An efficient synthesis of poly-substituted benzene and tricyclo[3.2.1. 02,7]oct-3-ene derivatives starting from Morita-Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tetlet.2012.11.020

Various poly-substituted benzenes including terphenyl, quaterphenyl, and quinquephenyl were synthesized starting from the Morita-Baylis-Hillman bromides. The synthesis was carried out via a three-step protocol, namely, a sequential Wittig reaction, Diels-Alder reaction with DMAD, and an aerobic oxidation.

Full text of DOI:10.1016/j.tetlet.2012.11.020

Tetrahedron Letters 54 (2013) 387–391
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Tetrahedron Letters
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An efficient synthesis of poly-substituted benzene and
tricyclo[3.2.1.02,7]oct-3-ene derivatives starting from Morita–Baylis–Hillman
adducts
⇑
Cheol Hee Lim, Sung Hwan Kim, Ka Hyun Park, Junseong Lee, Jae Nyoung Kim
Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Various poly-substituted benzenes including terphenyl, quaterphenyl, and quinquephenyl were synthe-
sized starting from the Morita–Baylis–Hillman bromides. The synthesis was carried out via a three-step
protocol, namely, a sequential Wittig reaction, Diels–Alder reaction with DMAD, and an aerobic
oxidation.
Received 24 September 2012
Revised 1 November 2012
Accepted 5 November 2012
Available online 15 November 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Poly-substituted benzenes
Tricyclo[3.2.1.02,7]oct-3-enes
Diels–Alder reaction
Aerobic oxidation
Morita–Baylis–Hillman adducts
Various chemical transformations of the Morita–Baylis–Hillman
(MBH) adducts have been studied extensively during the last two
decades.1,2 Among them the synthesis of aromatic compounds
produced dihydrobenzene derivative 3a.6 At the outset of our
experiment, we carried out an aerobic oxidation of crude 3a in
the presence of DBU (0.5 equiv) under O2 balloon atmo-
sphere.2d,2f,4a As expected, a terphenyl derivative 4a was obtained
in moderate yield (45%); however, an appreciable amount of
unknown compound (vide infra, 5a, 22%) was isolated. The
unknown compound has five different ester groups and must
be formed by the reaction of 3a and DMAD that remained in the
reaction mixture. The structure of this unknown compound was
including poly-substituted benzenes has received
a special
attention.2
Due to our continuous interest for the synthesis of poly-
substituted benzene derivatives,2c–m we presumed that a Diels–
Alder reaction between a 1,3-diene derivative 2a, prepared from
the MBH bromide 1a via a Wittig reaction,3 and a suitable
dienophile such as dimethyl acetylenedicarboxylate (DMAD)4
could provide an efficient way to synthesize poly-substituted
benzene 4a, as shown in Scheme 1.
The preparation of (E,E)-1,3-diene derivative 2a was carried out
via a sequential bromination of a MBH adduct with HBr to form
1a,5 formation of a phosphonium salt with PPh3, and a Wittig
reaction with benzaldehyde in the presence of K2CO3 in CH3CN.3
A subsequent Diels–Alder reaction of 2a with DMAD in toluene
confirmed as
a
tricyclo[3.2.1.02,7]oct-3-ene7 derivative 5a by
various spectroscopic data and unequivocally by its crystal
structure.8,9 The crystal structures of 3a and 5a are shown in
Figure 1.8 The tricyclo[3.2.1.02,7]oct-3-ene skeleton has been
found in many biologically interesting substances such as
Salvileucalin B7a,7b and various staphirine alkaloids.7c,d Thus, the
synthesis of this interesting backbone has received much
attention.7h–n
Ph
Ph
DMAD
COOMe
Ph
MeOOC
COOMe
COOMe
1. PPh3
2. PhCHO, K2CO3
Ph
toluene
reflux
DBU (cat)
O2 balloon
MeOOC
COOMe
COOMe
COOMe
Br
Ph
E
E
Ph
Ph
1a
2a
3a
4a
Scheme 1.
⇑
Corresponding author. Tel.: +82 62 530 3381; fax: +82 62 530 3389.
E-mail address: kimjn@chonnam.ac.kr (J.N. Kim).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.11.020

388
C. H. Lim et al. / Tetrahedron Letters 54 (2013) 387–391
Figure 1. ORTEP drawings of compounds 3a and 5a.
