Regioselective synthesis of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones based on [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones

Article abstract of DOI:10.1016/j.tet.2007.10.027

A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.

Full text of DOI:10.1016/j.tet.2007.10.027

Tetrahedron 63 (2007) 12562–12575
Regioselective synthesis of 4-chlorophenols, 10-chloro-7-
hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-
9H-fluoren-9-ones based on [3D3] cyclizations of
1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-silyloxy-2-en-1-ones
Mirza Arfan Yawer,a Ibrar Hussain,a Stefanie Reim,a Zafar Ahmed,a,b Ehsan Ullah,a,b
a
Inam Iqbal, Christine Fischer, Helmut Reinke, Helmar Gorls and Peter Langer
b
a
c
a,b,
*
€
aInstitut fu€r Chemie, Universita€t Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
bLeibniz-Institut fu€r Katalyse e. V. an der Universita€t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
cInstitut fu€r Anorganische und Analytische Chemie, Universita€t Jena, August-Bebel-Str. 2, 07740 Jena, Germany
Received 23 August 2007; revised 1 October 2007; accepted 4 October 2007
Available online 7 October 2007
Abstract—A variety of 4-chlorophenols, 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones, and 4-chloro-1-hydroxy-9H-fluoren-9-ones
were prepared by formal [3+3] cyclizations of 1,3-bis(silyloxy)-1,3-dienes with 2-chloro-3-(silyloxy)alk-2-en-1-ones.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
cyclizations of 1,3-bis(silyl enol ethers),18 which can be
regarded as electroneutral equivalents of 1,3-dicarbonyl dia-
nions.19 Recently, we reported the application of this method
to the synthesis of functionalized 4-chlorophenols.20 Herein,
we report full details of these studies. With regard to our pre-
liminary communication, the preparative scope was greatly
extended and a variety of novel chlorinated phenols and biar-
yls were regioselectively prepared. In addition, the synthesis
of novel 10-chloro-7-hydroxy-6H-benzo[c]chromen-6-ones
(dibenzo[b,d]pyran-6-ones, biaryl lactones) and 4-chloro-
1-hydroxy-9H-fluoren-9-ones, based on regioselective [3+3]
cyclizations, is reported. Notably, the functionalized chlori-
nated arenes reported herein are not readily available by
other methods.
4-Chlorophenols are of considerable pharmacological
relevance and occur in a variety of natural products. This
includes dibenzo[b,e][1,4]dioxepin-11-ones,1 spirocycles
(e.g. aspirochlorins, grisandions, griseofulvins),2,10 xan-
thones (austocystin A),3 tetracyclins,4 isochromanones
(ochratoxin A),5 terpenes (ascofuranol, ascochlorin),6 mac-
rocycles (radicicol, bazzanin K),7 dibenzo[b,d]pyran-6-ones
(graphislactone G),8 oligosaccharides (flambamycin),9 ben-
zophenones,10 polycycles,11 arenes,12 and biaryls (ambigol
A).13 Chloroarenes also represent useful starting materials
in transition metal catalyzed cross-coupling reactions.14,15
Classic syntheses of functionalized chlorophenols, based on
chlorination of phenols, often suffer from low regioselectiv-
ities and yields. A few syntheses of 4-chlorophenols based
on [4+2] cycloadditions of chloro-substituted buta-1,3-di-
enes have been reported. For example, Brassard and Savard
reported the synthesis of a chlorinated anthraquinone by
[4+2] cycloaddition of 2-chloro-1-methoxy-1,3-bis(trime-
thylsilyloxy)buta-1,3-diene with 2-chloronaphthoquinone.16a
A 4-chlorophenol was prepared also by [4+2] cycloaddi-
tion of a chlorinated thiophene with dimethyl acetylene-
dicarboxylate.16b Some years ago, Chan and co-workers
reported17 an elegant approach to salicylates based on [3+3]
2. Results and discussion
2.1. 4-Chlorophenols
2-Chloro-1,3-diketones 2a,b are readily available by reac-
tion of 1,3-diketones with N-chlorosuccinimide (NCS).21
The reaction of 2a and 2b with Me3SiCl/NEt3 afforded
2-chloro-3-(silyloxy)alk-2-en-1-ones 3a22 and 3b, respec-
tively (Scheme 1). 1,3-Bis(silyl enol ethers) 4a–j were pre-
pared from the corresponding b-ketoesters as reported.23,24
The TiCl4 mediated [3+3] cyclization of 3a,b with 1,3-bis-
(silyl enol ethers) 4a–j afforded the desired 4-chlorophenols
5a–l (Scheme 2, Table 1). The cyclizations were carried
* Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412;
e-mail: peter.langer@uni-rostock.de
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.027

M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
12563
O
O
following the general procedure reported for related cycliza-
O
tions.17,19 During optimization, the (high) concentration, the
stoichiometry, and the temperature proved to be important
parameters.
