Hypervalent Fluoroiodane-Triggered Synthesis of Fluoro-Azabenzoxazepines and Azaindoles

Article abstract of DOI:10.1002/ejoc.201800129

Fluorination reactions facilitated by hypervalent F-iodanes have experienced vivid attention recently, since they often lead to novel, fluorinated scaffolds not accessible with common electrophilic fluorination reagents. The fluorocyclization of styrenes equipped with an amide functionality in the ortho position using F-iodanes represents a transformation with unusual chemoselectivity. Within this context, the conversion of pyridine derivatives to fluoropyridyloxazepines, which constitutes a particular challenge due to the deactivating properties of the aza heterocycle, was accomplished in this work using the bench-stable λ³-F-benzoiodoxole under Lewis acid catalysis. The versatility of the obtained F-heterocycles as building blocks in organic synthesis was demonstrated by their straightforward conversion into azaindoles in a one-pot, three-step reaction sequence.

Full text of DOI:10.1002/ejoc.201800129

A Journal of
Accepted Article
Title: Hypervalent Fluoroiodane-triggered Synthesis of Fluoro-
Azabenzoxazepines and Azaindoles
Authors: Christoph Brunner, Anna Andries-Ulmer, Gabriel M. Kiefl, and
Tanja Gulder
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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
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the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800129
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800129
Supported by

European Journal of Organic Chemistry
10.1002/ejoc.201800129
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Hypervalent Fluoroiodane-triggered Synthesis of Fluoro-
Azabenzoxazepines and Azaindoles
Christoph Brunner, Anna Andries-Ulmer, Gabriel M. Kiefl, Tanja Gulder*
Abstract: Fluorination reactions facilitated by hypervalent F-iodanes
have experienced vivid attention recently as they mostly lead to novel,
fluorinated scaffolds not accessible with common electrophilic
fluorination reagents. The fluorocyclization of styrenes equipped with
an amide functionality in ortho position using F-iodanes represents
such a transformation exhibiting an unusual chemoselectivity. Within
this context, the conversion of pyridine derivatives to fluoro
pyridyloxazepines, which constitutes a particular challenge due to the
deactivating properties of the aza heterocycle, was accomplished in
Hypervalent fluoro iodanes are able to address these needs of
contemporary fluorine chemistry.[5] Their high reactivity together
with the chemical instability of these compounds, in particular of
the linear derivatives, however, has hampered their breakthrough
as versatile fluoro reagents for a long time. With the introduction
of the bench stable fluorobenziodoxole 1[6] in 2013,[7] a new
hypervalent iodine fluorine-transfer reagent has become available
that often offers
a
complementary reactivity and/or
chemoselectivity to common, previous F-reagents.[
7a,8]
The
3
this work using the bench-stable λ -F-benzoiodoxole under Lewis acid
reaction scope of 1, as yet explored, is capable of addressing both
intramolecular reactions, such as fluorolactonizations,[ as well
as intermolecular processes, exemplified here by the gem-
difluorinations[8d] and gem-oxyfluorinations[8b] (Scheme 1).
8a]
catalysis. The versatility of the obtained F-heterocycles as building
blocks in organic synthesis was demonstrated by their straightforward
conversion into azaindoles in
sequence.
a one-pot, three-steps reaction
Introduction
Fluorine is often named the ‘magical atom’, since its incorporation
into molecular scaffolds is in most cases accompanied with the
introduction of highly beneficial features. This characteristic
attributes to the uniqueness of fluorine compounds. It is thus not
surprising that the field of fluorination chemistry has evolved
rapidly within the last decades. Today, organo fluorine
compounds have a tremendous impact, not only on chemistry, but
also on our daily life. Fluorine-containing molecules are
[
1]
[2]
widespread, i.a., among pharmaceutical and agrochemical
products, diagnostics,[1c,1f,3] as well as materials.[4] In order to
further harness and improve the existing and to discover new
intriguing features of this compound class, the structural space of
fluorinated compounds must be continuously extended. The
perpetual development of new fluorination methods and reagents
is thus crucial to discover novel and distinct reactivities and
selectivities.
[
a]
Christoph Brunner, Dr. Anna Andries-Ulmer, Gabriel M. Kiefl, Prof.
Dr. Tanja Gulder
Department of Chemistry and Catalysis Research Center (CRC),
Technical University Munich,
Lichtenbergstrasse 4,
8
5748 Garching, Germany
Scheme 1. Selected examples for the use of F-iodane 1 in organic synthesis.
e-mail: tanja.gulder@tum.de
homepage: http://www.halogene.ch.tum.de
Results and Discussion
Supporting information of this article is available on the WWW under
http://
Our group recently demonstrated the unusual fluorination
reactivity of 1 in the conversion of o-amidyl styrenes 2. In contrast
to the common electrophilic aza fluorination agents, such as
selectfluor, employing 1 gave rise to a novel class of heterocyclic
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European Journal of Organic Chemistry
10.1002/ejoc.201800129
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products, the fluorinated benzoxazepines 3 (Scheme 1d).[9] Their
synthesis involves an unprecedented fluorination-rearrangement-
cyclization-cascade reaction.[10] To explore the general
applicability of this method, we set out to further explore the
boundaries of this transformation by expanding the substrate
scope of this fluorocyclization.
polar solvents likewise did not lead to any transformation of
starting material 4a with or without molecular sieve added (see
entries 1-2 and Table S2, SI). The significantly lowered reactivity
of the pyridyl substrates 4 towards electrophilic addition, when
compared to their benzene analogs 2, is the result of the highly
deactivated alkene moiety in
4 caused by the electron-
withdrawing properties of the pyridine ring. To test this hypothesis,
the reactivity of 1 was enhanced by adding different Lewis and
Brønsted acids to the reaction mixture (entries 3-10 and Table S1,
SI). Non-covalent interactions of the fluorine atom in 1 and the
additive should lead to a decreased electron density at the
hypervalent iodine atom and thus should activate it for the
nucleophilic attack of 4, the first step in the reaction sequence.[
Table 1. Optimization of the reaction conditions for the synthesis of
pyridyloxazepine 5a.
12]
3 2
Almost all additives tested, except for BF ·OEt (entry 8),
triggered the conversion of 4a with no starting material being
visible in the crude NMR spectra after the given time.
Nevertheless, the desired fluoro oxazepine 5a was only formed in
unsatisfying yields regardless if molecular sieve was present in
the reaction mixture or not. The best results were achieved using
trifluoroacetic acid (TFA, entry 5) giving 4a in 49% together with a
complex mixture of unidentifiable decomposition products. The
additive
time
conversion
yield of 5a
1a
4Å m. s.
-
21 h
21 h
2 h
-
-
-
2a
-
3a
AgBF c
4
>99%
>99%
>99%
>99%
>99%
19%
37%
24%
49%
37%
19%
n.d.
