A novel skeleton transformation of 2a-substituted 2a,8b-dihydro-3H-benzo[b] cyclobuta[d]pyran-3-ones to 2-(2-oxoethyl)-2H-1-benzopyrans promoted by a combination of ZnI2, organic base and H2O

Article abstract of DOI:10.1055/s-2008-1032044

The novel skeleton transformation reaction of 2a-substituted 2a,8b-dihydrobenzo[b]cyclobuta[d]pyran-3-one derivatives into 2-(2-substituted 2-oxoethyl)-2H-1-benzopyran derivatives has been accomplished using ZnI ₂ in the presence of an organic

Full text of DOI:10.1055/s-2008-1032044

428
LETTER
A Novel Skeleton Transformation of 2a-Substituted 2a,8b-Dihydro-3H-
benzo[b]cyclobuta[d]pyran-3-ones to 2-(2-Oxoethyl)-2H-1-benzopyrans
Promoted by a Combination of ZnI2, Organic Base and H2O
S
keleton Transform
a
ation of 2a
v
,8b-Dihydro
n
-
3
H
-benzo[
b
a
]cyclobuta
t
[
d
]pyra
h
n-3-ones Dnyanoba Yadav,a Masayuki Yamashita,*a Yumiko Saya,a Ai Kurume,a Ikuo Kawasaki,a,b Shunsaku Ohtaa
a
Department of Functional Molecular Chemistry, 21st COE Program, Kyoto Pharmaceutical University,
Misasagi-Nakauchi, Yamashina, Kyoto 607-8414, Japan
Fax +81(75)5954795; E-mail: yamasita@mb.kyoto-phu.ac.jp
b
School of Pharmaceutical Sciences, Mukogawa Women’s University, Koshien Kyuban-cho, Nishinomiya 663-8179, Japan
Received 24 October 2007
We expected that the transformation reaction of 3, which
had a C=C double bond between the 1- and 2-positions,
into 4 would proceed in the same manner as the conver-
sion of 1 into 2. The starting material, 2a-acetyl-2a,8b-di-
hydro-8-methoxy-1-phenyl-3H-benzo[b]cyclobuta[d]-
pyran-3-one (3a), was readily prepared by [2+2]-photocy-
cloaddition of a coumarin derivative 5a with phenyl acet-
ylene (Scheme 2).9 When the crude cyclobutene 3a was
purified by silica gel column chromatography with
EtOAc–n-hexane as the eluent, a new product 6a was ob-
tained in 17% yield together with the desired cyclobutene
3a (64%).
Abstract: The novel skeleton transformation reaction of 2a-substi-
tuted 2a,8b-dihydrobenzo[b]cyclobuta[d]pyran-3-one derivatives
into 2-(2-substituted 2-oxoethyl)-2H-1-benzopyran derivatives has
been accomplished using Znl2 in the presence of an organic base
and water in excellent yields.
Key words: heterocycles, Lewis acids, photochemistry, rearrange-
ments, ring opening
In organic synthesis, small cycloalkanes such as cyclopro-
panes and cyclobutanes play an important role owing to
the diversity of their reactions.1 We have been interested
in small cycloalkanes and have reported several reactions
including cyclopropane ring opening.2 In a previous
study, we found that benzocyclobutapyranones 1 could be
readily transformed into tetrahydrodibenzofuran deriva-
tives 2,3 which were convertible into a series of tricyclic
monoterpene chalcones such as Linderol A,4 and their an-
alogues (Scheme 1).5,6
Ph
MeO
O
O
MeO
O
H
Ph
Me
Me
hν, C6H6
O
O
O
70%
5a
3a (crude)
On the other hand, 2H-1-benzopyran derivatives are well-
known heterocyclic compounds7 and occur in a wide
range of natural products.8 In continuation of our study re-
lated to small cycloalkanes, we would like to describe
here a novel skeleton transformation reaction of 2a-substi-
tuted 2a,8b-dihydrobenzo[b]cyclobuta[d]pyran-3-one de-
rivatives 3 into 2-(2-substituted 2-oxoethyl)-2H-1-
benzopyran derivatives 6 using Znl2 as a Lewis acid in the
presence of base and water.
MeO
SiO2 column
Ph
O
chromatography
3a (pure)
+
EtOAc–n-hexane
Me
O
64%
6a 17%
Scheme 2 Novel reaction for converting 3a into 6a
The molecular formula of the unknown product 6a was
found to be C19H18O3 on the basis of high-resolution MS
determinations, and its IR spectrum showed a carbonyl
band at 1708 cm–1. The structure of 6a was confirmed by
spectral data, including detailed NMR analysis such as
HMBC and HMQC.
R
R
X1
H
H
9
6
X1
8
Y
CH2=S(O)Me2
DMF, r.t.