O
R1
Cl
i
R1
R2
R3
R2
R3
8a-f
7a-f
6a-b
ii
O
O
O
O
i
R1
R1
R1
R1
R1
O
O
Me3SiO
O
Cl
2a,b
R1
iii
R1
1a,b
O
OSiMe3
R1
ii
Cl
Cl
R2
9a-f
R2
10a-f
R3
R3
Cl
3a,b
Scheme 3. Synthesis of 2-chloro-3-silyloxy-2-en-1-ones 10a–f. Conditions:
(i) LDA (1.5 equiv), THF; (ii) NCS (1 equiv), CCl4, 75–80 ꢀC; (iii) NEt3
(1.6 equiv), Me3SiCl (1.8 equiv), C6H6, 20 ꢀC.
Scheme 1. Synthesis of 2-chloro-3-silyloxy-2-en-1-ones 3a,b. Conditions:
(i) NCS (1 equiv), CCl4, 75–80 ꢀC; (ii) NEt3 (1.6 equiv), Me3SiCl
(1.8 equiv), C6H6, 20 ꢀC.
Table 2. Synthesis of 2-chloro-3-silyloxy-2-en-1-ones 10a–f
Me3SiO OSiMe3
a
%
R1
R2
R3
R2
R3
O
OH
4a-j
8
9
10
R2
R1
R3
i
O
OSiMe3
b
a
b
c
d
e
f
Me
Me
Me
Me
Me
nPr
H
H
H
Me
OMe
OMe
H
F
Cl
H
H
H
—
36
38
33
37
72
95
90
80
73
72
76
84
R1
R1
R1
66
52
44
47
81
Cl
Cl
3a,b
5a-l
TiCl4
Me3SiCl
H+, H2O
_
a
Isolated yields.
Commercially available.
b
O
R3
O
O
Me3SiO
R2
R2
R1
R3
R1
R1
_
(Me3Si)2O
R1
Me3SiO
O
TiCl3
OTiCl3
Me3SiO
R4
OSiMe3
R5
Cl
Cl
OH
O
R4
R1
A
B
R5
4a,b,e,k
i
Scheme 2. Synthesis of 4-chlorophenols 5a–l. Conditions: (i) TiCl4,
CH2Cl2, ꢁ78/20 ꢀC.
O
OSiMe3
Cl
R2
11a-r
R1
R3
+
Cl
R2
R3
Table 1. Synthesis of chlorinated phenols 5a–l
R1
R2
R3
%a (5)
10a-f
3
4
5
Scheme 4. Synthesis of 3-aryl-4-chlorophenols 11a–r. Conditions: (i)
TiCl4, CH2Cl2, ꢁ78/20 ꢀC.
a
a
a
a
a
a
a
a
a
a
b
b
a
b
c
d
e
f
g
h
i
a
b
c
d
e
f
g
h
i
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
H
H
H
Me
Et
OMe
OMe
Me
Ph
OEt
OEt
OMe
OMe
OMe
OMe
(CH2)2OMe
OMe
OEt
62
50
44
55
56
67
53
36
26
35
52
54
Table 3. Synthesis of 3-aryl-4-chlorophenols 11a–r
nBu
(CH2)3Ph
(CH2)6Cl
4
10
11
R1
R2
R3
R4
R5
%a (11)
a
k
b
e
a
k
e
a
k
e
a
k
a
k
e
a
a
a
a
b
b
b
c
c
c
d
d
e
e
e
f
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
nPr
nPr
nPr
H
H
H
H
H
H
H
H
H
H
H
H
F
H
Me
H
Et
H
Me
Et
H
Me
Et
H
Me
H
Me
Et
H
Me
Et
OMe
OMe
Me
49
31
43
43
30
48
44
44
34
47
26
40
47
50
42
34
46
51
j
a
e
j
k
l
H
H
Et
Et
OEt
OMe
OMe
OEt
OMe
OMe
OEt
OMe
OMe
OMe
OMe
OEt
OMe
OMe
OEt
a
Isolated yields.
