A Fluorination/Aryl Migration/Cyclization Cascade for the Metal-Free Synthesis of Fluoro-Benzoxazepines

Article abstract of DOI:10.1002/chem.201504749

Fluorinated organic molecules are of high interest for many applications across chemical and medical disciplines. Efficient methods for the synthesis of such compounds are thus needed. Within this work, application of the bench-stable cyclic hypervalent i

Full text of DOI:10.1002/chem.201504749

DOI: 10.1002/chem.201504749
Communication
&
Fluorinated Organic Molecules |Hot Paper|
A Fluorination/Aryl Migration/Cyclization Cascade for the Metal-
Free Synthesis of Fluoro-Benzoxazepines
[
a]
Anna Ulmer, Christoph Brunner, Andreas M. Arnold, Alexander Pçthig, and Tanja Gulder*
Dedicated to Prof. Dr. Dr. h.c. mult. Gerhard Bringmann on the occasion of his 65th birthday
chemical and pharmacokinetic properties, when compared to
[
2b,d,3]
Abstract: Fluorinated organic molecules are of high inter-
est for many applications across chemical and medical dis-
ciplines. Efficient methods for the synthesis of such com-
pounds are thus needed. Within this work, application of
the bench-stable cyclic hypervalent iodine(III) fluoro re-
agent 1 facilitated the development of an efficient, metal-
free method for the preparation of the novel class of 4-
fluoro-1,3-benzoxazepines starting from readily available
styrenes. The efficacy and broad applicability of this con-
cept is demonstrated by the synthesis of 20 structurally di-
verse congeners in high yields, regio-, and diastereoselec-
tivities. The presented method provides complementary
chemoselectivity when compared to the common, com-
mercially available electrophilic fluorination reagents, such
as selectfluor. First mechanistic investigations with isotopi-
cally labeled substrates reveal a complex reaction mecha-
nism, proceeding via an unusual fluorination/1,2-aryl mi-
gration/cyclization cascade.
the corresponding CÀH analogue.
It is therefore not sur-
prising that fluorine compounds play a key role in the pharma-
[
2b,d,3,4]
ceutical and agrochemical industry today.
Organofluoro
compounds have even found their way into newly developing
fields, like, for example, non-invasive diagnostic techniques
[
2b,5]
such as positron emission tomography (PET),
or the devel-
[
6]
opment of ’intelligent’ materials. The tremendous benefit of
the CÀF structural scaffold is certainly accompanied with
a huge demand for effective, generally applicable, and selec-
tive strategies to generate such bonds. This not only includes
the development of new transformations in general, but also
providing a tool box of mild, sustainable, and efficient proto-
cols and reagents. In particular, the discovery of the robust
[
7]
fluoro aza reagents, such as selectfluor (11, see Table 1), ex-
tensively inspired the field of electrophilic fluorinations, unlock-
ing synthetic pathways to a large number of novel mole-
[
2k]
cules. These fluorination agents, with most of them being
commercially available today, suffer, for example, from high
costs which is due to the employment of F gas during their
2
production.
3
Hypervalent (l )-iodine-fluoro compounds constitute a re-
Although the first organofluoro compound was already de-
warding alternative to such N-fluoro transfer agents. However,
[
1]
scribed in 1835, the knowledge associated with fluorine
chemistry—and thus its application—limped behind that of
the other halogens. It was not until the turn of the millennium
that fluorination reactions have experienced a big boost,
fueled by the introduction of well manageable reagents, and
the development of the first selective fluorinations, etc. Since
the high reactivity and chemical instability of the linear di-
[
8]
fluoro aryl compounds have hampered their broad applica-
[
9]
[10]
tion. In 2013, Togni and Stuart reported on the preparation
[
11]
of the bench-stable, crystalline fluoro benziodoxole 1 using
easily accessible and cheap fluorides. In contrast to the struc-
[
12]
turally analogous Togni reagent,
which is successfully ap-
[2]
then, the field has rapidly evolved. The enormous interest in
CÀF bonds goes far beyond organic chemistry and is due to
the unique nature of this structural motif. With its small size
and high electronegativity, a fluorine substituent influences
the character of a molecule like no other element. Already
a single fluorine atom can significantly alter solubility, bioavail-
ability, and metabolic stability and thus often improves the
plied in trifluoromethylations, only a handful of applications of
[
a] A. Ulmer, C. Brunner, A. M. Arnold, Dr. A. Pçthig, Dr. T. Gulder
Department Chemie and Catalysis Research Center (CRC)
Technische Universität München
Lichtenbergstrasse 4, 85747 Garching (Germany)
E-mail: tanja.gulder@tum.de
Homepage: http://www.halogene.ch.tum.de
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201504749.