Table 1
Synthesis of poly-substituted benzene derivativesa
Entry
1,3-Diene
Dihyddrobenzeneb (%)
Productc (%)
E
Ph
Ph
Ph
E
E
E
E
E
E
1
Ph
2a (68)
Ph
3a (74)
Ph
Ph
4a (96)
Ph
E
Ph
E
E
E
E
E
E
2
3
4
5
Ar1
E
Ar1
3b (72)
Ph
Ar1
4b (97)
Ph
2b (71)
Ph
E
E
E
E
E
E
Ar2
Ar2
Ph
Ar2
4c (64)
Ph
2c (82)
3cd
E
Ph
E
E
E
E
E
E
Ar3
E
Ar3
3d (77)
Ph
Ar3
4d (94)
Ph
2d (51)
Ph
E
E
E
E
E
E
Ar4
Ar4
3e (64)
Ar4
4e (97)
2e (68)
E
Ar4
Ar4
Ar4
E
E
E
E
E
E
6
7
Ph
2f (69)
Ph
3f (63)
Ph
4f (95)
E
Ar4
Ar4
Ar4
E
E
E
E
E
E
Ar4
2g (65)
Ar4
3g (68)
Ar4
4g (95)
a
b
c
E = COOMe, Ar1 = p-chlorophenyl, Ar2 = p-nitrophenyl, Ar3 = p-methoxyphenyl, Ar4 = p-biphenyl.
Conditions: diene 2 (1.0 mmol), DMAD (3.0 equiv), toluene, reflux, 40 h.
Conditions: dihydrobenzene 3 (0.5 mmol), DBU (0.2 equiv), toluene, rt, 2 h.
1,2-Dichlorobenzene, 160 °C, 20 h, and 3c was not isolated (see text).
d

C. H. Lim et al. / Tetrahedron Letters 54 (2013) 387–391
389
6
H
8
COOMe
COOMe
DMAD (3.0 equiv)
Ph
7
MeOOC
MeOOC
DBU (0.1 equiv)
COOMe
DBU (0.2 equiv)
5
4
4a (96%) + no 5a
3a
+ 4a (7%)
1
N2 balloon
toluene, rt, 12 h
O2 balloon
toluene, rt, 2 h
3
Ph
2
H
3,8-Diphenyltricyclo[3.2.1.02,7]oct-3-ene-1,4,5,6,7
-pentacarboxylic acid pentamethyl ester (5a, 63%)
COOMe
MeOOC
COOMe
MeOOC
COOMe
COOMe
COOMe
COOMe
DMAD
COOMe
Ph
5a
Ph
MeOOC
Ph
MeOOC
COOMe
Ph
MeOOC
COOMe
H+
DBU
- H+
MeOOC
3a
Ph
Ph
H
H
H
I
II
Scheme 2.
III
When we subjected pure dihydrobenzene 3a (74%, entry 1 in
Table 1) in an aerobic oxidation condition a terphenyl 4a was iso-
lated in high yield (96%),6 whereas the reaction of 3a and DMAD in
the presence of a catalytic amount of DBU (0.1 equiv) produced 5a
in good yield (63%),9 as shown in Scheme 2. Although the reaction
was performed under N2 balloon atmosphere, the oxidation prod-
uct 4a was also formed in small amount (7%).10 The mechanism for
the formation of 5a could be proposed, as shown in Scheme 2.
DBU-catalyzed isomerization of the double bond of 3a and a subse-
quent deprotonation generated a carbanion intermediate I. An
intermolecular conjugate addition of I to DMAD and following
successive intramolecular conjugate additions afforded 5a.11
Encouraged by the results, various 1,3-diene derivatives 2b–g
were prepared from the corresponding MBH bromides,5 and the
syntheses of poly-substituted benzenes 4b–g were carried out.
The results are summarized in Table 1. The syntheses of dihydro-
benzenes 3b and 3d–g were carried out by the Diels–Alder reaction
of 2b and 2d–g with DMAD in refluxing toluene for 40 h. During
the preparation of dihydrobenzenes 3b and 3d–g, the correspond-
ing aromatized compounds 4b and 4d–g were observed in trace
amount (<5%). The Diels–Alder reaction of p-nitro derivative 2c
and DMAD was sluggish in refluxing toluene, thus we carried out
the reaction at 160 °C in o-dichlorobenzene for 20 h (entry 3). It
is interesting to note that an appreciable amount of p-nitro deriv-
ative 4c was formed during the preparation of 3c along with some
intractable side products even under N2 balloon atmosphere. Thus
we separated 3c and 4c together using a short-path column
chromatography and the mixture was treated with DBU to obtain
4c. However, the yield of 4c was moderate (64%). For the other
entries (entries 2 and 4–7), a subsequent aerobic oxidation of
dihydrobenzenes was carried out under the same conditions for
the preparation of 4a. In this way, various terphenyls 4b–d,4b,4c,4e
H
COOMe
COOMe
DMAD (3.0 equiv)
DBU (0.1 equiv)
Ph
MeOOC
MeOOC
COOMe
3b
+ 4b (4%)
N
2 balloon
Ar1
toluene, rt, 12 h
H
5b (59%, Ar1 = p-chlorophenyl)
H
COOMe
COOMe
DMAD (3.0 equiv)
DBU (0.1 equiv)
Ar4
MeOOC
COOMe
3g
+ 4g (6%)
N
2 balloon
Ar4
MeOOC
toluene, rt, 12 h
H
5c (54%, Ar4 = p-biphenyl)
Scheme 3.