F
F
2.2. 3-Aryl-4-chlorophenols
Cl
Cl
Cl
H
H
H
H
H
H
H
H
H
H
The 2-chloro-3-(silyloxy)alk-2-en-1-ones 10a–f were pre-
pared as follows. The LDA mediated reaction of ketones
6a,b with benzoyl chlorides 7a–f afforded the 1,3-diketones
8a–f. The chlorination of the latter with NCS afforded the
products 9a–f, which were transformed into 10a–f by silyla-
tion (Scheme 3, Table 2). The TiCl4 mediated cyclization of
1,3-bis(silyl enol ethers) 4a,b,e,k with 2-chloro-3-(silyl-
oxy)alk-2-en-1-ones 10a–f afforded the chlorinated biaryls
11a–r (Scheme 4, Table 3).
Me
Me
OMe
OMe
OMe
OMe
OMe
OMe
a
k
e
f
f
a
Isolated yields.

12564
M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
Table 4. Synthesis of 6H-benzo[c]chromen-6-ones 12a–f
11
12
R1
R2
R3
%a (12)
m
n
o
p
q
r
a
b
c
d
e
f
Me
Me
Me
nPr
nPr
nPr
H
Me
Me
Et
Me
Me
Et
73
78
67
88
54
48
Me
Et
H
Me
Et
a
Isolated yields.
Figure 1. ORTEP of 11a.
Figure 3. ORTEP of 12d.
2.4. 4-Chloro-1-hydroxy-9H-fluoren-9-ones
The reaction of chlorinated biaryls 11a,b,e,f,h,i with concd
sulfuric acid, following a protocol recently reported by
us,27 afforded the novel chlorinated fluorenones 13a–f by
an intramolecular Friedel–Crafts acylation (Scheme 6, Table
5). The chloride and the fluoride functions proved to be com-
patible with the harsh reaction conditions.
Figure 2. ORTEP of 11c.
The structures of products 11a,c were independently con-
firmed by X-ray crystal structure analyses (Figs. 1 and 2).25
In conclusion, a general method for the regioselective syn-
thesis of chlorinated, sterically encumbered phenols and
biaryls by formal [3+3] cyclizations of 1,3-bis(silyl enol
2.3. 10-Chloro-7-hydroxy-6H-benzo[c]chromen-6-ones
The chlorinated biaryls 11m–r contain an ortho-methoxy
group located at one of the aryl groups. Treatment of
11m–r with borontribromide and subsequent addition of an
aqueoussolutionofpotassiumtert-butanolate,followingapro-
tocol recently reported by us,26 afforded the novel 10-chloro-
7-hydroxy-6H-benzo[c]chromen-6-ones 12a–f (Scheme 5,
Table 4).
Me
Me
Cl
R2
Cl
R2
i
OH
OH
R1
O
OMe
O
R1
11a,b,e,f,h,i
13a-f
Scheme 6. Synthesis of fluorenones 13a–f. Conditions: (i) concd H2SO4,
20 ꢀC, 1 h.
The structure of 12d was independently confirmed by X-ray
crystal structure analysis (Fig. 3).25
Table 5. Synthesis of fluorenones 13a–f
R1
R1
R1
R2
%a (13)
R2
11
13
Cl
Cl
R2
MeO
i
a
b
e
f
h
i
a
b
c
d
e
f
H
H
F
F
Cl
Cl
H
Me
H
Me
H
Me
70
86
61
55
84
74
OH
OH
O
OR3
O
O
11m-r
12a-f
Scheme 5. Synthesis of dibenzo[b,d]pyran-6-ones 12a–f. Conditions: (i) (1)
BBr3 (4 equiv), CH2Cl2, 0/20 ꢀC, 18 h; (2) KOtBu, H2O, 15 min, 20 ꢀC.
a
Isolated yields.

M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
12565
ethers) with 2-chloro-3-(silyloxy)alk-2-en-1-ones was re-
ported. 4-Chlorophenols 5a–l are isolated in moderate to
good yields (except for 5i containing a labile u-chloroalkyl
group). The 3-aryl-4-chlorophenols 11a–r are formed in
moderate yields. The yields mainly depend on the individual
quality of the starting materials and on the handling of each
individual experiment. The combination of the [3+3] cycli-
zation with BBr3 or acid mediated cyclization reactions
provides a convenient approach to 10-chloro-7-hydroxy-6H-
benzo[c]chromen-6-ones 12 and 4-chloro-1-hydroxy-9H-
fluoren-9-ones 13. These transformations generally proceed
in good yields.
4.9 mmol), and TiCl4 (0.53 mL, 4.9 mmol), 5c was isolated
1
as a yellow solid (560 mg, 44%), mp¼199 ꢀC. H NMR
(250 MHz, acetone-d6): d¼2.15 (s, 3H, CH3), 2.39 (s, 3H,
CH3), 6.87 (s, 1H, ArH), 7.52–7.87 (m, 5H, ArH), 8.71 (s,
1H, OH). 13C NMR (75 MHz, acetone-d6): d¼17.6, 21.0
(CH3), 116.6 (CH), 126.1, 127.9 (C), 129.6 (2C), 130.0
(2C), 134.3 (CH), 134.5, 138.5, 138.7, 153.3, 196.9 (C).