Part of a Special Issue “Women in Chemistry” to celebrate International
Women’s Day 2016. To view the complete issue, visit: http://dx.doi.org/
chem.v22.11.
Scheme 1. Applications of fluoro iodane 1.
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the electrophilic F-source 1 are known to date (Scheme 1a).
Besides the monofluorination of 1,3-dicarbonyls reported by
polar aprotic solvents (entries 4–6). Lewis basic and thus
cation-stabilizing solvents dramatically accelerated the reaction
rate (<5 min; entry 5 and 6). To avoid possible hydrolysis of
1 under our reaction conditions, different desiccants were
added to the reaction mixture (entries 7–9). The best results
were achieved using 4 Š molecular sieves, which raised the
yield of 4-fluoro-4,5-dihydro-benz[d][1,3]-oxazepine (9a) to
90% (77% isolated yield). Interestingly, the change of the elec-
trophilic fluorine source from 1 to the fluoro aza compound
selectfluor (11) was accompanied with a completely altered
chemoselectivity. Now the oxazine 10a was formed solely in
[
10,13]
Stuart (reaction A),
the group of Szabó recently described
[14]
the use of fluoro iodane 1 in geminal difluorinations and flu-
[
15a]
orocyclizations
of alkenes. In both cases, the addition of
transition metal tetrafluoroborates, such as AgBF (reaction F),
4
Zn(BF ) ·xH O (reaction B and D), and [Cu(MeCN) ]BF (reaction
4
2
2
4
4
C) was necessary to obtain the fluorinated products in good
yields. These reports were complemented a few weeks ago by
[15b]
fluorolactonizations (reaction E).
Also in this case, activation
of 1 was needed to obtain product 6 in good yields.
[
20,21]
With our research focusing on the development and applica-
tion of novel halogenation concepts, especially in the field of
61% yield after 24 h (entry 10).
This result impressively
shows that the fluoro iodine(III) reagent 1 is not only signifi-
cantly more reactive but also provides a completely different
chemoselectivity when compared to the common electrophiles
such as 11. With the application of 1, novel paths in electro-
philic fluorinations are now available, leading to unprecedent-
ed fluorinated scaffolds.
[16]
iodine(III)-mediated halofunctionalizations,
we were in-
trigued by the straightforward access to 1 and the opportuni-
ties thereby provided to the synthetic community. Despite the
tremendous progress in fluorine chemistry and the utility of
fluorinated (hetero)cycles, the electrophilic fluoroaddition to
CÀC double bonds is still problematic. This results from the re-
duced reactivity of the well-established fluoro electrophiles
compared to their corresponding chloro, bromo, and iodo de-
rivatives.
Table 1. Optimization of the reaction conditions for the synthesis of 4-
fluoro-4,5-dihydro-benz[d][1,3]-oxazepine (9a).
We now report on the development of a metal-free, mild,
and easy-to-handle method for the generation of 4-fluoro-1,3-
benzoxazepines 9 (Scheme 1b). Using the obtained protocol,
various structurally diverse derivatives of the pharmacologically
interesting heterocycles 9 are accessible in a highly selective
manner. Starting from o-styryl benzamides 8, products 9 are
formed via a complex fluorination/aryl migration/cyclization
cascade, which is evident from our first studies on the reaction
mechanism. This sequence proceeds with high efficiency and
permits, for the first time, the direct synthesis of fluorinated
[a]
F reagent Solvent Additive
t
Yield [%]
9a/10a
[b]
[c]
[d]
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
11
DCM
DCM
DCM
toluene
HFIP
MeCN
MeCN
MeCN
AgBF
Zn(BF
–
–
–
–
4
18 h
5 min
–
–
[e]
[f]
4
)
2
·xH
2
O
89 (74)
1:0
1:0
1:0
1:0
1:0
1:0
1:0
1:0
0:1
15 min 83
15 min 76
<5 min 81
<5 min 82
<5 min 86
<5 min 83
<5 min 90 (77)
1
,3-benzoxazepines.