quaterphenyls 4e and 4f,12 and quinquephenyl 4g4c,12a,12b were
synthesized in high yields.
As shown in Scheme 3, the reactions of 3b and 3g with DMAD in
the presence of a catalytic amount of DBU (0.1 equiv) afforded the
corresponding tricyclic compounds 5b and 5c, respectively, in
moderate yields. As in the previous synthesis of 5a, trace amounts
of the aromatized compounds 4b and 4g were formed via an
aerobic oxidation even under N2 balloon atmosphere.
As a next entry, we examined a Diels–Alder reaction between
2a and N-phenylmaleimide,13,14 as shown in Scheme 4. In the
reaction, the corresponding Diels–Alder adduct 3h was isolated
in 75% as a single diastereomer; however, the stereochemistry
was not confirmed decisively.14 Compound 3h was converted into
a polyarylphthalimide 4h by DBU-catalyzed aerobic oxidation in
Ph
Ph
Ph
O
O
O
toluene
DBU (0.2 equiv)
toluene
MeOOC
MeOOC
reflux, 40 h
2a
+
N
Ph
N
Ph
N
Ph
Ph
O
2 balloon
rt, 15 h
O
O
O
Ph
3h (75%)
4h (66%)
Ar4
Ar4
O
O
O
toluene
DBU (0.2 equiv)
toluene
MeOOC
MeOOC
reflux, 40 h
N
Ph
N
2f
+
N
Ph
O2 balloon
rt, 15 h
O
O
O
Ph
Ph
4i (62%)
(Ar4 = p-biphenyl)
3i (74%)
Scheme 4.

390
C. H. Lim et al. / Tetrahedron Letters 54 (2013) 387–391
6. Typical procedure for the synthesis of 3a and 4a: A stirred mixture of 2a (264 mg,
1.0 mmol) and DMAD (426 mg, 3.0 mmol) in toluene (2.5 mL) was heated to
reflux for 40 h under N2 atmosphere. After aqueous extractive workup and
column chromatographic purification process (hexanes/CH2Cl2/Et2O, 15:5:1),
compound 3a was obtained as a white solid, 301 mg (74%). To a stirred solution
of 3a (203 mg, 0.5 mmol) in toluene (2.0 mL) was added DBU (15 mg,
0.1 mmol), and the reaction mixture was stirred at room temperature for 2 h
under O2 balloon atmosphere. After aqueous extractive workup and column
chromatographic purification process (hexanes/CH2Cl2/Et2O, 4:1:1), compound
4a was obtained as a white solid, 194 mg (96%). Other compounds were
synthesized similarly, and the selected spectroscopic data of 3a, 3d, 3h, 4a, 4f,
and 4h are as follows.
moderate yield (66%). Similarly, the reaction of 2f and N-phenyl-
maleimide afforded 3i in 74%. DBU treatment of 3i afforded
polyarylphthalimide 4i in moderate yield (62%).15 The oxidation
of tetrahydrobenzenes 3h and 3i required somewhat a longer
reaction time (15 h) than the previous dihydrobenzene derivatives
3a–g (2 h).
In summary, we disclosed an efficient synthesis of poly-substi-
tuted aromatic compounds from MBH bromides via a sequential
Wittig reaction, Diels–Alder reaction with DMAD or N-phenyl-
maleimide, and an aerobic oxidation process. In addition, an
interesting consecutive conjugate addition pathway to form a no-
vel tricyclo[3.2.1.02,7]oct-3-ene scaffold has been found
serendipitously.
Compound 3a: 74%; white solid, mp 134–136 °C; IR (KBr) 2952, 1735,
1521 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.46 (s, 3H), 3.53 (s, 3H), 3.59 (s,
;
3H), 4.78 (dd, J = 6.9 and 3.0 Hz, 1H), 4.99 (dd, J = 6.9 and 1.2 Hz, 1H), 6.97 (dd,
J = 3.0 and 1.2 Hz, 1H), 7.18–7.37 (m, 10H); 13C NMR (CDCl3, 75 MHz) d 42.87,
44.77, 51.78, 51.98, 52.11, 127.40, 127.77, 128.55, 128.64, 128.76, 128.92,
129.04, 133.17, 135.71, 136.84, 139.34, 139.70, 165.79, 167.07, 167.36; ESIMS
m/z 429 [M++Na]. Anal. Calcd for C24H22O6: C, 70.92; H, 5.46. Found: C, 71.08;
H, 5.33.