-
4a
5a
6a
AgBF
d
4
3 h
Lewis acid AgBF
4
(entries 3 and 4), which was already
successfully employed in the gem-difluorination of styrenes (cf.
Scheme 1b),[8d,8e] gave the ring-closed compound 5a as the only
defined product already after 2h in 37% yield. To our surprise, no
difluorination of 4a was observed.
The breakthrough in the fluoro cyclization of 4a was accomplished
by increasing the amount of the F-iodane 1 to 2.5 eq. in the
TFAd
CSAd
18 h
21 h
18 h
18 h
18 h
18 h
2 h
7a
Zn(BF
BF ·OEt
[Cu(MeCN)
[Pd(MeCN)
AgBF c
d
4 2
)
8a
d
2
3
presence of a Lewis acid (entries 11-14 and Table 2, SI). AgBF
4
9a
d
]BF
4
>99%
decomp.
>99%
>99%
>99%
6%
4
in acetonitrile showed again the highest reaction rate together
with a clean conversion of 4a to 5a. Only catalytic amounts (20
0a
BF
]
d
-
1
1
1
1
1
4
4
2
mol%) of AgBF
4
were necessary to exclusively deliver the
1b
quant.
4
benzoxazepine 5a within 3h and 63% isolated yield (entry 12). A
similar outcome was achieved using the Cu(I)-acetonitrile salt
2b
AgBF
d
4
3 h
quant. (63%)e
(
entry 13), but only after prolonged reaction times of 18h and with
3b
d
quant. (50%)e
a lower isolated amount of 5a (50%).
4
[Cu(MeCN) ]BF
4
18 h
21 h
4b
-
n.d.
Having discovered the optimum reaction conditions, we
moved on to evaluate the substrate scope of our method. The
versatility of this strategy was demonstrated in the preparation of
a focused library showing that our method is applicable to a
variety of structurally different starting materials 4 (Scheme 2).
The pyridyl heterocycles 5 were obtained, in general, in slightly
lower yields (up to 78%) than their phenyl derivatives 3.[ Starting
The reactions were carried out using pyridylstyrene 4a (1.0 eq.), fluoroiodane
and additive in MeCN (0.2 M). The reaction mixture was stirred at rt for the
allotted time and then filtered over a silica plug. After solvent evaporation the
yield was determined by H-NMR spectroscopy using an internal standard.
.2 eq. 1 was used; b2.5 eq. 1 was used; 1.0 eq. additive was used; d20
1
1
a
c
1
e
mol% additive was used; isolated yield; m.s. = molecular sieve; n.d. = not
determined.
9]
1
material 4, bearing different aryl amide fragments R ( 5e and
2
5
f) as well as substituents on the aryl portion R ( 5g and 5h),
We decided to focus on starting materials bearing nitrogen
containing heterocycles such as 4. Since the pyridyl moiety
represents a structural motif often responsible for exquisite
pharmaceutical properties,[11] we reasoned that the preparation of
such scaffolds is of high interest to the synthetic community and
thus constitutes an intriguing platform for our hypervalent F-
iodane triggered reactions. We chose pyridyl styrene 4a as our
model substrate and treated it with 1 (Table 1), first using the
conditions applied successfully for the conversion of the
corresponding aniline-derived styrenes 2.[9] However, no
conversion of 4a was achieved under these standard conditions
were tolerated in this transformation. Besides the gem-
disubstituted styrenes 4a - 4h, trisubstituted olefins, which are
usually difficult to convert in electrophilic addition reactions, are
likewise accepted as substrates. The corresponding products 5i
and 5j showed, however, a high chemical instability, attributing for
the rather low yields of 27% and 25% realized in the reaction of
4i and 4j. We also varied the position of the nitrogen in the pyridyl
ring during this evaluation process. With exception of the 4-vinyl
derivative 4c, all other pyridine derivatives 4a, 4b and 4d gave the
corresponding heterocycles 5a, 5b and 5d in good 61%-78% yield.
(
entry 1). Exchanging acetonitrile (MeCN) by polar as well as non-
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European Journal of Organic Chemistry
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FULL PAPER
Scheme 3. Possible pathways for the fluorocyclization of 4: a) involving a 1,2-
aryl shift via the phenonium ion 7 and b) following a 6-exo ring closure reaction
without 1,2-aryl migration.
The only tested substrates seemingly not following the proposed
fluorination-1,2-aryl migration-cyclization cascade are the 1,1-
diaryl substituted alkenes 4k and 4l (Scheme 4). These
compounds overall exhibited a very low reactivity towards the
electrophilic addition of the hypervalent iodane 1. Heating of the
reaction mixture to 50°C for several days was indispensable in
order to trigger any conversion at all. Under these conditions,
hydrolysis of the F-reagent 1 became a competing reaction
pathway to the fluorination of the C,C-double bond. The then in
situ formed, non-fluorinated iodane species can likewise react
with 4, but now in a direct, 6-exo cyclization mode (cf. Scheme
3b), as usually observed for the treatment of such starting
materials with common electrophiles.[9,14] This mechanism was
exclusively followed when the pyridyl amide 4k was employed and
the oxazine 6k was delivered as the only product. To corroborate
the above hypothesis, 4k was also treated with the hydroxy
analog of 1. This transformation led to the exclusive formation of
the six-membered heterocycle 6k.
Scheme 2. Substrate scope for the synthesis of fluoro azabenzoxazepines 5.
The reactions were carried out using pyridylstyrene 4 (0.20 mmol, 1.0 eq.),
fluoroiodane 1 (140 mg, 0.50 mmol, 2.5 eq.) and AgBF
4
(7.78 mg, 0.04 mmol,
2
0 mol%) in 1.00 mL MeCN (0.2 M). The reaction mixture was stirred at rt for
a
1
b
the allotted time. d.r. was determined from the crude H-NMR spectrum. NMR
yield; the shown major diastereomer of 5j was isolated in 15%; d.r. =
c
diastereomeric ratio.
It is noteworthy that all substrates 4a – 4j perform an 1,2-aryl
shift via the phenonium ion intermediate 7 during the reaction
sequence, thus solely furnishing the azabenzoxazepine scaffold
5
(Scheme 3, pathway A). Non-rearranged F-oxazine products 6,
arising from a direct attack of the activated olefin portion in 4
Scheme 3, pathway B), were not detected in the crude reaction
(
mixture. Given the electron-poor nature of the pyridine ring, the
addressed synthesis of fluoro azabenzoxazepines 5 was not
expected at the first sight, since the generation of phenonium ions
7
should be highly dependent on the electronic properties of the
aryl portion with regard to stabilization/destabilization of the cation.