W
Y
2a
3
O
W
4
O
O
An increase in 6a and a decrease in 3a were observed with
increasing time spent on the column when 3a was chro-
matographed on silica gel for 30 minutes, three hours, and
eight hours. This meant that silica gel acted as an acid cat-
alyst.
5
5
H
OH
W = electron-withdrawing
group
2: X–Y = C–C
4: X–Y = C=C
1: X–Y = C–C
3: X–Y = C=C
Scheme 1 Previous work on transforming 1 into 2 and synthetic
plan for conversion of 3 into 4
The effects of various acids, including Lewis acids, on the
model compound 3b were therefore examined, and the re-
sults are shown in Table 1. When ZnCl2 and ZnI2 were
used as the acid catalyst, the yields of 6b were 30% and
38%, respectively (entries 4 and 5). Unexpectedly, stirring
in the presence of silica gel in EtOAc–n-hexane gave only
SYNLETT 2008, No. 3, pp 0428–0432
Advanced online publication: 16.01.2008
DOI: 10.1055/s-2008-1032044; Art ID: U10207ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
0
8

LETTER
Skeleton Transformation of 2a-Substituted 2a,8b-Dihydro-3H-benzo[b]cyclobuta[d]pyran-3-ones
429
a trace amount of 6b together with 65% recovery of 3b Table 2 Effect of Addition of Base
(entry 1). When THF–H2O (100:1) was used as solvent,
Ph
the yield of 6b rose to 60% after 40 hours (entry 6). The
structure of the compound 6b was confirmed by X-ray
crystal structure analysis (Figure 1).
base (3 equiv)
ZnI2
O
O
H
Ph
O
Ph
THF–H2O (30:1)
reflux
O
Ph
O
Table 1 Effects of Solvent and Acid
3b
6b
Ph
Entrya Base
Time (h) Yield (%)b
O
O
H
Ph
1
2
3
4
5
6
7
8
Et3N
16
15
24
2
78
82
80
69
67
93
65
76
acid (1.0 equiv)
solvent, reflux
O
Ph
DIPEA
O
O
Ph
3b
6b
pyridine
DBU
Entry Acid
Solvent
Time
Yield (%)a,b
trace (65)
complex (–)
trace (30)
30 (42)
1
2
3
4
5
6
silica gelc EtOAc–n-hexane (1:1)
3 dd
10 h
10 h
6 d
pyrrolidine
piperidine
12
2
PPTS
AlCl3
ZnCl2
ZnI2
MeOH
THF
2,2,6,6-tetramethylpiperidine
morpholine
15
15
THF
a The reaction was carried out using 3b (0.14 mmol) and ZnI2 (1
equiv) with THF–H2O (3.1 mL) at reflux under a N2 atmosphere.
b Isolated yield.
THF
3 d
38 (52)
ZnI2
THF–H2O (100:1)
40 h
60 (10)
a Isolated yield of 6b.
b The value in parentheses is the isolated yield of the recovered 3b.
c Silica gel (200 mg) and 3b (100 mg) were used.
d The reaction was carried out at r.t.
and the reaction times were improved in all cases
(Table 2).
In particular, when piperidine was used as a base, the yield
of 6b increased to 93%, and the reaction time was short-
ened to two hours (entry 6). The conditions of entry 6
were adopted as the optimal reaction conditions.
The scope of this reaction was explored next. The cyclo-
butabenzopyranones 3c–l were prepared by [2+2]-photo-
cycloaddition of the corresponding 3-substituted
coumarins 5 with monosubstituted alkynes, and purified
by silica gel column chromatograpy.10 The pure cyclobut-
abenzopyranones 3c–l were subjected to the optimized re-
action conditions, and the results are summarized in
Table 3.
When the compounds 3c–l, with electron-withdrawing
groups such as acyl and ester groups at the 2a-position,
were used, the desired products 6c–l were obtained in
good to excellent yields (71–100%) regardless of the na-
ture of the substituent groups at the 1-position and on the
benzene ring of 3.
We have proposed a plausible reaction mechanism as
shown in Scheme 3. After the lactone ring of the zinc
complex 7 is opened by the hydroxide ion, the cy-
clobutene ring would be opened by the phenoxide anion
because of its highly strained structure to form an ortho-
quinone methide 10 with subsequent regeneration of the
phenoxide anion 11. The intramolecular 1,4-addition of
the phenoxide anion 11 would proceed easily, producing
the 2H-1-benzopyran derivative 12. Finally, decarboxyla-
tion of b-carbonyl carboxylic acid derivative 12 occurs to
give 6 after keto–enol tautomerism.
