An efficient oxidative conversion of aldehydes into 2-substituted 2-oxazolines using 1,3-diiodo-5,5-dimethylhydantoin

Article abstract of DOI:10.1055/s-0029-1216843

Various aromatic and aliphatic aldehydes were converted into the corresponding 2-aryl and 2-alkyl-2-oxazolines, respectively, in good to high yields by reaction with 2-aminoethanol and 1,3-diiodo-5,5-dimethylhydantoin. Moreover, chiral bis-2-oxazolines, which can be used as chiral ligands in asymmetric synthesis, could be also prepared in moderate yields by the reaction of dialdehydes with (R)-(-)-2-phenylglycinol under the same conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1216843

PAPER
2329
An Efficient Oxidative Conversion of Aldehydes into 2-Substituted
2-Oxazolines Using 1,3-Diiodo-5,5-dimethylhydantoin
O
xidative Con
h
version of
A
o
ldehyde
s
int
g
2-Substitut
o
e
d
2-Oxazolines Takahashi, Hideo Togo*
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
Fax +81(43)2902874; E-mail: togo@faculty.chiba-u.jp
Received 5 February 2009; revised 26 February 2009
using molecular iodine and potassium carbonate.11 How-
ever, the yields of 2-alkyl-2-oxazolines from the corre-
sponding aliphatic aldehydes were quite low, especially
when secondary and primary alkyl aldehydes were used,
Abstract: Various aromatic and aliphatic aldehydes were convert-
ed into the corresponding 2-aryl and 2-alkyl-2-oxazolines, respec-
tively, in good to high yields by reaction with 2-aminoethanol and
1,3-diiodo-5,5-dimethylhydantoin. Moreover, chiral bis-2-oxazo-
lines, which can be used as chiral ligands in asymmetric synthesis, due to such side reactions as the aldol reaction. As a result,
could be also prepared in moderate yields by the reaction of dialde-
the preparation of 2-substituted 2-oxazolines from alde-
hydes with (R)-(–)-2-phenylglycinol under the same conditions.
hydes using molecular iodine or tert-butyl hypochlorite
Key words: 2-aryl-2-oxazoline, 2-alkyl-2-oxazoline, 1,3-diiodo-
5,5-dimethylhydantoin, aldehyde, 2-aminoethanol, chiral oxazoline
was not effective, although the preparation of 2-aryl- and
2-alkyl-2-imidazolines from corresponding aldehydes
with ethylenediamines using molecular iodine and tert-
butyl hypochlorite was quite effective.11,12
At present, many 2-oxazoline-containing natural products
and biologically active compounds in marine organisms
are known.1 Because of this, the preparation of 2-oxazo-
lines has drawn great interest and is of importance in
pharmaceutical2 and synthetic material applications.3
Moreover, chiral 2-oxazolines have recently gained popu-
larity for use in asymmetric synthesis as chiral ligands on
metals.4 Generally, 2-oxazolines are prepared by the reac-
tion of acyl halides, esters, carboxylic acids, nitriles, or
carboxylic acid derivatives with 2-aminoethanols.5 The
BF3-promoted Ritter reaction of epoxides with nitriles
provides the corresponding 2-oxazolines in moderate
yields.6 Treatment of acyl halides or amides with alkenes
in the presence of oxidants, such as nitridomanganese
complex or t-BuOI, gave the corresponding 2-oxazolines
in moderate to good yields.7
Here, as part of our synthetic study on 1,3-diiodo-5,5-
dimethylhydantoin (DIH; Figure 1),13 which is more reac-
tive than molecular iodine or N-iodosuccinimide (NIS),
we would like to report an efficient method for the prepa-
ration of 2-aryl- and 2-alkyl-2-oxazolines, and chiral ox-
azoline ligands from the corresponding aldehydes and
amino alcohols using DIH.
O
N
I
N
I
O
Figure 1 Structure of DIH
2-Aminoethanol (ethanolamine) was added to a solution
of p-tolualdehyde in tert-butyl alcohol, and the obtained
mixture was stirred for 30 minutes at room temperature.
Then, DIH (1.5 equiv) was added and the obtained mix-
ture was stirred for 24 hours at 50 °C. The results are
shown in Table 1.