Interestingly, such substrate independence for the aryl
migration has been observed already earlier,
a
[
8a,8d,8e,9,13]
i.a., for the
fluoro cyclization of the phenyl derivatives 2. The reactions there
proceeded equally well for both types of substrates 2, those
bearing electron-rich and electron-poor aryl rings.[9] In our opinion,
the +π-effect of the amide nitrogen significantly contributes to the
stabilization of the positive charge in 7 by the formation of 8. This
effect guarantees for the excellent chemo- and regioselectivity
observed in the fluorination of 2 and 3 regardless of the electronic
nature of the phenyl ring.
Scheme 4. Reactions of aryl-substituted azastyrenes 4. The
reactions were carried out using pyridylstyrene 4 (0.20 mmol, 1.0
eq.), fluoroiodane 1 (140 mg, 0.50 mmol, 2.5 eq.) and AgBF
4
(7.78 mg, 0.04 mmol, 20 mol%) in 1.00 mL MeCN (0.2 M). The
a
reaction mixture was stirred at 50 °C for 2-3 days. NMR yield;
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European Journal of Organic Chemistry
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b
1
the ratio of 5l : 6l was determined from the H-NMR spectrum of
power and uniqueness of hypervalent F-iodanes, a reagent class
that will continue to have a decisive impact on fluorine chemistry
in the future.
1
the crude H-NMR spectrum.
For the pyridine benzamide substrate 4l a 59 : 41-mixture of both
the fluorinated seven-membered ring product 5l and alcohol 6l
was obtained in 37% yield,[15] showing nicely the two pathways Experimental Section
operative. If the reaction was performed under anhydrous
conditions, in order to steer the product selectivity towards the
fluoro benzoxazepines 5l, the desired product 5l was built only in
traces.
General information: Solvents used in reactions were p.A. grade.
Solvents for chromatography were technical grade and distilled prior to use.
Anhydrous dichloromethane, diethylether and THF were obtained from a
MBraun MB-SPS 800 solvent purification system. Other dry solvents were
obtained from Fluka and Acros in the highest purity available and used
without further purification. Reagents were purchased at the highest
commercial quality and used without further purification. The fluoroiodane
Having the structurally new azabenzoxazepines 5 in hands,
we were curious to verify if these compounds can be utilized in
further transformations. Hydrolysis of 5a under basic conditions
resulted in the formation of the benzyl ketone 9a together with
significant amounts of the 2-methyl azaindole 10a in overall
quantitative yield (Scheme 5). Intrigued by these results, we set
out to optimize the reaction conditions to convert the oxazepines
1
was purchased from Fluorochem and used without further purification.
1
Yields refer to chromatographically and spectroscopically ( H NMR)
homogeneous materials, unless otherwise stated. Reactions were
monitored by thin layer chromatography (TLC) carried out on Merck silica
gel aluminium plates with F-254 indicator using UV light as the visualizing
agent and an acidic solution of anisaldehyde, phosphomolybdic acid, or
ceric ammonium molybdate, and heat as developing agents. Silica gel
5
directly to the corresponding heterocycles 10. We reasoned that
the development of such a one-pot synthesis constitutes a highly
rewarding endeavor, as azaindoles 10[11b,16] represent an
important compound class due to its significance as
pharmaceuticals.[17] The best results were realized by heating 5 in
Merck 60 (particle size 40
– 60 µm) was used for flash column
chromatography. Solvent mixtures are understood as volume/volume.
NMR spectra were recorded on Bruker AV300, Bruker AV400, Bruker
AV500, or Bruker AV500-cryo spectrometers. The spectra were calibrated
6
M NaOH. Subsequent treatment of the crude mixture with 6M HCl
using residual undeuterated solvent as an internal reference (CHCl3
@
@
again at elevated temperatures was necessary to complete the
cyclocondensation of the ketone intermediate 9 (for further details
on the optimization reactions see Table S3, SI). The last reaction
step was accompanied by N-debenzoylation, giving rise to the
unprotected indoles 11 in
sequence with excellent isolated yields, reaching from 97% to
quantitative for the selected examples shown in Scheme 5.
7.26 ppm, MeCN-d
3
@ 1.94 ppm and 2.13 ppm 1H NMR, CHCl
3
77.00 ppm, MeCN-d
3
@ 1.32 ppm and 128.1 ppm 13C NMR). The following
abbreviations (or combinations thereof) were used to explain the
multiplicities: s = singlet, d = doublet, dd = doublet of doublets, t = triplet,
dt = doublet of triplets, q = quartet, m = multiplet, br = broad. In addition,
the following abbreviations were used: EtOAc = ethyl acetate, MeCN =
acetonitrile, TLC = thin layer chromatography, rt = room temperature, sat
a one-pot, three-steps reaction
=
4
saturated, Bz = Benzoyl. IR spectra were recorded on a JASCO FT-IR-
100 (ATR) and are reported in terms of frequency of absorption (cm ).
-
1
Mass spectra were conducted on a Finnigan MAT SSQ 7000 (MS-EI, 70
eV; CI, 100 eV), or a Thermo Scientific LTQ-FT ultra and ThermoFisher
Scientific LTQ Orbitrap XL spectrometer (ESI HRMS). The following
method was used for separation: 60 °C 3 min, 15 °C/min → 250 °C, 250 °C
5
min.
General Procedure for the Synthesis of Pyridyl Oxazepines 5 (GP-A):
The corresponding pyridyl styrene 4 (0.20 mmol, 1.0 eq.) was dissolved in
MeCN (1.0 mL, 0.2 M) and fluoroiodane 1 (140 mg, 0.50 mmol, 2.5 eq.)
4
together with AgBF (7.78 mg, 0.04 mmol, 20 mol%) were added and the
mixture was stirred at room temperature until all the starting material was
consumed according to TLC. The solvent was removed under reduced
pressure and the crude product was purified by column chromatography
on silica gel to yield the corresponding products 5.
Scheme 5. Transformation of oxazepines 5 into azaindoles 5.
