A metal-free route to 2-aminooxazoles by taking advantage of the unique ring opening of benzoxazoles and oxadiazoles with secondary amines

Article abstract of DOI:10.1002/chem.201100910

Toss an amine into the ring: A new metal-free protocol for the amination of oxazoles has been developed by using iodobenzene diacetate to couple various oxazoles with amines (see scheme). The reaction proceeds through a ring-opening and subsequent ring-closing pathway. The optimal conditions are very mild and the substrate scope is broad, producing a range of 2-aminooxazoles, an important pharmacophore with high bioactivity. Copyright

Full text of DOI:10.1002/chem.201100910

DOI: 10.1002/chem.201100910
A Metal-Free Route to 2-Aminooxazoles by Taking Advantage of the Unique
Ring Opening of Benzoxazoles and Oxadiazoles with Secondary Amines
Jomy Joseph, Ji Young Kim, and Sukbok Chang*[a]
Recognizing the value of (hetero)arylamine motifs in bio-
logical and pharmaceutical sciences, chemists continue to
devise novel and more practical methods for their synthe-
sis.[1] Buchwald–Hartwig-type amination reactions and those
mediated by copper are the most powerful and reliable
methods available for N arylation.[2] However, since these
procedures employ aryl halides as the starting material, the
cently, Miura developed a milder catalytic protocol for the
amination of azoles.[5] Despite the fact that the reaction pro-
ceeds at ambient temperature, it requires chloroamine pre-
cursors as the amine source.
We have previously revealed an oxidative dehydrogena-
tive approach for the amination of azoles by using stoichio-
metric amounts of silver.[6a] More recently, we also devel-
oped a catalytic version of this approach by using Co or Mn
catalysts in the presence of peroxide as the oxidant and a
carboxylic acid additive.[6b] In the latter procedure, we found
À
direct amination of a C H bond in heteroaromatics would
be beneficial, thus avoiding additional halogenation steps to
obtain halogenated derivatives. In this context, recent exam-
À
ples of metal-mediated C N bond formation in azoles repre-
sent important contributions to this area (Scheme 1).
that
a
ring-opened adduct, o-hydroxyamidine (A,
Scheme 1), was also generated as a minor product along
with the desired amination product when the reaction was
carried out in the absence of the acid additive.[6b] Subse-
quent studies revealed that secondary amines are capable of
opening benzoxazoles to afford amidine adducts, especially
under neat conditions. At first glance, this result was surpriz-
ing as the ring opening of benzoxazoles under neutral condi-
tions had not been reported previously, although some car-
banions were known to open azole rings under harsher con-
ditions. For example, allyl magnesium halides are capable of
performing ring-opening reactions on benzoxazoles and ben-
zothiazoles at low temperatures.[7a,b] Nitrobenzoxazoles also
provide ring-opened products through addition of base or
carbanions.[7c] In addition, the generation of an unstable
ring-opened intermediate of isocyanophenolate was pro-
posed in the Pd-catalyzed direct arylation of benzoxazoles.[8]
Although amidines are a prevalent structural motif in me-
dicinal chemistry, displaying high bioactivities,[9] their use as
a synthon for the formation of various amine-containing
compounds has been less widespread. This is especially
noteable upon considering that although imines exhibit a va-
riety of reactivity through addition, reduction, or cycloaddi-
tion reactions, the structurally analogous amidines have not
been frequently utilized except in limited cyclization se-
quences.[10] As we were particularly interested in the synthe-
sis of 2-aminooxazoles, the easily obtainable ortho-hydrox-
yamidine adducts triggered our curiosity about the posibility
for a subsequent cyclization reaction leading to the desired
products. As the ring-closing reaction of ortho-hydroxyi-
mines is already known,[11,15] we were curious whether the
same oxidation conditions could be employed for the ring
closure of ortho-hydroxyamidines. Presented herein is a new
route, based on our hypothesis, for the highly efficient ami-
nation of oxazoles by using iodobenzene diacetate as the ox-
idant.[12] Our findings are highly significant as they provide
À
Scheme 1. Amination of the C H bond in oxazoles.
