, we next set out to demonstrate the generality
and practicality in detail with various 3-nitroquinolines, and
the results are summarized in Table 3. The reaction could be
carried out with a series of substituted 3-nitroquinolines, af-
fording the corresponding products in moderate to good
yields. Both electron-donating and electron-withdrawing
groups at the C2-position were tolerated under the reaction
conditions and there was also no significant influence of the
position of the 2-aryl substituents. Besides, the yield decreases
with aryl>alkenylꢀalkynyl>alkyl substituents at the C2-posi-
tion. Notably, in terms of reactivity, the dearomatization pro-
After screening bases for the selective elimination, a >99:1
ratio of 2a/1a was achieved (entry 10, Table 1). Therefore, we
envisaged a one-pot transformation of 3-nitroquinolines to 3-
fluoroquinolines. With diethyl-2,6-dimethyl-1,4-dihydropyridine-
3,5-dicarboxylate (HEH) as the hydrogen source for the initial
partial reduction process and Selectfluor as the fluorinating re-
Table 2. Optimization of reaction parameters for the one-pot transforma-
tion.[a]
Table 1. Screening of conditions for the selective elimination of nitrous
acid.[a]
Entry
Conditions
Conversion [%][b]
Ratio of 2a/1a[b]
Entry
Solvents
Acid
Conversion [%][b]
1
2
3
4
5
6
7
8
9
Heat (508C)
<5
<5
<5
–
–
–
DDQ (1.1 equiv)
p-TsOH·H2O (1.1 equiv)
Et3N (4.0 equiv)
1
2
3
4
5
6
7
8
9
CH3CN
THF
1,4-dioxane
toluene
Et2O
CH3CN
CH3CN
CH3CN
CH3CN
BPA
BPA
BPA
BPA
96
76
57
58
44
<5
<5
94
>95
>95
>95
>95
>95
>95
>95
>95
>95
86:14
82:18
93:7
93:7
93:7
>99:1
>99:1
99:1
>99:1
DABCO (4.0 equiv)
Na2CO3 (2.0 equiv)
K2CO3 (2.0 equiv)
Cs2CO3 (2.0 equiv)
KOtBu (4.0 equiv)
KOtBu (2.0 equiv)
KOtBu (2.0 equiv)
KOtBu (2.0 equiv)
BPA
AcOH
o-nitrobenzoic acid
l-CSA
p-TsOH·H2O
10
11[c]
12[d]
97
[a] Reaction conditions: 1a (0.20 mmol), HEH (1.1 equiv), and acid
(5 mol%) in solvent (3.0 mL) were stirred for 10 h at RT; then Selectfluor
(1.3 equiv) was added and after about 20 h KOtBu (2.0 equiv) was added
[a] Reaction condition: 4a (0.20 mmol), CH3CN (3.0 mL), RT, 12 h. [b] De-
termined by 1H NMR spectroscopy. [c] At 08C. [d] At 508C. DDQ=2,3-di-
1
and the mixture was stirred for 5.5 h. [b] Determined by H NMR spectros-
chloro-5,6-dicyano-p-benzoquinone;
octane.
DABCO=1,4-diazabicyclo[2.2.2]
copy. l-CSA=(L)-camphorsulfonic acid; p-TsOH·H2O=p-toluenesulfonic
acid monohydrate; BPA=1,1’-binaph-thyl-2,2’-diyl hydrogenphosphate.
&
&
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
2
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
5.3 Hz), 128.9 (d, 5JFC =2.4 Hz), 128.7 (s), 128.4 (d, 3JFC =5.4 Hz),
127.4 (s), 126.9 (d, 4JFC =4.8 Hz), 119.8 ppm (d, 2JFC =19.4 Hz);
19F NMR (376 MHz, CDCl3): d=À124.2 ppm (s); HRMS (ESI): m/z
calcd for C15H10FN: 224.0877 [M+H]+; found: 224.0870 (see the
Supporting Information for spectroscopic data).