4
-Fluoro-4-methyl-2-phenyl-4,5-dihydro-6N-pyridooxazepine
(5a):
Following GP-A using 4a (47.7 mg, 0.20 mmol), product 5a was isolated
after 3 h at room temperature as a brown oil (32.3 mg, 0.13 mmol) in 63%
Conclusions
yield. R
f
= 0.65 (EtOAc/hexanes 65:35); 1H NMR (500 MHz, CDCl
3
) δ =
8
7
3
.38 (d, J = 4.7 Hz, 1H), 8.19 (d, J = 7.7 Hz, 2H), 7.61 (d, J = 7.9 Hz, 1H),
.50 – 7.55 (m, 1H), 7.42 – 7.49 (m, 2H), 7.31 (dd, J = 8.1, 4.6 Hz, 1H),
.41 – 3.52 (m, 2H), 1.78 (d, J = 17.8 Hz, 3H) ppm; 13C NMR (126 MHz,
In summary, we succeeded to extend the substrate scope of
our unusual fluorocyclization triggered by the hypervalent λ F-
3
iodane 1. Employing the reaction conditions developed here,
even highly deactivated styrenes 4 can be converted into the
corresponding seven-membered ring products 5 in very good
yields. Despite the electron-poor nature of the aryl moiety in 4, all
transformations proceeded via a fluorination-aryl migration-
cyclization mechanism. This again impressively demonstrates the
CDCl
133.5, 133.2, 131.9, 129.1, 128.5, 123.6, 121.8 (d, J = 229.4 Hz), 45.57 (d,
J = 30.0 Hz), 25.22 (d, J = 29.3 Hz) ppm; 19F NMR (471 MHz, CDCl
) δ =
73.51 (dtd, J = 24.0, 17.7, 8.9 Hz) ppm; IR (ATR): 3060, 1627, 1203, 1188,
3
) δ = 153.9 (d, J = 2.2 Hz), 147.4 (d, J = 11.3 Hz), 146.3, 140.0,
3
–
-
1
1105, 1061, 896, 768, 739, 691, 675 cm ; MS (EI, 70 eV): m/z (%) = 257
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European Journal of Organic Chemistry
10.1002/ejoc.201800129
FULL PAPER
+
+
(
2
100) [M+H] ; HRMS (ESI) calcd for C15
57.1085.
H
14FN
2
O [M+H] 257.1085, found
4-Fluoro-4,7-methyl-2-phenyl-4,5-dihydro-6N-pyridooxazepine (5g):
Following GP-A using 4g (50.5 mg, 0.20 mmol), product 5g was isolated
after 18 h at room temperature as a yellow oil (34.0 mg, 126 µmol) in 63%
yield. R
f
= 0.31 (EtOAc/hexanes 20:80); 1H NMR (400 MHz, CDCl
.15 – 8.19 (m, 2H), 7.49 – 7.54 (m, 2H), 7.43 – 7.48 (m, 2H), 7.17 (d, J =
.1 Hz, 1H), 3.38 – 3.53 (m, 2H), 2.58 (s, 3H), 1.80 (d, J = 17.8 Hz, 3H)
) δ = 155.3, 153.1 (d, J = 2.2 Hz), 146.5
d, J = 11.0 Hz), 137.4, 133.8, 133.7, 131.7, 129.0, 128.5, 123.2, 121.4 (d,
J = 228.8 Hz), 45.67 (d, J = 29.8 Hz), 25.37 (d, J = 29.2 Hz), 24.16 ppm;
19F NMR (376 MHz, CDCl
) δ = –74.56 (br) ppm; IR (film) 휐̃ 푚푎푥 = 1628,
459, 1387, 1243, 1208, 1105, 1059, 896, 832, 773, 758, 691 cm ; MS
3
) δ =
4
-Fluoro-4-methyl-2-phenyl-4,5-dihydro-7N-pyridooxazepine
(5b):
8
8
Following GP-A using 4b (47.7 mg, 0.20 mmol), product 5b was isolated
after 48 h at 60 °C as a colorless oil (40.0 mg, 0.16 mmol) in 78% yield. R
f
ppm; 13C NMR (126 MHz, CDCl
1
3
=
=
–
1
0.51 (EtOAc/hexanes 65:35); H NMR (300 MHz, CDCl
3
) δ = 8.57 (d, J
(
5.3 Hz, 1H), 8.47 (s, 1H), 8.14 – 8.24 (m, 2H), 7.52 – 7.60 (m, 1H), 7.41
7.51 (m, 2H), 7.22 (d, J = 5.3 Hz, 1H), 3.25 (dd, 14.4, 7.4, 1H) 3.18 (dd,
4.6, 5.2, 1H), 1.75 (d, J = 17.7 Hz, 3H) ppm; 13C NMR (101 MHz, CDCl
3
3
)
-
1
1
δ = 157.4, 154.9, 145.8 (d, J = 15.8 Hz), 133.2, 132.5, 129.8, 129.2, 128.7,
27.8, 121.5 (d, J = 231.1 Hz), 39.93 (d, J = 30.9 Hz), 25.33 (d, J = 28.8
+
+
(
EI, 70 eV): m/z (%) = 270 (94) [M] , 250 (57) [M-HF] , 221 (36) [M-HF-
1
+
+
+
+
Hz) ppm; 9F NMR (471 MHz, CDCl
1
2Me] , 208 (87), 145 (19) [M-HF-PhCO] , 105 (100) [PhCO] , 77 (47) [Ph] ;
3
) δ = –75.67 (s) ppm; IR (ATR): 1594,
+
HRMS (ESI) calcd for C16
H16FN
2
O [M+H] 271.1241, found 271.1242.
1577, 1176, 1062, 766, 719, 691, 669; MS (EI, 70 eV): m/z (%) = 256 (85)
+
+
H14FN
2
O [M+H]+
[M] , 194 (100) [M-C
2 3
H
FO] ; HRMS (ESI) calcd for C15
257.1085, found 257.1086.