IR (KBr, cmꢁ1): ~n¼3355 (s), 1657 (s), 1597 (m), 1578
(m), 1277 (m), 1239 (m), 1107 (m), 921 (m), 712 (w).
GC–MS (EI, 70 eV): m/z (%)¼262 ([M]+, [37Cl], 17), 260
([M]+, [35Cl], 51), 259.1 (100), 242.0 (20), 224.1 (33),
183.0 (30), 105.1 (31), 77.1 (63). Elemental analysis calcd
(%) for C15H13ClO2 (260.72): C 69.10, H 5.03; found: C
69.12, H 5.08.
3. Experimental section
3.1. General comments
3.1.4. Ethyl 3-chloro-6-hydroxy-2,4,5-trimethylbenzoate
(5d). Starting with 1,3-bis-silyl enol ether 4d (500 mg,
1.7 mmol), silyl enol ether 3a (359 mg, 1.7 mmol), and
TiCl4 (0.19 mL, 1.7 mmol), 5d was isolated as a yellow oil
(230 mg, 55%). H NMR (300 MHz, CDCl3): d¼1.42 (t,
All solvents were dried by standard methods and all reac-
tions were carried out under an inert atmosphere. For H
1
1
and 13C NMR spectra, the deuterated solvents indicated
were used. Mass spectrometric (MS) data 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.
3H, J¼7.0 Hz, CH3), 2.20 (s, 3H, CH3), 2.36 (s, 3H, CH3),
2.58 (s, 3H, CH3), 4.43 (q, 2H, J¼7.1 Hz, OCH2), 11.60
(s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼12.5, 14.1,
18.3, 20.0 (CH3), 61.8 (CH2), 111.5, 123.9, 126.9, 134.5,
141.4, 158.0, 171.5 (C). IR (neat, cmꢁ1): ~n¼2982 (m),
2935 (m), 1654 (s), 1599 (m), 1448 (m), 1381 (s), 1342
(m), 1305 (m), 1284 (s), 1243 (s), 1182 (s), 1099 (m),
1034 (m), 1015 (m), 801 (m). MS (EI, 70 eV): m/z
(%)¼244 ([M]+, [37Cl], 8), 242 ([M]+, [35Cl], 26), 196.0
(100), 168.0 (68), 105.0 (28), 77.0 (30). Elemental analysis
calcd (%) for C12H15ClO3 (242.70): C 59.38, H 6.22; found:
C 59.42, H 5.99.
3.1.1. Methyl 3-chloro-6-hydroxy-2,4-dimethylbenzoate
(5a). Starting with 1,3-bis-silyl enol ether 4a (2.00 g,
7.6 mmol), silyl enol ether 3a (1.58 g, 7.6 mmol), and
TiCl4 (0.85 mL, 7.6 mmol), 5a was isolated as a colorless
1
solid (1.01 g, 62%), mp¼59–60 ꢀC. H NMR (250 MHz,
CDCl3): d¼2.35 (s, 3H, CH3), 2.60 (s, 3H, CH3), 3.96 (s,
3H, OCH3), 6.76 (s, 1H, ArH), 10.83 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼19.9, 21.9, 52.3 (CH3), 111.9
(C), 117.4 (CH), 126.8, 137.9, 143.6, 159.9, 171.3 (C). IR
(KBr, cmꢁ1): ~n¼3426 (w), 3000 (w), 2952 (s), 2874 (m),
1663 (s), 1603 (s), 1564 (s), 1449 (s), 1381 (m), 1358 (s),
1310 (s), 1229 (s), 1190 (s), 1104 (m), 943 (m). MS (EI,
70 eV): m/z (%)¼216 ([M]+, [37Cl], 29), 214 ([M]+, [35Cl],
88), 184 (100), 154 (61), 91 (64). Elemental analysis calcd
(%) for C10H11ClO3 (214.65): C 55.95, H 5.16; found: C
55.97, H 5.12.