Aldehydes are an attractive choice as starting substrates
because they are easily available. However, today, studies
of direct oxidative conversion of aldehydes into 2-oxazo-
lines are limited. The BF3-promoted formation of 2-aryl
and 2-alkyl-2-oxazolines in good yields from the reaction
of azido alcohols with aromatic and aliphatic aldehydes
was reported, although azide must be handled with care.8
2-Aryl-2-oxazolines could be obtained in good yields by
the reaction of aromatic aldehydes with 2-aminoethanol
and pyridinium hydrobromide perbromide, although only
aromatic aldehydes could give such good yields.9 Recent-
ly, high-yield method for the preparation of 2-aryl- and 2-
alkyl-2-oxazolines from aromatic and aliphatic alde-
hydes, respectively, and amino alcohols using N-bromo-
succinimide (NBS) was reported.10 We have also reported
the preparation of 2-aryl and 2-alkyl-2-oxazolines from
aromatic and aliphatic aldehydes with 2-aminoethanol,
Use of various kinds of aromatic aldehydes bearing an
electron-donating group or an electron-withdrawing
group produced the corresponding 2-aryl-2-oxazolines in
good yields, except for 2-thienylaldehyde (entries 1–12).
Overall, the yields are higher than those with the molecu-
lar iodine method.11 NIS also worked well, although 3.0
equivalents were required to obtain a good yield (entry 2).
tert-Butyl hypochlorite, in contrast, did not work well (en-
try 3). For 1,3-benzenedicarboxaldehyde, the yield was
slightly improved by using K2CO3 as the base additive
(entries 11, 12). On the other hand, the yields of 2-alkyl-
2-oxazolines were low under the same conditions from al-
iphatic aldehydes (entries 13, 20, 25). However, the addi-
tion of K2CO3 as base improved the yields of 2-alkyl-2-
oxazolines significantly, as shown in entries 14, 17, 21,
and 26, due to the promotion of HI elimination in the in-
SYNTHESIS 2009, No. 14, pp 2329–2332
x
x.
x
x
.
2
0
0
9
Advanced online publication: 25.05.2009
DOI: 10.1055/s-0029-1216843; Art ID: F03509SS
© Georg Thieme Verlag Stuttgart · New York

2330
S. Takahashi, H. Togo
PAPER
much lower, as shown in entries 15, 18, and 23 for NIS,
and in entries 16, 19, and 24 for tert-butyl hypochlorite.
Table 1 Preparation of 2-Substituted 2-Oxazolines from Aldehydes
with DIH
Based on these results, the reactions of p-tolualdehyde,
1,3-benzenedicarboxaldehyde, and 2,6-pyridinedicarbox-
aldehyde with (R)-(–)-phenylglycinol and DIH in the
presence of K2CO3 were successfully carried out to pro-
vide the corresponding chiral 2-substituted 2-oxazolines
in good to moderate yields, as shown in Scheme 1. NBS
had shown a good reactivity for the efficient preparation
of 2-aryl- and 2-alkyl-2-oxazolines from aromatic and al-
iphatic aldehydes and amino alcohols.10 However, DIH
showed higher reactivity than NBS in those reactions
(Scheme 1 and Table 1).
1)
2)
(1.5 equiv)
HO
NH2
O
N
t-BuOH, r.t., 30 min
R
CHO
R
DIH (1.5 equiv)
base (2.0 equiv)
t-BuOH, 50 °C, 24 h
Entry
R
Base
–
Yield (%)a
1
85
83
3
2b
3c
4
5
6
7
–
–
–
–
82
86
93
89
MeO
Br
Ph
1)
(1.5 equiv)
HO
NH2
O
N
t-BuOH, r.t., 30 min
CHO
DIH (1.5 equiv)
K2CO3 (2.0 equiv)
t-BuOH, 50 °C, 24 h
2)
O2N
NC
Ph
85% [ 65%a ]
Ph
1)
(3.0 equiv)
HO
NH2
8
9
–
–
77
42
t-BuOH, r.t., 30 min
N
2)
O
DIH (3.0 equiv)
K2CO3 (5.0 equiv)
t-BuOH, 50 °C, 24 h
O
X
OHC
X
CHO
N
N
S
Ph
Ph
X = CH 76% [ 43%a ]
X = N
45% [ 21%a
a Ref. 10 conditions with NBS
10
–
–
70
]
11
12
64
73
K2CO3
Scheme 1 Preparation of chiral 2-oxazolines
13
14
15b
16c
–
11
53
17
12
In summary, 2-aryl-2-oxazolines could be easily and effi-
ciently obtained in high yields by the reaction of aromatic
aldehydes with 2-aminoethanol using DIH in tert-butyl al-
cohol. Under the same conditions, 2-alkyl-2-oxazolines
could be also obtained in moderate to good yields by the
reaction of aliphatic aldehydes with 2-aminoethanol.
