Synthesis of 7-hydroxy-6H-benzo[c]chromen-6-ones based on?a '[3+3] cyclization/domino retro-Michael-aldol-lactonization' strategy

Article abstract of DOI:10.1016/j.tet.2006.07.084

The TiCl₄-mediated [3+3] cyclization of 2,4-bis(trimethylsilyloxy)penta-1,3-diene with 3-silyloxyalk-2-en-1-ones afforded 2-acetylphenols, which were transformed into functionalized chromones. The Me₃SiOTf-mediated condensation of the latter with 1,3-bis(silyl enol ethers) and subsequent domino 'retro-Michael-aldol-lactonization' reaction afforded 7-hydroxy-6H-benzo[c]chromen-6-ones.

Full text of DOI:10.1016/j.tet.2006.07.084

Tetrahedron 62 (2006) 9694–9700
Synthesis of 7-hydroxy-6H-benzo[c]chromen-6-ones based on a
‘[3D3] cyclization/domino retro-Michael–aldol–lactonization’
strategy
Ehsan Ullah,a,b,c Bettina Appel,c Christine Fischerb and Peter Langera,b,
*
aInstitut fu€r Chemie, Universita€t Rostock, Albert-Einstein-Str. 3a, D-18059 Rostock, Germany
bLeibniz-Institut fu€r Katalyse e. V. an der Universita€t Rostock, Albert-Einstein-Str. 29a, D-18059 Rostock, Germany
cInstitut fu€r Biochemie, Universita€t Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany
Received 26 April 2006; revised 11 July 2006; accepted 25 July 2006
Abstract—The TiCl4-mediated [3+3] cyclization of 2,4-bis(trimethylsilyloxy)penta-1,3-diene with 3-silyloxyalk-2-en-1-ones afforded 2-
acetylphenols, which were transformed into functionalized chromones. The Me3SiOTf-mediated condensation of the latter with 1,3-bis(silyl
enol ethers) and subsequent domino ‘retro-Michael–aldol–lactonization’ reaction afforded 7-hydroxy-6H-benzo[c]chromen-6-ones.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
endothelic cells6 and represent estrogen receptors.7 Ellagic
and coruleoellagic acid, which have been isolated mainly
from plant sources,8 occur both as glycosides and aglycons.
Dibenzo[c,d]chromen-6-ones occur in a number of natural
antibiotics and antitumor agents, such as the gilvocarcins,
chrysomycins, and ravidomycins.9
Functionalized 6H-benzo[c]chromen-6-ones (dibenzo[b,d]-
pyran-6-ones) are present in a number of pharmacologically
relevant natural products. For example, autumnariol has been
isolated from Eucomis autumnalis Greab. (Liliaceae).1 The
isolation of related 6H-benzo[c]chromen-6-ones, such as
autumnariniol,2 alternariol,3 or altenuisol,4 has been reported
(Chart 1).5 It has been demonstrated that 6H-benzo[c]-
chromen-6-ones are specific inhibitors of the growth of
6H-Benzo[c]chromen-6-ones have been prepared by cycliza-
tions of o-bromobenzoic acids with phenols,10 intramole-
cular palladium(II) catalyzed coupling reactions of aryl
benzoates,11 and Suzuki reactions.12–14 Harris et al. reported
the synthesis of 9-O-methylalternariol by condensation of the
dianion of acetylacetone with a protected salicylate.15,16 We
have recently reported17 the synthesis of 7-hydroxy-6H-ben-
zo[c]chromen-6-ones by condensation of 1,3-bis(silyl enol
ethers)18 with 4-silyloxybenzopyrylium triflates, in situ gen-
erated from chromones,19 and subsequent base-mediated
domino ‘retro-Michael–aldol–lactonization’ reaction. The
preparative scope of this method severely depends on the
availability of the chromones as starting materials. Chan
and co-workers developed an elegant approach to arenes by
[3+3] cyclization of 1,3-bis(silyl enol ethers) with 3-siloxy-
alk-2-en-1-ones.20 Based on this work we herein report
a new approach to functionalized chromones by [3+3] cycli-
zation of 2,4-bis(trimethylsilyloxy)penta-1,3-diene with 3-
silyloxyalk-2-en-1-ones. The combination of these reactions
with the domino reaction of chromones with 1,3-bis(silyl
enol ethers) provides a versatile strategy for the synthesis
of 7-hydroxy-6H-benzo[c]chromen-6-ones. Notably, this
strategy relies on the sequential use of 1,3-bis(silyl enol
ethers)18 at two stages of the synthesis.
Me
Me
OH
OH
HO
O
O
HO
O
O
OMe
autumnariniol
autumnariol
OH
Me
OH
HO
MeO
OH
OH
HO
O
O
O
O
alternariol
altenuisol
Chart 1. 7-Hydroxy-6H-benzo[c]chromen-6-ones in nature.
Keywords: Chromones; Cyclizations; Domino reactions; Oxygen hetero-
cycles; Silyl enol ethers.
* Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412;
e-mail: peter.langer@uni-rostock.de
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.084

E. Ullah et al. / Tetrahedron 62 (2006) 9694–9700
9695
2. Results and discussion
The combination of two different cyclization reactions of
1,3-bis(silyl enol ethers) allows a facile approach to a num-
ber of novel 7-hydroxy-6H-benzo[c]chromen-6-ones. The
core structure of the products contains 13 carbon atoms
out of which 9 carbons are derived from the two 1,3-bis(silyl
enol ethers), 3 carbons from the 3-silyloxyalk-2-en-1-one
and 1 carbon from the orthoformate.
The TiCl4-mediated [3+3] cyclization of 2,4-bis(trimethyl-
silyloxy)penta-1,3-diene (2) with 3-silyloxyalk-2-en-1-
ones, following the conditions reported by Chan20 and us,21
afforded the 2-acetylphenols 3a–f (Scheme 1, Table 1). The
synthesis of chloro-21e and acetoxy-substituted21f salicylates
by [3+3] cyclizations of 1,3-bis(silyl enol ethers) with appro-
priate 3-silyloxyalk-2-en-1-ones has been previously re-
ported. The cyclization of 1,3-bis(silyl enol ether) 2 with
1d and 1e proceeded with very good regioselectivity, which
can be explained as previously reported.20,21i Treatment of
the acetylphenols with HC(OEt)3 and HClO4 afforded the
chromones 4a–f. During the formation of 4f, the acet-
oxy group was cleaved to give a hydroxyl group. The
Me3SiOTf-mediated condensation of 4a–f with 1-ethoxy or
1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (5a,b)
gave the 2,3-dihydrobenzopyrans 6a–f. Treatment of the
latter with NEt3 in EtOH afforded the novel 7-hydroxy-6H-
benzo[c]chromen-6-ones 7a–f. The formation of the latter
can be explained by a domino ‘retro-Michael–aldol–lactoni-
zation’ reaction.17 The synthesis of compounds 3b,22 3c,23
and 4c24 has been previously reported.