Figure 1 ORTEP drawing of 6b
The benzopyran 6 had one carbonyl group less than the
starting compound 3. This meant that decarboxylation oc-
curred after opening of the lactone ring of 3. So a base was
added to accelerate the lactone ring opening in the pres-
ence of water. Various bases were examined, and the re-
sults are shown in Table 2. As expected, the yields of 6b
Synlett 2008, No. 3, 428–432 © Thieme Stuttgart · New York

430
N. D. Yadav et al.
LETTER
Table 3 Transformation Reaction of 3 into 611
R2
R3
R3
H
O
R2
O
R1
R4
O
R1
R4
O
O
3
6
Entry
3/6
R1
R2
R3
R4
H
Yield (%)a
1
2
3
4
5
6
7
8
9
c
d
e
f
OMe
Ph
Ph
H
91
84
71
76
82
86
90
95
98
n-Bu
Ph
H
H
CHMe2
Ph
H
H
Ph
OMe
OMe
OMe
TMS
TMS
TMS
H
g
h
i
OMe
OEt
OMe
Me
Ph
H
Ph
OMe
H
Ph
j
Ph
H
k
Ph
n-Bu
H
Ph
H
O
Ph
10
100
O
Ph
O
O
O
Ph
3l
6l
a Isolated yield.
103, 1213. (g) Baird, M. Chem. Rev. 2003, 103, 1271.
(h) Nakamura, M.; Isobe, H.; Nakamura, E. Chem. Rev.
2003, 103, 1295. (i) Lee-Ruff, E.; Mladenova, G. Chem.
Rev. 2003, 103, 1449. (j) Namyslo, J. C.; Kaufmann, D. E.
Chem. Rev. 2003, 103, 1485. (k) Donaldson, W. A.
Tetrahedron 2001, 57, 8589. (l) Sydnes, L. K. Eur. J. Org.
Chem. 2000, 3511. (m) Iwasawa, N.; Narasaka, K. Top.
Curr. Chem. 2000, 207, 69. (n) de Meijere, A.;
Kozhushkov, S. I.; Khlebnikov, A. F. Top. Curr. Chem.
2000, 207, 89. (o) de Meijere, A.; Kozhushkov, S. I.;
Hadjiarapoglou, L. P. Top. Curr. Chem. 2000, 207, 149.
(p) Nemoto, H.; Fukumoto, K. Synlett 1997, 863.
(q) Brandi, A.; Cordero, F. M.; De Sarlo, F.; Goti, A.;
Guarna, A. Synlett 1993, 1.
In conclusion, we have found and developed an interest-
ing Lewis acid promoted skeleton transformation into 2-
(2-substituted 2-oxoethyl)-2H-1-benzopyran derivatives
6 by reaction of 2a-substituted 2a,8b-dihydro-3H-ben-
zo[b]cyclobuta[d]pyran-3-ones derivatives 3 promoted by
a combination of ZnI2, piperidine and H2O. Further stud-
ies into the scope, mechanism, and synthetic application
of this reaction are being carried out.
Acknowledgment
This research was supported in part by the Frontier Research Pro-
gram and the 21st Century COE Program ‘Development of Drug
Discovery Frontier Integrated from Tradition to Proteome’ of the
Ministry of Education, Culture, Sports, Science and Technology of
Japan, and a Grant-in-Aid for the Promotion of the Advancement of
Education and Research in Graduate Schools from The Promotion
and Mutual Aid Corporation for Private Schools of Japan.
(2) (a) Yamashita, M.; Okuyama, K.; Kawajiri, T.; Takada, A.;
Inagaki, Y.; Nakano, H.; Tomiyama, M.; Ohnaka, A.;
Terayama, I.; Kawasaki, I.; Ohta, S. Tetrahedron 2002, 58,
1497. (b) Yamashita, M.; Okuyama, K.; Ohhara, T.;
Kawasaki, I.; Michihiro, Y.; Sakamaki, K.; Ito, S.; Ohta, S.
Chem. Pharm. Bull. 1999, 47, 1439. (c) Yamashita, M.;
Okuyama, K.; Ohhara, T.; Kawasaki, I.; Ohta, S. Synlett
1996, 547. (d) Yamashita, M.; Okuyama, K.; Ohhara, T.;
Kawasaki, I.; Sakai, K.; Nakata, S.; Kawabe, T.; Kusumoto,
M.; Ohta, S. Chem. Pharm. Bull. 1995, 43, 2075.
(e) Yamashita, M.; Okuyama, K.; Kawasaki, I.; Ohta, S.
Tetrahedron Lett. 1995, 36, 5603. (f) Yamashita, M.;
Okuyama, K.; Ohhara, T.; Kawasaki, I.; Ohta, S. Chem.
Pharm. Bull. 1995, 43, 708.
References and Notes
(1) Recent reviews: (a) Dolbier, W. R. Jr.; Battiste, M. A. Chem.
Rev. 2003, 103, 1071. (b) Fedoryński, M. Chem. Rev. 2003,
103, 1099. (c) Sydnes, L. K. Chem. Rev. 2003, 103, 1133.