Na
2 4
SO
MgSO
4
Our studies on the fluoro iodoxole triggered generation of
[f]
9
MeCN 4 Š MS
MeCN
F-heterocycles commenced by treating benzamide 8a with 1,
initially expecting a 6-exo cyclization with concomitant forma-
tion of an exocyclic fluoromethylene unit to give benzoxazine
[g]
10
–
24 h
61
[
17]
1
0a (Table 1). As an entry point, we tested the optimized
conditions for the electrophilic addition of 1 to olefins report-
[
14,15a]
ed by Szabó et al.
While the addition of AgBF did not
1
4
[a] The yield was determined by H NMR spectroscopy of the crude prod-
yield any fluorinated product (entry 1), the use of catalytic
uct using an internal standard. [b] The reaction was conducted at 408C.
[
[
c] 10 mol% AgBF
f] Isolated yield. [g] 2.4 equiv 11 were used.
4 4 2 2
. [d] 15% 8a was re-isolated. [e] 5 mol% Zn(BF ) ·xH O.
amounts of Zn(BF) gave a single product. However, this was
4
not the expected benzoxazine 10a, but the fluorinated 1,3-
benzoxazepine 9a obtained in very good 89% (entry 2). Ben-
zoxazepines are per se a class of highly bioactive com-
[
18]
pounds. Nevertheless, efficient strategies to the 1,3-deriva-
With the optimized reaction conditions in hand, we explored
[19]
tives are generally rare and do not exist at all for fluorinated
analogues 9 obtained here. We thus embarked on the optimi-
zation and application of our observed reactivity to provide an
efficient synthetic method to these exciting fluorinated scaf-
folds.
the scope of this transformation by converting a variety of
structurally diverse styrenes 8 into the corresponding benzoxa-
zepines 9 (20 examples, Scheme 2). The fluorocyclization gen-
erally occurred in very good yields (61%–85%), forming exclu-
sively the seven-ring products 9. In all cases the carboxyl
oxygen atom served as the only intramolecular nucleophile.
Attack of the amide aromatic portion and a therewith associat-
ed carbocyclization leading to the likewise possible dibenzaze-
pinone derivatives was never observed. In general, the reaction
is very robust towards structural changes. Variation of the
amide functionality showed that aryl as well as alkyl carbox-
In-depth studies to improve the reaction conditions showed
that the conversion of 8a with 1 also occurred without a Lewis
acidic additive. In this case, the reaction time slightly increased
from 5 min to 15 min, but the heterocycle 9a was obtained in
similar yields (83%, entry 3). A screening of different solvents
revealed that the transformation tolerates nonpolar as well as
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8
g) were transformed on a gram scale, yielding the corre-
sponding products in comparable yields. Besides heterocycles
, the only other component identified in the reaction mixture
9
was the benzyl alcohol 12, which is generated from 1 after
fluorine atom transfer. Alcohol 12 was isolated in excellent
9
1% yield and was then re-subjected to generate reagent 1.
This significantly contributes to the sustainability of the de-
scribed transformation.
The formation of the C-4 alkylated benzoxazepines 9 from
styrenes 8 follows a complex mechanism, which formally in-
volves a 7-endo cyclization followed by migration of the alkyl
moiety from C-5 to C-4. To get insights into the detailed mech-
anism of this transformation, stable isotopically labeled starting
13
materials [ C]-8a und [D ]-8r were treated with fluoro benz-
2
iodoxole 1 under standard conditions (Scheme 3). Analysis of
13
the products [ C]-9a and [D ]-9r revealed that the isotopically
2
labeled atoms are exclusively located in the benzylic position
of 9, clearly pointing at a 1,2-shift of the backbone aryl moiety
rather than migration of the alkyl group.
Scheme 2. Substrate scope of the metal-free fluorocyclization. 1.00 mmol
1.0 equiv) 8 together with 336 mg 1 (1.20 mmol, 1.2 equiv) and 4 Š molecu-
lar sieve (50 mg) were stirred at room temperature in 10 mL absolute MeCN
(
[a]
1
(
0.1m). d.r. was determined from the crude H NMR spectrum.