Table 3. Scope for the transformation of 3-nitroquinolines 1 to 3-fluoro-
quinolines 2[a]
Entry
R
R’
Yield [%][b]
Acknowledgements
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
C6H5
H
H
H
H
H
H
H
H
H
H
H
H
H
F
OMe
OMe
94 (2a)
95 (2b)
93 (2c)
91 (2d)
73 (2e)
93 (2 f)
78 (2g)
93 (2h)
81 (2i)
93 (2j)
80 (2k)
63 (2l)
78 (2m)
87 (2n)
61 (2o)
51 (2p)
2-MeC6H4
3-MeC6H4
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-CF3C6H4
2-naphthyl
(E)-styryl
phenylethynyl
4-chlorophenylethynyl
Ph
We are grateful for financial support from the National Natural
Science Foundation of China (21125208 & 21032003) and the
National Basic Research Program of China (2010CB833300).
Keywords: fluorination · heterocycles · hydrogenation · nitro
compounds · rearomatization
[1] For selected reviews on the unique role of fluorine in organic, agricul-
tural, medicinal, and material chemistry, see: a) H. Schofield, J. Fluorine
Chem. 1999, 100, 7; b) H. J. Bçhm, D. Banner, S. Bendels, M. Kansy, B.
Kuhn, K. Muller, U. Obst-Sander, M. Stahl, ChemBioChem 2004, 5, 637;
c) K. Muller, C. Faeh, F. Diederich, Science 2007, 317, 1881; d) W. K. Hag-
mann, J. Med. Chem. 2008, 51, 4359; e) D. O’Hagan, Chem. Soc. Rev.
2008, 37, 308; f) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem.
Soc. Rev. 2008, 37, 320; for books on fluorine in organic and medicinal
chemistry, see: g) P. Kirsch, Modern Fluoroorganic Chemistry: Synthesis,
Reactivity, Applications, Wiley-VCH, Weinheim, 2004; h) Fluorine in Me-
dicinal Chemistry and Chemical Biology (Ed.: I. Ojima), Wiley, Chichester,
2009.
Ph
nBu
[a] Reaction conditions: 1 (0.20 mmol), HEH (1.1 equiv), and p-TsOH·H2O
(5 mol%) in CH3CN (3.0 mL) were stirred for 2 h at RT; then Selectfluor
(1.3 equiv) was added and after about 5 min KOtBu (2.0 equiv) was added
and the mixture was stirred for 5.5 h. [b] Isolated yield.
[2] For recent reviews on the construction of carbon–fluorine bonds, see:
a) T. Furuya, C. A. Kuttruff, T. Ritter, Curr. Opin. Drug Discovery Dev. 2008,
11, 803; b) T. Furuya, A. S. Kamlet, T. Ritter, Nature 2011, 473, 470; c) T.
Liang, C. N. Neumann, T. Ritter, Angew. Chem. 2013, 125, 8372; Angew.
Chem. Int. Ed. 2013, 52, 8214.
[3] For selected work and reviews on traditional fluorination reactions of
aromatic compounds, see: a) G. Balz, G. Schiemann, Ber. Dtsch. Chem.
Ges. 1927, 60, 1186; b) G. C. Finger, C. W. Kruse, J. Am. Chem. Soc. 1956,
78, 6034; c) G. A. Olah, J. T. Welch, Y. D. Vankar, M. Nojima, L. Kerekes,
J. A. Olah, J. Org. Chem. 1979, 44, 3872; d) D. J. Adams, J. H. Clark,
Chem. Soc. Rev. 1999, 28, 225.
[4] For recent reviews on transition-metal-catalyzed fluorinations, see:
a) V. V. Grushin, Acc. Chem. Res. 2010, 43, 160; b) T. Furuya, J. E. M. N.