Acknowledgments
Compound 3d: 77%; white solid, mp 118–120 °C; IR (KBr) 3028, 1717,
1600 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.41 (s, 3H), 3.46 (s, 3H), 3.52 (s,
;
This research was supported by Basic Science Research
Program through the National Research Foundation of Korea
(NRF) funded by the Ministry of Education, Science and Technology
(2012R1A1B3000541). Spectroscopic data were obtained from the
Korea Basic Science Institute, Gwangju branch.
3H), 3.72 (s, 3H), 4.66 (dd, J = 6.9 and 3.0 Hz, 1H), 4.90 (dd, J = 6.9 and 0.9 Hz,
1H), 6.79 (d, J = 8.4 Hz, 2H), 6.88 (dd, J = 3.0 and 0.9 Hz, 1H), 7.05 (d, J = 8.4 Hz,
2H), 7.10–7.23 (m, 5H); 13C NMR (CDCl3, 75 MHz) d 42.74, 43.94, 51.76, 52.02,
52.09, 55.24, 114.25, 127.34, 128.51, 128.75, 128.78, 129.74, 131.26, 133.65,
135.07, 137.09, 139.77, 159.08, 165.84, 167.06, 167.52; ESIMS m/z 459
[M++Na]. Anal. Calcd for C25H24O7: C, 68.80; H, 5.54. Found: C, 68.95; H, 5.27.
Compound 3h: 75%; white solid, mp 150–152 °C; IR (KBr) 2953, 1738,
1596 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.48–3.54 (m, 2H), 3.63 (s, 3H),
;
References and notes
4.05–4.10 (m, 1H), 4.94 (s, 1H), 6.66–6.70 (m, 2H), 7.09–7.12 (m, 2H), 7.16–7.33
(m, 11H), 7.38 (d, J = 4.2 and 3.0 Hz, 1H); 13C NMR (CDCl3, 75 MHz) d 37.43,
41.04, 43.40, 47.52, 52.15, 125.91, 126.93, 127.16, 127.87, 128.35, 128.71,
128.85, 129.14, 129.30, 131.34, 132.90, 137.63, 140.19, 141.48, 166.02, 174.88,
176.37; ESIMS m/z 438 [M+H]+. Anal. Calcd for C28H23NO4: C, 76.87; H, 5.30; N,
3.20. Found: C, 77.03; H, 5.52; N, 3.09.
1. For the general review on Morita–Baylis–Hillman reaction, see: (a) Basavaiah,
D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (b) Basavaiah,
D.; Reddy, B. S.; Badsara, S. S. Chem. Rev. 2010, 110, 5447–5674; (c) Singh, V.;
Batra, S. Tetrahedron 2008, 64, 4511–4574; (d) Declerck, V.; Martinez, J.;
Lamaty, F. Chem. Rev. 2009, 109, 1–48; (e) Ciganek, E. In Organic Reactions;
Paquette, L. A., Ed.; John Wiley & Sons: New York, 1997; Vol. 51, pp 201–350;
(f) Kim, J. N.; Lee, K. Y. Curr. Org. Chem. 2002, 6, 627–645; (g) Lee, K. Y.;
Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc. 2005, 26, 1481–1490; (h)
Gowrisankar, S.; Lee, H. S.; Kim, S. H.; Lee, K. Y.; Kim, J. N. Tetrahedron 2009, 65,
8769–8780; (i) Shi, M.; Wang, F.-J.; Zhao, M.-X.; Wei, Y. The Chemistry of the
Morita–Baylis–Hillman Reaction; RSC Publishing: Cambridge, UK, 2011.
2. For the synthesis of poly-substituted benzenes from MBH adducts, see: (a) Xie,
P.; Huang, Y.; Chen, R. Chem. Eur. J. 2012, 18, 7362–7366; (b) Clary, K. N.;
Parvez, M.; Back, T. G. J. Org. Chem. 2010, 75, 3751–3760; (c) Kim, E. S.; Kim, K.