Scheme 3. Control experiments with stable isotopically labeled 8.
ylates at the nitrogen are tolerated, leading to the correspond-
ing benzoxazepines 9a–9d in 66%–83% yield. Heteroaromatic
moieties, such as 3-thiophene, were likewise accepted in this
oxidative transformation (9d, 79% yield). Electron-rich as well
as electron-poor substituents at the aniline delivered the de-
sired heterocycles 9 in good to excellent yields (64%–85%).
Ring closure proceeded smoothly under these mild conditions,
even with substrates bearing strongly activated and therefore
oxidation sensitive benzene rings, such as the dioxolane substi-
tuted styrene 8i. No fluorination or oxidation of the aromatic
system was detectable. The positions of the substituents had,
furthermore, no significant impact on product formation. This
was probed by treatment of different regioisomeric tolyl com-
pounds 8e–8h (71%–80% yield). The X-ray crystal structures,
which were obtained for the tolyl 9g and the fluoro benzene
analogue 9j, unambiguously verified the formation of an oxa-
zepine ring system with a quaternary carbon center at C-4.
Substrates bearing differently substituted CÀC double bonds
were tested next (Scheme 2b), giving rise to benzoxazepines
Based on the obtained information, we conclude that the
formation of benzoxazepines 9 follows a novel fluorination/
[
15b]
1,2-aryl migration/cyclization cascade (Scheme 4).
In the
first step, the fluoro reagent 1 is nucleophilically attacked by
the olefinic double bond, forming the iodo(III)ranium ion 14.
The three-membered heterocycle is then selectively opened at
the benzylic position by an intramolecular 1,2-fluoro shift. A
mechanism proceeding via the likewise conceivable benzylic
carbocation 13 seems unlikely because of the good diastereo-
selectivity in the formation of 9t. The 1,2-iodofluorine species
9
p–9t in 61%–79%. Here, even the challenging, trisubstituted
styrenes, such as the C-4 and C-5 methylated 8t, were easily
converted under the developed conditions (76%). The ring clo-
sure proceeded with good diastereoselectivities (80:20), the
relative configuration of the methyl groups (cis) being con-
served in the major diastereomer. To test the practicability of
our fluorocyclization method, selected examples (8a, 8b, and
Scheme 4. Postulated mechanism for the formation of 9.
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1
5 obtained from 14 is stabilized by displacement of the iodo-
ley, T. Martinez del Campo, A. L. Thompson, G. T. Giuffredi, M. Bettati, M.
Walker, R. Borman, V. Gouverneur, Angew. Chem. Int. Ed. 2011, 50, 8105–
benzene 12 by nucleophilic attack of the aryl ring, furnishing
the cyclopropyl compound 16. The latter is in an equilibrium
with phenonium ion 17.
clopropyl ring in 17 takes place intramolecularly via a 6-endo
cyclization with simultaneous ring expansion to the seven-
8109; Angew. Chem. 2011, 123, 8255–8259; i) J. R. Wolstenhulme, V.
Gouverneur, Acc. Chem. Res. 2014, 47, 3560–3570; j) J. R. Wolstenhulme,
J. Rosenqvist, O. Lozano, J. Ilupeju, N. Wurz, K. M. Engle, G. W. Pidgeon,
P. R. Moore, G. Sandford, V. Gouverneur, Angew. Chem. Int. Ed. 2013, 52,
[
22]
[14,23,24]
Ring opening of the spirocy-
9
796–9800; Angew. Chem. 2013, 125, 9978–9982; k) P. A. Champagne,
J. Desroches, J.-D. Hamel, M. Vandamme, J.-F. Paquin, Chem. Rev. 2015,
15, 9073–9174.
[
23a,e]
membered oxazepine 9. In contrast to previous reports,
1
the nucleophilic attack of the amide oxygen here occurs regio-
selectively at the higher substituted and thus more electrophil-
ic carbon atom of the cyclopropane unit. This exclusively leads
to the C-4 alkylated products 9.
[3] S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008,
37, 320–330.
[
4] a) K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881–1886; b) P.
Jeschke, ChemBioChem 2004, 5, 570–589; c) T. Fujiwara, D. O’Hagan, J.
Fluorine Chem. 2014, 167, 16–29.