Chiral 2-substituted 2-oxazolines could also successfully
prepared by this method. The reactivity of DIH is higher
than that of molecular iodine, NIS, and tert-butyl hy-
pochlorite. DIH is a pale yellow solid that does not sub-
lime like molecular iodine, and has low toxicity. Thus, the
present method is another useful alternative for the prepa-
ration of 2-substituted 2-oxazolines from aldehydes and
amino alcohols.
K2CO3
K2CO3
K2CO3
17
K2CO3
K2CO3
K2CO3
50
32
18
18b
19c
20
21
22
23b
24c
–
26
75
53
19
14
K2CO3
NaHCO3
K2CO3
K2CO3
25
26
–
K2CO3
36
93
a Isolated yield.
1H NMR and 13C NMR spectra were recorded on Jeol JNM-GSX-
400, Jeol JNM-LA-400, and Jeol JNM-LA-500 spectrometers.
Chemical shifts are expressed in ppm downfield from TMS in d
units. Mass spectra were recorded on Jeol HX-110 and Jeol JMS-
ATII 15 spectrometers. IR spectra were recorded on a Jasco FT/IR-
4100 spectrometer. Melting points were determined using a Yamato
melting point apparatus model MP-21. Silica gel 60 (Kanto Kagaku
Co.) was used for column chromatography, and Wakogel B-5F was
used for preparative TLC.
b NIS (3.0 equiv) was used, instead of DIH.
c t-BuOCl (3.0 equiv) was used, instead of DIH.
termediates. When NIS and tert-butyl hypochlorite were
used for the same aliphatic aldehydes under the same re-
action conditions, the yields of 2-alkyl-2-oxazolines were
Synthesis 2009, No. 14, 2329–2332 © Thieme Stuttgart · New York

PAPER
Oxidative Conversion of Aldehydes into 2-Substituted 2-Oxazolines
2331
2-Oxazolines from Aldehydes; 2-(4¢-Methylphenyl)-2-oxazo-
line; Typical Procedure
HRMS (FAB): m/z calcd for C8H9N2O (M + H): 149.0715; found:
149.0707 (M + H).
To a solution of p-tolualdehyde (120.2 mg, 1 mmol) in tert-butyl al-
cohol (10 mL) was added 2-aminoethanol (91.6 mg, 1.5 mmol). The
mixture was stirred at r.t. under argon for 30 min, and then DIH
(569.9 mg, 1.5 mmol) was added and the mixture was stirred at
50 °C. After 24 h, the mixture was quenched with sat. aq Na2SO3
until the color of I2 had almost disappeared, and was extracted with
CHCl3 (3 × 15 mL). The combined organic layers were washed with
aq K2CO3 (10 mL) and brine (10 mL), and dried (Na2SO4). After fil-
tration, the mixture was evaporated and the residue was chromato-
graphed on silica gel (eluent: EtOAc) to give 2-(4¢-methylphenyl)-
2-oxazoline; yield: 137 mg (85%); mp 71–72 °C (Lit.5k mp 69–
71 °C).
2-(1¢-Naphthyl)-2-oxazoline
Liquid; bp 150 °C/2 mmHg.
IR (neat): 2970, 1640, 1590, 1320, 1120, 1000, 780 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.17 (t, J = 9.4 Hz, 2 H), 4.39 (t,
J = 9.4 Hz, 2 H), 7.44–7.51 (m, 2 H), 7.56–7.61 (m, 1 H), 7.84 (d,
J = 8.3 Hz, 1 H), 7.92 (d, J = 8.3 Hz, 1 H), 8.08 (dd, J = 7.3, 0.2 Hz,
1 H), 9.13 (d, J = 8.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 55.6, 66.4, 124.4, 124.5, 126.0,
126.3, 127.2, 128.3, 128.5, 131.0, 131.8, 133.6, 164.3.