(d) Reissig, H.-U.; Zimmer, R. Chem. Rev. 2003, 103, 1151.
(e) Baldwin, J. E. Chem. Rev. 2003, 103, 1197. (f) Brandi,
A.; Cicchi, S.; Cordero, F. M.; Goti, A. Chem. Rev. 2003,
Synlett 2008, No. 3, 428–432 © Thieme Stuttgart · New York

LETTER
Skeleton Transformation of 2a-Substituted 2a,8b-Dihydro-3H-benzo[b]cyclobuta[d]pyran-3-ones
431
R1
Chromanones, and Chromones, Vol. 31; John Wiley &
R1
1
Sons: New York, 1977, 1. (d) Brogden, P. J.; Gabbutt, C.
D.; Hepworth, J. D. In Comprehensive Heterocyclic
Chemistry, Vol. 3; Katritzky, A. R.; Rees, C. W.; Boulton,
A. J.; McKillop, A., Eds.; Pergamon Press: Oxford, 1984,
574. (e) Ellis, G. P. In Comprehensive Heterocyclic
Chemistry, Vol. 3; Katritzky, A. R.; Rees, C. W.; Boulton,
A. J.; McKillop, A., Eds.; Pergamon Press: Oxford, 1984,
647. (f) Hepworth, J. D. In Comprehensive Heterocyclic
Chemistry, Vol. 3; Katritzky, A. R.; Rees, C. W.; Boulton,
A. J.; McKillop, A., Eds.; Pergamon Press: Oxford, 1984,
737.
R
H
R
H
O
ZnI2
2a
O
I
Zn
3
O
O
O
O
I
3
7
– OH *
R
R1
R1
H
R
H
O
O
I
Zn
H
O
Zn
O
–O
I
O
O
(8) For example: (a) Kanadaswami, C.; Lee, L.-T.; Lee, P.-P.
H.; Hwang, J.-J.; Ke, F.-C.; Huang, Y.-T.; Lee, M.-T. In
Vivo 2005, 19, 895. (b) Tanaka, T.; Higa, S.; Hirano, T.;
Arimitsu, J.; Naka, T.; Shima, Y.; Ohshima, S.; Fujimoto,
M.; Yamadori, T.; Kawase, I. Recent Res. Dev. Allergy Clin.
Immunol. 2004, 5, 1. (c) Haraguchi, H. In Bioactive
Compounds from Natural Sources; Tringali, C., Ed.; Taylor
& Francis Ltd.: London, 2001, 337. (d) Ishikawa, T.
Heterocycles 2000, 53, 453.
(9) (a) Yamashita, M.; Yadav, N. D.; Nagahama, M.; Inaba, T.;
Nishino, Y.; Miura, K.; Kosaka, S.; Fukao, J.; Kawasaki, I.;
Ohta, S. Heterocycles 2005, 65, 2411. (b) Schwebel, D.;
Margaretha, P. Helv. Chim. Acta 2000, 83, 1168.
H
O
I
H
N
H
9
8
R1
R1
O
H
O–
O
R
–
O
O
R
O
O
O
Zn
O
Zn
I
I
10
11
R1
–
– CO2
– OH
R
O
(10) The cyclobutabenzopyrans 3 were relatively stable under
these conditions except for 3a.
– "Zn"
O
O
H
(11) General Procedure: ZnI2 (0.142 mmol) and piperidine
(0.426 mmol) were added to a solution of 2a-substituted
2a,8b-dihydrobenzo[b]cyclobuta[d]pyran-3-one 3 (0.142
mmol) in THF–H2O (3 mL:0.1 mL) at r.t., and the whole was
refluxed. After disappearance of 3 was checked by TLC, the
reaction mixture was acidified with 10% HCl. The mixture
was extracted with EtOAc (3 × 15 mL). The combined
extracts were washed, dried, and evaporated. The residue
was chromatographed to give 2-(2-substituted 2-oxoethyl)-
2H-1-benzopyran 6.12
12
R1
O
R
6
O
O
6'
H
+
*
– OH
N H
NH2
+ H2O
+
(12) 5-Methoxy-2-(2-oxopropyl)-3-phenyl-2H-1-benzopyran
(6a): yellowish oil. 1H NMR (300 MHz, CDCl3): d = 2.15 (s,
3 H), 2.34 (dd, J = 2.2, 15.9 Hz, 1 H), 3.10 (dd, J = 10.2, 15.9
Hz, 1 H), 3.84 (s, 3 H), 5.89 (dd, J = 2.3, 10.2 Hz, 1 H), 6.49
(d, J = 8.1 Hz, 1 H), 6.51 (d, J = 8.1 Hz, 1 H), 7.09 (t, J = 8.3
Hz, 1 H), 7.19 (s, 1 H), 7.24–7.39 (m, 3 H), 7.49–7.53 (m, 2
H). 13C NMR (75 MHz, CDCl3): d = 31.0, 45.6, 55.6, 72.1,
103.7, 109.5, 111.8, 114.5, 125.1, 127.9, 128.8, 129.4,
132.3, 136.2, 151.4, 155.6, 206.1. IR (CHCl3): 1708, 1594
cm–1. MS: m/z (%) = 294 (20.3) [M+], 237 (100). HRMS:
m/z [M+] calcd for C19H18O3: 294.1256; found: 294.1257.