Klein, T. Ritter, Synthesis 2010, 1804; c) A. Vigalok, Organometallics 2011,
30, 4802; d) C. Hollingworth, V. Gouverneur, Chem. Commun. 2012, 48,
2929; e) G. Liu, Org. Biomol. Chem. 2012, 10, 6243.
[5] For selected reviews and work on typical catalytic fluorinations through
CÀH functionalization, see: a) K. M. Engle, T.-S. Mei, X. Wang, J.-Q. Yu,
Angew. Chem. 2011, 123, 1514; Angew. Chem. Int. Ed. 2011, 50, 1478;
b) D. Leow, G. Li, T.-S. Mei, J.-Q. Yu, Nature 2012, 486, 518; c) K. M. Engle,
T.-S. Mei, M. Wasa, J.-Q. Yu, Acc. Chem. Res. 2012, 45, 788; d) K. L. Hull,
W. Q. Anani, M. S. Sanford, J. Am. Chem. Soc. 2006, 128, 7134; e) X.
Wang, T.-S. Mei, J.-Q. Yu, J. Am. Chem. Soc. 2009, 131, 7520; f) K. S. L.
Chan, M. Wasa, X. Wang, J.-Q. Yu, Angew. Chem. 2011, 123, 9247; Angew.
Chem. Int. Ed. 2011, 50, 9081; g) B. Yao, Z.-L. Wang, H. Zhang, D.-X.
Wang, L. Zhao, M.-X. Wang, J. Org. Chem. 2012, 77, 3336; h) S. J. Lou,
D. Q. Xu, A. B. Xia, X. F. Wang, Y. K. Liu, X. H. Du, Z. Y. Xu, Chem.
Commun. 2013, 49, 6218; i) T. Truong, K. Klimovica, O. Daugulis, J. Am.
Chem. Soc. 2013, 135, 9342.
[6] For selected work on transition-metal-mediated or -catalyzed CÀF bond
formations, see: a) T. Furuya, H. M. Kaiser, T. Ritter, Angew. Chem. 2008,
120, 6082; Angew. Chem. Int. Ed. 2008, 47, 5993; b) T. Furuya, T. Ritter,
Org. Lett. 2009, 11, 2860; c) T. Furuya, A. E. Strom, T. Ritter, J. Am. Chem.
Soc. 2009, 131, 1662; d) D. A. Watson, M. J. Su, G. Teverovskiy, Y. Zhang,
J. Garcia-Fortanet, T. Kinzel, S. L. Buchwald, Science 2009, 325, 1661; e) P.
Tang, T. Furuya, T. Ritter, J. Am. Chem. Soc. 2010, 132, 12150; f) P. Tang,
T. Ritter, Tetrahedron 2011, 67, 4449; g) T. Noꢁl, T. J. Maimone, S. L. Buch-
wald, Angew. Chem. 2011, 123, 9062; Angew. Chem. Int. Ed. 2011, 50,
8900; h) E. Lee, A. S. Kamlet, D. C. Powers, C. N. Neumann, G. B. Boursali-
an, T. Furuya, D. C. Choi, J. M. Hooker, T. Ritter, Science 2011, 334, 639;
cess of alkyl-, alkynyl-, and alkenyl-substituted substrates was
faster than that of aryl-substituted ones, while in turn the fluo-
rination and rearomatization process of the former substrates
was slower than that of the latter ones.
In conclusion, we have developed an efficient and transi-
tion-metal-free procedure to synthesize a series of fluorinated
heteroaromatics in moderate to excellent yields through
formal substitution of a nitro group by fluorine. This one-pot
procedure features a triple-relay transformation of rapid dearo-
matization, electrophilic fluorination, and eliminative rearoma-
tization processes. This novel fluorination method also allows
for the possibility of late-stage fluorination.[6e,6 h,6k] Further in-
vestigations on new types of combinations of partial reduc-
tions and other reactions are underway in our laboratory.