In summary, we succeeded in developing an effective and
transition-metal free pathway for the synthesis of novel 4-
fluoro-1,3-benzoxazepines 9 starting from readily available sty-
renes 8 and the bench-stable, non-toxic, and easily obtainable
fluoro iodane 1. The presented cyclization reaction was con-
ducted with a variety of structurally diverse substrates and pro-
ceeded with complete regioselectivity. Because of the mild re-
action conditions of this oxidative transformation, even chemi-
cally sensitive functionalities, like, for example, electron-rich
structural elements with a high susceptibility towards oxida-
tion, were tolerated, giving the desired products 9 in high
yields. Furthermore, the execution of this fluorocyclization is
experimentally very simple and proceeds with very short reac-
tion times. In contrast to traditional electrophilic fluorinating
agents, such as selectfluor (11), the hypervalent fluoro iodane
[
5] a) P. W. Miller, N. J. Long, R. Vilar, A. D. Gee, Angew. Chem. Int. Ed. 2008,
47, 8998–9033; Angew. Chem. 2008, 120, 9136–9172; b) M. Tredwell, V.
Gouverneur, Angew. Chem. Int. Ed. 2012, 51, 11426–11437; Angew.
Chem. 2012, 124, 11590–11602; c) A. Harsanyi, G. Sandford, Org. Process
Res. Dev. 2014, 18, 981–992.
[
[
[
6] R. Berger, G. Resnati, P. Metrangolo, E. Weber, J. Hulliger, Chem. Soc. Rev.
2011, 40, 3496–3508.
7] R. E. Banks, S. N. Mohialdin-Khaffaf, G. S. Lal, I. Sharif, R. G. Syvret, J.
Chem. Soc. Chem. Commun. 1992, 595–596.
8] a) S. Hara, M. Sekiguchi, A. Ohmori, T. Fukuhara, N. Yoneda, Chem.
Commun. 1996, 1899–1900; b) M. Sawaguchi, S. Ayuba, S. Hara, Synthe-
sis 2002, 1802–1803; c) M. Sawaguchi, S. Hara, T. Fukuhara, N. Yoneda,
J. Fluorine Chem. 2000, 104, 277–280; d) C. Ye, B. Twamley, J. M.
Shreeve, Org. Lett. 2005, 7, 3961–3964.
[
9] V. Matou sˇ ek, E. Pietrasiak, R. Schwenk, A. Togni, J. Org. Chem. 2013, 78,
6
763–6768.
[10] G. C. Geary, E. G. Hope, K. Singh, A. M. Stuart, Chem. Commun. 2013, 49,
263–9265.
11] C. Y. Legault, J. PrØvost, Acta Crystallogr. Sect. E 2012, 68, o1238.
12] a) J. Charpentier, N. Früh, A. Togni, Chem. Rev. 2015, 115, 650–682; b) N.
Santschi, A. Togni, Chimia 2014, 68, 419–424; c) P. Eisenberger, S. Gi-
schig, A. Togni, Chem. Eur. J. 2006, 12, 2579–2586.
9
[
[
1
dramatically differs in its chemoselectivity. While 11 facilitates
the formation of oxazines 10, the structurally novel seven-
membered ring products 9 were obtained as the only product
in all cases when 1 was applied. Mechanistically, the reaction
follows a fluorination/1,2-aryl migration/cyclization cascade
that opens access to a new class of fluorinated heterocycles,
whose pharmacological potential needs to be explored in the
future. In general, the presented fluorination method using hy-
pervalent iodo-fluoro reagents constitutes a promising new
tool, capable of creating unprecedented reactivities, thus push-
ing the boundaries in organofluorine chemistry.
[
[
13] G. C. Geary, E. G. Hope, K. Singh, A. M. Stuart, RSC Adv. 2015, 5, 16501–
1
6506.
14] N. O. Ilchenko, B. O. A. Tasch, K. J. Szabó, Angew. Chem. Int. Ed. 2014, 53,
2897–12901; Angew. Chem. 2014, 126, 13111 –13115.
[15] a) W. Yuan, K. J. Szabó, Angew. Chem. Int. Ed. 2015, 54, 8533–8537;
Angew. Chem. 2015, 127, 8653–8657. b) During the preparation of this
manuscript the following article on a fluorination/1,2-aryl shift/lactoni-
zation cascade was published by G. C. Geary, E. G. Hope, A. M. Stuart,
Angew. Chem. Int. Ed. 2015, 53, 14911–14914; Angew. Chem. 2015, 127,
15124–15127.