H.; Kim, S. H.; Kim, J. N. Tetrahedron Lett. 2009, 50, 5098–5101; (d) Kim, S. C.;
Lee, K. Y.; Lee, H. S.; Kim, J. N. Tetrahedron 2008, 64, 103–109; (e) Kim, S. J.; Kim,
S. H.; Kim, K. H.; Kim, J. N. Bull. Korean Chem. Soc. 2008, 29, 876–878; (f) Park, D.
Y.; Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Bull. Korean Chem. Soc. 2008, 29, 701–
704; (g) Park, D. Y.; Lee, K. Y.; Kim, J. N. Tetrahedron Lett. 2007, 48, 1633–1636;
(h) Park, D. Y.; Gowrisankar, S.; Kim, J. N. Tetrahedron Lett. 2006, 47, 6641–
6645; (i) Park, D. Y.; Kim, S. J.; Kim, T. H.; Kim, J. N. Tetrahedron Lett. 2006, 47,
6315–6319; (j) Kim, S. C.; Lee, H. S.; Lee, Y. J.; Kim, J. N. Tetrahedron Lett. 2006,
47, 5681–5685; (k) Lee, M. J.; Lee, K. Y.; Park, D. Y.; Kim, J. N. Tetrahedron 2006,
62, 3128–3136; (l) Lee, M. J.; Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Tetrahedron
Lett. 2006, 47, 1355–1358; (m) Kim, J. N.; Im, Y. J.; Kim, J. M. Tetrahedron Lett.
2002, 43, 6597–6600.
Compound 4a: 96%; white solid, mp 196–198 °C; IR (KBr) 2949, 1740, 1720,
1609 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.50 (s, 3H), 3.59 (s, 3H), 3.60 (s, 3H),
;
7.24–7.26 (m, 2H), 7.37–7.46 (m, 8H), 7.92 (s, 1H); 13C NMR (CDCl3, 75 MHz) d
52.28, 52.34, 52.53, 127.79, 127.84, 128.16, 128.17, 128.46, 128.52, 132.26,
133.55, 133.61, 134.66, 137.65, 138.86, 139.24, 140.19, 167.20, 167.79, 168.01;
ESIMS m/z 427 [M++Na]. Anal. Calcd for C24H20O6: C, 71.28; H, 4.98. Found: C,
71.01; H, 5.14.
Compound 4f: 95%; white solid, mp 158–160 °C; IR (KBr) 2925, 1726,
1608 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.45 (s, 3H), 3.53 (s, 3H), 3.54 (s,
;
3H), 7.23–7.41 (m, 10H), 7.55–7.61 (m, 4H), 7.86 (s, 1H); 13C NMR (CDCl3,
75 MHz) d 52.35, 52.46, 52.55, 126.41, 127.01, 127.46, 128.17, 128.18, 128.55,
128.80, 128.97, 132.32, 133.58, 133.65, 134.72, 136.64, 138.84, 138.89, 140.25,
140.39, 140.42, 167.25, 167.85, 168.01; ESIMS m/z 503 [M++Na], 449 [M+-
OMe]. Anal. Calcd for C30H24O6: C, 74.99; H, 5.03. Found: C, 75.30; H, 5.15.
Compound 4h: 66%; white solid, mp 174–176 °C; IR (KBr) 2988, 1726,
1435 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.55 (s, 3H), 7.21–7.33 (m, 7H),
;
7.35–7.44 (m, 6H), 7.53–7.57 (m, 2H), 8.03 (s, 1H); 13C NMR (CDCl3, 75 MHz) d
52.54, 126.64, 127.77, 128.06, 128.17, 128.39, 128.61, 128.81, 129.04, 129.40,
129.47, 129.67, 131.24, 134.74, 135.26, 137.18, 138.23, 139.42, 140.51, 165.40,
165.58, 167.05; ESIMS m/z 434 [M++H]. Anal. Calcd for C28H19NO4: C, 77.59; H,
4.42; N, 3.23. Found: C, 77.67; H, 4.61; N, 3.12.
7. For the biologically interesting substances bearing a tricyclo[3.2.1.02,7]oct-3-
ene skeleton and their synthesis, see: (a) Levin, S.; Nani, R. R.; Reisman, S. E. J.
