An expedient synthesis of arene-fused phthalimides from Morita–Baylis–Hillman carbonates

Full text of DOI:10.1002/bkcs.10919

Note
DOI: 10.1002/bkcs.10919
BULLETIN OF THE
B. K. Min et al.
KOREAN CHEMICAL SOCIETY
An Expedient Synthesis of Arene-fused Phthalimides from
Morita–Baylis–Hillman Carbonates
*
Beom Kyu Min, Jin Woo Lim, Hwa Jung Roh, and Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-
57, Korea. *E-mail: kimjn@chonnam.ac.kr
7
Received July 10, 2016, Accepted August 5, 2016, Published online September 23, 2016
Keywords: Arene-fused phthalimides, 6π-Electrocyclization, Morita–Baylis–Hillman carbonates, Wittig
reaction
Recently, we reported synthesis of 3,4-diarylidene-N-phe-
nylpyrrolidine-2,5-dione derivatives from Morita–Baylis–
Hillman (MBH) carbonates. The compounds have been
Encouraged by the successful result, the reactions of 2a
with various aromatic aldehydes were examined. We
selected five-membered heteroaromatic aldehydes and
1
7
synthesized from MBH carbonates via the formation of
MBH ylides, reaction with phenyl isocyanate to form amide
ylides, and a subsequent acid-catalyzed stereoselective Wit-
naphthaldehydes that have small resonance energy, in
order to overcome the high activation energy during the 6π-
electrocyclization. The results are summarized in Table 1.
The reaction of 2a with 2-thiophenecarboxaldehyde (3b)
afforded 4b in a similar yield (59%). The reactions
1
tig reaction with various aldehydes. More recently, amino-
naphthalene has been synthesized from the amide ylide 2a
via 6π-electrocyclic ring closure of the ketenimine interme-
with
5-methylfurfural
(3c)
and
5-methyl-2-
2
diate, as shown in Scheme 1. As a continuing study, we
thiophenecarboxaldehyde (3d) afforded 4c and 4d, respec-
tively, in moderate yields (59 and 57%). The reaction of
3-furaldehyde (3e) gave 4e in a similar yield (62%).
1-Naphthaldehyde (3f) and 2-naphthaldehyde (3g) also
afforded 4f and 4g in moderate yields (56 and 57%),
respectively. In addition, other amide ylides 2b and 2c were
reasoned out that 6π-electrocyclization reaction of 3,4-dia-
rylidene-N-phenylpyrrolidine-2,5-dione I and a subsequent
aerobic oxidation of intermediate II would produce furan-
fused phthalimide derivative 4a, as also shown in Scheme
1
. Various arene-fused phthalimides have been synthe-
3,4
1
sized and found their usefulness in the areas of dual fluo-
rescent dyes as a probe for ratiometric detection of DNA,
organic light-emitting devices, and for the synthesis of
conjugated polymers.
Thermal 6π-electrocyclization reaction of conjugated
triene has been studied extensively.
prepared according to the reported method, and the reac-
4a
tions were also examined. The reactions of 4-chlorophenyl
derivative 2b with 3c and 3d also afforded 4h (57%) and 4i
(59%) in moderate yields, respectively.
4
b
4
c
However, the reaction of amide ylide 2c, bearing a 2-
thienyl moiety, showed somewhat different result. The
reaction of 2c and 3b afforded the desired product 4j in
5
,6
Double bond of
aromatic compounds could also be involved in 6π-
electrocyclization reactions. Recently, we also reported
2
low yield (42%) along with benzo[b]thiophene 5 in
6
π-electrocyclization reactions of conjugated trienes bearing
appreciable amount (14%), as shown in Scheme 2. A
dipolar interaction between the sulfur atom and phospho-
rous atom in 2c might facilitate an abstraction of amide
6
a–d
an aromatic double bond.
be conducted at relatively lower temperature when the
resonance energy of the arene ring is small, such as furan,
thiophene, or naphthalene.