HRMS (FAB): m/z calcd for C13H12NO (M + H): 198.0919; found:
198.0904 (M + H).
IR (KBr): 3040, 2940, 1650, 1355, 1260, 1070, 940 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.39 (s, 3 H), 4.04 (t, J = 9.4 Hz,
2 H), 4.41 (t, J = 9.4 Hz, 2 H), 7.21 (d, J = 8.1 Hz, 2 H), 7.83 (d,
J = 8.1 Hz, 2 H).
2-(2¢-Thienyl)-2-oxazoline
Mp 57–59 °C (Lit.14 mp 58–60 °C).
IR (KBr): 3165, 2880, 1645, 1530, 1055, 1015, 740 cm–1.
2-(4¢-Methoxyphenyl)-2-oxazoline
Mp 61.5–62 °C (Lit.14 mp 62.5–63.5 °C).
1H NMR (400 MHz, CDCl3): d = 4.05 (t, J = 9.4 Hz, 2 H), 4.43 (t,
J = 9.4 Hz, 2 H), 7.08 (dd, J = 5.0, 3.6 Hz, 1 H), 7.45 (dd, J = 5.0,
1.0 Hz, 1 H), 7.59 (dd, J = 3.6, 1.0 Hz, 1 H).
IR (KBr): 2905, 1645, 1510, 1255, 1165, 1070, 940 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.85 (s, 3 H), 4.04 (t, J = 9.5 Hz,
2 H), 4.41 (t, J = 9.5 Hz, 2 H), 6.92 (d, J = 8.8 Hz, 2 H), 7.89 (d,
J = 8.8 Hz, 2 H).
2-(1¢-Adamantyl)-2-oxazoline
Mp 40–41 °C (Lit.16 mp 39–40 °C).
IR (mull): 1660, 1345, 1225, 1060, 955 cm–1.
2-(4¢-Bromophenyl)-2-oxazoline
Mp 95–97 °C.
1H NMR (400 MHz, CDCl3): d = 1.69–1.76 (m, 6 H), 1.89–1.90 (m,
6 H), 2.01 (m, 3 H), 3.80 (t, J = 9.4 Hz, 2 H), 4.19 (t, J = 9.4 Hz, 2
H).
IR (KBr): 2910, 1645, 1395, 1260, 1075, 835, 730 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.06 (t, J = 9.6 Hz, 2 H), 4.42 (t,
J = 9.6 Hz, 2 H), 7.55 (d, J = 8.5 Hz, 2 H), 7.81 (d, J = 8.5 Hz, 2 H).
2-Cyclohexyl-2-oxazoline
Liquid; bp 90 °C/2 mm Hg (Lit.15 bp 120 °C/15 mm Hg).
13C NMR (100 MHz, CDCl3): d = 55.0, 67.7, 125.9, 126.7, 129.7,
131.6, 163.9.
IR (neat): 3050, 2980, 1560, 1120, 1000, 810, 780 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.20–1.47 (m, 4 H), 1.63–1.95 (m,
6 H), 2.30 (t, J = 11.3 Hz, 1 H) 3.82 (t, J = 9.5 Hz, 2 H), 4.21 (t,
J = 9.5 Hz, 2 H).
HRMS (FAB): m/z calcd for C9H9BrNO (M + H): 225.9868;
found: 225.9859 (M + H).
2-(4¢-Nitrophenyl)-2-oxazoline
Mp 174 °C (Lit.15 mp 178–179 °C).
2-Heptyl-2-oxazoline
Oil.
IR (KBr): 2360, 1650, 1520, 1335, 1070, 940, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 7.1 Hz, 3 H), 1.27–
1.33 (m, 8 H), 1.63 (m, 2 H), 2.26 (t, J = 7.6 Hz, 2 H), 3.82 (t, J = 9.5
Hz, 2 H), 4.22 (t, J = 9.5 Hz, 2 H).
1H NMR (400 MHz, CDCl3): d = 4.13 (t, J = 9.7 Hz, 2 H), 4.51 (t,
J = 9.7 Hz, 2 H), 8.12 (d, J = 8.9 Hz, 2 H), 8.28 (d, J = 8.9 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 13.97 (s), 22.53 (d), 25.91 (d),
27.91 (d), 28.86 (d), 29.13 (d), 31.60 (d), 54.30 (d), 67.05 (d),
168.64 (q).