Am. Chem. Soc. 2011, 133, 774–776; (b) Tseng, C.-C.; Ding, H.; Li, A.; Guan, Y.;
Chen, D. Y.-K. Org. Lett. 2011, 13, 4410–4413; (c) Pelletier, S. W.; Mody, N. V.;
Djarmati, Z.; Lajsic, S. D. J. Org. Chem. 1976, 41, 3042–3044; (d) Ng, S. M.;
Beaudry, C. M.; Trauner, D. Org. Lett. 2003, 5, 1701–1704; (e) Leverrier, A.;
Martin, M.-T.; Servy, C.; Ouazzani, J.; Retailleau, P.; Awang, K.; Mukhtar, M. R.;
Gueritte, F.; Litaudon, M. J. Nat. Prod. 2010, 73, 1121–1125; (f) Hong, Y. J.;
Tantillo, D. J. J. Am. Chem. Soc. 2010, 132, 5375–5386; (g) Corey, E. J.; Wess, G.;
Xiang, Y. B.; Singh, A. K. J. Am. Chem. Soc. 1987, 109, 4717–4718; (h) Zhu, S.; Wu,
L.; Huang, X. RSC Adv. 2012, 2, 132–134; (i) Barluenga, J.; Tudela, E.; Vicente, R.;
Ballesterous, A.; Tomas, M. Angew. Chem., Int. Ed. 2011, 50, 2107–2110; (j) Wu,
T.-C.; Chen, J.-J.; Wu, Y.-T. Org. Lett. 2011, 13, 4794–4797; (k) Yamaguchi, K.;
Eto, M.; Yoshitake, Y.; Harano, K. Chem. Pharm. Bull. 2009, 57, 749–751; (l)
Skropeta, D.; Rickards, R. W. Tetrahedron Lett. 2007, 48, 3281–3284; (m) Mehta,
G.; Ravikrishna, C. Tetrahedron Lett. 1996, 37, 2655–2658; (n) Brand, R. A.;
Mulvaney, J. E. J. Org. Chem. 1980, 45, 633–636.
3. For the synthesis of 1,3-dienes from MBH adducts and their synthetic
applications, see: (a) Zhou, R.; Wang, C.; Song, H.; He, Z. Org. Lett. 2010, 12,
976–979; (b) Lee, C. G.; Lee, K. Y.; Kim, S. J.; Kim, J. N. Bull. Korean Chem. Soc.
2007, 28, 719–720; (c) Crist, R. M.; Reddy, P. V.; Borhan, B. Tetrahedron Lett.
2001, 42, 619–621; (d) Muthiah, C.; Kumar, K. S.; Vittal, J. J.; Swamy, K. C. K.
Synlett 2002, 1787–1790; (e) Palmelund, A.; Myers, E. L.; Tai, L. R.; Tisserand, S.;
Butts, C. P.; Aggarwal, V. K. Chem. Commun. 2007, 4128–4130. 1,3-Diene
derivatives were prepared according to the reported procedure, and the
selected spectroscopic data of 2g are as follows. Compound 2g: 65%; pale yellow
solid, mp 122–124 °C; IR (KBr) 1726, 1510, 1435 cmÀ1 1H NMR (CDCl3, 300
;
MHz) d 3.83 (s, 3H), 7.08 (d, J = 16.5 Hz 1H), 7.25–7.60 (m, 20H); 13C NMR
(CDCl3, 75 MHz) d 52.17, 121.74, 126.89, 127.02, 127.10, 127.17, 127.33,
127.36, 127.72, 128.78, 128.88, 129.67, 130.75, 134.41, 134.52, 136.48, 138.71,
140.18, 140.56, 140.64, 141.48, 167.95; ESIMS m/z 417 [M++H]. Anal. Calcd for
C30H24O2: C, 86.51; H, 5.81. Found: C, 86.29; H, 5.96.
4. For the selected Diels–Alder reaction between 1,3-dienes and various
dienophiles including DMAD, see: (a) Horie, H.; Kurahashi, T.; Matsubara, S.
Chem. Commun. 2012, 48, 3866–3868; (b) Thirion, D.; Poriel, C.; Rault-
Berthelot, J.; Barriere, F.; Jeannin, O. Chem. Eur. J. 2010, 16, 13646–13658; (c)
Davis, M. C.; Groshens, T. J. Synth. Commun. 2011, 41, 206–218; (d) Muraoka, O.;
Tanabe, G.; Yamamoto, E.; Ono, M.; Minematsu, T.; Kimura, T. J. Chem. Soc.
Perkin Trans. 1 1997, 2879–2890; (e) Fieser, L. F.; Haddadin, M. J. J. Am. Chem.
Soc. 1964, 86, 2392–2395.
5. For the preparation of MBH bromides, see: (a) Das, B.; Damodar, K.; Bhunia, N.;
Shashikanth, B. Tetrahedron Lett. 2009, 50, 2072–2074; (b) Basavaiah, D.;
Reddy, K. R.; Kumaragurubaran, N. Nat. Protoc. 2007, 2, 2665–2676; (c) Das, B.;
Banerjee, J.; Ravindranath, N. Tetrahedron 2004, 60, 8357–8361; (d)
Gowrisankar, S.; Kim, S. H.; Kim, J. N. Bull. Korean Chem. Soc. 2009, 30, 726–
728. and further references cited therein.