In 2009, Mori et al.[3] and Schreiber et al.[4] reported the
copper-catalyzed amination and amidation of heteroaromat-
ics, respectively. Although C N bond formation takes place
regioselectively at the 2-position of azoles, the reaction con-
ditions employed were rather harsh (120–1408C). More re-
À
[a] Dr. J. Joseph, J. Y. Kim, Prof. Dr. S. Chang
Department of Chemistry and
Molecular-Level Interface Research Center
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon 305-701 (Republic of Korea)
Fax : (+82)42-350-2810
E-mail: sbchang@kaist.ac.kr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100910.
8294
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 8294 – 8298

COMMUNICATION
Table 2. Substrate scope with regard to benzoxazoles.[a,b]
the first example of a metal-free route to 2-aminooxazoles[13]
under very mild conditions.
5-Methylbenzoxazole (1a) was chosen as a model sub-
strate to react with pyrrolidine (2a) for the optimization of
the ring-opening and subsequent ring-closing reaction
(Table 1). Although poor conversion was observed in solu-
Entry
R1
t
Yield of 3
Yield of 4
[min]
[%][c]
[%][c]
1
2
3
4
5
6
OMe
Me
H
Ph
Cl
1b
1a
1c
1d
1e
1 f
25
30
15
5
5
1
98
99
96
98
99
60
3ba
73
91
75
73
93
53
4ba
Table 1. Optimization of the reaction conditions.[a,b]
3aa
3ca
3da
3ea
3 fa
4aa
4ca
4da
4ea
4 fa
NO2
[a] Amidine formation: 1 (0.5 mmol) and 2a (1 mmol), neat. [b] Ring-
closing step: 3 (0.5 mmol) and PhI(OAc)2 (1.1 equiv) in CH2Cl2 (3 mL) at
AHCTUNGTRENNUNG
258C for 5 min under an air atmosphere. [c] Isolated yields.
and closing steps. In fact, amidine adducts were obtained in
high yields irrespective of the substituentsꢁ electronic prop-
erties. Oxidative cyclization of amidines readily proceeded
by using iodobenzene diacetate (1.1 equiv) within 5 min at
258C to afford 2-pyrrolidinylbenzoxazole derivatives in
good yields. The relatively moderate yield obtained from 5-
nitrobenzoxazole (Table 2, entry 6) is due to the instability
of the amidine adduct (3 fa) and the 2-aminobenzoxazole
product (4 fa).
Entry
Oxidant
Solvent
t
T
Yield
[%][c]
<5[d]
<5[d]
<5[d]
94
73
56
30
40
A
[oC]
1
2
3
4
5
6
7
8
9
oxone
A
120
120
120
5
80
80
80
25
25
25
25
25
25
25
K2S2O8
ACHTUNGTRENNUNG
T-HYDRO[e]
ACHTUNGTRENNUNG
PhI
PhI(OPiv)2
PhI(OCOCF3)2
PhI(OH)OTs
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
A
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
dioxane
toluene
CH3CN
N
5
5
5
15
15
15
E
G
We next investigated the tolerance for the amine counter-
part in the ring-opening reaction of 5-methylbenzoxazole
and the subsequent ring closing of the corresponding ortho-
hydroxyarylamidines (Table 3). Cyclic amines, such as piper-
idine (2b), 2-methylpyrrolidine (2c), morpholine (2d), and
N-methylpiperazine (2e), all smoothly underwent the ring-
opening reaction with 1a to provide amidine adducts in ex-
cellent yields (Table 3, entries 1–4). In addition, the subse-
quent cyclization of the amidines was easy under the mild
conditions (5 min at 258C), leading to the corresponding 2-
amino-5-methylbenzoxazoles in good yields. The reaction of
cyclic amines bearing functional groups such as N-bezyloxy-
carbonylpiperazine (2 f) was also smooth, providing the de-
sired product 4af in an acceptable yield (Table 3, entry 5).