8-Chloro-4-fluoro-4-metyl-2-phenyl-4,5-dihydro-6N-pyridooxazepine
5h): Following GP-A using 4h (54.5 mg, 0.20 mmol), product 5h was
(
isolated after 14 h at room temperature as a yellow oil (33.7 mg, 116 µmol)
4
-Fluoro-4-methyl-2-phenyl-4,5-dihydro-8N-pyridooxazepine
(5d):
1
in 58% yield. R
f
= 0.58 (EtOAc/hexane 20:80); H NMR (300 MHz, CDCl
3
)
Following GP-A using 4d (47.7 mg, 0.20 mmol), product 5d was isolated
δ = 8.33 (d, J = 2.3 Hz, 1H), 8.20 – 8.13 (m, 2H), 7.62 (d, J = 2.3 Hz, 1H),
7.57 – 7.50 (m, 1H), 7.50 – 7.41 (m, 2H), 3.44 (d, J = 7.0 Hz, 2H), 1.78 (d,
after 7 h at room temperature as a yellow oil (31.2 mg, 0.12 mmol) in 61%
= 0.62 (EtOAc/hexanes 65:35); 1H NMR (300 MHz, CDCl
yield. R ) δ =
f
3
J = 17.8 Hz, 3H) ppm; 13C NMR (126 MHz, CDCl
3
) δ = 154.6 (d, J = 2.1
8
.55 (dd, J = 4.9, 1.8 Hz, 1H), 8.23 – 8.31 (m, 2H), 7.51 – 7.61 (m, 1H),
.40 – 7.52 (m, 3H), 7.12 (dd, J = 7.4, 4.9 Hz, 1H), 3.20 (dd, J = 14.4, 8.2
Hz), 145.7 (d, J = 11.1 Hz), 144.9, 140.6, 133.2, 132.9, 132.2, 131.6, 129.2,
128.5, 121.1 (d, J = 229.8 Hz), 45.17 (d, J = 30.1 Hz), 25.30 (d, J = 29.1
7
Hz, 1H), 3.10 (dd, J = 14.4, 4.0 Hz, 1H), 1.71 (d, J = 17.7 Hz, 3H) ppm; 13C
Hz) ppm; 19F NMR (471 MHz, CDCl
ppm; IR (film) 휐̃ 푚푎푥 = 1626, 1569, 1448, 1276, 1198, 1182, 1106, 1060,
) δ = –74.86 (tq, J = 17.2, 8.7, 7.1 Hz)
3
NMR (75 MHz, CDCl ) δ = 156.9, 155.7 (d, J = 2.3 Hz), 149.1, 137.9, 133.0,
3
1
4
32.3, 129.6, 128.4, 123.1 (d, J = 9.42 Hz), 122.4 (d, J = 229.1 Hz), 120.9,
-
1
+
1.51 (d, J = 31.5 Hz), 24.80 (d, J = 29.7 Hz) ppm; 19F NMR (471 MHz,
901, 885, 767, 690 cm ; MS (EI, 70 eV): m/z (%) = 290 (66) [M] , 270 (38)
+
+
+
[
M-HF] , 228 (85), 165 (13) [M-HF-COPh] , 105 (100) [PhCO] , 77 (43)
[Ph] ; HRMS (ESI) calcd for C15
CDCl
3
) δ = –73.82 (dddd, J = 26.0, 21.8, 15.3, 6.2 Hz) ppm; IR (ATR):
+
O [M+H]+ 291.0695, found
-
1
H
13ClFN
2
3
101, 1652, 1595, 1578, 1189, 1132, 1084, 797, 701 cm ; MS (EI, 70 eV):
m/z (%) = 257 (100) [M+H] ; HRMS (ESI) calcd for C15H14FN
2
O [M+H]+
+
291.1693.
257.1085, found 257.1085.
4,5-Dimethyl-4-fluoro-2-phenyl-4,5-dihydro-6N-pyridooxazepine (5i):
Following GP-A using 4i (50.5 mg, 0.20 mmol), product 5i was isolated
after 18 h at room temperature as a yellow oil (14.6 mg, 54.0 µmol) in 27%
4
-Fluoro-4-methyl-2-(4’-methoxyphenyl)-4,5-dihydro-6N-
pyridooxazepine (5e): Following GP-A using 4e (53.7 mg, 0.20 mmol),
product 5e was isolated after 3 h at room temperature as a yellow oil
1
yield and d.r. = 70:30. R
CDCl
8
1
f
= 0.38 (EtOAc/hexane 20:80); H NMR (400 MHz,
1
3
) δ = 8.42 (dd, J = 4.7, 1.6 Hz, 1H), 8.38 (dd, J = 4.7, 1.6 Hz, 1H),
.23 – 8.16 (m, 3H), 7.68 (dd, J = 8.0, 1.6 Hz, 1H), 7.64 (dd, J = 7.9, 1.7 Hz,
H), 7.56 – 7.49 (m, 2H), 7.49 – 7.43 (m, 3H), 7.30 (ddd, J = 8.0, 4.7, 2.0
(
35.0 mg, 0.12 mmol) in 61% yield. R
NMR (300 MHz, CDCl
H), 7.58 (dd, J = 8.0, 1.6 Hz, 1H), 7.31 (dd, J = 8.0, 4.8 Hz, 1H), 6.96 (d,
f
= 0.50 (EtOAc/hexanes 40:60); H
3
) δ = 8.36 (dd, J = 4.8, 1.6 Hz, 1H), 8.20 – 8.07 (m,
2
Hz, 2H), 3.72 (p, J = 7.4 Hz, 1H), 3.60 – 3.49 (m, 1H), 1.70 (d, J = 17.9 Hz,
3H), 1.60 (d, J = 18.8 Hz, 2H), 1.45 (d, J = 7.1 Hz, 3H), 1.35 (d, J = 7.3 Hz,
J = 9.0 Hz, 2H), 3.88 (s, 3H), 3.58 – 3.35 (m, 2H), 1.76 (d, J = 17.8 Hz,
H) ppm; 13C NMR (126 MHz, CDCl
3
1
3
) δ = 162.9, 154.3 (d, J = 2.5 Hz),
47.3 (d, J = 11.6 Hz), 145.7, 140.6, 133.13, 131.07, 125.8, 123.6, 122.1
2
1
H) ppm; 13C NMR (126 MHz, CDCl
51.1, 149.6 (d, J = 2.2 Hz), 146.1 (d, J = 13.5 Hz), 142.8, 139.6, 137.8,
3
) δ = 153.0, 151.9 (d, J = 12.8 Hz),
(
d, J = 229.6 Hz), 113.9, 55.61, 45.23 (d, J = 30.3 Hz), 25.10 (d, J = 29.2
Hz) ppm; 9F NMR (471 MHz, CDCl
1
136.2, 134.1, 133.8, 133.5, 131.8, 131.6, 129.0, 128.8, 128.5, 128.4, 127.6
(d, J = 178.8 Hz), 123.3, 123.2, 118.0 (d, J = 223.1 Hz), 51.19 (d, J = 25.8
Hz), 47.35 (d, J = 26.6 Hz), 25.95 (d, J = 30.3 Hz), 21.98 (d, J = 29.1 Hz),
3
) δ = –72.97 (br) ppm; IR (film) 휐̃
푚푎푥
=
-
1
1
604, 1508, 1250, 1167, 1105, 1027, 896, 812 cm ; MS (EI, 70 eV): m/z
+
+
(%) = 286 (94) [M] , 266 (6) [M-HF] , 224 (13), 209 (34), 135 (100) [M-
12.39, 11.39 (d, J = 2.2 Hz) ppm; 19F NMR (376 MHz, CDCl
+
+
+
3
) δ = –77.89
MeOPhCO] , 107 (6) [PhOMe] , 77 (15) [Ph] ; HRMS (ESI) calcd for
C
+
(br), –88.81 (qd, J = 18.6, 8.0 Hz) ppm; Due to broad signals of the minor
diastereomer in the 13C and 19FNMR spectra, not all coupling signals could
H16FN O
16 2 2
[M+H] 287.1190; found 287.1190.
be determined. IR (film) 휐̃
= 1652, 1629, 1431, 1287, 1240, 1183, 1068,
푚푎푥
4
-Fluoro-4-methyl-2-(3-thiophen)-4,5-dihydro-6N-pyridooxazepine
-
1
+
9
01, 770, 693 cm ; MS (EI, 70 eV): m/z (%) = 270 (40) [M] , 250 (31) [M-
(
5f): Following GP-A using 4f (48.9 mg, 0.20 mmol), product 5f was
+
+
+
HF] , 221 (19), 207 (100), 105 (58) [PhCO] , 77 (33) [Ph] ; HRMS (ESI)
isolated after 2 h at room temperature as a yellow oil (37.0 mg, 0.14 mmol)
in 71% yield. R
+
2
calcd for C16H16FN O [M+H] 271.1241, found 271.1242.