3.1.5. Ethyl 3-chloro-5-ethyl-6-hydroxy-2,4-dimethyl-
benzoate (5e). Starting with 1,3-bis-silyl enol ether 4e
(600 mg, 1.9 mmol), silyl enol ether 3a (410 mg,
1.9 mmol), and TiCl4 (0.21 mL, 1.9 mmol), 5e was isolated
as a yellow oil (285 mg, 56%). 1H NMR (250 MHz,
CDCl3): d¼1.10 (t, 3H, J¼7.3 Hz, CH3), 1.42 (t, 3H,
J¼7.3 Hz, CH3), 2.40 (s, 3H, CH3), 2.59 (s, 3H, CH3), 2.74
(q, 2H, J¼7.6 Hz, CH2), 4.43 (q, 2H, J¼7.1 Hz, OCH2),
11.11 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼13.2,
14.1, 17.6, 20.0 (CH3), 20.2, 61.8 (CH2), 111.8, 127.2,
130.0, 134.6, 140.8, 157.8, 171.4 (C). IR (neat, cmꢁ1):
~n¼2972 (m), 2935 (w), 2874 (w), 1655 (s), 1598 (m), 1447
(m), 1372 (s), 1306 (s), 1262 (s), 1231 (s), 1180 (s), 1110
(m), 1039 (m), 807 (m). MS (EI, 70 eV): m/z (%)¼258
([M]+, [37Cl], 12), 256 ([M]+, [35Cl], 35), 210.0 (100), 195.0
(17), 182.0 (99), 167.0 (14). Elemental analysis calcd (%)
for C13H17ClO3 (256.72): C 60.82, H 6.67; found: C 61.02,
H 6.41.
3.1.2. 1-(3-Chloro-6-hydroxy-2,4-dimethylphenyl)etha-
none (5b). Starting with 1,3-bis-silyl enol ether 4b (1.10 g,
4.5 mmol), silyl enol ether 3a (930 mg, 4.5 mmol), and
TiCl4 (0.50 mL, 4.5 mmol), 5b was isolated as a colorless
solid (432 g, 49%), mp¼99 ꢀC. 1H NMR (250 MHz,
CDCl3): d¼2.35 (s, 3H, CH3), 2.57 (s, 3H, CH3), 2.61 (s,
3H, OCH), 6.75 (s, 1H, ArH), 11.15 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼20.8, 21.7, 32.7 (CH3), 117.9
(CH), 122.4, 126.8, 136.1, 143.8, 158.6, 205.4 (C). IR
(KBr, cmꢁ1): ~n¼3176 (s), 1661 (s), 1606 (m), 1451 (m),
1398 (m), 1358 (m), 1310 (m), 1237 (s), 845 (m). MS (EI,
70 eV): m/z (%)¼200 ([M]+, [37Cl], 12), 198 ([M]+, [35Cl],
36), 183.1 (100), 91.1 (22). Elemental analysis calcd (%)
for C10H1ClO2 (198.64): C 60.46, H 5.58; found: C 60.56,
H 5.64.
3.1.6. Methyl 3-chloro-6-hydroxy-5-methoxy-2,4-di-
methyl-benzoate (5f). Starting with 1,3-bis-silyl enol ether
4f (0.436 g, 1.50 mmol), 3-chloro-4-trimethylsilanyloxy-
pent-3-en-2-one (3a) (0.310 g, 1.50 mmol), and TiCl4
(0.2 mL, 1.50 mmol) in CH2Cl2 (3 mL), 5f was isolated after
column chromatography (silica gel, n-heptane/EtOAc 20:1)
1
as a white solid (0.246 g, 67%), mp 62–63 ꢀC. H NMR
(300 MHz, CDCl3): d¼2.36 (s, 3H, CH3), 2.55 (s, 3H,
CH3), 3.82 (s, 3H, OCH3), 3.97 (s, 3H, OCH3), 10.63 (s,
1H, OH). 13C NMR (75 MHz, CDCl3): d¼14.6, 19.5
(CH3), 52.5, 60.3 (OCH3), 113.0, 126.6, 132.4, 136.2,
3.1.3. (3-Chloro-6-hydroxy-2,4-dimethylphenyl)(phe-
nyl)methanone (5c). Starting with 1,3-bis-silyl enol ether
4c (1.50 g, 4.9 mmol), silyl enol ether 3a (1.01 g,

12566
M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
145.1, 153.3 (C), 171.3 (C]O). IR (KBr, cmꢁ1): ~n¼2957
(m), 2944 (m), 2851 (w), 1740 (w), 1700 (w), 1656 (s),
1600 (w), 1560 (w), 1443 (s), 1406 (s), 1362 (s), 1308 (s),
1287 (s), 1257 (s), 1217 (s), 1166 (w), 1119 (w), 1078 (m),
1062 (m), 1037 (w), 1006 (m). MS (EI, 70 eV): m/z
(%)¼246 ([M]+, [37Cl], 15), 244 ([M]+, [35Cl], 43), 214
(35), 213 (33), 212 (100), 186 (31), 185 (25), 184 (94),
183 (48), 169 (33). Anal. Calcd for C11H13ClO4 (244.67):
C, 54.00; H, 5.36. Found: C, 54.16; H, 5.60.