Acyclic amines also turned out to be facile reactants al-
though some substrates needed higher reaction tempera-
tures to obtain full conversion in the ring-opening step. For
instance, the reaction of dibenzylamine (2g) with 1a pro-
ceeded efficiently at 808C to give adduct 3ag, which was
subsequently cyclized to form 4ag in good yield (Table 3,
entry 6). In addition, the two-step procedure with both N-
methylcyclohexylamine (2h) and diisobutylamine (2i) took
place readily (Table 3, entries 7 and 8, respectively). It is
noteable that most functional groups examined were com-
patible with the conditions, as demonstrated by the reaction
of both diallylamine (2j, Table 3, entry 9) and N-methyl-N-
propargylamine (2k, Table 3, entry 10). The amination reac-
tion could be scaled up without difficulty (Table 3, entry 9).
However, when primary amines were subjected to the stan-
dard conditions, poor yields of the corresponding amidines
N
28
55
10
G
[a] Conditions for amidine formation: 1a (0.5 mmol) and 2a (1 mmol) for
30 min at 258C. [b] Conditions for the cyclization reaction: amidine 3aa
(0.5 mmol) and oxidant (0.55 mmol) in the indicated solvent (3 mL).
[c] NMR spectroscopic yield. [d] 5-Methylbenzoxazole was recovered in
about 30% yield. [e] T-HYDRO is the trademark name for 70wt% tert-
butyl hydroperoxide in water.
tion, such as in methanol or dichloromethane, a quantitative
yield of o-hydroxybenzamidine (3aa) was obtained with the
use of pyrrolidine (2 equiv) in 30 min at room temperature.
Equipped with a simple but highly efficient route to ami-
dines, we next scrutinized the ring-closing reaction under
various conditions. Although cyclization was sluggish with
oxone, persulfate, or peroxide oxidants (Table 1, entries 1–
3), hypervalent iodine species cyclize 3aa to form 2-amino-
benzoxazole 4aa, the efficiency of which varied depending
on the iodinate employed. For instance, the use of iodoben-
zene diacetate (1.1 equiv) in dichloromethane resulted in
complete conversion within 5 min at room temperature to
give 4aa in 94% yield as shown by NMR spectroscopy
(Table 1, entry 4). On the other hand, other iodine
ces, such as PhI(OPiv)2 (Piv=tert-butylcarbonyl), PhI-
(OCOCF3), or PhI(OH)OTs (Ts=tosyl, the Koser reagent),
ACHTUNGTRENUN(NG III) sour-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
offered lower yields under otherwise identical conditions.
Benzoxazoles substituted with various functional groups
also underwent the two step amination reaction in high
overall yields (Table 2). Interestingly, little electronic effect
of the substituents was observed in both the ring-opening
Chem. Eur. J. 2011, 17, 8294 – 8298
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8295

S. Chang et al.
Table 3. Scope of amines to react with 5-methylbenzoxazole.[a,b]
than the tautomeric enol form, as shown by the
NMR and IR spectral data.[14] Pleasingly, the subse-
quent oxidative ring-closing step of the obtained
amidine adducts takes place smoothly under the
aforementioned optimized mild conditions.
When the reaction of 2-substituted oxadiazoles
with piperidine (3 equiv, 2b) was carried out neat,
the ring-opened adducts were obtained in excellent
yields. In addition, the reaction efficiency was
hardly influenced by electronic variations in the
substituents on the non-fused heterocycle.
Entry
Amine 2
T
t
Yield of 3
Yield of 4
[oC]
[h]
[%][c]
[%][c]
1
2
2b
2c
25
25
1
5
99
96
3ab
74
69
4ab
3ac
4ac
Indeed, oxadiazoles bearing phenyl (5a), 1-naph-
thyl (5b), 4-trifluoromethyl- (5c), 4-chloro- (5d),
and 4-methoxyphenyl (5e) groups all underwent
the ring-opening reaction with piperidine to give
the corresponding acylhydrazino amidines 6ab–eb
in excellent yields. Oxidative cyclization of acyclic
intermediates 6 also proceeded efficiently to give
the 2-aminooxadiazoles 7ab–eb under mild condi-
tions.