In conclusion, we have reported the synthesis of 7-hydroxy-
6H-benzo[c]chromen-6-ones based on sequential reactions
of 1,3-bis(silyl enol ethers) with 3-silyloxyalk-2-en-1-ones
and chromones.
3. Experimental
3.1. General comments
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For the 1H and
13C NMR spectra the deuterated solvents indicated were
used. Chemical shifts d are reported in parts per million rel-
ative to CHCl3 (1H, 7.26 ppm) and CDCl3 (13C, 77.0 ppm) as
internal standards. 13C NMR spectral assignments are
supported by DEPT analyses. Mass spectral data (MS)
were obtained by electron ionization (EI, 70 eV), chemical
ionization (CI, H2O), or electrospray ionization (ESI). For
preparative scale chromatography silica gel (60–200 mesh)
was used. Melting points are uncorrected.
R3
Me
OSiMe3
OSiMe3
R3 Me
R2
R1
R2
R1
O
a
O
+
[3+3]
OSiMe3
1a-f
OH
3a-f
2
3.2. General procedure for the synthesis of 2-acetyl-
phenols 3a–f
b
Me3SiO
OSiMe3
OR4
R3
O
O
R3
O
O
O
To a stirred CH2Cl2 solution (2 mL/mmol) of 1,3-bis(silyl
enol ether) 2 (1.0 mmol) and 3-siloxyalk-2-en-1-one 1
(1.0 mmol) was added TiCl4 (1.0 mmol) at ꢀ78 ꢁC under
argon atmosphere. The temperature of the reaction mixture
was allowed to rise to 20 ꢁC during 20 h and a saturated
aqueous solution of NaHCO3 (10 mL) was added. The
organic layer was separated and extracted with diethyl ether
(3ꢂ30 mL). The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated
in vacuo. The residue was purified by column chromato-
graphy (silica gel, EtOAc/heptane¼1:4).
R2
R1
R2
R1
OR4
5a,b
c
O
4a-f
6a-f
d
Domino 'retro-Michael-aldol-lactonization' reaction
R3
O
R3
R2
R1
R2
OH
O
OH
O
R1
O
O
OR4
3.2.1. 1-(3-Chloro-2,4-diethyl-6-hydroxyphenyl)etha-
none (3a). Starting with 4-chloro-5-(trimethylsilyloxy)hept-
4-en-3-one (1a) (1.021 g, 4.3 mmol), 2,4-bis(trimethylsilyl-
oxy)penta-1,3-diene (2) (1.041 g, 4.3 mmol), and TiCl4
(0.812 g, 4.3 mmol), 3a was obtained (0.490 g, 50%) as
7a-f
Scheme 1. Synthesis of 7-hydroxy-6H-benzo[c]chromen-6-ones 7a–f:
(a) TiCl4, CH2Cl2, ꢀ78 ꢁC; (b) HC(OEt)3, HClO4 (70%), reflux, 12 h;
(c) (1) Me3SiOTf (1.3 equiv), 20 ꢁC, 1 h; (2) 5a,b (1.3 equiv), CH2Cl2,
0/20 ꢁC, 12 h; (3) HCl (10%); (d) NEt3 (2.0 equiv), EtOH, 20 ꢁC, 12 h.
Table 1. Products and yields
R1
R2
R3
R4
3 (%)a
4 (%)a
6 (%)a
7 (%)a
a
b
c
d
e
f
Et
Cl
Me
H
Et
Me
Me
Me
Et
Et
50
51
40
36
20
42
—
80
70
84
78
69
—
70
77
65
68
61
73
—
68
28 (48)
22 (42)
24 (46)
50
35 (60)
—
33 (40)
Me
Me
Me
Me
Me
Me
–CH2)4–
–(CH2)3–
Et
Me
Me
Me
OAc
OH
Me
Me
f
Yields of isolated products; the synthesis of compounds 3b,22 3c,23 and 4c24 has been previously reported; values in brackets: yields based on recovered
starting material.
a

9696
E. Ullah et al. / Tetrahedron 62 (2006) 9694–9700
1
a yellow solid; mp 60 ꢁC. H NMR (250 MHz, CDCl3):
d 10.40 (s, 1H, OH), 6.74 (s, 1H, Ar-H), 3.00 (q, 2H,
J¼7.6 Hz, CH2), 2.75 (q, 2H, J¼7.3 Hz, CH2), 2.67 (s, 3H,
CH3), 1.32–1.19 (m, 6H, CH3). 13C NMR (75 MHz,
CDCl3): d 205.8 (CO), 157.9 (C–OH), 148.7, 141.6 (C),
125.8 (C–Cl), 122.8 (C), 116.8 (CH), 32.8 (CH3), 28.3, 26.0
(CH2), 14.7, 13.7 (CH3). IR (Nujol, cmꢀ1): ~n 3229 (w), 1678
(m), 1225 (s), 1081 (s), 856 (w). MS (EI, 70 eV): m/z (%)
226 (M+, 34), 211 (100), 193 (17), 173 (10). Anal. Calcd for
C12H15O2Cl (226.0): C 63.57, H 6.62; found: C 63.97, H 6.57.
(12), 91 (16), 43.0 (24). HRMS (EI) calcd for C12H14O2
[M]+: 190.0988; found: 190.0985.
3.2.6. 1-[3-(Acetoxy)-6-hydroxy-2,4-dimethylphenyl]-
ethanone (3f). Starting with 1f (1.005 g, 4.37 mmol), 2
(1.066 g, 4.37 mmol), and TiCl4 (0.825 g, 4.37 mmol), 3f
(0.410 g, 42%) was obtained as a yellow oil. 1H NMR
(250 MHz, CDCl3): d 11.80 (s, 1H, OH), 6.71 (s, 1H, Ar-H),
2.61 (s, 3H, CH3COO), 2.34 (s, 3H, CH3), 2.31 (s, 3H, CH3),
2.21 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): d 205.5,
169.1(CO), 159.5, 141.0, 138.6, 130.4, 121.2 (C), 118.3
(CH), 33.3, 20.7, 17.5, 16.5 (CH3). IR (KBr, cmꢀ1): ~n 3407
(br), 2929 (w), 1760 (s), 1198 (s), 908 (w). MS (EI, 70 eV):
m/z (%) 222 (M+, 9), 180 (84), 165 (100), 43 (23). HRMS
(EI) calcd for C12H14O4 [M]+: 222.0887; found: 222.0881.