1
f
= 0.45 (EtOAc/hexanes 65:35); H NMR (500 MHz, CDCl
3
)
δ = 8.36 (dd, J = 4.8, 1.6 Hz, 1H), 8.05 (dd, J = 3.1, 1.1 Hz, 1H), 7.68 (dd,
J = 5.1, 1.2 Hz, 1H), 7.57 (dd, J = 8.0, 1.6 Hz, 1H), 7.34 (dd, J = 5.1, 3.1
Hz, 1H), 7.30 (dd, J = 8.0, 4.8 Hz, 1H), 3.47 (dd, 14.3, 7.7, 1H) 3.43 (dd,
4
,5-Dimethyl-4-fluoro-2-phenyl-4,5-dihydro-8N-pyridooxazepine (5j):
Following GP-A using 4j (50.5 mg, 0.20 mmol) the product 5j was
produced in 25% yield and a diastereomeric mixture of 59:41 after 47 h at
room temperature. The major diastereomer of product 5h was isolated as
a colorless oil (8.20 mg, 30.2 μmol) in 15% yield; The minor diastereomer
4.1, 5.9, 1H), 1.75 (d, J = 17.8 Hz, 3H) ppm; 13C NMR (126 MHz, CDCl
1
3
)
δ = 150.6 (d, J = 2.3 Hz), 147.4 (d, J = 11.3 Hz), 146.2, 140.1, 137.2, 133.2,
1
2
=
7
30.8, 127.9; 126.3, 123.6, 121.7 (d, J = 229.6 Hz), 45.51 (d, J = 30.1 Hz),
5.19 (d, J = 29.1 Hz) ppm; 19F NMR (471 MHz, CDCl
) δ = –73.80 (dtd, J
of 5i could not be isolated due to elimination followed by decomposition
3
1
during purification. R
CDCl
= 7.6, 1.8 Hz, 1H), 7.54 – 7.41 (m, 3H), 7.14 (dd, J = 7.5, 4.8 Hz, 1H), 3.33
p, J = 7.3 Hz, 1H), 1.57 (d, J = 18.7 Hz, 3H), 1.32 (d, J = 7.2 Hz, 3H) ppm;
f
= 0.27 (Pentane/EtOAc 50:50); H NMR (300 MHz,
24.6, 17.5, 6.9 Hz) ppm; IR (film) 휐̃
= 1627, 1247, 1193, 1107, 891,
푚푎푥
-
1
+
3
) δ = 8.56 (dd, J = 4.8, 1.9 Hz, 1H), 8.32 – 8.26 (m, 2H), 7.57 (dd, J
92 cm ; MS (ESI): m/z (%) = 263 [M+H] ; HRMS (ESI) calcd for
+
C
13 2
H12FN OS [M+H] 263.0649, found 263.0648.
(
1
3C NMR (101 MHz, CDCl
3
) δ = 154.2, 151.6, 148.8, 138.1, 133.4, 132.0,
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800129
FULL PAPER
1
29.4, 128.6 (d, J = 9.9 Hz), 128.4, 120.9, 118.6 (d, J = 224.0 Hz), 46.9 (d,
J = 26.1 Hz), 26.1 (d, J = 30.6 Hz), 12.2 (d, J = 2.3 Hz) ppm; 19F NMR (376
MHz, CDCl ) δ – 87.32 (qd, J = 18.9, 7.6 Hz) ppm; IR (film) 휐̃ 푚푎푥 = 3058,
987, 2924, 2853, 1652, 1577, 1428, 1285, 1263, 1207, 1124, 911, 780,
This work was funded by the Emmy-Noether (DFG, GU 1134-3)
and Heisenberg (DFG, GU 1134-4) program of the German
Research Foundation (DFG).
3
2
6
-
1
+
95 cm ; MS (EI, 70 eV): m/z (%) = 270 (90) [M] , 207 (100), 105 (58);
+
HRMS (ESI) calcd for C16
H16FN
2
O [M+H] 271.1241; found 271.1240.
Keywords: fluorinations • hypervalent iodine • fluoro
benzoxazepines • azaindoles
2,4-Diphenyl-4,5-dihydropyrido[3,2-d][1,3]oxazepin-4-ol
(6k):
Following GP-A using 4k (60.1 mg, 0.20 mmol), product 6k was isolated
after stirring for 3 d at 50 °C as a colorless oil (43.7 mg, 0.14 mmol) in 69%
= 0.67 (EtOAc/hexanes 65:35); 1H NMR (300 MHz, CDCl
[1]
a) D. E. Yerien, S. Bonesi, A. Postigo, Org. Biomol. Chem. 2016, 14,
yield. R
.49 (dd, J = 4.8, 1.6 Hz, 1H), 8.33 – 8.21 (m, 2H), 7.64 (dd, J = 8.0, 1.6
f
3
) δ =
8398-8427; b) E. A. Ilardi, E. Vitaku, J. T. Njardarson, J. Med. Chem.
8
2
014, 57, 2832-2842; c) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J.
Hz, 1H), 7.59 – 7.43 (m, 3H), 7.29 – 7.21 (m, 3H), 7.40 – 7.29 (m, 3H),
4
.60 (d, J = 11.8 Hz, 1H), 4.39 (d, J = 11.8 Hz, 1H), 3.53 (s, 1H) ppm; 13C
Donnelly, N. A. Meanwell, J. Med. Chem. 2015, 58, 8315−8359; d) K.
Mueller, C. Faeh, F. Diederich, Science 2007, 317, 1881-1886; e) J.
Wang, M. Sanchez-Rosello, J. L. Acena, C. del Pozo, A. E. Sorochinsky,
S. Fustero, V. A. Soloshonok, H. Liu, Chem. Rev. 2014, 114, 2432-2506;
f) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
NMR (75 MHz, CDCl
3
) δ = 157.6, 147.0, 146.7, 139.5, 136.4, 132.4, 132.2,
1
31.8, 128.6, 128.6, 128.6, 128.5, 125.8, 124.6, 83.66, 68.69 ppm; IR (film)
-
1
휐̃ 푚푎푥 = 3356, 1616, 1564, 1432, 1263, 696 cm ; MS (EI, 70 eV): m/z (%) =
+
[M+H]+ 317.1285,
317 (100) [M+H] ; HRMS (ESI) calcd for C20
17 2 2
H N O
2008, 37, 320-330.
found 317.1284.