Thus, at the outset of our experiment, the reaction of 2a
and 2-furaldehyde (3a) was carried out in refluxing toluene
The electrocyclization could
proton and subsequent elimination of Ph P O to form a
3
7
ketenimine intermediate. The ketenimine underwent 6π-
electrocyclization reaction to produce 5, as already
2
reported in our previous report.
in the presence of a catalytic amount of AcOH under O bal-
It is also interesting to note that the reaction of 2c and 3a
afforded a mixture of 4k and 4k (1:2, 35%) along with
2
0
loon atmosphere. However, 4,6-diphenyl-1-oxa-6-azainda-
cene-5,7-dione (4a) was not formed at all. Instead, the
formation of diarylidene intermediate I was observed, as in
5 (8%), as shown in Scheme 3. Although the stereochemis-
try of both double bonds of 3,4-diarylidene-N-phenylpyrro-
lidine-2,5-dione intermediate I (see Scheme 1) could be
1
our previous paper. When the reaction was conducted at
ꢀ
ꢀ
higher temperature (160 C) in 1,2-dichlorobenzene (ODCB)
controlled under mild conditions (benzene, 80 C, 30 min)
1
for 4 h, 4a was obtained in good yield (61%) to our delight.
Compound 4a might be formed via an acid-catalyzed cycli-
zation of 2a to form imide ring, a subsequent Wittig reaction
in our previous paper, the double bonds might be isomer-
ized in part under the drastic conditions (ODCB, 160 C,
4 h), as shown in Scheme 3. Thus, both double bonds of
ꢀ
10
1
with 3a to form I, thermal 6π-electrocyclization to II, and a
furan and thiophene could be involved in a following 6π-
8
,9
0
final aerobic oxidation to 4a.
electrocyclization reaction to produce 4k and 4k .
Bull. Korean Chem. Soc. 2016, Vol. 37, 1724–1727
© 2016 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library 1724

Note
BULLETIN OF THE
ISSN (Print) 0253-2964 | (Online) 1229-5949
KOREAN CHEMICAL SOCIETY
Scheme 1. Synthetic rationale of furan-fused phthalimide 4a.
Table 1. Synthesis of arene-fused phthalimides.
COOMe
2a: R1 = Ph, 2b: R1 = 4-ClC H , 2c: R = 2-thienyl
1
R1
6 4
3
a-3g (1.5 equiv)
4a-4j
3a: 2-Furaldehyde, 3b: 2-Thiophenecarboxaldehyde
O
Ph3P
ODCB, AcOH (cat)
O2 balloon
3c: 5-Methylfurfural,3d: 5-Methyl-2-thiophenecarboxaldehyde
NHPh
a-2c
3
e: 3-Furaldehyde, 3f: 1-Naphthaldehyde,3g: 2-Naphthaldehyde
2
160 °C, 4 h
Ph
Ph
Ph
Ph
Ph
O
O
O
O
O
O
N–Ph
N–Ph
Me
N–Ph Me
N–Ph
N–Ph
O
S
O
S
O
O
O
O
O
O
4
a (61%)
4b (59%)
(2a/3b)
4c (59%)
(2a/3c)
4d (57%)
(2a/3d)
4e (62%)
(2a/3e)
(2a/3a)
S
Ph
Ph
O
N–Ph Me
Ar
Ar
O
O
O
N–Ph
N–Ph Me
N–Ph
N–Ph
O
S
S
O
O
O
O
O
a
a
b
4
f (56%)
4g (57%)
(2a/3g)
4h (57%)
2b/3c)
4i (59%)
(2b/3d)
4j (42%)
(2c/3b)
(2a/3f)
(
a
6 4
Ar is 4-ClC H –.
Benzo[b]thiophene 5 (14%) was isolated (see Scheme 2).
b
0
Unfortunately, the separation of 4k and 4k was impossible
3b, ODCB
AcOH(cat)
COOMe
COOMe
O
S
1
and the ratio was determined based on its H NMR spec-
4
j (42%) +
S
trum (see, Supporting information). When we used benzal-
dehyde (3h) in the reaction of 2c, compound 4b was
obtained in low yield (38%) along with 5 (11%). Com-
pound 4b was not formed in an appreciable amount. The
result clearly stated that the double bond of thiophene, that
has small resonance energy as compared to that of
O2 balloon
160 °C, 4 h
P
NHPh
(14%)
Ph
NHPh
Ph
Ph
5
2
c
0
S
COOMe
H
N
7
Ph
benzene, was used preferentially in a 6π-electrocyclization
reaction.
Scheme 2. Competitive formation benzo[b]thiophene 5.
As a next trial, the reaction of 2a and benzaldehyde (3h)
was also examined. The resonance energy of benzene ring
of conjugated triene bearing an aromatic double bond and a
following aerobic oxidation process.
is larger than that of the above heteroaromatic rings (3a–
7
3
e) or naphthalene ring (3f and 3g); however, the reaction
3f
afforded 4l in a reasonable yield (38%) under the typical
reaction condition (160 C, 4 h). The yield of 4l was
improved slightly to 44% under refluxing ODCB (180 C,
ꢀ
Experimental
ꢀ
4
h) condition, as shown in Scheme 4.