3.2.2. 1-(6-Hydroxy-2,3,4-trimethylphenyl)ethanone
(3b). The synthesis of 3b has been previously reported.22
Starting with 3-methyl-4-(trimethylsilyloxy)pent-3-en-2-
one (1b) (0.500 g, 2.68 mmol), 2 (0.653 g, 2.68 mmol),
and TiCl4 (0.506 g, 2.68 mmol), 3b (0.241 g, 51%) was
obtained as a slight yellow solid; mp 62 ꢁC. 1H NMR
(250 MHz, CDCl3): d 10.87 (s, 1H, OH), 6.66 (s, 1H,
Ar-H), 2.58 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.26 (s, 3H,
CH3), 2.12 (s, 3H, CH3). 13C NMR (62 MHz, CDCl3):
d 206.3 (CO), 157.7, 144.2, 136.4, 128.1, 122.3 (C), 116.6
(CH), 32.7, 21.5, 20.2, 15.0 (CH3). IR (Nujol, cmꢀ1): ~n
3191 (m), 2975 (s), 1661 (m), 1450 (s), 1304 (m), 845 (s).
MS (EI, 70 eV): m/z (%) 178 (M+, 30), 163 (100), 135 (8),
91 (12), 44 (14). Anal. Calcd for C11H14O2 (178.1): C
74.15, H 7.86; found: C 74.00, H 7.96.
3.3. General procedure for the synthesis of chromones
4a–f
To ethanone 3 (1.0 equiv) were slowly added triethyl ortho-
formate (20 equiv) and perchloric acid (70%, 1.3 equiv)
and the reaction mixture was refluxed for 20 h at 80 ꢁC. After
cooling to 20 ꢁC, the reaction mixture was filtered and
washed with cold water. The organic layer was separated
and the aqueous layer was extracted with CH2Cl2
(3ꢂ30 mL). The combined organic layers were washed
with water, dried (Na2SO4), filtered, and the filtrate was
concentrated in vacuo. The residue was purified by column
chromatography (silica gel).
3.2.3. 1-(6-Hydroxy-2,4-dimethylphenyl)ethanone (3c).
The synthesis of 3c has been previously reported.23 Starting
with 4-trimethylsilyloxy-pent-3-en-2-one (1b) (1.000 g,
5.81 mmol), 2 (1.417 g, 5.81 mmol), and TiCl4 (1.098 g,
5.81 mmol), 3b (0.380 g, 40%) was obtained as a slight
yellow solid; mp 42 ꢁC.
3.3.1. 6-Chloro-5,7-diethylchromen-4-one (4a). Starting
with 3a (0.302 g, 1.33 mmol), triethyl orthoformate (3.936 g,
26.60 mmol, 20 equiv), and perchloric acid (70%) (0.172 g,
1.72 mmol), 4a (0.251 g, 80%) was obtained as a colorless
1
3.2.4. 1-(2-Hydroxy-4-methyl-5,6,7,8-tetrahydronaph-
thalen-1-yl)ethanone (3d). Starting with 1-(2-trimethylsilyl-
oxycyclohex-1-enyl)ethanone (1d) (0.500 g, 2.35 mmol), 2
(0.573 g, 2.35 mmol), and TiCl4 (0.444 g, 2.35 mmol), 3d
(0.172 g, 36%) was obtained as a brownish solid; mp
solid; mp 80 ꢁC. H NMR (250 MHz, CDCl3): d 7.68 (d,
1H, J¼6.1 Hz, CH), 7.18 (s, 1H, Ar-H), 6.23 (d, 1H,
J¼5.8 Hz, CH), 3.55 (q, 2H, J¼7.3 Hz, CH2), 2.85 (q, 2H,
J¼7.6 Hz, CH2), 1.32–1.19 (m, 6H, CH3). 13C NMR
(62 MHz, CDCl3): d 178.4 (CO), 156.5 (C), 153.1 (CH),
148.0, 144.2, 131.7, 121.0 (C), 116.3, 114.4 (CH), 28.0,
24.3 (CH2), 13.7, 13.3 (CH3). IR (KBr, cmꢀ1): ~n 3436 (br),
2970 (w), 1648 (s), 1436 (s), 1254 (s), 843 (s). MS (EI,
70 eV): m/z (%) 236 (M+, 89), 219 (100), 193 (20), 115
(11). Anal. Calcd for C13H13O2Cl (236.0): C 66.10, H 5.55;
found: C 65.97, H 5.63.
1
55 ꢁC. H NMR (250 MHz, CDCl3): d 11.49 (s, 1H, OH),
6.67 (s, 1H, Ar-H), 2.93 (t, 2H, J¼6.4 Hz, CH2), 2.64 (s,
3H, CH3), 2.57 (t, 2H, J¼6.7 Hz, CH2), 2.19 (s, 3H, CH3),
1.87–1.68 (m, 4H, CH2). 13C NMR (62 MHz, CDCl3):
d 206.1 (CO), 158.9, 145.1, 137.6, 127.3, 121.0 (C), 117.2
(CH), 33.4 (CH3), 31.3, 26.6, 22.9, 22.6 (CH2), 20.4 (CH3).
IR (Nujol, cmꢀ1): ~n 3410 (w), 2950 (s), 1629 (m), 1460 (s),
1340 (s), 1298 (m). MS (EI, 70 eV): m/z (%) 204 (M+, 64),
189 (100), 161 (43), 146 (15), 44 (39). HRMS (EI) calcd
for C13H16O2 [M]+: 204.1145; found: 204.1141.
3.3.2. 5,6,7-Trimethylchromen-4-one (4b). Starting with
3b (0.202 g, 1.15 mmol), triethyl orthoformate (3.400 g,
23.00 mmol), and perchloric acid (70%) (0.152 g,
1.50 mmol), 4b (0.151 g, 70%) was obtained as a white
1
3.2.5. 1-(5-Hydroxy-7-methylindan-4-yl)ethanone (3e).
Starting with 2-(1-trimethylsilyloxy-ethylidene)cyclopenta-
none (1a) (1.000 g, 5.04 mmol), 2 (1.230 g, 5.04 mmol), and
TiCl4 (0.952 g, 5.04 mmol), 3e (0.200 g, 20%) was obtained
solid; mp 124 ꢁC. H NMR (250 MHz, CDCl3): d 7.64 (d,
1H, J¼5.8 Hz, CH), 7.07 (s, 1H, Ar-H), 6.20 (d, 1H,
J¼5.7 Hz, CH), 2.83 (s, 3H, CH3), 2.37 (s, 3H, CH3), 2.23
(s, 3H, CH3). 13C NMR (62 MHz, CDCl3): d 180.0 (CO),
156.0 (C), 153.0 (CH), 143.0, 138.5, 133.2, 121.3 (C),
116.2, 114.1 (CH), 21.6, 17.3, 15.2 (CH3). IR (KBr,
cmꢀ1): ~n 3438 (br), 2925 (w), 1647 (s), 1428 (s), 1236 (s),
1001 (s), 848 (s). MS (EI, 70 eV): m/z (%) 188 (M+, 100),
173 (57), 145 (9), 91 (7). Anal. Calcd for C12H12O2
(188.0): C 76.60, H 6.38; found: C 76.20, H 6.31.