3-Phenyl-2-(2-phenyl-2-oxoethyl)-2H-1-benzopyran
(6b): colorless crystals (recrystallized from EtOAc); mp
136–138 °C. 1H NMR (300 MHz, CDCl3): d = 2.78 (dd, J =
2.2, 16.5 Hz, 1 H), 3.80 (dd, J = 9.6, 16.4 Hz, 1 H), 6.20 (dd,
J = 2.2, 9.7 Hz, 1 H), 6.72 (d, J = 7.9 Hz, 1 H), 6.88 (s, 1 H),
6.93 (td, J = 1.1, 7.4 Hz, 1 H), 7.09 (dd, J = 1.7, 7.8 Hz, 1 H),
7.13 (td, J = 1.5, 7.2 Hz, 1 H), 7.29–7.42 (m, 5 H), 7.50–7.58
(m, 3 H), 7.82–7.86 (m, 2 H). 13C NMR (75 MHz, CDCl3):
d = 41.1, 72.7, 116.9, 120.0, 121.8, 122.5, 125.4, 127.0,
128.2, 128.3, 128.5, 128.9, 129.4, 133.2, 134.7, 136.1,
137.0, 151.0, 197.2. IR (CHCl3): 1677, 1594 cm–1. MS: m/z
(%) = 326 (5.8) [M+], 207 (100), 178 (11.5). HRMS: m/z
[M+] calcd for C23H18O2: 326.1307; found: 326.1303. Anal.
Calcd for C23H18O2: C, 84.64; H, 5.56. Found: C, 84.51; H,
5.57.
Scheme 3 A plausible reaction mechanism for the formation of 6
from 3
(3) (a) Yamashita, M.; Inaba, T.; Nagahama, M.; Shimizu, T.;
Kosaka, S.; Kawasaki, I.; Ohta, S. Org. Biomol. Chem. 2005,
3, 2296. (b) Yamashita, M.; Inaba, T.; Shimizu, T.;
Kawasaki, I.; Ohta, S. Synlett 2004, 1897.
(4) Mimaki, Y.; Kameyama, A.; Sashida, Y.; Miyata, Y.; Fujii,
A. Chem. Pharm. Bull. 1995, 43, 893.
(5) Orjala, J.; Wright, A. D.; Erdelmeier, C. A. J.; Sticher, O.;
Rali, T. Helv. Chim. Acta 1993, 76, 1481.
(6) (a) Yamashita, M.; Yadav, N. D.; Sawaki, T.; Takao, I.;
Kawasaki, I.; Sugimoto, Y.; Miyatake, A.; Murai, K.;
Takahara, A.; Kurume, A.; Ohta, S. J. Org. Chem. 2007, 72,
5697. (b) Yamashita, M.; Yadav, N. D.; Sumida, Y.;
Kawasaki, I.; Kurume, A.; Ohta, S. Tetrahedron Lett. 2007,
48, 5619. (c) Yamashita, M.; Shimizu, T.; Inaba, T.; Takada,
A.; Takao, I.; Kawasaki, I.; Ohta, S. Heterocycles 2005, 65,
1099. (d) Yamashita, M.; Ohta, N.; Shimizu, T.; Matsumoto,
K.; Matsuura, Y.; Kawasaki, I.; Tanaka, T.; Maezaki, N.;
Ohta, S. J. Org. Chem. 2003, 68, 1216. (e) Yamashita, M.;
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(7) For example: (a) Merlini, L. In Advances in Heterocyclic
Chemistry, Vol. 18; Katritzky, A. R.; Boulton, A. J., Eds.;
Academic Press: New York, 1975, 159. (b) Ellis, G. P.;
Lockhart, I. M. In The Chemistry of Heterocyclic
Methyl (3-Phenyl-2H-1-benzopyran-2-yl)acetate (6c):
colorless needles (recrystallized from EtOAc–n-hexane);
mp 182–183 °C. 1H NMR (300 MHz, CDCl3): d = 2.46 (dd,
J = 2.9, 15.2 Hz, 1 H), 2.87 (dd, J = 9.9, 15.2 Hz, 1 H), 3.66
Compounds: Chromans and Tocopherols, Vol. 31; John
Wiley & Sons: New York, 1981, 1. (c) Ellis, G. P. The
Chemistry of Heterocyclic Compound: Chromenes,
Synlett 2008, No. 3, 428–432 © Thieme Stuttgart · New York