1
[16] a) D. C. Fabry, M. Stodulski, S. Hoerner, T. Gulder, Chem. Eur. J. 2012, 18,
10834–10838; b) M. Stodulski, A. Goetzinger, S. V. Kohlhepp, T. Gulder,
Chem. Commun. 2014, 50, 3435–3438; c) A. Ulmer, M. Stodulski, S. V.
Kohlhepp, C. Patzelt, A. Poethig, W. Bettray, T. Gulder, Chem. Eur. J.
Acknowledgements
2015, 21, 1444–1448.
We like to thank C. Seel and M. Geißler for technical support.
This work was funded by the Emmy-Noether program of the
German Research Foundation (DFG, GU 1134/3-1).
[17] Toste et al. reported on the formation of the bromo derivative of 10a
in an enantioselective bromocylization: Y.-M. Wang, J. Wu, C. Hoong, V.
Rauniyar, F. D. Toste, J. Am. Chem. Soc. 2012, 134, 12928–12931.
[
18] Selected examples for bioactive benzoxazepines: a) J. Anireddy, A. T.
Rao, M. A. Reddy, J. Pharm. Res. Dev. 2013, 6, 389–394; b) B. Banerji,
S. K. Pramanik, P. Sanphui, S. Nikhar, S. C. Biswas, Chem. Biol. Drug Des.
Keywords: 1,2-aryl shift · benzoxazepines · fluorination ·
hypervalent iodine
2013, 82, 401–409; c) A. F. Donnell, C. Michoud, K. C. Rupert, X. Han, D.
Aguilar, K. B. Frank, A. J. Fretland, L. Gao, B. Goggin, J. H. Hogg, K. Hong,
C. A. Janson, R. F. Kester, N. Kong, K. Le, S. Li, W. Liang, L. J. Lombardo,
Y. Lou, C. M. Lukacs, S. Mischke, J. A. Moliterni, A. Polonskaia, A. D.
Schutt, D. S. Solis, A. Specian, R. T. Taylor, M. Weisel, S. W. Remiszewski,
J. Med. Chem. 2013, 56, 7772–7787; d) S. K. D. Dwivedi, K. Samanta, M.
Yadav, A. K. Jana, A. K. Singh, B. Chakravarti, S. Mondal, R. Konwar, A. K.
Trivedi, N. Chattopadhyay, S. Sanyal, G. Panda, Bioorg. Med. Chem. Lett.
2013, 23, 6816–6821; e) B. M. Fox, H. P. Beck, P. M. Roveto, F. Kayser, Q.
Cheng, H. Dou, T. Williamson, J. Treanor, H. Liu, L. Jin, G. Xu, J. Ma, S.
Wang, S. H. Olson, J. Med. Chem. 2015, 58, 5256–5273; f) L. M. Greene,
D. P. Nolan, D. Regan-Komito, G. Campiani, D. C. Williams, D. M. Zisterer,
Int. J. Oncol. 2013, 43, 927–935; g) M. Ichikawa, M. Ohtsuka, H. Ohki, M.
Ota, N. Haginoya, M. Itoh, Y. Shibata, K. Sugita, Y. Ishigai, K. Terayama, A.
[
[
1] J. Dumas, E. PØligot, Ann. Pharm. 1835, 15, 59.
2] a) C. Chatalova-Sazepin, R. Hemelaere, J.-F. Paquin, G. M. Sammis, Syn-
thesis 2015, 47, 2554–2569; b) E. P. Gillis, K. J. Eastman, M. D. Hill, D. J.
Donnelly, N. A. Meanwell, J. Med. Chem. 2015, 58, 8315–8359; c) T.
Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 2013, 52, 8214–
8
264; Angew. Chem. 2013, 125, 8372–8423; d) J. Wang, M. Sµnchez-
Roselló, J. L. AceÇa, C. del Pozo, A. E. Sorochinsky, S. Fustero, V. A. Solo-
shonok, H. Liu, Chem. Rev. 2014, 114, 2432–2506; e) X. Yang, T. Wu, R. J.