3
4
2d
2e
80
25
12
10
96
98
3ad[d]
3ae
70
78
4ad
4ae
5
6
2 f
2g
25
80
10
12
96
79
3af
61
79
4af
3ag
4ag
Under the aforementioned standard reaction con-
ditions, a range of secondary amines readily partici-
pated in the ring-opening and -closing transforma-
tion of 2-phenyloxadiazole (5a) to afford 2-amino-
1,3,4-oxadiazoles in good yields (Table 5). For in-
stance, pyrrolidine (2a), a substituted piperidine 2l,
morpholine (2d), and N-methylpiperazine (2e)
were all readily aminated at the 2-position of oxa-
diazole (Table 5, entries 1, 2, 3, and 4, respectively).
Functional groups such as benzyloxycarbonyl (2 f)
or a bisallyl moiety (2j) were compatible with the
employed conditions (Table 5, entries 5–6).
As the outcome of this process is identical to the
oxidative nucleophilic substitution of hydrogen
(ONSH)[15] with amine nucleophiles, an equilibrium
might be operating between the ring-opened o-hy-
droxyarylamidine species and the ring-closed ben-
zoxazoline adduct.[6b] As a result, it was envisioned
that a one-pot procedure could be performed by
mixing the benzoxazole, amine, and iodobenzene
7
2h
2i
80
80
80
12
12
12
98
89
96
3ah
3ai
61
90
78
4ah
4ai
4aj
8
9[e]
2j
3aj
10
11
2k
25
80
12
12
89
3ak
62
–
4ak
<5
–
[a] Conditions for amidine formation: 1a (0.5 mmol) and 2 (1 mmol), neat. [b] Condi-
tions for ring-closing step: 3 (0.5 mmol) and PhI(OAc)2 (1.1 equiv) in CH2Cl2 (3 mL)
at 258C for 5 min under an air atmosphere. [c] Isolated yields. [d] NMR yield of 3ad
AHCTUNGTRENNUNG
due to its instability. [e] This reaction was carried out on a gram scale.
were obtained (Table 3, entry 11). Aniline derivatives were
also unreactive under these conditions.
diacetate together. However, the desired product was not
obtained under the new reaction conditions and it was ob-
served that iodobenzene diacetate completely decomposed.
Further studies revealed that secondary amines quickly re-
acted with iodobenzene diacetate at room temperature,
leading to the decomposition of the oxidant. To overcome
this limitation, a sequential one-pot procedure was consid-
ered, in which the reagents were added step by step in one
pot. After confirming complete conversion of benzoxazole
to the amidine adduct by TLC, dichoromethane was added
to the reaction mixture as the solvent, followed by the addi-
tion of iodobenzene diacetate (2.2 equiv). A complete cycli-
zation reaction was observed within a few minutes at room
temperature for a range of amine substrates, as shown in
Scheme 2, demonstrating that the one-pot procedure is
simple and convenient to carry out for the preparation of 2-
aminoazoles starting from azoles and amines.
After successful exploration of the scope of the reaction
towards reactants, benzoxazoles and amines, we turned our
attention to other types of azole. Accordingly, we selected
1,3,4-oxadiazoles to search for a similar ring-opening and
-closing reaction to afford 2-aminated oxadiazoles. This con-
sideration was for two reasons: 2-aminooxadiazoles are one
of the highly interesting pharmaceutical motifs that show a
broad spectrum of biological activities.[13] In addition, it was
intriguing to see whether the same ring-opening process
takes place with this type of non-fused heterocycle. We were
delighted to observe that oxadiazoles do indeed undergo the
two-step procedure, although an elevated temperature
(808C) was required for the ring-opening step (Table 4). It
should be mentioned that the isolated amidine adducts (6)
are present in the form of acylhydrazino amidines rather
8296
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 8294 – 8298

2-Aminooxazole Formation
COMMUNICATION
Table 4. Preparation of 2-aminooxadiazoles.[a,b]
any kinetic isotope effects [Eq. (1)]. It was observed that
the oxidative cyclization reaction does not exhibit kinetic
isotope effects (kH/kD =1.0), which implies that the cleavage
À
of the C H bond alpha to the nitrogen of the amidine
adduct is not involved in the rate-determining step.