1
as a yellow solid; mp 58 ꢁC. H NMR (250 MHz, CDCl3):
d 12.18 (s, 1H, OH), 6.74 (s, 1H, Ar-H), 2.92 (t, 2H,
J¼7.3 Hz, CH2), 2.83 (t, 2H, J¼7.6 Hz, CH2), 2.66 (s, 3H,
CH3), 2.48 (s, 3H, CH3), 2.07 (quint, 2H, J¼7.6 Hz, CH2).
13C NMR (62 MHz, CDCl3): d 205.8 (CO), 161.8. 152.0,
135.4, 134.1, 120.3 (C), 111.6 (CH), 33.8 (CH2), 33.0
(CH3), 31.5, 24.3 (CH2), 20.5 (CH3). IR (Nujol, cmꢀ1): ~n
2952 (s), 1622 (w), 1470 (s), 1353 (s), 1234 (w), 841 (w).
MS (EI, 70 eV): m/z (%) 190 (M+, 40), 175 (100), 115
3.3.3. 5,7-Dimethylchromen-4-one (4c). The synthesis of
4c has been previously reported.24 Starting with 3c

E. Ullah et al. / Tetrahedron 62 (2006) 9694–9700
9697
(0.175 g, 1.07 mmol), triethyl orthoformate (3.502 g,
21.34 mmol), and perchloric acid (70%) (0.140 g,
1.40 mmol), 4c (0.156 g, 84%) was obtained as a brownish
3.4. General procedure for the synthesis of 4-(chroman-
2-yl)-3-oxobutyrates 6a–f
1
solid; mp 58 ꢁC. H NMR (250 MHz, CDCl3): d 7.66 (d,
To chromone 4 (1.0 equiv) was added Me3SiOTf (1.3 equiv)
at 20 ꢁC. After stirring for 1 h, CH2Cl2 (8 mL) and the 1,3-
bis(silyl enol ether) 5 (1.3 equiv) were added at 0 ꢁC. The
mixture was stirred for 12 h at 20 ꢁC and was subsequently
poured into an aqueous solution of hydrochloric acid
(10%). The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 (3ꢂ80 mL). The combined
organic layers were washed with water, dried (Na2SO4), fil-
tered, and the filtrate was concentrated in vacuo. The residue
was purified from polar side-products by column flash chro-
matography (silica gel, n-hexane/EtOAc¼1:1) to give 6a–f.
Products 6a–f were isolated and characterized and subse-
quently transformed into 7a–f.
2H, J¼5.8 Hz, CH), 7.04 (s, 1H, Ar-H), 6.92 (s, 1H,
Ar-H), 6.20 (d, 2H, J¼6.1 Hz, CH), 2.80 (s, 3H, CH3),
2.38 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3): d 179.6
(CO), 158.1 (C), 153.5 (CH), 143.7, 140.7 (C), 129.2
(CH), 121.0 (C), 116.3, 114.5 (CH), 22.7, 21.5 (CH3). IR
(KBr, cmꢀ1): ~n 3432 (br), 2925 (m), 1648 (s), 1350 (s),
1239 (s), 827 (s). MS (EI, 70 eV): m/z (%) 174 (M+,
100), 159 (12), 145 (30), 91 (36), 39 (21). Anal. Calcd
for C11H10O2 (174.1): C 75.58, H 5.74; found: C 75.23,
H 5.80.
3.3.4. 6-Methyl-7,8,9,10-benzo[f]chromen-1-one (4d).
Starting with 3d (0.150 g, 0.73 mmol), triethyl orthoformate
(2.161 g, 14.60 mmol), and perchloric acid (0.095 g,
0.95 mmol), 4d (0.122 g, 78%) was obtained as a white
3.4.1. 4-(6-Chloro-5,7-diethyl-4-oxochroman-2-yl)-3-
oxobutyric acid methyl ester (6a). Starting with 4a
(0.212 g, 0.89 mmol), TMSOTf (0.256 g, 1.15 mmol), and
1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (5a)
(0.300 g, 1.15 mmol), 6a (0.240 g, 77%) was obtained as
1
solid; mp 70 ꢁC. H NMR (250 MHz, CDCl3): d 7.66 (d,
1H, J¼5.7 Hz, CH), 7.07 (s, 1H, Ar-H), 6.23 (d, 1H,
J¼6.1 Hz, CH), 3.45 (t, 2H, J¼6.4 Hz, CH2), 2.64 (t, 2H,
J¼5.4 Hz, CH2), 2.31 (s, 3H, CH3), 1.80–1.77 (m, 4H,
CH2). 13C NMR (75 MHz, CDCl3): d 179.9 (CO), 156.2
(C), 153.3 (CH), 143.6, 139.7, 133.3, 120.9 (C), 116.5,
114.7 (CH), 30.1, 27.8, 23.1, 22.5 (CH2), 20.8 (CH3). IR
(KBr, cmꢀ1): ~n 3437 (br), 2925 (s), 1620 (s), 1605 (s),
1455 (s), 1232 (s), 850 (m). MS (EI, 70 eV): m/z (%) 214
(M+, 100), 199 (80), 181 (29), 131 (33), 69 (51). Anal. Calcd
for C14H14O2 (214.1): C 78.85, H 6.94; found: C 78.70, H
6.30.
1
a brownish solid; mp 72 ꢁC. H NMR (250 MHz, CDCl3):
d 6.73 (s, 1H, Ar-H), 4.95–4.84 (m, 1H, CH chain), 3.76 (s,
3H, OCH3), 3.56 (s, 2H, CH2), 3.32–3.27 (m, 2H, CH2),
2
3
3.14 (dd, 1H, J¼17.0 Hz, J¼7.3 Hz, CH2), 2.90 (dd, 1H,
3
2J¼17.0 Hz, J¼7.1 Hz, CH2), 2.79–2.70 (m, 4H, CH2),
1.22 (t, 3H, J¼7.6 Hz, CH3), 1.16 (t, 3H, J¼7.3 Hz, CH3).
13C NMR (62 MHz, CDCl3): d 199.0, 191.4, 160.9 (CO),
150.3, 148.1, 148.5, 145.5, 145.4 (C), 115.9, 73.0 (CH),
53.0 (OCH3), 50.0, 47.7, 44.4, 28.5, 24.7 (CH2), 14.0 (2C,
CH3). IR (KBr, cmꢀ1): ~n 3437 (br), 2977 (m), 1746 (s),
1677 (s), 1417 (s), 1194 (s), 867 (m). MS (EI, 70 eV): m/z
(%) 352 (M+, 78), 320 (14), 237 (100), 167 (40), 115 (9).
Anal. Calcd for C18H21O5Cl (352.0): C 61.27, H 5.95; found:
C 61.19, H 6.10.