Experimental Section
Typical procedure for the one-pot transformation
A solution of 2-phenyl-3-nitroquinoline (1a, 50 mg, 0.20 mmol),
HEH (1.1 equiv), and p-TsOH·H2O (5 mol%) in CH3CN (3.0 mL) was
stirred at RT for 2 h. A yellow solid formed gradually; then Select-
fluor (1.3 equiv) was added and after about 5 min KOtBu
(2.0 equiv) was added and the mixture was stirred until the reac-
tion was complete. All volatiles were removed under reduced pres-
sure. Purification was performed on a silica gel column eluted with
hexane/EtOAc (80:1–50:1) to give the desired product 2a (42 mg,
0.19 mmol, 94% yield) as a white solid. M.p.=36–388C; 1H NMR
(400 MHz, CDCl3): d=8.16 (d, J=8.5 Hz, 1H), 8.07 (d, J=7.3 Hz,
2H), 7.87–7.61 (m, 3H), 7.56–7.44 ppm (m, 4H); 13C NMR (100 MHz,
1
2
CDCl3): d=155.2 (d, JFC =261.0 Hz), 149.2 (d, JFC =14.5 Hz), 145.4
(d, 5JFC =2.9 Hz), 135.9 (d, 4JFC =5.2 Hz), 129.7 (s), 129.5 (d, JFC
=
3
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
3
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ

Communication
i) T. J. Maimone, P. J. Milner, T. Kinzel, Y. Zhang, M. K. Takase, S. L. Buch-
wald, J. Am. Chem. Soc. 2011, 133, 18106; j) P. S. Fier, J. F. Hartwig, J. Am.
Chem. Soc. 2012, 134, 10795; k) E. Lee, J. M. Hooker, T. Ritter, J. Am.
Chem. Soc. 2012, 134, 17456; l) P. S. Fier, J. Luo, J. F. Hartwig, J. Am.
Chem. Soc. 2013, 135, 2552; m) Y. Ye, M. S. Sanford, J. Am. Chem. Soc.
2013, 135, 4648; n) N. Ichiishi, A. J. Canty, B. F. Yates, M. S. Sanford, Org.
Lett. 2013, 15, 5134; o) A. Mazzotti, M. Campbell, P. Tang, J. Murphy, T.
Ritter, J. Am. Chem. Soc. 2013, 135, 14012; p) H. G. Lee, P. J. Milner, S. L.
Buchwald, Org. Lett. 2013, 15, 5602; q) Y. Ye, S. D. Schimler, P. S. Hanley,
M. S. Sanford, J. Am. Chem. Soc. 2013, 135, 16292; r) P. S. Fier, J. F. Hart-
wig, Science 2013, 342, 956; s) X. Mu, H. Zhang, P. Chen, G. Liu, Chem.
Sci. 2014, 5, 275.
Y.-G. Zhou, Chem. Rev. 2012, 112, 2557; g) Q.-A. Chen, Z.-S. Ye, Y. Duan,
Y.-G. Zhou, Chem. Soc. Rev. 2013, 42, 497.
[10] For reviews on asymmetric transfer hydrogenations by using Hantzsch
esters, see: a) S. G. Ouellet, A. M. Walji, D. W. C. Macmillan, Acc. Chem.
Res. 2007, 40, 1327; b) S.-L. You, Chem. Asian J. 2007, 2, 820; c) S. J.
Connon, Org. Biomol. Chem. 2007, 5, 3407; d) M. Rueping, E. Sugiono,
F. R. Schoepke, Synlett 2010, 852; e) M. Rueping, J. Dufour, F. R.
Schoepke, Green Chem. 2011, 13, 1084; f) C. Zheng, S.-L. You, Chem. Soc.
Rev. 2012, 41, 2498.
[11] X.-F. Cai, M.-W. Chen, Z.-S. Ye, R.-N. Guo, L. Shi, Y. Li, Y.-G. Zhou, Chem.
Asian J. 2013, 8, 1381.
[12] For selected work on electrophilic fluorinations of enamines, see: a) R.