In summary, various arene-fused phthalimides were
Typical Procedure for the Synthesis of 4a. To a stirred
mixture of amide ylide 2a (278 mg, 0.5 mmol) and 2-
furaldehyde (3a, 72 mg, 0.75 mmol) in ODCB (1.5 mL)
synthesized via one-pot reaction of amide ylides and aro-
matic aldehydes in the presence of AcOH in ODCB at
was added two drops of AcOH, and the reaction mixture
ꢀ
ꢀ
160 C. The reaction involved 6π-electrocyclization reaction
was heated to 160 C for 4 h under O balloon atmosphere.
2
Bull. Korean Chem. Soc. 2016, Vol. 37, 1724–1727
© 2016 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 1725

BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
Scheme 3. Partial double bond isomerization.
Ph
Ph
500 MHz) δ 7.22 (dd, J = 5.1, 3.6 Hz, 1H), 7.35–7.40 (m,
O
O
3
h, ODCB
2
7
8
H), 7.43–7.50 (m, 4H), 7.57 (dd, J = 5.1, 1.2 Hz, 1H),
AcOH (cat)
2a
N
Ph
N Ph
.62 (dd, J = 5.6, 0.8 Hz, 1H), 7.74 (d, J = 5.6 Hz, 1H),
O2 balloon
13
.47 (d, J = 0.8 Hz, 1H); C NMR (CDCl , 125 MHz) δ
180 °C,4 h
3
O
O
4
l (44%)
118.7, 124.3, 125.3, 126.8, 127.2, 127.7, 127.9, 128.1,
1
1
29.1, 129.88, 129.91, 131.6, 131.9, 134.3, 144.6, 144.8,
66.4, 166.8; ESIMS m/z 362 [M +H]. Anal. Calcd for
Scheme 4. Synthesis of benzene-fused phthalimide.
+
C H NO S : C, 66.46; H, 3.07; N, 3.88. Found: C,
20
11
2 2
6
6.81; H, 3.34; N, 3.69.
After removal of ODCB and column chromatographic puri-
fication process (hexanes/CH Cl , 1:1) compound 4a was
2
2
Acknowledgments. This research was supported by Basic
Science Research Program through the National Research
Foundation of Korea (NRF) funded by the Ministry of Edu-
cation, Science and Technology (2014R1A1A2053606).
Spectroscopic data were obtained from the Korea Basic
Science Institute, Gwangju branch.
obtained as a pale yellow solid, 104 mg (61%). Other com-
pounds were synthesized similarly, and the selected spec-
troscopic data of 4a, 4d, 4e, and 4j are as follows.
Compound 4a. Yield 61%; pale yellow solid, mp
ꢀ
−1 1
1
5
1
96–197 C; IR (KBr) 1714, 1374 cm ; H NMR (CDCl ,
3
00 MHz) δ 6.89 (dd, J = 2.3, 0.9 Hz, 1H), 7.35–7.39 (m,
H), 7.42–7.55 (m, 7H), 7.59–7.62 (m, 2H), 7.86 (d,
J = 2.3 Hz, 1H), 8.08 (d, J = 0.9 Hz, 1H); C NMR
1
3
Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
(
CDCl , 125 MHz) δ 107.4, 107.9, 122.0, 126.8, 128.1,
3
1
1
3
3
28.3, 129.1 (2C), 129.7, 129.9, 131.9, 133.5, 133.9,
36.0, 149.1, 157.3, 166.8, 167.0; ESIMS m/z
References
+
40 [M +H]. Anal. Calcd for C H NO : C, 77.87; H,
2
2
13
3
.86; N, 4.13. Found: C, 77.74; H, 3.98; N, 3.95.
1. K. H. Kim, S. Y. Kim, J. Y. Ryu, J. Lee, J. N. Kim, Tetrahe-
dron Lett. 2016, 57, 479.
2. B. K. Min, H. J. Roh, J. Y. Ryu, J. Lee, J. N. Kim, Bull.
Korean Chem. Soc. 2016, 37, 1140.