CH2), 1.78 (q, J¼6.8 Hz, 2H, CH2), 2.39 (s, 3H, CH3),
2.58 (s, 3H, CH3), 2.71 (t, J¼6.8 Hz, 2H, CH2), 3.53 (t,
J¼6.8 Hz, 2H, CH2), 3.96 (s, 3H, OCH3), 11.07 (s, 1H,
OH). 13C NMR (75 MHz, CDCl3): d¼17.9, 20.1 (CH3),
26.7, 26.8, 28.8, 29.0, 32.6, 45.1 (CH2), 52.3 (OCH3),
111.6, 127.3, 128.6, 134.8, 141.2, 158.0 (C), 172.0
(C]O). IR (KBr, cmꢁ1): ~n¼3422 (br, w), 3015 (w), 2954
(s), 2925 (s), 2854 (m), 1654 (s), 1596 (m), 1558 (w),
1438 (s), 1388 (s), 1361 (s), 1311 (s), 1267 (s), 1251 (s),
1234 (s), 1198 (s), 1163 (s), 1131 (w), 1099 (w), 1033
(w). MS (EI, 70 eV): m/z (%)¼334 ([M]+, [37Cl], 17), 332
([M]+, [35Cl], 26), 287 (37), 285 (62), 265 (27), 198 (33),
197 (31), 196 (100), 195 (60). Anal. Calcd for
C16H22Cl2O3 (333.25): C, 57.67; H, 6.65. Found: C,
57.57; H, 6.85.
3.1.7. Methyl 3-butyl-5-chloro-2-hydroxy-4,6-dimethyl-
benzoate (5g). Starting with 1,3-bis-silyl enol ether 4g
(0.475 g, 1.50 mmol), 3-chloro-4-trimethylsilanyloxy-pent-
3-en-2-one (3a) (0.310 g, 1.50 mmol), and TiCl4 (0.2 mL,
1.50 mmol) in CH2Cl2 (3 mL), 5g was isolated after column
chromatography (silica gel, n-heptane/EtOAc 20:1) as
a white solid (0.217 g, 53%), mp 72–73 ꢀC. 1H NMR
(300 MHz, CDCl3): d¼0.92–0.97 (m, 3H, CH3), 1.35–1.51
(m, 4H, CH2), 2.39 (s, 3H, CH3), 2.58 (s, 3H, CH3), 2.71
(t, J¼7.6 Hz, 2H, CH2), 3.96 (s, 3H, OCH3), 11.05 (s, 1H,
OH). 13C NMR (75 MHz, CDCl3): d¼14.0, 17.9, 20.1
(CH3), 22.9, 26.8, 31.2 (CH2), 52.3 (OCH3), 111.6, 127.3,
128.9, 134.6, 141.3, 158.0 (C), 172.0 (C]O). IR (KBr,
cmꢁ1): ~n¼3421 (br, w), 3018 (w), 2961 (s), 2929 (m),
2873 (m), 2860 (m), 1655 (s), 1599 (m), 1558 (w), 1438
(s), 1389 (s), 1363 (s), 1310 (s), 1280 (s), 1243 (s), 1194
(s), 1163 (s), 1117 (m), 1035 (m). MS (GC–MS, 70 eV):
m/z (%)¼272 ([M]+, [37Cl], 10), 270 ([M]+, [35Cl], 30),
225 (32), 223 (100), 196 (57), 195 (42). Anal. Calcd for
C14H19ClO3 (270.75): C, 62.10; H, 7.07. Found: C, 62.10;
H, 7.11.
3.1.10. (2-Methoxyethyl) 3-chloro-6-hydroxy-2,4-di-
methyl-benzoate (5j). Starting with 1,3-bis-silyl enol ether
4j (0.457 g, 1.50 mmol), 3-chloro-4-trimethylsilanyloxy-
pent-3-en-2-one (3a) (0.310 g, 1.50 mmol), and TiCl4
(0.2 mL, 1.50 mmol) in CH2Cl2 (3 mL), 5j was isolated after
column chromatography (silica gel, n-heptane/EtOAc 20:1)
as a yellow oil (0.137 g, 35%). 1H NMR (300 MHz, CDCl3):
d¼2.37 (s, 3H, CH3), 2.63 (s, 3H, CH3), 3.42 (s, 3H, OCH3),
3.73 (t, J¼4.8 Hz, 2H, CH2), 4.51 (t, J¼4.8 Hz, 2H, CH2),
6.77 (s, 1H, CH), 10.47 (s, 1H, OH). 13C NMR (75 MHz,
CDCl3): d¼19.7, 21.8 (CH3), 58.9 (OCH3), 64.4, 69.9
(CH2), 112.5 (C), 117.4 (CH), 126.9, 138.1, 143.4, 159.4
(C), 170.2 (C]O). IR (neat, cmꢁ1): ~n¼3409 (br, w), 2985
(m), 2956 (m), 2928 (m), 2892 (m), 2821 (w), 1731 (m),
1661 (s), 1610 (s), 1565 (m), 1456 (s), 1375 (s), 1347 (s),
1306 (s), 1229 (s), 1192 (s), 1116 (s), 1065 (m), 1026 (s).