432
N. D. Yadav et al.
LETTER
(s, 3 H), 5.89 (dd, J = 2.9, 10.1 Hz, 1 H), 6.82 (s, 1 H), 6.87
(d, J = 8.1 Hz, 1 H), 6.93 (td, J = 1.1, 7.4 Hz, 1 H), 7.11 (dd,
J = 1.7, 7.5 Hz, 1 H), 7.16 (td, J = 1.7, 7.7 Hz, 1 H), 7.28–
calcd for C19H18O4: 310.1205; found: 310.1201.
Ethyl (5,7-Dimethoxy-3-phenyl-2H-1-benzopyran-2-
yl)acetate (6h): colorless oil. 1H NMR (300 MHz, CDCl3):
d = 1.25 (t, J = 7.2 Hz, 3 H), 2.44 (dd, J = 2.9, 15.4 Hz, 1 H),
2.88 (dd, J = 10.3, 15.4 Hz, 1 H), 3.78 (s, 3 H), 3.84 (s, 3 H),
4.06–4.23 (m, 2 H), 5.85 (dd, J = 2.9, 9.9 Hz, 1 H), 6.08 (d,
J = 2.2 Hz, 1 H), 6.10 (d, J = 2.2 Hz, 1 H), 7.13 (s, 1 H), 7.23–
7.35 (m, 1 H), 7.36–7.42 (m, 2 H), 7.49–7.54 (m, 2 H). 13
C
NMR (75 MHz, CDCl3): d = 38.1, 51.8, 73.0, 116.7, 120.2,
121.8, 122.2, 125.3, 127.0, 128.2, 128.9, 129.5, 134.1,
136.1, 150.8, 170.8. IR (CHCl3): 1725, 1612 cm–1. MS: m/z
(%) = 280 (8.8) [M+], 207 (100), 178 (12.6). HRMS: m/z
[M+] calcd for C18H16O3: 280.1099; found: 280.1101. Anal.
Calcd for C18H16O3: C, 77.12; H, 5.75. Found: C, 76.50; H,
5.98.
3-Butyl-2-(2-phenyl-2-oxoethyl)-2H-1-benzopyran (6d):
yellowish oil. 1H NMR (300 MHz, CDCl3): d = 0.94 (t, J =
7.2 Hz, 3 H), 1.30–1.45 (m, 2 H), 1.45–1.65 (m, 2 H), 2.13
(t, J = 7.8 Hz, 2 H), 2.83 (dd, J = 3.1, 15.8 Hz, 1 H), 3.64 (dd,
J = 9.0, 15.8 Hz, 1 H), 5.40 (dd, J = 3.1, 9.0 Hz, 1 H), 6.23
(s, 1 H), 6.62 (d, J = 8.1 Hz, 1 H), 6.86 (td, J = 1.1, 7.3 Hz,
1 H), 6.97 (dd, J = 1.7, 7.3 Hz, 1 H), 7.02 (td, J = 1.6, 7.7 Hz,
1 H), 7.35–7.45 (m, 2 H), 7.50–7.60 (m, 1 H), 7.85–7.90 (m,
2 H). 13C NMR (75 MHz, CDCl3): d = 13.9, 22.3, 29.4, 32.5,
41.2, 74.2, 116.5, 118.8, 121.4, 122.5, 125.9, 128.3, 128.4,
128.5, 133.2, 137.1, 137.6, 150.7, 197.6. IR (CHCl3): 1676
cm–1. MS: m/z (%) = 306 (6.2) [M+], 187 (100), 157 (13.8).
HRMS: m/z [M+] calcd for C21H22O2: 306.1620; found:
306.1625.
7.28 (m, 1 H), 7.34–7.39 (m, 2 H), 7.50–7.52 (m, 2 H). 13
NMR (75 MHz, CDCl3): d = 14.2, 37.9, 55.4, 55.6, 60.7,
73.0, 92.3, 94.3, 105.3, 114.7, 124.9, 127.4, 128.8 (2), 136.6,
152.6, 156.5, 161.5, 170.6. IR (CHCl3): 1721, 1608 cm–1.
MS: m/z (%) = 354 (11.2) [M+], 267 (100). HRMS: m/z [M+]
calcd for C21H22O5: 354.1467; found: 354.1459.