Compound 4d. Yield 57%; pale yellow solid, mp
ꢀ
−1
1
2
5
7
33–234 C; IR (KBr) 1712, 1369 cm ; H NMR (CDCl ,
3
00 MHz) δ 2.61 (s, 3H), 7.02 (s, 1H), 7.32–7.38 (m, 1H),
.40–7.47 (m, 4H), 7.48–7.55 (m, 5H), 8.33 (s, 1H);
13
3. For
synthesis
of
arene-fused
phthalimides,
see:
C
(a) M. A. Hariri, F. Pautet, H. Fillion, Synlett 1994, 459;
(b) S.-M. Yang, J.-M. Fang, J. Org. Chem. 1999, 64, 394;
(c) L. Zhou, B. Xu, J. Zhang, Angew. Chem. Int. Ed. 2015,
NMR (CDCl , 125 MHz) δ 16.7, 117.7, 122.8, 123.3,
3
1
1
26.8, 127.0, 127.9, 128.2, 128.7, 129.0, 129.8, 132.0,
35.0, 136.1, 144.6, 144.8, 146.7, 166.9, 167.2; ESIMS m/
5
4, 9092; (d) M. Adeva, H. Sahagun, E. Caballero, R. Pelaez-
Lamamie de Clairac, M. Medarde, F. Tome, J. Org. Chem.
000, 65, 3387; (e) S. Mukherjee, G. P. Jana, B. K. Ghorai,
+
z 370 [M +H]. Anal. Calcd for C H NO S: C, 74.78; H,
2
3
15
2
4
.09; N, 3.79. Found: C, 74.91; H, 4.33; N, 3.92.
2
ꢀ
Compound 4e. Yield 62%; white solid, mp 217–219 C; IR
J. Organomet. Chem. 2009, 694, 4100; (f ) K. H. Kim,
C. H. Lim, J. W. Lim, J. N. Kim, Adv. Synth. Catal. 2014,
−1
1
(KBr) 1715, 1373 cm ; H NMR (CDCl , 500 MHz) δ
3
3
2
56, 697; (g) Y. Fang, S.-Y. Wang, S.-J. Ji, Tetrahedron
015, 71, 2768; (h) X.-Y. Shi, A. Renzetti, S. Kundu, C.-
7
7
1
1
1
.05 (d, J = 2.1 Hz, 1H), 7.34–7.40 (m, 1H), 7.43–7.57 (m,
H), 7.68–7.74 (m, 2H), 7.87 (d, J = 2.1 Hz, 1H), 8.20 (s,
1
3
J. Li, Adv. Synth. Catal. 2014, 356, 723; (i) X.-F. Dong,
J. Fan, X.-Y. Shi, K.-Y. Liu, P.-M. Wang, J.-F. Wei,
J. Organomet. Chem. 2015, 779, 55; (j) X. Wu, Y. Zhao,
H. Ge, J. Am. Chem. Soc. 2015, 137, 4924; (k) Y. Nishina,
T. Kida, T. Ureshino, Org. Lett. 2011, 13, 3960; (l) F. Ilhan,
D. S. Tyson, M. A. Meador, Org. Lett. 2006, 8, 577.
H); C NMR (CDCl , 125 MHz) δ 108.4, 116.9, 123.5,
3
26.6, 126.8, 128.0, 128.1, 128.2, 129.1, 129.4, 130.3,
30.6, 132.0, 132.9, 149.5, 155.9, 166.8, 167.1; ESIMS m/
+
z 340 [M +H]. Anal. Calcd for C H NO : C, 77.87; H,
2
2
13
3
3.86; N, 4.13. Found: C, 77.79; H, 4.04; N, 4.08.
Compound 4j. Yield 42%; pale yellow solid, mp
2
4. For synthetic applications of arene-fused phthalimides, see:
(a) P. Nandhikonda, M. D. Heagy, Org. Lett. 2010, 12, 4796;
ꢀ
14–215 C; IR (KBr) 1717, 1368 cm ; H NMR (CDCl ,
3
−1 1
Bull. Korean Chem. Soc. 2016, Vol. 37, 1724–1727
© 2016 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 1726

BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
(
4
b) P. Nandhikonda, M. D. Heagy, Chem. Commun. 2010,
6, 8002; (c) H. Wang, Q. Shi, Y. Lin, H. Fan, P. Cheng,
8. For tandem 6π-electrocyclization and oxidative aromatization
process, see: (a) B. E. Moulton, H. Dong, C. T. O’Brien,
S. B. Duckett, Z. Lin, I. J. S. Fairlamb, Org. Biomol. Chem.
2008, 6, 4523; (b) R. von Essen, D. Frank,
H. W. Sunnemann, D. Vidovic, J. Magull, A. de Meijere,
Chem. Eur. J. 2005, 11, 6583; (c) R. W. Rickards,
D. Skropeta, Tetrahedron 2002, 58, 3793; (d) C. Dell’Erba,
A. Gabellini, A. Mugnoli, M. Novi, G. Petrillo, C. Tavani,
Tetrahedron 2001, 57, 9025; (e) K. Voigt, P. von Zezschwitz,
K. Rosauer, A. Lansky, A. Adams, O. Reiser, A. de Meijere,
Eur. J. Org. Chem. 1998, 1521.