3.3.5. 4-Methyl-2,3-dihydro-1H-6-oxacyclopenta[a]-
naphthalen-9-one (4e). Starting with 3e (0.240 g,
1.30 mmol), triethyl orthoformate (3.863 g, 26.10 mmol),
and perchloric acid (0.170 g, 1.70 mmol), 4e (0.180 g,
1
69%) was obtained as a colorless solid; mp 130 ꢁC. H
NMR (250 MHz, CDCl3): d 7.70 (d, 1H, J¼6.1 Hz, CH),
7.03 (s, 1H, Ar-H), 6.21 (d, 1H, J¼5.8 Hz, CH), 3.50 (t,
2H, J¼7.6 Hz, CH2), 2.81 (t, 2H, J¼7.6 Hz, CH2), 2.33 (s,
3H, CH3), 2.15 (p, 2H, J¼7.6 Hz, CH2). 13C NMR
(62 MHz, CDCl3): d 179.4 (CO), 157.0 (C), 154.6 (CH),
144.6, 141.3, 140.7, 133.9 (C), 116.4, 113.9 (CH), 34.0,
29.3, 24.0 (CH2), 20.3 (CH3). IR (KBr, cmꢀ1): ~n 3438 (br),
2914 (w), 1662 (s), 1603 (s), 1230 (m), 849 (m). MS (EI,
70 eV) m/z (%) 199 (M+, 100), 184 (5), 128 (12), 115 (7).
HRMS (EI, 70 eV) calcd for C13H11O2 [M]+: 199.0754;
found: 199.0747.
3.4.2. 3-Oxo-4-(5,6,7-trimethyl-4-oxochroman-2-yl)-
butyric acid ethyl ester (6b). Starting with 4b (0.13 g,
0.70 mmol), TMSOTf (0.20 g, 0.91 mmol), and 1-ethoxy-
1,3-bis(trimethylsilyloxy)buta-1,3-diene
0.91 mmol), 6b (0.145 g, 65%) was obtained as a yellow
(5b)
(0.25 g,
1
solid; mp 56 ꢁC. H NMR (250 MHz, CDCl3): d 6.63 (s,
1H, Ar-H), 4.90–4.79 (m, 1H, CH), 4.20 (q, 2H, J¼7.0 Hz,
CH2), 3.53 (s, 2H, CH2), 3.15 (dd, 1H, 2J¼16.7 Hz,
2
3
3J¼7.3 Hz, CH2), 2.85 (dd, 1H, J¼16.7 Hz, J¼7.3 Hz,
CH2), 2.72–2.70 (m, 2H, CH2), 2.67 (s, 3H, CH3), 2.58 (s,
3H, CH3), 2.26 (s, 3H, CH3), 1.28 (t, 3H, J¼7.3 Hz, CH3).
13C NMR (62 MHz, CDCl3): d 199.4, 193.2, 166.8 (CO),
159.9, 145.0, 139.7, 129.6, 118.0 (C), 116.2, 72.4 (CH),
61.6, 50.0, 47.5, 44.4 (CH2), 21.7, 17.5, 14.9, 14.0 (CH3).
IR (KBr, cmꢀ1): ~n 3435 (br), 2982 (w), 1741 (s), 1677 (s),
1271 (s), 1100 (m), 857 (w). MS (EI, 70 eV): m/z (%) 318
(M+, 60), 272 (20), 203 (9), 189 (42), 162 (100), 91 (16).
HRMS (EI, 70 eV) calcd for C18H22O5 [M]+: 318.1462;
found: 318.1458. Anal. Calcd for C18H22O5 (318.0): C
67.92, H 6.91; found: C 68.44, H 6.75.
3.3.6. 6-Hydroxy-5,6-dimethylchromen-4-one (4f). Start-
ing with 3f (0.205 g, 0.90 mmol), triethyl orthoformate
(2.666 g, 18.01 mmol), and perchloric acid (70%)
(0.117 g, 1.17 mmol), 4f (0.120 g, 70%) was obtained as
a colorless solid; mp 140 ꢁC. 1H NMR (250 MHz, CDCl3):
d 7.67 (d, 1H, J¼5.8 Hz, CH), 7.10 (s, 1H, Ar-H), 6.20 (d,
1H, J¼7.1 Hz, CH), 2.81 (s, 3H, CH3), 2.36 (s, 3H, CH3).
13C NMR (62 MHz, CDCl3): d 177.0 (CO), 154.8 (CH),
149.5, 148.5, 131.6, 121.7, 119.4 (C), 117.0, 113.0 (CH),
17.7, 13.9 (CH3). IR (Nujol, cmꢀ1): ~n 3410 (br), 2950 (s),
1642 (w), 1634 (w), 1294 (w), 1280 (w). MS (EI, 70 eV):
m/z (%) 190 (M+, 94), 161 (56), 147 (54), 43 (100).
HRMS (EI, 70 eV) calcd for C11H10O3 [M]+: 190.0624;
found: 190.0621.
3.4.3. 4-(5,7-Dimethyl-4-oxochroman-2-yl)-3-oxobutyric
acid ethyl ester (6c). Starting with 4c (0.228 g,
1.30 mmol), TMSOTf (0.375 g, 1.70 mmol), and 1-ethoxy-
1,3-bis(trimethylsilyloxy)buta-1,3-diene (5b) (0.465 g,
1.70 mmol), 6c (0.265 g, 68%) was obtained as a yellow

9698
E. Ullah et al. / Tetrahedron 62 (2006) 9694–9700
oil. 1H NMR (250 MHz, CDCl3): d 6.61 (s, 2H, Ar-H), 4.93–
4.82 (m, 1H, CH), 4.21 (q, 2H, J¼7.3 Hz, CH2), 3.53 (s, 2H,
CH2), 3.14 (dd, 1H, 2J¼16.7 Hz, 3J¼7.3 Hz, CH2), 2.85 (dd,
1H, 2J¼16.7 Hz, 3J¼7.3 Hz, CH2), 2.71–2.67 (m, 2H, CH2),
2.58 (s, 3H, CH3), 2.27 (s, 3H, CH3), 1.28 (t, 3H, J¼7.3 Hz,
CH3). 13C NMR (75 MHz, CDCl3): d 199.3, 192.2, 166.5
(CO), 162.07, 146.0, 141.9 (C), 126.2 (CH), 117.2 (C),
116.3, 73.1 (CH), 61.9, 50.3, 47.8, 44.2 (CH2), 23.0, 22.0,
14.5 (CH3). IR (Nujol, cmꢀ1): ~n 3436 (br), 2979 (m), 1744
(s), 1614 (s), 1326 (s), 1029 (s), 846 (w). MS (EI, 70 eV):
m/z (%) 304 (M+, 71), 189 (34), 175 (100), 148 (96), 91
(40). Anal. Calcd for C17H20O5 (304.1): C 67.67, H 6.57;
found: C 67.84, H 6.61.