Methyl (3-Phenyl-5-trimethylsilyl-2H-1-benzopyran-2-
yl)acetate (6i): colorless oil. 1H NMR (300 MHz, CDCl3):
d = 0.26 (s, 9 H), 2.47 (dd, J = 2.8, 16.1 Hz, 1 H), 2.92 (dd,
J = 9.2, 16.1 Hz, 1 H), 3.61 (s, 3 H), 6.06 (dd, J = 2.8, 9.2 Hz,
1 H), 6.78 (s, 1 H), 6.92 (t, J = 7.3 Hz, 1 H), 7.11 (dd, J = 1.5,
7.3 Hz, 1 H), 7.25 (dd, J = 1.8, 7.3 Hz, 1 H), 7.28–7.35 (m,
1 H), 7.35–7.43 (m, 2 H), 7.48–7.55 (m, 2 H). 13C NMR (75
MHz, CDCl3): d = –0.95, 38.1, 51.7, 73.0, 120.6, 121.0,
121.3, 125.4, 126.7, 128.1, 128.4, 128.9, 133.3, 135.1,
136.3, 155.8, 170.9. IR (CHCl3): 1727, 1589 cm–1. MS: m/z
(%) = 352 (8.1) [M+], 279 (100). HRMS: m/z [M+] calcd for
C21H24O3Si: 352.1495; found: 352.1496.
C
2-(3-Methyl-2-oxobutyl)-3-phenyl-2H-1-benzopyran
(6e): colorless needles (recrystallized from EtOAc–n-
hexane); mp 75–77 °C. 1H NMR (300 MHz, CDCl3): d =
1.00 (d, J = 7.0 Hz, 3 H), 1.05 (d, J = 7.0 Hz, 3 H), 2.28 (dd,
J = 2.2, 16.2 Hz, 1 H), 2.51 (septet, J = 7.0 Hz, 1 H), 3.23
(dd, J = 10.0, 16.2 Hz, 1 H), 6.02 (dd, J = 2.2, 9.9 Hz, 1 H),
6.80 (d, J = 7.2 Hz, 1 H), 6.82 (s, 1 H), 6.92 (td, J = 1.0, 7.4
Hz, 1 H), 7.09–7.16 (m, 2 H), 7.28–7.41 (m, 3 H), 7.49–7.53
(m, 2 H). 13C NMR (75 MHz, CDCl3): d = 17.6, 17.7, 41.8,
42.8, 72.6, 116.6, 119.7, 121.7, 122.5, 125.3, 126.9, 128.2,
128.9, 129.4, 134.6, 136.0, 150.9, 212.4. IR (CHCl3): 1703,
1594 cm–1. MS: m/z (%) = 292 (7.9) [M+], 207 (100), 178
(12.8). HRMS: m/z [M+] calcd for C20H20O2: 292.1463;
found: 292.1464. Anal. Calcd for C20H20O2: C, 82.34; H,
6.89. Found: C, 82.34; H, 6.66.
5-Methoxy-3-phenyl-2-(2-phenyl-2-oxoethyl)-2H-1-
benzopyran (6f): yellowish oil. 1H NMR (300 MHz,
CDCl3): d = 2.76 (dd, J = 2.2, 16.5 Hz, 1 H), 3.83 (dd, J =
9.7, 16.3 Hz, 1 H), 3.89 (s, 3 H), 6.17 (dd, J = 2.2, 9.6 Hz, 1
H), 6.38 (d, J = 8.3 Hz, 1 H), 6.49 (d, J = 7.7 Hz, 1 H), 7.04
(t, J = 8.3 Hz, 1 H), 7.22–7.33 (m, 2 H), 7.35–7.42 (m, 3 H),
7.38 (s, 1 H), 7.48–7.55 (m, 1 H), 7.55–7.60 (m, 2 H), 7.80–
7.86 (m, 2 H). 13C NMR (75 MHz, CDCl3): d = 40.7, 55.7,
72.1, 103.6, 109.9, 111.9, 114.5, 125.3, 127.9, 128.3, 128.5,
128.8, 129.3, 132.5, 133.2, 136.3, 137.0, 151.6, 155.5,
197.4. IR (CHCl3): 1680, 1594 cm–1. MS: m/z (%) = 356
(5.9) [M+], 237 (100), 222 (11.7). HRMS: m/z [M+] calcd for
C24H20O3: 356.1412; found: 356.1410.
2-(2-Oxopropyl)-3-phenyl-5-trimethylsilyl-2H-1-
benzopyran (6j): colorless oil. 1H NMR (300 MHz, CDCl3):
d = 0.24 (s, 9 H), 2.09 (s, 3 H), 2.40 (dd, J = 2.1, 17.8 Hz, 1
H), 3.21 (dd, J = 9.0, 17.8 Hz, 1 H), 6.17 (dd, J = 2.0, 9.0 Hz,
1 H), 6.77 (s, 1 H), 6.92 (t, J = 7.2 Hz, 1 H), 7.10 (dd, J = 1.7,
7.3 Hz, 1 H), 7.24 (dd, J = 1.7, 7.3 Hz, 1 H), 7.26–7.33 (m,
1 H), 7.34–7.42 (m, 2 H), 7.44–7.52 (m, 2 H). 13C NMR (75
MHz, CDCl3): d = –0.94, 30.6, 46.4, 71.1, 120.2, 121.1,
121.3, 125.2, 126.8, 128.1, 128.4, 128.9, 133.8, 135.0,
136.1, 155.8, 205.1. IR (CHCl3): 1714, 1579 cm–1. MS: m/z
(%) = 336 (8.4) [M+], 279 (100). HRMS: m/z [M+] calcd for
C21H24O2Si: 336.1546; found: 336.1545.