MS (EI, 70 eV): m/z (%)¼260 ([M]+, [37Cl], 7), 258
([M]+, [35Cl], 20), 184 (35), 183 (25), 182 (100). Anal. Calcd
for C12H15ClO4 (258.70): C, 55.71; H, 5.84. Found: C,
55.60; H, 5.74.
3.1.8. Methyl 3-chloro-6-hydroxy-2,4-dimethyl-5-(3-
phenyl-propyl)-benzoate (5h). Starting with 1,3-bis-silyl
enol ether 4h (0.568 g, 1.50 mmol), 3-chloro-4-trimethyl-
silanyloxy-pent-3-en-2-one (3a) (0.310 g, 1.50 mmol),
and TiCl4 (0.2 mL, 1.50 mmol) in CH2Cl2 (3 mL), 5h
was isolated after column chromatography (silica gel, n-
heptane/EtOAc 20:1) as a white solid (0.180 g, 36%), mp
50–52 ꢀC. 1H NMR (300 MHz, CDCl3): d¼1.77–1.87
(m, 2H, CH2), 2.34 (s, 3H, CH3), 2.59 (s, 3H, CH3),
2.70–2.79 (m, 4H, CH2), 3.97 (s, 3H, OCH3), 7.18–7.24
(s, 3H, CH), 7.27–7.32 (m, 2H, CH), 11.09 (s, 1H, OH).
13C NMR (75 MHz, CDCl3): d¼17.8, 20.0 (CH3), 26.7,
30.4, 36.0 (CH2), 52.3 (OCH3), 111.6 (C), 125.7 (CH),
127.3 (C), 128.2, 128.3, 128.3, 128.4 (CH), 134.8, 141.3,
142.2, 158.1 (C), 171.9 (C]O). IR (KBr, cmꢁ1):
~n¼3421 (br, w), 3083 (w), 3060 (w), 3027 (m), 2951
(m), 2930 (m), 2856 (w), 1659 (s), 1593 (m), 1558 (w),
1495 (w), 1439 (s), 1386 (m), 1347 (s), 1307 (s), 1263
(s), 1230 (s), 1196 (s), 1158 (s), 1142 (s), 1087 (m),
1039 (m), 1030 (m). MS (EI, 70 eV): m/z (%)¼334
([M]+, [37Cl], 9), 332 ([M]+, [35Cl], 28), 198 (31), 197
(16), 196 (100).
3.1.11. Methyl 3-chloro-2,4-diethyl-6-hydroxybenzoate
(5k). Starting with 1,3-bis-silyl enol ether 4a (1.00 g,
3.8 mmol), silyl enol ether 3b (0.90 g, 3.8 mmol), and
TiCl4 (0.42 mL, 3.8 mmol), 5k was isolated as a colorless
1
oil (477 mg, 52%). H NMR (250 MHz, CDCl3): d¼1.20
(t, 3H, J¼7.3 Hz, CH3), 1.23 (s, 3H, J¼7.3 Hz, CH3), 2.75
(q, 2H, J¼7.0 Hz, CH2), 3.08 (q, 2H, J¼7.3 Hz, CH2),
3.97 (s, 3H, OCH3), 6.78 (s, 1H, ArH), 10.81 (s, 1H, OH).
13C NMR (75 MHz, CDCl3): d¼13.3, 13.7 (CH3), 26.3,
28.0 (CH2), 52.4 (CH3), 111.5 (C), 116.1 (CH), 125.9,
143.7, 149.2, 160.3, 171.2 (C). IR (neat, cmꢁ1): ~n¼2971
(m), 2938 (m), 2876 (w), 1665 (s), 1602 (m), 1562 (m),
1431 (m), 1354 (m), 1312 (s), 1224 (s), 1189 (m), 1109
(m), 806 (m), 687 (w). GC–MS (EI, 70 eV): m/z (%):
242.1 ([M]+, 15), 210.0 (100), 167.0 (65), 91.0 (23), 77.0
(28), 77.1 (63). Elemental analysis calcd (%) for
C12H15ClO3 (242.70): C 59.39, H 6.23; found: C 59.56, H
6.36.