4.77 (m, 1H, ring CH), 3.75 (s, 3H, OCH3), 3.56 (s, 2H, chain
CH2), 3.19–3.07 (m, 1H, ring CH2), 2.91–2.80 (m, 1H, ring
CH2), 2.72–2.66 (m, 2H, chain CH2), 2.55 (s, 3H, CH3), 2.42
(s, 3H, CH3). 13C NMR (62 MHz, CDCl3): d 199.2, 192.7,
169.0 (CO), 159.5 (C–OH), 147.1, 138.9, 133.4, 133.1 (C),
117.7, 73.1 (CH), 53.0 (OCH3), 50.0, 47.8, 44.6 (CH2),
17.6, 14.6 (CH3). IR (Nujol, cmꢀ1): ~n 3476 (br), 2955 (w),
1748 (s), 1614 (s), 1196 (s), 1073 (m), 862 (w). MS (EI,
70 eV): m/z (%) 306 (M+, 97), 274 (18), 191 (51), 164
(100), 135 (10). HRMS (EI, 70 eV) calcd for C16H18O6
[M]+: 306.1098; found: 306.1097.
3.5. General procedure for the synthesis of 7-hydroxy-
6H-benzo[c]chromen-6-ones 7a–f
3.4.4. 4-(6-Methyl-1-oxo-2,3,7,8,9,10-hexahydro-1H-
benzo[f]chromen-3-yl)-3-oxobutyric acid ethyl ester
(6d). Starting with 4d (0.092 g, 0.43 mmol), TMSOTf
(0.124 g, 0.56 mmol), and 1-ethoxy-1,3-bis(trimethylsilyl-
oxy)buta-1,3-diene (5b) (0.153 g, 0.56 mmol), 6d (0.091 g,
61%) was obtained as a yellow oil. 1H NMR (keto/
enol¼10:1, 250 MHz, CDCl3, only keto tautomer was
listed): d 6.63 (s, 1H, Ar-H), 4.91–4.80 (m, 1H, CH), 4.21
(q, 2H, J¼7.3 Hz, CH2), 3.53 (s, 2H, CH2), 3.17–3.0 (m,
1H, CH2), 2.85 (dd, 1H, 2J¼16.3 Hz, 3J¼7.1 Hz, CH2),
2.70–2.67 (m, 2H, CH2), 2.31 (s, 3H, CH3), 1.19–1.17 (m,
2H, CH2), 1.73–1.66 (m, 6H, CH2), 1.28 (t, 3H, J¼7.0 Hz,
CH3). 13C NMR (75 MHz, CDCl3): d 199.3, 192.7, 166.7
(CO), 159.9, 145.6, 140.7, 130.0, 117.1 (C), 116.3,
72.4 (CH), 61.3, 49.9, 47.3, 44.3, 30.9, 26.8, 23.3,
22.6 (CH2), 20.41, 14.03 (CH3). IR (Nujol, cmꢀ1): ~n 3437
(br), 2925 (s), 1620 (s), 1605 (s), 1455 (s), 1232 (s),
850 (m). MS (EI, 70 eV): m/z (%) 344 (M+, 73), 298
(15), 272 (17), 214 (100), 188 (85), 91 (11). Anal. Calcd
for C20H24O5 (344.2): C 69.73, H 6.97; found: C 69.72, H
7.16.
To an EtOH solution (10 mL) of 6 was added NEt3
(2.0 equiv) and the mixture was refluxed for 12 h at 80 ꢁC.
After cooling down to 20 ꢁC, an aqueous solution of hydro-
chloric acid (1 M) and Et2O (50 mL) was added. The organic
layer was separated and the aqueous layer was extracted with
Et2O (3ꢂ100 mL). The combined organic layers were
washed with water, dried (Na2SO4), filtered, and the filtrate
was concentrated in vacuo. The residue was purified by col-
umn chromatography (silica gel, n-hexane/EtOAc¼20:1/
3:1) to give product 7.
3.5.1. 3-Chloro-2,4-diethyl-8-hydroxy-10H-phenanth-
ren-9-one (7a). Starting with 6a (0.170 g, 0.48 mmol) and
NEt3 (0.097 g, 0.96 mmol), 7a (0.041 g, 28%; 48% based
on recovered starting material) was obtained as a colorless
solid; mp 140 ꢁC. Starting material 6a (0.070 g) was recov-
1
ered. H NMR (250 MHz, CDCl3): d 11.70 (s, 1H, OH),
8.14–8.06 (m, 2H, Ar-H), 7.55 (s, 1H, Ar-H), 7.47 (dd,
1H, J¼6.4 Hz, J¼2.7 Hz, Ar-H), 3.30 (q, 2H, J¼7.3 Hz,
CH2), 2.82 (q, 2H, J¼7.6 Hz, CH2), 1.50 (t, 3H, J¼7.3 Hz,
CH3), 1.28 (t, 3H, J¼7.3 Hz, CH3). 13C NMR (62 MHz,
CDCl3): d 165.7, 163.2, 150.0, 145.0, 140.2 (C), 137.0
(CH), 135.8, 133.0, 117.3 (C), 116.7, 116.5, 116.0
(CH), 107.0 (C), 27.6, 26.2 (CH2), 13.3, 12.7 (CH3).
IR (Nujol, cmꢀ1): ~n 3430 (br), 2910 (s), 1678 (s), 1224
(m), 1081 (w), 856 (w). MS (EI, 70 eV): m/z (%) 302 (M+,
100), 287 (44), 267 (20), 152 (15), 57 (20). HRMS (EI,
70 eV) calcd for C17H15O3Cl [M]+: 302.0704; found:
302.0704.
3.4.5. 4-(9-Methyl-8-oxo-1,2,3,6,7,8-hexahydro-5-oxacy-
clopenta[b]naphthalen-6-yl)-3-oxabutyric acid methyl
ester (6e). Starting with 4e (0.100 g, 0.54 mmol), TMSOTf
(0.155 g, 0.70 mmol), and 1-methoxy-1,3-bis(trimethylsilyl-
oxy)buta-1,3-diene (5a) (0.182 g, 0.70 mmol), 6e (0.125 g,
1
73%) was obtained as a yellow solid; mp 68 ꢁC. H NMR
(250 MHz, CDCl3): d 6.59 (s, 1H, Ar-H), 4.93–4.82 (m,
1H, CH), 3.76 (s, 3H, OCH3), 3.57 (s, 2H, CH2), 3.28 (t,
2H, J¼7.9 Hz, CH2), 3.18 (dd, 1H, 2J¼16.7 Hz, 3J¼
7.3 Hz, CH2), 2.88 (dd, 1H, 2J¼16.5 Hz, 3J¼7.3 Hz, CH2),
2.72–2.66 (m, 4H, CH2), 2.24 (s, 3H, CH3), 2.15–2.06 (m,
2H, CH2). 13C NMR (62 MHz, CDCl3): d 199.4, 192.4,
167.2 (CO), 160.8, 148.6, 146.4, 142.8, 138.0 (C), 116.6,
73.5 (CH), 53.0 (OCH3), 50.0, 47.8, 43.8, 34.7, 30.5, 25.2
(CH2), 21.0 (CH3). IR (KBr, cmꢀ1): ~n 3435 (br), 2982 (w),
1741 (s), 1677 (s), 1271 (s), 1100 (m), 857 (w). MS (EI,
70 eV): m/z (%) 316 (M+, 59), 284 (15), 200 (100), 174
(50), 115 (12). HRMS (EI, 70 eV) calcd for C18H20O5
[M]+: 316.1305; found: 316.1303.