X. Zhan, Y. Li, D. Zhu, Macromolecules 2011, 44, 4213;
d) S. K. Sen, S. Banerjee, RSC Adv. 2012, 2, 6274.
(
5
. For recent trienyl 6π-electrocyclizations, see: (a) P. Yang,
M. Yao, J. Li, Y. Li, A. Li, Angew. Chem. Int. Ed. 2016, 55,
6
964; (b) Z. Meng, H. Yu, L. Li, W. Tao, H. Chen, M. Wan,
P. Yang, D. J. Edmonds, J. Zhong, A. Li, Nat. Commun.
015, 6, 6096; (c) F. Yoshimura, T. Abe, K. Tanino, Org.
2
Lett. 2016, 18, 1630; (d) A. D. Yamaguchi, K. M. Chepiga,
J. Yamaguchi, K. Itami, H. M. L. Davies, J. Am. Chem. Soc.
2
015, 137, 644; (e) D. Zhang, G. Xu, D. Ding, C. Zhu, J. Li,
9. For our recent reports on aerobic oxidation, see:
(a) C. H. Lim, S. H. Kim, K. H. Park, J. Lee, J. N. Kim, Tet-
rahedron Lett. 2013, 54, 387; (b) H. R. Moon, J. Yu,
K. H. Kim, J. N. Kim, Bull. Korean Chem. Soc. 2015, 36,
1189 and further references cited therein; (c) J. Yu,
K. H. Kim, H. R. Moon, J. N. Kim, Bull. Korean Chem. Soc.
2014, 35, 1692; (d) S. H. Kim, H. S. Lee, B. R. Park,
J. N. Kim, Bull. Korean Chem. Soc. 2011, 32, 1725;
(e) J. Yu, J. W. Lim, S. Y. Kim, J. Kim, J. N. Kim, Tetrahe-
dron Lett. 2015, 56, 1432; (f ) J. W. Lim, K. H. Kim,
H. R. Moon, J. N. Kim, Tetrahedron Lett. 2016, 57, 784.
J. Sun, Angew. Chem. Int. Ed. 2014, 53, 11070; (f )
J. M. Hammann, T. A. Unzner, T. Magauer, Chem. Eur. J.
2
014, 20, 6733; (g) J. Li, P. Yang, M. Yao, J. Deng, A. Li,
J. Am. Chem. Soc. 2014, 136, 16477.
6
. For our recent reports involving 6π-electrocyclization, see:
(
a) J. W. Lim, K. H. Kim, S. H. Kim, J. N. Kim, Tetrahedron
2
014, 70, 6831; (b) J. W. Lim, K. H. Kim, S. H. Kim,
J. N. Kim, Tetrahedron Lett. 2013, 54, 2595; (c) J. W. Lim,
K. H. Kim, S. H. Kim, J. N. Kim, Tetrahedron Lett. 2012,
5
3, 5449; (d) J. W. Lim, S. H. Kim, J. Kim, J. N. Kim, Bull.
Korean Chem. Soc. 2015, 36, 1351; (e) K. H. Kim,
H. R. Moon, J. Lee, J. Kim, J. N. Kim, Adv. Synth. Catal.
10. For
(a) J. C. A. Boeyens, C. C. Allen, G. W. Perold, J. Chem.
Soc. Perkin Trans. 1993, 1161; (b) O. Crescente,
similar
double
bond
isomerization,
see:
2
015, 357, 1532; (f ) C. H. Lim, S. H. Kim, K. H. Kim,
2
J. N. Kim, Tetrahedron Lett. 2013, 54, 2476.
. A. J. Gordon, R. A. Ford, The Chemist’s Companion, Wiley,
New York, 1972, p. 130.
H. G. Heller, S. Oliver, J. Chem. Soc. Perkin Trans. 1 1979,
150; (c) B. Otto, K. Ruck-Braun, Eur. J. Org. Chem. 2003,
2409; (d) A. M. Asiri, Tetrahedron Lett. 2002, 43, 6815.
7
Bull. Korean Chem. Soc. 2016, Vol. 37, 1724–1727
© 2016 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 1727