8. Crystal data of compound 3a: solvent of crystal growth (MeOH); empirical
formula
C
24H22O6, Fw = 406.42, crystal dimensions 0.20 Â 0.15 Â 0.12 mm3,
triclinic, space group P-1, a = 9.6339(2) Å, b = 10.8386(2) Å, c = 11.0779(2) Å,
a
= 91.7120(10)°, b = 100.6100(10)°,
c
= 112.3090(10)°, V = 1045.50(3) Å3, Z = 2,
MoK (k = 0.71073 Å), R1 = 0.0495,
Dcalcd = 1.291 mg/m3,
F000 = 428,
a
wR2 = 0.1246, GOF = 1.038 (I >2 (I)). We omitted hydrogen atoms for clarity
(Fig. 1). The X-ray data have been deposited in CCDC with number 882797.
Crystal data of compound 5a: solvent of crystal growth (MeOH); empirical
formula C30H28O10, Fw = 548.52, crystal dimensions 0.30 Â 0.15 Â 0.12 mm3,
monoclinic, space group P2(1)/c, a = 8.99910(10) Å, b = 16.2594(3) Å,
c = 18.6196(3) Å,
a
= 90.00°, b = 100.6950(10)°,
c
= 90.00°, V = 2677.09(7) Å3,
(k = 0.71073 Å), R1 = 0.0539,
Z = 4, Dcalcd = 1.361 mg/m3, F000 = 1152, MoK
a

C. H. Lim et al. / Tetrahedron Letters 54 (2013) 387–391
391
wR2 = 0.1396, GOF = 1.034 (I >2 (I)). We omitted hydrogen atoms for clarity
(Fig. 1). The X-ray data have been deposited in CCDC with number 882798.
9. Typical procedure for the synthesis of 5a: To a stirred solution of 3a (203 mg,
0.5 mmol) and DMAD (213 mg, 1.5 mmol) in toluene (2.0 mL) was added DBU
(8 mg, 0.05 mmol), and the reaction mixture was stirred at room temperature
for 12 h under N2 atmosphere. After aqueous extractive workup and column
chromatographic purification process (hexanes/CH2Cl2/Et2O, 4:3:1), compound
5a was obtained as a white solid, 173 mg (63%) along with 4a (14 mg, 7%).
Other compounds were synthesized similarly, and the selected spectroscopic
data of 5a and 5c are as follows.
Am. Chem. Soc. 1997, 119, 4779–4780; (b) Gil, M. V.; Roman, E.; Serrano, J. A.
Tetrahedron Lett. 2001, 42, 4625–4628; (c) Kim, S. H.; Lee, H. S.; Park, B. R.; Kim,
J. N. Bull. Korean Chem. Soc. 2011, 32, 1725–1728.
11. For the similar successive conjugate addition reaction, see: (a) Hu, B.; Meng, L.-
G.; Liu, Y.-L.; Liang, M.; Xue, S. Synthesis 2009, 4137–4142; (b) Takasu, K.;
Mizutani, S.; Noguchi, M.; Makita, K.; Ihara, M. J. Org. Chem. 2000, 65, 4112–
4119; (c) Hagiwara, H.; Yamada, Y.; Sakai, H.; Suzuki, T.; Ando, M. Tetrahedron
1998, 54, 10999–11010; (d) Ihara, M.; Fukumoto, K. Angew. Chem., Int. Ed. 1993,
32, 1010–1022; (e) MacKay, J. A.; Landis, Z. C.; Motika, S. E.; Kench, M. H. J. Org.
Chem. 2012, 77, 7768–7774; (f) Hata, T.; Imade, H.; Urabe, H. Org. Lett. 2012, 14,
2450–2453.
12. For the synthesis and applications of oligoarenes including quaterphenyls and
quinquephenyls, see: (a) Dong, Z.; Liu, X.; Yap, G. P. A.; Fox, J. M. J. Org. Chem.
2007, 72, 617–625; (b) Ishikawa, S.; Manabe, K. Chem. Commun. 2006, 2589–
2591; (c) Read, M. W.; Escobedo, J. O.; Willis, D. M.; Beck, P. A.; Strongin, R. M.
Org. Lett. 2000, 2, 3201–3204; (d) Wang, M.; Han, F.; Yuan, H.; Liu, Q. Chem.
Commun. 2010, 46, 2247–2249; (e) Hsieh, B. R.; Wan, W. C.; Yu, Y.; Gao, Y.;
Goodwin, T. E.; Gonzalez, S. A.; Feld, W. A. Macromolecules 1998, 31, 631–636.