3-Butyl-2-(2-phenyl-2-oxoethyl)-5-trimethylsilyl-2H-1-
benzopyran (6k): yellowish oil. 1H NMR (300 MHz,
CDCl3): d = 0.10 (s, 9 H), 0.92 (t, J = 7.2 Hz, 3 H), 1.33–1.41
(m, 2 H), 1.48–1.59 (m, 2 H), 2.08 (t, J = 7.7 Hz, 2 H), 2.95
(dd, J = 3.4, 17.0 Hz, 1 H), 3.63 (dd, J = 8.2, 17.1 Hz, 1 H),
5.59 (dd, J = 3.3, 8.3 Hz, 1 H), 6.19 (s, 1 H), 6.85 (t, J = 7.2
Hz, 1 H), 6.97 (dd, J = 1.7, 7.3 Hz, 1 H), 7.13 (dd, J = 1.7,
7.2 Hz, 1 H), 7.37–7.44 (m, 2 H), 7.51–7.53 (m, 1 H), 7.87–
7.91 (m, 2 H). 13C NMR (75 MHz, CDCl3): d = –0.93, 13.9,
22.4, 29.3, 32.5, 41.5, 73.1, 119.0, 120.9, 121.4, 126.5,
127.3, 128.2, 128.5, 133.2, 133.9, 137.0, 137.1, 155.7,
197.1. IR (CHCl3): 1682, 1594 cm–1. MS: m/z (%) = 378
(5.18) [M+], 260 (23.7), 259 (100). HRMS: m/z [M+] calcd
for C24H30O2Si: 378.2015; found: 378.2013.
2-Phenyl-(2-phenyl-2-oxoethyl)-3H-naphtho[2,1-
b]pyran (6l): yellowish oil. 1H NMR (300 MHz, CDCl3):
d = 2.79 (dd, J = 2.2, 16.3 Hz, 1 H), 3.93 (dd, J = 9.8, 16.3
Hz, 1 H), 6.29 (dd, J = 2.1, 9.6 Hz, 1 H), 6.97 (d, J = 8.8 Hz,
1 H), 7.30–7.70 (m, 12 H), 7.75–7.85 (m, 3 H), 8.13 (d, J =
8.6 Hz, 1 H). 13C NMR (75 MHz, CDCl3): d = 40.3, 72.8,
115.2, 115.8, 118.4, 121.3, 123.9, 125.4, 126.8, 128.2,
128.3, 128.5, 128.7, 129.0, 129.6, 129.8, 123.0, 133.1,
133.2, 136.4, 137.0, 149.0, 197.3. IR (CHCl3): 1721, 1600
cm–1. MS: m/z (%) = 376 (6.4) [M+], 257 (100), 228 (7.0).
HRMS: m/z [M+] calcd for C27H20O2: 376.1463; found:
376.1457.
Methyl (5-Methoxy-3-phenyl-2H-1-benzopyran-2-
yl)acetate (6g): colorless oil. 1H NMR (300 MHz, CDCl3):
d = 2.45 (dd, J = 2.9, 15.2 Hz, 1 H), 2.89 (dd, J = 10.1, 15.2
Hz, 1 H), 3.67 (s, 3 H), 3.86 (s, 3 H), 5.86 (dd, J = 2.9, 10.1
Hz, 1 H), 6.49 (d, J = 8.3 Hz, 1 H), 6.53 (d, J = 8.1 Hz, 1 H),
7.10 (t, J = 8.3 Hz, 1 H), 7.21 (s, 1 H), 7.24–7.35 (m, 1 H),
7.35–7.40 (m, 2 H), 7.50–7.60 (m, 2 H). 13C NMR (75 MHz,
CDCl3): d = 37.8, 51.8, 55.7, 72.6, 103.8, 109.8, 111.8,
114.8, 125.3, 127.9, 128.8, 129.5, 132.0, 136.4, 151.4,
155.6, 170.9. IR (CHCl3): 1726, 1593 cm–1. MS: m/z (%) =
310 (10.8) [M+], 237 (100), 222 (15.6). HRMS: m/z [M+]
Synlett 2008, No. 3, 428–432 © Thieme Stuttgart · New York

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