Entry
R1
Yield of 6
Yield of 7
[%][c]
[%][c]
1
2
5a
5b
98
99
6ab
73
80
7ab
6bb
7bb
3
4
5
5c
5d
5e
96
93
91
6cb
6db
6eb
78
65
72
7cb
7db
7eb
Although the exact mechanistic details are not clear at
this stage, it is assumed that the IIII species initially coordi-
nates to the amidino nitrogen rather than the phenolic
oxygen. This is followed by a ring closure to form the de-
sired product through a benzoxazoline adduct, which may
be the key species sensitive to oxidation, with concurrent
elimination of iodobenzene and acetic acid (Scheme 3).[16]
On the other hand, if an alternative pathway operates, in
which the IIII [17] species reacts first with the phenolic oxygen,
a quinone-type intermediate might be produced[18] that
could inhibit the desired oxidative ring-closing step.
In summary, we have developed a new metal-free system
for the amination of azoles with amines through a unique
ring-opening and subsequent ring-closing strategy. The addi-
tion of amines to azoles is highly efficient under neat and
mild conditions to give the amidine adducts. Oxidative cycli-
zation of the amidine adducts was readily achieved within a
short time at room temperature by using iodobenzene diac-
eate as the oxidant. The two-step procedure can also be per-
formed in a one-pot process without isolation of the amidine
intermediate. The overall reaction is highly attractive from a
synthetic point of view in that the reaction is free from the
use of acid, base, or metallic catalysts and the optimal reac-
tion conditions are mild. This procedure, therefore, is antici-
pated to be a powerful tool for the synthesis of 2-aminoben-
zoxazoles and oxadiazoles, which are important pharmaco-
phores of high biological activity.
[a] Amidine formation: 5 (0.5 mmol) and 2b (1.5 mmol), neat. [b] Condi-
tions for ring-closing step: 6 (0.5 mmol) and PhI(OAc)2 (1.5 equiv) in
CH2Cl2 (3 mL) at 258C for 2 h under an air atmosphere. [c] Isolated
AHCTUNGTRENNUNG
yields.
Table 5. Substrate scope with regard to amines in the reaction with oxa-
diazole 5a.[a,b]
Entry
1
Amine 2
t
Yield of 6
Yield of 7
[h]
[%][c]
[%][c]
2a
2l
3
81
97
6aa
61
73
7aa
2
5.5
6al
7al
3
4
2d
2e
9
98
94
6ad
6ae
72
76
7ad
7ae
10
5
6
2 f
2j
12
12
97
60
6af
6aj
69
65
7af
7aj
Experimental Section
Representative procedure: Pyrrolidine (2a, 1 mmol) was added to a
round-bottomed flask charged with neat 5-methylbenzoxazole (1a,
0.5 mmol) and the solution was stirred for 30 min at 258C under an air
atmosphere. The crude product mixture was diluted with CH2Cl2
(15 mL), washed with a saturated solution of NaCl (3ꢂ10 mL) and the
aqueous layer was again extracted with CH2Cl2 (3ꢂ10 mL). The com-
bined organic layers were dried over MgSO4 and concentrated under re-
duced pressure to obtain analytically pure 4-methyl-2-(pyrrolidin-1-ylme-
thyleneamino)phenol (3aa) in 99% yield. After dissolving this amidine
[a] Amidine formation: 5a (0.5 mmol) and 2 (1.5 mmol), neat. [b] Condi-
tions for ring-closing step: 6 (0.5 mmol) and PhI(OAc)2 (1.5 equiv) in
CH2Cl2 (3 mL) at 258C for 2 h under an air atmosphere. [c] Isolated
AHCTUNGTRENNUNG
yields.