13. The Diels–Alder reaction between 2a and other alkynes such as
diphenylacetylene or ethyl propiolate was examined; however, no reaction
was observed even under refluxing ODCB conditions.
14. For some selected examples of Diels–Alder reaction with N-substituted
maleimides, see: (a) Xiong, X.-F.; Zhou, Q.; Gu, J.; Dong, L.; Liu, T.-Y.; Chen,
Y.-C. Angew. Chem., Int. Ed. 2012, 51, 4401–4404; (b) Tripoteau, F.; Verdelet, T.;
Hercouet, A.; Carreaux, F.; Carboni, B. Chem. Eur. J. 2011, 17, 13670–13675; (c)
Jacobsen, M. J.; Funder, E. D.; Cramer, J. R.; Gothelf, K. V. Org. Lett. 2011, 13,
3418–3421; (d) Aljarilla, A.; Murcia, M. C.; Csaky, A. G.; Plumet, J. Eur. J. Org.
Chem. 2009, 822–832; (e) Urabe, H.; Kusaka, K.; Suzuki, D.; Sato, F. Tetrahedron
Lett. 2002, 43, 285–289.
15. For the synthesis of polyarylphthalimides, see: (a) Vanel, R.; Berthiol, F.;
Bessieres, B.; Einhorn, C.; Einhorn, J. Synlett 2011, 1293–1295; (b) Alvarez, L. X.;
Bessieres, B.; Einhorn, J. Synlett 2008, 1376–1380; (c) Ding, L.; Ying, H.-Z.; Zhou,
Y.; Lei, T.; Pei, J. Org. Lett. 2010, 12, 5522–5525; (d) Nishina, Y.; Kida, T.;
Ureshino, T. Org. Lett. 2011, 13, 3960–3963.
Compound 5a: 63%; white solid, mp 172–174 °C; IR (KBr) 2951, 1725, 1602,
1520, 1434 cmÀ1
;
1H NMR (CDCl3, 300 MHz) d 3.29 (s, 3H), 3.62 (s, 3H), 3.67 (s,
3H), 3.76 (s, 3H), 3.79 (s, 1H), 3.84 (s, 3H), 4.24 (s, 1H), 4.34 (s, 1H), 7.02–7.05
(m, 2H), 7.24–7.26 (m, 3H), 7.32–7.38 (m, 5H); 13C NMR (CDCl3, 75 MHz) d
31.79, 39.27, 42.67, 49.39, 49.70, 51.51, 52.33, 52.67, 52.83 (2C), 58.13, 123.02,
127.77, 128.05, 128.11, 128.15, 128.31, 128.43, 133.23, 137.52, 139.23, 166.92,
167.28, 167.89, 168.47, 169.19; ESIMS m/z 571 [M++Na]. Anal. Calcd for
C
30H28O10: C, 65.69; H, 5.15. Found: C, 65.45; H, 5.30.
Compound 5c: 54%; white solid, mp 186–188 °C; IR (KBr) 2950, 1739, 1721,
1609, 1435 cmÀ1 1H NMR (CDCl3, 300 MHz) d 3.26 (s, 3H), 3.58 (s, 3H), 3.63 (s,
;
3H), 3.71 (s, 3H), 3.78 (s, 1H), 3.81 (s, 3H), 4.21 (s, 1H), 4.32 (s, 1H), 7.05 (d,
J = 8.1 Hz, 2H), 7.22–7.45 (m, 10H), 7.48–7.56 (m, 6H); 13C NMR (CDCl3,
75 MHz) d 31.83, 39.39, 42.78, 49.36, 49.62, 51.62, 52.40, 52.74, 52.89, 52.92,
58.22, 123.07, 126.79, 126.98, 127.10, 127.24, 127.30, 127.51, 128.27, 128.64,
128.70, 128.82, 132.31, 136.42, 139.11, 140.53, 140.55, 140.68, 141.25, 167.02,
167.31, 167.89, 168.50, 169.25; ESIMS m/z 669 [M+ÀOMe]. Anal. Calcd for
C42H36O10: C, 71.99; H, 5.18. Found: C, 71.67; H, 5.42.
10. When we added an equivalent amount of DBU in order to shorten the reaction
time, the amount of oxidation product 4a increased. The mechanism for the
aromatization of 3–4 is not clear at this stage. DBU-mediated
dehydrogenation2d could be one of the possible mechanisms, while
a
sequential deprotonation, hydroperoxide formation, and
dehydration process cannot be ruled out.
a
following
For some additional references
on the base-mediated aerobic oxidations, see: (a) Ikeda, S.-i.; Mori, N.; Sato, Y. J.
2f,4a