[
[
2]
3]
a) P. Jeschke, ChemBioChem 2004, 5, 570-589; b) F. Leroux, P.
Jeschke, M. Schlosser, Chem. Rev. 2005, 105, 827-856; c) P. Jeschke,
Pest Manage. Sci. 2010, 66, 10-27; d) P. Jeschke, T. Kaiho, Iodine Chem.
Appl. 2015, 439-455.
General Procedure for the Synthesis of Indoles (GP-B): The pyridyl
azepine 5 (0.10 mmol, 1.0 eq.) was dissolved in 1,4-dioxane (0.5 mL, 0.2
M) and 6M NaOH (0.5 mL, 0.2M) and the reaction mixture was heated to
a) P. W. Miller, N. J. Long, R. Vilar, A. D. Gee, Angew. Chem., Int. Ed.
80 °C until all the starting material was consumed according to TLC. The
2008, 47, 8998-9033; b) M. Tredwell, V. Gouverneur, Angew. Chem., Int.
solvent was removed under reduced pressure and the crude product was
dissolved in 6M HCl (1.0 mL, 0.1M) and again stirred at 80 °C. Upon
Ed. 2012, 51, 11426-11437.
[
[
4]
5]
R. Berger, G. Resnati, P. Metrangolo, E. Weber, J. Hulliger, Chem. Soc.
Rev. 2011, 40, 3496-3508.
completion, the reaction was neutralized with 10% aq. NH
aqueous phase was extracted with CH Cl . The combined organic layers
were dried over Na SO , filtered and the organic solvent was removed
3
and the
2
2
a) S. V. Kohlhepp, T. Gulder, Chem. Soc. Rev. 2016, 45 6270-6288; b)
A. M. Arnold, A. Ulmer, T. Gulder, Chem. Eur. J. 2016, 22, 8728 –8739;
c) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016, 116, 3328-3435; d)
P. A. Champagne, J. Desroches, J.-D. Hamel, M. Vandamme, J.-F.
Paquin, Chem. Rev. 2015, 115, 9073-9174.
2
4
under reduced pressure. The crude product was purified by column
chromatography on silica gel to yield the corresponding indoles 11.
2
(
-Methyl-1H-pyrrolo[3,2-b]pyridine (11a):[18] Following GP-B using 5a
25.6 mg, 0.10 mmol), product 11a was isolated after stirring for 48 h at
[
[
6]
7]
C. Y. Legault, J. Prevost, Acta Crystallogr., Sect. E 2012, 68, 1238.
a) G. C. Geary, E. G. Hope, K. Singh, A. M. Stuart, Chem. Commun.
8
0 °C as a brown oil (13.2 mg, 0.10 mmol) in quantitative yield. R
f
= 0.22
2013, 49, 9263-9265; b) V. Matoušek, E. Pietrasiak, R. Schwenk, A.
1
(EtOAc/hexanes 65:35); H NMR (300 MHz, CDCl
3
) δ = 9.04 (s, 1H), 8.36
Togni, J. Org. Chem. 2013, 78, 6763-6768.
(dd, J = 4.8, 1.4 Hz, 1H), 7.59 (dt, J = 8.0, 1.1 Hz, 1H), 7.02 (dd, J = 8.1,
[
8]
a) G. C. Geary, E. G. Hope, A. M. Stuart, Angew. Chem., Int. Ed. 2015,
4
.8 Hz, 1H), 6.42 (s, 1H), 2.50 (d, J = 0.9 Hz, 3H) ppm; MS (EI, 70 eV):
54, 14911-14914; b) W. Yuan, L. Eriksson, K. J. Szabó, Angew. Chem.,
+
m/z (%) = 132 (68) [M] , 131 (100).
Int. Ed. 2016, 55, 8410-8415; c) N. O. Ilchenko, M. A. Cortes, K. J. Szabó,
ACS Catal. 2016, 6, 447-450; d) N. O. Ilchenko, B. O. A. Tasch, K. J.
Szabó, Angew. Chem., Int. Ed. 2014, 53, 12897-12901; e) N. O. Ilchenko,
K. J. Szabó, J. Fluorine Chem. 2017, 203, 104-109; f) W. Yuan, K. J.
Szabó, Angew. Chem., Int. Ed. 2015, 54, 8533-8537; g) N. O. Ilchenko,
M. Hedberg, K. J. Szabó, Chem. Sci. 2017, 8, 1056-1061.
2
5
8
,3-Dimethyl-1H-pyrrolo[3,2-b]pyridine (11i):[19] Following GP-B using
i (27.0 mg, 0.10 mmol), product 11i was isolated after stirring for 20 h at
0 °C as colorless crystals (14.2 mg, 97.1 μmol) in 97% yield. R = 0.18
f
(
EtOAc/hexanes 65:35); m.p. = >230 °C (DCM); 1H NMR (300 MHz,
CDCl ) δ = 8.39 (dd, J = 4.9, 1.4 Hz, 1H), 8.11 (br s, 1H), 7.54 (dd, J = 8.1,
.4 Hz, 1H), 7.02 (dd, J = 8.0, 4.7 Hz, 1H), 2.44 (s, 3H), 2.33 (s, 3H) ppm;
3
[
[
9]
A. Ulmer, C. Brunner, A. M. Arnold, A. Poethig, T. Gulder, Chem. Eur. J.
1
2
016, 22, 3660-3664.
10] T. Yan, B. Zhou, X.-S. Xue, J.-P. Cheng, J. Org. Chem. 2016, 81, 9006-
011.
+
MS (EI, 70 eV): m/z (%) = 146 (92) [M] , 145 (100).
9
2
5
8
0
,3-Dimethyl-1H-pyrrolo[2,3-b]pyridine (11j):[20] Following GP-B using
j (27.0 mg, 0.10 mmol), product 11j was isolated after stirring for 48 h at
[11] a) E. Vitaku, D. T. Smith, J. T. Njardarson, J. Med. Chem. 2014, 57,
10257-10274; b) C. Cabrele, O. Reiser, J. Org. Chem. 2016, 81, 10109-
10125.
0 °C as colorless crystals (14.6 mg, 0.10 mmol) in quantitative yield. R
.52 (Pentane/EtOAc 50:50); m.p. = 127 °C (DCM); 1H NMR (300 MHz,
) δ = 11.13 (br s, 1H), 8.20 (dd, J = 4.8, 1.2 Hz, 1H), 7.77 (dd, J =
.8, 1.4 Hz, 1H), 7.02 (dd, J = 7.8, 4.8 Hz, 1H), 2.46 (s, 3H), 2.23 (d, J =
f
=
[12] B. Zhou, T. Yan, X.-S. Xue, J.-P. Cheng, Org. Lett. 2016, 18, 6128-6131.