A competition experiment between an ortho-hydroxyami-
dine (3aa) and its deuterated derivative (3aa-d), which was
easily prepared according to the procedure presented herein
upon the reaction of pyrrolidine with 2-deuterated 5-methyl-
benzoxazole,[14] was subsequently performed to determine
adduct in dichloromethane (3 mL), PhIACHTNUTRGNEUNG(OAc)2 (1.1 equiv) was added,
and the reaction mixture was stirred for 5 min at 258C under an air at-
mosphere. The mixture was then diluted with CH2Cl2 (15 mL), washed
with a saturated solution of NaHCO3 (3ꢂ15 mL) and the aqueous layer
was extracted with CH2Cl2 (3ꢂ15 mL). The combined organic layers
Chem. Eur. J. 2011, 17, 8294 – 8298
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
8297

S. Chang et al.
[4] Q. Wang, S. L. Schreiber, Org.
Lett. 2009, 11, 5178–5180.
[5] T. Kawano, K. Hirano, T. Satoh,
M. Miura, J. Am. Chem. Soc.
2010, 132, 6900–6101.
[6] a) S. H. Cho, J. Y. Kim, S. Y. Lee,
S. Chang, Angew. Chem. 2009,
121, 9291–9294; Angew. Chem.
Int. Ed. 2009, 48, 9127–9130;
b) J. Y. Kim, S. H. Cho, J. Joseph,
S. Chang, Angew. Chem. 2010,
122, 10095-10099; Angew. Chem.
Int. Ed. 2010, 49, 9899-9903.
[7] a) F. Babudri, G. Bartoli, F. Cimi-
nale, S. Florio, G. Ingrosso, Tetra-
hedron Lett. 1984, 25, 2047–2050;
Scheme 2. The one-pot procedure for the preparation of 2-aminobenzoxazoles.[14]
b) S. Florio, Tetrahedron 1984, 40,
5089–5095; c) M. Makosza, J.
Stalewski, Tetrahedron 1995, 51,
7277–7286.
[8] R. S. Sꢃnchez, F. A. Zhuravlev, J. Am. Chem. Soc. 2007, 129, 5824–
5825.
[9] a) D. D. Dꢄaz, M. G. Finn, Chem. Commun. 2004, 2514–2516; b) A.
Porcheddu, G. Giacomelli, I. Piredda, J. Comb. Chem. 2009, 11,
126–130; c) L. Cai, Y. Han, S. Ren, L. Huang, Tetrahedron 2000, 56,
8253–8262, and references therein.
[10] a) L. M. Naumova, V. N. Charushin, O. N. Chupakhin, G. C. Izmailo-
va, Chem. Heterocycl. Compd. 1985, 21, 326–331; b) V. A. Doro-
khov, A. R. Amamchyan, V. S. Bogdanov, Russ. Chem. Bull. 1989,
38, 2197–2199; c) A. G. Mikhailovskii, M. I. Bakrin, Chem. Hetero-
cycl. Compd. 1991, 27, 1091–1094.
[11] Y.-X. Chen, L.-F. Qian, W. Zhang, B. Han, Angew. Chem. 2008, 120,
9470–9473; Angew. Chem. Int. Ed. 2008, 47, 9330–9333.
[12] For recent works from this laboratory on the metal-mediated trans-
formations of heteroarenes, see: a) S. H. Cho, S. J. Hwang, S. Chang,
J. Am. Chem. Soc. 2008, 130, 9254–9256; b) S. J. Hwang, S. H. Cho,
S. Chang, J. Am. Chem. Soc. 2008, 130, 16158–16159; c) M. Kim, J.
Kwak, S. Chang, Angew. Chem. 2009, 121, 9097–9101; Angew.
Chem. Int. Ed. 2009, 48, 8935–8939; d) S. H. Kim, S. Chang, Org.
Lett. 2010, 12, 1868–1871; e) J. Kim, S. Chang, J. Am. Chem. Soc.
2010, 132, 10272–10274.