Surmont, B. De Corte, N. De Kimpe, Tetrahedron Lett. 2009, 50, 3877;
b) P. N. Gichuhi, M. Kuriyama, O. Onomura, Heterocycles 2014, 88, 331;
c) Y. Huang, A. M. Walji, C. H. Larsen, D. W. C. MacMillan, J. Am. Chem.
Soc. 2005, 127, 15051.
[7] a) Nitro Compounds: Recent Advances in Synthesis and Chemistry; Organ-
ic Nitro Chemistry Series (Eds.: H. Feuer, A. T. Nielsen), Wiley-VCH, Wein-
heim, 1990; b) N. Ono, The Nitro Group in Organic Synthesis, Wiley-VCH,
Weinheim, 2001.
[13] Typical procedure: a solution of 2-phenyl-3-nitroquinoline (1a, 50 mg,
0.20 mmol), HEH (1.1 equiv), and BPA (5 mol%) in CH3CN (3.0 mL) was
stirred at RT for 2 h. A yellow solid formed gradually; then Selectfluor
(1.3 equiv) was added and the reaction was monitored by TLC. Notably,
Selectfluor should be added after the first transformation is complete,
because otherwise HEH would be oxidized by Selectfluor preferentially.
[14] 3-Fluoro-3-nitro-2-phenyl-3,4-dihydroquinoline (4a) was comparatively
stable when kept in cold storage. Once isolated, it should be subjected
to the base evaluation experiments as soon as possible. Traces of elimi-
native by-product 2a could be observed in the 1H NMR spectrum due
to the deterioration of 4a in CDCl3.
[8] For selected work on nucleophilic fluorodenitration processes, see:
Ref. [3b]; see also: a) D. J. Adams, J. H. Clark, D. J. Nightingale, Tetrahe-
dron 1999, 55, 7725; b) S. D. Kuduk, R. M. DiPardo, M. G. Bock, Org. Lett.
2005, 7, 577; c) P. D. O’Shea, D. Gauvreau, F. Gosselin, G. Hughes, C.
Nadeau, A. Roy, C. S. Shultz, J. Org. Chem. 2009, 74, 4547; d) P. La-
Beaume, M. Placzek, M. Daniels, I. Kendrick, P. Ng, M. McNeel, R. Afroze,
A. Alexander, R. Thomas, A. E. Kallmerten, G. B. Jones, Tetrahedron Lett.
2010, 51, 1906; e) R. Song, W. Lin, Q. Jiang, Tetrahedron Lett. 2011, 52,
4965.
[9] For reviews on asymmetric hydrogenations of aromatic compounds,
see: a) P. J. Dyson, Dalton Trans. 2003, 2964; b) F. Glorius, Org. Biomol.
Chem. 2005, 3, 4171; c) S.-M. Lu, X.-W. Han, Y.-G. Zhou, Chin. J. Org.
Chem. 2005, 25, 634; d) Y.-G. Zhou, Acc. Chem. Res. 2007, 40, 1357; e) R.
Kuwano, Heterocycles 2008, 76, 909; f) D.-S. Wang, Q.-A. Chen, S.-M. Lu,
Received: February 20, 2014
Published online on && &&, 0000
&
&
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
4
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
COMMUNICATION
&
Synthetic Methods
R.-N. Guo, X.-F. Cai, L. Shi,* Z.-P. Chen,
Y.-G. Zhou*
&& – &&
An efficient and transition-metal-free
approach was developed to access
cedure features a triple-relay transfor-
mation of rapid dearomatization, fluori-
nation, and rearomatization processes,
which represents a conceptually novel
strategy of combining partial hydroge-
nation and electrophilic fluorination.
Synthesis of Fluorinated
a series of fluorinated heteroaromatics
in moderate to excellent yields through
formal substitution of a nitro group by
fluorine (see scheme). This one-pot pro-
Heteroaromatics through Formal
Substitution of a Nitro Group by
Fluorine under Transition-Metal-Free
Conditions
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