2-(4¢-Cyanophenyl)-2-oxazoline
Mp 113–114 °C.
IR (KBr): 2225, 1650, 1265, 1070, 940, 850, 670 cm–1.
HRMS (FAB): m/z calcd for C10H20NO (M + H): 170.1542;
found: 170.1545 (M + H).
1H NMR (400 MHz, CDCl3): d = 4.11 (t, J = 9.7 Hz, 2 H), 4.49 (t,
J = 9.7 Hz, 2 H), 7.71 (d, J = 8.5 Hz, 2 H), 8.05 (d, J = 8.5 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 55.1, 68.0, 114.6, 118.2, 128.6,
131.8, 132.1, 163.0.
2-(2¢-Phenylethyl)-2-oxazoline
Oil.
HRMS (FAB): m/z calcd for C10H9N2O (M + H): 173.0715;
found: 173.0722 (M + H).
1H NMR (400 MHz, CDCl3): d = 2.58 (t, J = 8.1 Hz, 2 H), 2.96 (t,
J = 8.1 Hz, 2 H), 3.80 (t, J = 9.4 Hz, 2 H), 4.21 (t, J = 9.4 Hz, 2 H),
7.20–7.30 (m, 5 H).
2-(2¢-Pyridyl)-2-oxazoline
Liquid; bp 90 °C/2 mmHg.
HRMS (FAB): m/z calcd for C11H14NO (M + H): 176.1079;
found: 176.1075 (M + H).
IR (neat): 2940, 1640, 1370, 1100, 945, 800 cm–1.
(4R)-2-(4¢-Methylphenyl)-4-phenyl-2-oxazoline
Oil.
1H NMR (400 MHz, CDCl3): d = 4.13 (t, J = 9.7 Hz, 2 H), 4.54 (t,
J = 9.7 Hz, 2 H), 7.39–7.42 (m, 1 H), 7.79 (t, J = 7.8 Hz, 1 H), 8.05
(d, J = 7.8 Hz, 1 H), 8.71 (d, J = 4.9 Hz, 1 H).
1H NMR (400 MHz, CDCl3): d = 2.38 (s, 3 H), 4.23 (t, J = 8.3 Hz,
1 H), 4.72–4.78 (m, 1 H), 5.33–5.37 (m, 1 H), 7.22 (d, J = 8.2 Hz, 2
H), 7.25–7.35 (m, 5 H), 7.93 (d, J = 8.2 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 54.9, 68.0, 123.6, 125.3, 136.4,
146.5, 149.5, 163.6.
Synthesis 2009, No. 14, 2329–2332 © Thieme Stuttgart · New York

2332
S. Takahashi, H. Togo
PAPER
(3) For examples: (a) Menges, F.; Neuburger, M.; Pfaltz, A.
HRMS (FAB): m/z calcd for C16H16NO (M + H): 238.1235;
found: 238.1232 (M + H).
Org. Lett. 2002, 4, 4713. (b) Evans, D. A.; Downey, C. W.;
Hubbs, J. L. J. Am. Chem. Soc. 2003, 125, 8706. (c) Bhor,
S.; Anilkumar, G.; Tse, M. K.; Klawonn, M.; Döbler, C.;
Bitterlich, B.; Grotevendt, A.; Beller, M. Org. Lett. 2005, 7,
3393.
1,3-Bis[(4¢R)-4¢-phenyl-2¢-oxazoline-2¢-yl]benzene
Mp 129–130 °C.
1H NMR (400 MHz, CDCl3): d = 4.30 (t, J = 8.3 Hz, 2 H), 4.80–
4.84 (m, 2 H), 5.39–5.44 (m, 2 H), 7.29–7.38 (m, 10 H), 7.52 (t,
J = 7.7 Hz, 1 H), 8.20 (dd, J = 7.7, 1.7 Hz, 2 H), 8.69 (t, J = 1.7 Hz,
1 H).
(4) For reviews: (a) Ghosh, A. K.; Mathivanan, P.; Cappiello, J.