3.5.2. 7-Hydroxy-1,2,3-trimethylbenzo[c]chromen-6-one
(7b). Starting with 6b (0.120 g, 0.37 mmol) and NEt3
(0.076 g, 0.75 mmol), 7b (0.021 g, 22%; 42% based on
recovered starting material) was obtained as a white solid;
mp 182 ꢁC. Starting material (6b) (0.040 g) was recovered.
1H NMR (250 MHz, CDCl3): d 11.68 (s, 1H, OH), 7.68 (d,
1H, J¼7.9 Hz, Ar-H), 7.66 (s, 1H, Ar-H), 7.06–7.03 (m,
2H, Ar-H), 2.71 (s, 3H, CH3), 2.38 (s, 3H, CH3), 2.29 (s,
3H, CH3). 13C NMR (75 MHz, CDCl3): d 166.2, 162.8,
152.2, 149.9, 139.9 (C), 136.9 (CH), 135.0, 134.0, 117.9 (C),
116.6, 116.4, 115.9 (CH), 107.3 (C), 21.6, 21.5, 16.7 (CH3).
IR (KBr, cmꢀ1): ~n 2952 (s), 1671 (w), 1477 (s), 1371 (s),
1238 (w), 817 (w). MS (EI, 70 eV): m/z (%) 254 (M+, 100),
239 (32), 211 (47), 149 (19), 91 (5). HRMS (EI, 70 eV) calcd
for C16H14O3 [M]+: 254.0937; found: 254.0940.
3.4.6. Methyl 4-(3,4-dihydroxy-5,7-dimethyl-4-oxo-2H-
chromen-2-yl)-3-oxobutanoate (6f). Starting with 4f
(0.082 g, 0.45 mmol), TMSOTf (0.129 g, 0.58 mmol), and
1-methoxy-1,3-bis(trimethylsilyloxy)buta-1,3-diene (5a)
(0.150 g, 0.58 mmol), 6f (0.093 g, 68%) was obtained as
1
a yellow oil. H NMR (keto/enol¼10:3, 250 MHz, CDCl3,
3.5.3. 7-Hydroxy-1,3-dimethylbenzo[c]-6-one (7c). Start-
ing with 6c (0.091 g, 0.30 mmol) and NEt3 (0.060 g,
only keto tautomer was listed): d 6.69 (s, 1H, Ar-H), 4.95–

E. Ullah et al. / Tetrahedron 62 (2006) 9694–9700
9699
0.60 mmol), 7c (0.017 g, 24%; 46% based on recovered start-
ing material) was obtained as a white solid; mp 180 ꢁC. Start-
ing material (6c) (0.042 g) was recovered. 1H NMR
(250 MHz, CDCl3): d 11.79 (s, 1H, OH), 7.80 (d, 1H,
J¼7.6 Hz, Ar-H), 7.70 (t, 1H, J¼8.2 Hz, Ar-H), 7.08 (s,
1H, Ar-H), 7.31 (d, 1H, J¼7.0 Hz, Ar-H), 7.30 (s, 1H,
Ar-H), 7.25 (s, 1H, Ar-H), 2.82 (s, 3H, CH3), 2.40 (s,
3H, CH3). 13C NMR (75 MHz, CDCl3): d 166.2, 162.8,
152.2, 149.4, 140.1, 136.8, 136.7 (C), 136.6, 130.6, 116.6,
116.2, 115.7 (CH), 115.2, 106.3 (C), 25.4, 20.9, 16.7
(CH3). IR (Nujol, cmꢀ1): ~n 3410 (br), 2930 (s), 1675 (m),
1460 (s), 1225 (w), 814 (w). MS (EI, 70 eV): m/z (%) 240
(M+, 100), 197 (15), 165 (10), 111 (21), 97 (30). HRMS
(EI, 70 eV) calcd for C15H12O3 [M]+: 240.0781; found:
240.0781.
m/z (%) 256 (M+, 100), 213 (5), 207 (10), 165 (8), 57 (10).
HRMS (ESI) calcd for C15H13O4 [M+H]+: 257.08084;
found: 257.08069.
Acknowledgements
We thank Dr. M. Lalk for his help with the HRMS measure-
ments. Financial support by the Deutsche Forschungsge-
meinschaft, the BASF AG, and by the state of
Mecklenburg-Vorpommern (Landesforschungsschwerpunkt
‘Neue Wirkstoffe und Screeningverfahren’) is gratefully
acknowledged.
References and notes
3.5.4. 4-Hydroxy-8-methyl-9,10,11,12-tetrahydro-6-oxa-
benzo[c]phenanthren-5-one (7d). Starting with 6d
(0.072 g, 0.20 mmol) and NEt3 (0.041 g, 0.40 mmol), 7d
(0.028 g, 50%) was obtained as a slight yellow solid; mp
115 ꢁC. 1H NMR (250 MHz, CDCl3): d 11.82 (s, 1H, OH),
7.78–7.66 (m, 2H, Ar-H), 7.08–7.03 (m, 2H, Ar-H), 3.45
(t, 2H, J¼6.1 Hz, CH2), 2.84 (t, 2H, J¼5.4 Hz, CH2), 2.31
(s, 3H, CH3), 1.89–1.77 (m, 4H, CH2). 13C NMR
(75 MHz, CDCl3): d 169.6, 163.0, 149.4, 139.0, 137.4 (C),
136.6 (CH), 123.9, 118.5, 118.2 (C), 116.8, 115.9 (CH),
107.2 (C), 33.3, 30.9, 23.8, 22.7 (CH2), 20.5 (CH3). IR
(Nujol, cmꢀ1): ~n 3130 (br), 1719 (w), 1663 (w), 1098 (w),
700 (w). MS (EI, 70 eV): m/z (%) 280 (M+, 100), 265
(25), 214 (15), 149 (13), 57 (18). HRMS (EI, 70 eV) calcd
for C18H16O3 [M]+: 280.1094; found: 280.1090.