Phipps, F. D. Toste, Chem. Rev. 2015, 115, 826–870; f) C. Hollingworth, V.
Gouverneur, RSC Catal. 2013, 11, 193–261; g) C. Hollingworth, V. Gou-
verneur, Chem. Commun. 2012, 48, 2929–2942; h) O. Lozano, G. Bless-
Chem. Eur. J. 2016, 22, 3660 – 3664
www.chemeurj.org
3663
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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Kanda, H. Usui, ACS Med. Chem. Lett. 2013, 4, 932–936; h) G. A. Kang,
M. Lee, D. Song, H. K. Lee, S. Ahn, C. H. Park, C. O. Lee, C. S. Yun, H.
Jung, P. Kim, J. D. Ha, S. Y. Cho, H. R. Kim, J. Y. Hwang, Bioorg. Med.
Chem. Lett. 2015, 25, 3992–3998; i) F. Khaleghi, I. Jantan, L. B. Din, W. A.
Yaacob, M. A. Khalilzadeh, S. N. A. Bukhari, J. Nat. Med. 2014, 68, 351–
[21] During the preparation of our manuscript, the synthesis of benzoxa-
zines 10 using selectfluor (11) was published by J.-F. Zhao, X.-H. Duan,
H. Yang, L.-N. Guo, J. Org. Chem. 2015, 80, 11149–11155.
[22] a) D. J. Cram, J. Am. Chem. Soc. 1949, 71, 3863–3870; b) G. A. Olah, R. D.
Porter, J. Am. Chem. Soc. 1971, 93, 6877–6887; c) G. A. Olah, R. D.
Porter, J. Am. Chem. Soc. 1970, 92, 7627–7629.
3
57; j) W. R. Martínez, G. C. G. Milit¼o, T. G. da Silva, R. O. Silva, P. H. Me-
[
23] Selected examples of phenonium ion mediated oxidative transforma-
tions: a) I. Tellitu, E. Domínguez, Tetrahedron 2008, 64, 2465–2470;
b) A. C. Boye, D. Meyer, C. K. Ingison, A. N. French, T. Wirth, Org. Lett.
nezes, RSC Adv. 2014, 4, 14715–14718; k) S. Naganathan, D. L. Ander-
sen, N. G. Andersen, S. Lau, A. Lohse, M. D. Sørensen, Org. Process Res.
Dev. 2015, 19, 721–734.
2003, 5, 2157–2159; c) U. Farid, F. Malmedy, R. Claveau, L. Albers, T.
[
19] a) M. Arisawa, Y. Ando, M. Yamanaka, M. Nakagawa, A. Nishida, Synlett
Wirth, Angew. Chem. Int. Ed. 2013, 52, 7018–7022; Angew. Chem. 2013,
2
002, 1514–1516; b) T. Besson, G. Guillaumet, C. Lamazzi, C. W. Rees,
Synlett 1997, 704–706; c) G. Capozzi, R. Ottana, G. Romeo, Heterocycles
987, 26, 39–42; d) S. Fukamachi, H. Konishi, K. Kobayashi, Helv. Chim.
1
2
25, 7156–7160; d) F. V. Singh, J. Rehbein, T. Wirth, Chem. Open 2012, 1,
45–250; e) L. Fra, A. Millµn, J. A. Souto, K. MuÇiz, Angew. Chem. Int. Ed.
1
2014, 53, 7349–7353; Angew. Chem. 2014, 126, 7477–7481.
Acta 2011, 94, 987–992; e) S. Fukamachi, H. Konishi, K. Kobayashi, Het-
erocycles 2011, 83, 883–889; f) M. D. Ganton, M. A. Kerr, Org. Lett. 2005,
[
24] Formation of electron-poor phenonium ions in iodine(III)-mediated re-
actions was observed in the lactonization of pentenoic acid derivatives
by T. Wirth and co-workers, see Ref. [23b].
7, 4777–4779; g) Y. Nishiyama, Y. Naitoh, N. Sonoda, Synlett 2004,
0
886–0888.
[
20] To obtain compound 10a in a chemically homogeneous form, 2.4 equiv
1 had to be used.
1
Received: November 25, 2015
Published online on December 23, 2015
Chem. Eur. J. 2016, 22, 3660 – 3664
www.chemeurj.org
3664
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