Tetrahedron: Asymmetry 1998, 9, 1. (b) Johnson, J. S.;
Evans, D. A. Acc. Chem. Res. 2000, 33, 325. (c) Helmchen,
G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336. (d) Meyers,
A. I. J. Org. Chem. 2005, 70, 6137. For recent papers:
(e) Li, Y.; Feng, J.; Wang, W.; Chen, J.; Cao, X. J. Org.
Chem. 2007, 72, 2344. (f) Liu, H.; Xu, J.; Du, D. Org. Lett.
2007, 9, 4725. (g) Schizuka, M.; Snapper, M. L. Angew.
Chem. Int. Ed. 2008, 47, 5049. (h)Nakamura, S.;Hirata, N.;
Yamada, R.; Kita, T.; Shibata, N. Chem. Eur. J. 2008, 14,
5519. (i) Sibi, M. P.; Nie, X.; Shackleford, J. P.; Stanley, L.
M.; Bouret, F. Synlett 2008, 2655.
13C NMR (125 MHz, CDCl3): d = 70.25 (t), 74.99 (d), 126.76 (t),
127.69 (t), 128.02 (q), 128.56 (t), 128.59 (t), 128.80 (t), 131.40 (t),
142.23 (q), 164.10 (q).
HRMS (FAB): m/z calcd for C7H15N2 (M + H): 369.1603; found:
369.1603 (M + H).
2,6-Bis[(4¢R)-4¢-phenyl-2¢-oxazoline-2¢-yl]pyridine
Mp 170–172 °C.
(5) (a) Witte, H.; Seeliger, W. Angew. Chem., Int. Ed. Engl.
1972, 11, 287. (b) Apple, R. Angew. Chem., Int. Ed. Engl.
1975, 14, 801. (c) Lowenthal, A.; Abiko, A.; Masamune, S.
Tetrahedron Lett. 1990, 31, 6005. (d) Zhou, P.; Blubarum,
J. E.; Burns, C. T.; Natale, N. R. Tetrahedron Lett. 1977, 38,
7019. (e) Vorbrüggen, H.; Krolikiewicz, K. Tetrahedron
1993, 49, 9353. (f) Rajaram, S.; Sigman, M. S. Org. Lett.
2002, 4, 3399. (g) Cwik, A.; Hell, Z.; Hegedüs, A.; Finta, Z.;
Horvath, Z. Tetrahedron Lett. 2002, 43, 3985. (h) Bandgar,
B. P.; Pandit, S. S. Tetrahedron Lett. 2003, 44, 2331.
(i) Katritzky, A. R.; Cai, C.; Suzuki, K.; Singh, S. K. J. Org.
Chem. 2004, 69, 811. (j) Kangani, C. O.; Kelly, D. E.
Tetrahedron Lett. 2005, 46, 8917. (k) Mohammadpoor-
Baltork, I.; Khosropour, A. R.; Hojati, S. F. Synlett 2005,
2747. (l) Ohshima, T.; Iwasaki, J.; Mashima, K. Chem.
Commun. 2006, 2711. (m) Whelligan, D. K.; Bolm, C.
J. Org. Chem. 2006, 71, 4609. (n) Kangani, C. O.; Kelley,
D. E.; Day, B. N. Tetrahedron Lett. 2006, 47, 6497.
(o) Fukuhara, T.; Hasegawa, C.; Hara, J. Synthesis 2007,
1528. (p) May, A. E.; Willoughby, P. H.; Hoye, T. R. J. Org.
Chem. 2008, 23, 3292. (q) Chudasama, V.; Wilden, J. D.
Chem. Commun. 2008, 3768.
(6) (a) Fotadar, U.; Becu, C.; Borremans, F. A. M.; Anteunis, M.
J. O. Tetrahedron 1978, 34, 3537. (b) Feske, B. D.;
Kaluzna, I. A.; Stewart, J. D. J. Org. Chem. 2005, 70, 9654.
(7) (a) Minakarta, S.; Nishimura, M.; Takahashi, T.;
Oderaotoshi, Y.; Komatsu, M. Tetrahedron Lett. 2001, 42,
9019. (b) Nishimura, M.; Minakata, S.; Takahashi, T.;
Oderaotoshi, Y.; Komatsu, M. J. Org. Chem. 2002, 67,
2101. (c) Minakata, S.; Morino, Y.; Ide, T.; Oderaotoshi, Y.;
Komatsu, M. Chem. Commun. 2007, 3279.