1. Sidwell, W. T. L.; Fritz, H.; Tamm, C. Helv. Chim. Acta 1971,
54, 207.
2. Tamm, C. Arzneim.-Forsch. 1972, 22, 1776.
3. Raistrick, H.; Stilkings, C. E.; Thomas, R. Biochemistry 1953,
55, 421.
4. Pero, R. W.; Harvan, D.; Blois, M. C. Tetrahedron Lett. 1973,
14, 945.
5. Ro€mpp Lexikon Naturstoffe; Steglich, W., Fugmann, B., Lang-
Fugmann, S., Eds.; Thieme: Stuttgart, 1997.
6. Schmidt, J. M.; Tremblay, G. B.; Page, M.; Mercure, J.; Feher,
M.; Dunn-Dufault, R.; Peter, M. G.; Redden, P. R. J. Med.
Chem. 2003, 46, 1289.
7. Pandey, J.; Jha, A. K.; Hajela, K. Bioorg. Med. Chem. 2004, 12,
2239.
8. (a) Sayer, J. M.; Haruhiko Yagi, H.; Wood, A. W.; Conney,
A. H.; Jerina, D. M. J. Am. Chem. Soc. 1982, 104, 5562;
(b) Geevanada, Y. A.; Gunawardana, P.; Kumar, N. S.;
Sultanbawa, M. U. S. Phytochemistry 1979, 18, 1017.
9. (a) McGee, L. R.; Confalone, P. N. J. Org. Chem. 1988, 53,
3695; (b) Hart, D. J.; Mannino, A. Tetrahedron 1996, 52,
3841; (c) Fischer, C.; Lipata, F.; Rohr, J. J. Am. Chem. Soc.
2003, 125, 7818 and references cited therein.
10. Hurtley, W. R. H. J. Chem. Soc. 1929, 1870.
11. Bringmann, G.; Reuscher, H. Tetrahedron Lett. 1989, 30, 5249.
12. Alo, B. I.; Kandil, A.; Patil, P. A.; Sharp, M. J.; Siddiqui, M. A.;
Snieckus, V.; Joseph, P. D. J. Org. Chem. 1991, 56, 3763.
13. Nguyen, V. T. H.; Langer, P. Tetrahedron Lett. 2005, 46, 1013.
14. Zhou, Q. J.; Worm, K.; Dolle, R. E. J. Org. Chem. 2004, 69,
5147.
15. Review: Harris, T. M.; Harris, C. M. Tetrahedron 1977, 33,
2159.
16. Harris, T. M.; Hay, J. V. J. Am. Chem. Soc. 1977, 99, 1631.
17. Appel, B.; Saleh, N. N. R.; Langer, P. Chem.—Eur. J. 2006, 12,
1221.
18. For a review of 1,3-bis(silyl enol ethers), see: Langer, P.
Synthesis 2002, 441.
19. Lee, Y.-G.; Ishimaru, K.; Iwasaki, H.; Ohkata, K.; Akiba, K.
J. Org. Chem. 1991, 56, 2058.
3.5.5. 8-Hydroxy-4-methyl-2,3-dihydro-1H-6-oxacyclo-
penta[c]phenanthren-7-one (7e). Starting with 6e
(0.100 g, 0.31 mmol) and NEt3 (0.063 g, 0.63 mmol), 7e
was obtained (0.030 g, 35%; 60% based on recovered start-
ing material) as a colorless solid; mp 202 ꢁC. Starting mate-
rial (6e) (0.041 g) was recovered. 1H NMR (250 MHz,
CDCl3): d 11.74 (s, 1H, OH), 7.68 (t, 1H, J¼7.0 Hz, Ar-H),
7.63 (s, 1H, Ar-H), 7.06–7.03 (m, 2H, Ar-H), 3.42 (t, 2H,
J¼7.3 Hz, CH2), 2.90 (t, 2H, J¼7.9 Hz, CH2), 2.34 (s, 3H,
CH3), 2.30–2.18 (m, 2H, CH2). 13C NMR (75 MHz,
CDCl3): d 181.6, 165.9, 162.6, 150.0, 141.4, 140.6, 136.8
(C), 135.8, 115.3, 114.6, 114.6 (CH), 106.2 (C), 35.1, 29.5,
23.8 (CH2), 18.5 (CH3). IR (Nujol, cmꢀ1): ~n 3420 (br),
2910 (s), 1653 (w), 1320 (w), 1229 (w), 846 (w). MS (EI,
70 eV): m/z (%) 266 (M+, 100), 251 (24), 207 (10), 165 (8),
57 (10). HRMS (EI, 70 eV) calcd for C17H14O3 [M]+:
266.0937; found: 266.0930.
3.5.6. 2,7-Dihydroxy-1,3-dimethyl-6H-benzo[c]chromen-
6-one (7f). Starting with 6f (0.120 g, 0.41 mmol) and NEt3
(0.083 g, 0.82 mmol), 7f (0.035 g, 33%; 40% based on re-
covered starting material) was obtained as a slight brownish
solid mp 190 ꢁC. Starting material (6f) (0.020 g) was recov-
ered. 1H NMR (250 MHz, DMSO-d6): d 11.69 (s, 1H, OH),
8.65 (s, 1H, OH), 7.87–7.77 (m, 2H, Ar-H), 7.12 (s, 1H,
Ar-H), 7.09 (dd, 1H, J¼8.2, 7.3 Hz, Ar-H), 2.64 (s, 3H,
CH3), 2.29 (s, 3H, CH3). 13C NMR (62 MHz, DMSO-d6):
d 165.3, 161.8, 151.0, 144.5 (C), 137.2 (CH), 136.6, 129.2,
122.8 (C), 117.6, 117.5, 116.3, 115.6 (CH), 106.3 (C),
17.3, 17.0 (CH3). IR (Nujol, cmꢀ1): ~n 3415 (br), 2940 (s),
1635 (m), 1240 (s), 1120 (m), 810 (w). MS (EI, 70 eV):
20. For [3+3] cyclizations of 1,3-bis(silyl enol ethers), see: (a)
Chan, T.-H.; Brownbridge, P. J. Am. Chem. Soc. 1980, 102,
3534; (b) Brownbridge, P.; Chan, T.-H.; Brook, M. A.; Kang,
G. J. Can. J. Chem. 1983, 61, 688.
21. For [3+3] cyclizations from our laboratory, see: (a) Dede, R.;
Langer, P. Tetrahedron Lett. 2004, 45, 9177; (b) Bose, G.;
€
Nguyen, V. T. H.; Ullah, E.; Lahiri, S.; Gorls, H.; Langer,
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V. T. H.; Bellur, E.; Appel, B.; Langer, P. Synthesis 2006,
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Mamat, C.; Pundt, T.; Schmidt, A.; Langer, P. Tetrahedron
22. Hanifin, J. W.; Cohen, E. J. Org. Chem. 1971, 36, 910.
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