[13] a) A. C. Boye, D. Meyer, C. K. Ingison, A. N. French, T. Wirth, Org. Lett.
2003, 5, 2157-2159; b) F. V. Singh, J. Rehbein, T. Wirth, Chem. Open
2012, 1, 245-250; c) L. Fra, A. Millan, J. A. Souto, K. Muñiz, Angew.
Chem., Int. Ed. 2014, 53, 7349-7353.
CDCl
3
7
0
+
.6 Hz, 3H) ppm; MS (EI, 70 eV): m/z (%) = 146 (59) [M] , 145 (100), 131
(
35).
[
14] a) V. Rauniyar, A. D. Lackner, G. L. Hamilton, F. D. Toste, Science 2011,
34, 1681-1684; b) Y.-M. Wang, J. Wu, C. Hoong, V. Rauniyar, F. D.
3
Toste, J. Am. Chem. Soc. 2012, 134, 12928-12931.
Acknowledgements
[
[
15] Products 5l and 6l decomposed rapidly upon isolation and purification.
16] For selected examples on the synthesis of azaindoles 10 see ref. 17e
and: a) S. Ortgies, A. Breder, Org. Lett. 2015, 17, 2748-2751; b) H. A.
Sharma, M. Todd Hovey, K. A. Scheidt, Chem. Commun. 2016, 52,
9283-9286; c) M. Livecchi, G. Calvet, F. Schmidt, J. Org. Chem. 2012,
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800129
FULL PAPER
7
7, 5006-5016; d) M. McLaughlin, M. Palucki, I. W. Davies, Org. Lett.
Ceballos-Picot, M. Noble, J. Endicott, J.-M. Vierfond, L. Meijer, J. Med.
Chem. 2003, 46, 222-236; g) M. H. Norman, N. Chen, Z. Chen, C. Fotsch,
C. Hale, N. Han, R. Hurt, T. Jenkins, J. Kincaid, L. Liu, Y. Lu, O. Moreno,
V. J. Santora, J. D. Sonnenberg, W. Karbon, J. Med. Chem. 2000, 43,
4288-4312; h) F. Pin, F. Buron, F. Saab, L. Colliandre, S. Bourg, F.
Schoentgen, R. Le Guevel, C. Guillouzo, S. Routier, MedChemComm
2011, 2, 899-903; i) R. Rai, A. Kolesnikov, P. A. Sprengeler, S. Torkelson,
T. Ton, B. A. Katz, C. Yu, J. Hendrix, W. D. Shrader, R. Stephens, R.
Cabuslay, E. Sanford, W. B. Young, Bioorg. Med. Chem. Lett. 2006, 16,
2270-2273; j) D. P. Power, O. Lozach, L. Meijer, D. H. Grayson, S. J.
Connon, Bioorg. Med. Chem. Lett. 2010, 20, 4940-4944.
2006, 8, 3307-3310; e) J.-Y. Merour, S. Routier, F. Suzenet, B. Joseph,
Tetrahedron 2013, 69, 4767-4834; f) S. H. Spergel, D. R. Okoro, W. Pitts,
J. Org. Chem. 2010, 75, 5316-5319; g) D. Thomae, M. Jeanty, J. Coste,
G. Guillaumet, F. Suzenet, Eur. J. Org. Chem. 2013, 2013, 3328-3336;
h) A. Frischmuth, P. Knochel, Angew. Chem., Int. Ed. 2013, 52, 10084-
10088; i) N. M. Barl, E. Sansiaume-Dagousset, K. Karaghiosoff, P.
Knochel, Angew. Chem., Int. Ed. 2013, 52, 10093-10096.
[
17] a) S. Naud, I. M. Westwood, A. Faisal, P. Sheldrake, V. Bavetsias, B.
Atrash, K.-M. J. Cheung, M. Liu, A. Hayes, J. Schmitt, A. Wood, V. Choi,
K. Boxall, G. Mak, M. Gurden, M. Valenti, A. de Haven Brandon, A.
Henley, R. Baker, C. McAndrew, B. Matijssen, R. Burke, S. Hoelder, S.
A. Eccles, F. I. Raynaud, S. Linardopoulos, R. L. M. van Montfort, J.
Blagg, J. Med. Chem. 2013, 56, 10045-10065; b) V. Bavetsias, A. Faisal,
S. Crumpler, N. Brown, M. Kosmopoulou, A. Joshi, B. Atrash, Y. Perez-
Fuertes, J. A. Schmitt, K. J. Boxall, R. Burke, C. Sun, S. Avery, K. Bush,
A. Henley, F. I. Raynaud, P. Workman, R. Bayliss, S. Linardopoulos, J.
Blagg, J. Med. Chem. 2013, 56, 9122-9135; c) L. C. Cooper, G. G.
Chicchi, K. Dinnell, J. M. Elliott, G. J. Hollingworth, M. M. Kurtz, K. L.
Locker, D. Morrison, D. E. Shaw, K. L. Tsao, A. P. Watt, A. R. Williams,
C. J. Swain, Bioorg. Med. Chem. Lett. 2001, 11, 1233-1236; d) H.
Koolman, T. Heinrich, H. Boettcher, W. Rautenberg, M. Reggelin, Bioorg.
Med. Chem. Lett. 2009, 19, 1879-1882; e) T. C. Leboho, S. F. van
Vuuren, J. P. Michael, C. B. de Koning, Org. Biomol. Chem. 2014, 12,
[18] C. Hudson, T. C. Barden, J. Jia, A. Mermerian, B. Peng, J. Yang, X. Y.
Yu, K. Sprott, Ironwood Pharmaceuticals, WO 2012/088431 A1, June 28,
2012.
[19] a) K. Parrick, J. Chem. Soc. 1970, 303 – 307; b) M. J. D. Pires, D. L.
Poeira, S. I. Purificaçao, M. M. B. Marques, Org. Lett. 2016, 18, 3250 –
3253.
[20] a) K. Parrick, Can. J. Chem. 1966, 44, 2455 – 2457; b) R. S. Alekseyev,
S. R. Amirova, E. V. Kabanova, V. I. Terenin, Chem. Heterocycl. Compd.
2014, 50, 1305.
307-315; f) Y. Mettey, M. Gompel, V. Thomas, M. Garnier, M. Leost, I.
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European Journal of Organic Chemistry
10.1002/ejoc.201800129
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The
Lewis
acid
catalyzed
Fluorinations
fluorocyclization of electron deficient
heterocyclic styrenes using hypervalent
fluoro iodanes has been accomplished
involving a 1,2-aryl migration in their
mechanism.
Christoph Brunner, Anna Andries-Ulmer,
Gabriel M. Kiefl, Tanja Gulder*
Page No. – Page No.
Hypervalent Fluoroiodane-triggered
Synthesis of Fluoro-
Azabenzoxazepines and Azaindoles
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