1H NMR (400MHz, CDCl3): d = 4.43 (t, J = 8.5 Hz, 2 H), 4.91–4.95
(m, 2 H), 5.44–5.49 (m, 2 H), 7.29–7.39 (m, 10 H), 7.92 (t, J = 7.9
Hz, 1 H), 8.35 (d, J = 7.9 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 70.29 (t), 75.50 (d), 126.32 (t),
126.83 (t), 127.79 (t), 128.81 (t), 137.49 (t), 141.73 (q), 146.75 (q),
163.47 (q).
HRMS (FAB): m/z calcd for C23H20N3O2 (M + H): 370.1559;
found: 370.1556 (M + H).
Acknowledgment
Financial support in the form of a Grant-in-Aid for Scientific
Research (No. 20550033) from the Ministry of Education, Culture,
Sports, Science, and Technology, Japan is gratefully acknowledged.
The authors thank Nippon Chemicals Co. for the gift of DIH.
References
(1) (a) Bergeron, R. J. Chem. Rev. 1984, 84, 587. (b)Davidson,
B. S. Chem. Rev. 1993, 93, 1771. (c) Yeh, V. S. C.
Tetrahedron 2004, 60, 11995.
(2) (a) Boyd, G. V. In Comprehensive Heterocyclic Chemistry,
Vol. 6; Katritzky, A. R.; Rees, C. W., Eds.; Pergamon:
Oxford, 1984, 178–233. (b) Gilman, A. G.; Goodman, L. S.
The Pharmacological Basis of Therapeutics, 10th ed.;
Macmillan & Co: New York, 2001. (c) Genet, J. P.;
Thorimbert, S.; Touzin, A. M. Tetrahedron Lett. 1993, 34,
1159. (d) Wipf, P.; Venkatraman, S. Synlett 1997, 1.
(e) Rodriguez, A. D.; Ramirez, C.; Rodriguez, I. I.;
(8) (a) Badiang, J. G.; Aubé, J. J. Org. Chem. 1996, 61, 2484.
(b) Chakraborty, R.; Franz, V.; Bez, G.; Vasadia, D.; Popuri,
C.; Zhao, C. Org. Lett. 2005, 7, 4145.
Gonzalez, E. Org. Lett. 1999, 1, 527. (f) Li, Q.; Woods, K.
W.; Claiborne, A.; Gwaltney, S. L. H.; Barr, K. J.; Liu, G.;
Gehrke, L.; Credo, R. B.; Hua-Hui, Y.; Lee, L.; Warner, R.
B.; Kovar, P.; Nukkala, M. A.; Zielinski, N. A.; Tahir, S. K.;
Fitzgerald, M.; Kim, K. H.; Marsh, K.; Frost, D.; Ng, S. C.;
Rosenberg, S.; Fattorusso, C.; Catalanotti, B.; Ramunno, A.;
Nacci, V.; Novellino, E.; Grewer, C.; Ionescu, D.; Rauen, T.;
Griffiths, R.; Sinclair, C.; Fumagalli, E.; Mennini, T. J. Med.
Chem. 2001, 44, 2507. (g) Prisinzano, T.; Law, H.; Dukat,
M.; Slassi, A.; MaClean, N.; Demchyshyn, L.; Glennon, R.
A. Bioorg. Med. Chem. 2001, 9, 613. (h) Brage, A. L.;
Lüdtke, D. S.; Vargas, F.; Braga, R. C. Synlett 2006, 1453.
(9) Sayama, S. Synlett 2006, 1479.
(10) Schwekendiek, K.; Glorius, F. Synthesis 2006, 2996.
(11) Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474.
(12) (a) Ishihara, M.; Togo, H. Synlett 2006, 227. (b) Ishihara,
M.; Togo, H. Synthesis 2007, 1939.
(13) (a) Iida, S.; Togo, H. Synlett 2007, 407. (b) Iida, S.; Togo,
H. Tetrahedron 2007, 63, 8274.
(14) George, B.; Papadopoulos, E. P. J. Org. Chem. 1977, 42,
441.
(15) Raush, D. M. Synth. Commun. 1985, 15, 675.
(16) Poindexter, G. S. J. Heterocycl. Chem. 1983, 20, 1431.
Synthesis 2009, No. 14, 2329–2332 © Thieme Stuttgart · New York