Scheme 3. A proposed pathway for the PhIACHTNUTRGNEUNG(OAc)2-mediated ring-closing
reaction of o-hydroxy-N-aryl-N,N-dialkylformamidine.
were dried over MgSO4 and concentrated under reduced pressure. The
resulting residue was purified by column chromatography on silica gel to
afford 5-methyl-2-(pyrrolidin-1-yl)benzoxazole (4aa, 91%).
Acknowledgements
This research was supported by a Korea Research Foundation Grant
(KRF-2008-C00024, Star Faculty Program) and the MIRC (NRF-2010-
0001957).
[13] a) H. L. Yale, K. Losee, J. Med. Chem. 1966, 9, 478–483; b) Y. Sato,
M. Yamada, S. Yoshida, T. Soneda, M. Ishikawa, T. Nizato, K.
Suzuki, F. Konno, J. Med. Chem. 1998, 41, 3015–3021; c) S. Yoshida,
T. Watanabe, Y. Sato, Bioorg. Med. Chem. 2007, 15, 3515–3523;
d) Y. A. Al-Soud, H. H. Al-Saꢁdoni, H. A. S. Amajaour, K. S. M.
Salih, M. S. Mubarak, N. A. Al-Masoudi, I. H. Jaber, Z. Naturforsch.
B 2008, 63, 83–89; e) J. Neyts, E. D. Clercq, R. Singha, Y. H. Chang,
A. R. Das, S. K. Chakraborty, S. C. Hong, S.-C. Tsay, M.-H. Hsu,
J. R. Hwu, J. Med. Chem. 2009, 52, 1486–1490.
[14] See the Supporting Information for details.
[15] M. Makosza, Chem. Soc. Rev. 2010, 39, 2855–2868.
[16] A similar pathway was previously proposed in the oxidative intra-
molecular cyclization of phenolic Schiff bases by using iodobenzene
diacetate: R. S. Varma, R. K. Saini, O. Prakash, Tetrahedron Lett.
1997, 38, 2621–2622.
À
Keywords: amination · azoles · C N bond formation ·
iodine · ring-opening processes · ring-closing processes
[1] a) R. Hili, A. K. Yudin, Nat. Chem. Biol. 2006, 2, 284–287;
b) Amino Group Chemistry: From Synthesis to the Life of Sciences
(Ed.: A. Ricci), Wiley-VCH, Weinheim, 2007.
[2] a) A. R. Muci, S. L. Buchwald, Top. Curr. Chem. 2002, 219, 131–
209; b) D. S. Surry, S. L. Buchwald, Angew. Chem. 2008, 120, 6438–
6461; Angew. Chem. Int. Ed. 2008, 47, 6338–6361; c) J. F. Hartwig,
Acc. Chem. Res. 2008, 41, 1534–1544; d) D. M. T. Chan, K. L.
Monaco, R.-P. Wang, M. P. Winters, Tetrahedron Lett. 1998, 39,
2933–2936; e) D. Ma, Q. Cai, H. Zhang, Org. Lett. 2003, 5, 2453–
2455; f) H. Rao, H. Fu, Y. Jiang, Y. Zhao, Angew. Chem. 2009, 121,
1134–1136; Angew. Chem. Int. Ed. 2009, 48, 1114–1116; g) J. Kim,
S. Chang, Chem. Commun. 2008, 3052–3054; h) J. Kim, S. Y. Lee, J.
Lee, Y. Do, S. Chang, J. Org. Chem. 2008, 73, 9454–9457; i) M. Kim,
S. Chang, Org. Lett. 2010, 12, 1640–1643.
[17] For a review on the chemistry of hypervalent iodine species, see: T.
Wirth, Angew. Chem. 2005, 117, 3722–3731; Angew. Chem. Int. Ed.
2005, 44, 3656–3665.
[18] Y. Tamura, T. Yakura, H. Tohma, K. Kikuchi, Y. Kita, Synthesis
1989, 126–127.
[3] D. Monguchi, T. Fujiwara, H. Furukawa, A. Mori, Org. Lett. 2009,
11, 1607–1610.
Received: May 11, 2011
Published online: June 7, 2011
8298
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 8294 – 8298