3.1.9. Methyl 3-chloro-5-(6-chloro-hexyl)-6-hydroxy-2,4-
dimethyl-benzoate (5i). Starting with 1,3-bis-silyl enol
ether 4i (0.569 g, 1.50 mmol), 3-chloro-4-trimethylsila-
nyloxy-pent-3-en-2-one (3a) (0.310 g, 1.50 mmol), and
TiCl4 (0.2 mL, 1.50 mmol) in CH2Cl2 (3 mL), 5i was iso-
lated after column chromatography (silica gel, n-heptane/
EtOAc 20:1) as a white solid (0.128 g, 26%), mp 51–
3.1.12. Ethyl 3-chloro-2,4,5-triethyl-6-hydroxybenzoate
(5l). Starting with 1,3-bis-silyl enol ether 4e (600 mg,
1.9 mmol), silyl enol ether 3b (466 mg, 1.9 mmol), and
TiCl4 (0.21 mL, 1.9 mmol), 5l was isolated as a colorless
1
oil (305 mg, 54%). H NMR (250 MHz, CDCl3): d¼1.14
(t, 3H, J¼7.3 Hz, CH3), 1.18 (s, 3H, J¼7.3 Hz, CH3), 1.23
(t, 3H, J¼7.3 Hz, CH3), 1.43 (t, 3H, J¼7.0 Hz, CH3), 2.71
1
53 ꢀC. H NMR (300 MHz, CDCl3): d¼1.44–1.51 (m, 6H,

M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
12567
(q, 2H, J¼7.3 Hz, CH2), 2.85 (q, 2H, J¼7.3 Hz, CH2), 3.06
(q, 2H, J¼7.3 Hz, CH2), 4.44 (q, 2H, J¼7.3 Hz, OCH2),
11.11 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼13.6,
13.8, 13.9, 14.0 (CH3), 20.0, 24.5, 26.4, 61.8 (CH2), 111.5,
126.2, 129.8, 140.6, 146.5, 158.3, 171.3 (C). IR (neat,
cmꢁ1): ~n¼2978 (s), 2935 (m), 2875 (m), 1657 (s), 1394
(s), 1372 (s), 1309 (s), 1267 (s), 1244 (m), 1220 (s), 1170
(s), 1151 (m), 1027 (w), 817 (w). GC–MS (EI, 70 eV): m/z
(%)¼286 ([M]+, [37Cl], 10), 284 ([M]+, [35Cl], 32), 238.0
(100), 210.0 (16), 175.0 (59), 115.0 (18). Elemental analysis
calcd (%) for C15H21ClO3 (284.78): C 63.26, H 7.43; found:
C 63.19, H 7.43.
1330 (s), 1209 (m), 742 (s). MS (EI, 70 eV): m/z
(%)¼262.0 (M+, [37Cl], 33), 260 (M+, [35Cl], 99), 247 (34),
245 (100), 212 (1), 210 (34), 183 (4), 181 (32), 152 (28).
Anal. Calcd for C15H13O2Cl (260.50): C 69.09, H 5.00;
found: C 69.28, H 5.20.
3.1.16. Ethyl 6-chloro-4-ethyl-3-hydroxy-5-methyl[1,10-
biphenyl]-2-carboxylate (11d). Starting with bis-silyl
enol ether 4e (0.452 g, 1.65 mmol), TiCl4 (0.313 g,
1.65 mmol), CH2Cl2 (3 mL), and silyl enol ether 10a
(0.403 g, 1.5 mmol), 11d was isolated (0.205 g, 43%) by
column
chromatography
(silica
gel,
n-heptane/
EtOAc¼30:1/20:1) as a colorless solid. 1H NMR
(CDCl3, 300 MHz): d¼0.56 (t, J¼7.2 Hz, 3H, CH3), 1.04
(t, J¼7.5 Hz, 3H, CH3), 2.34 (s, 3H, CH3), 2.71 (q,
J¼7.4 Hz, 2H, CH2), 3.77 (q, J¼7.2 Hz, 2H, OCH2), 6.99–
7.03 (m, 2H, Ar), 7.19–7.21 (m, 2H, Ar), 7.25–7.28 (m,
1H, Ar), 11.19 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d¼11.8, 12.1, 16.3 (CH3), 19.2 (CH2), 59.9 (OCH2),
110.2, 124.9 (C), 125.6 (CH), 126.4 (2CH), 127.7 (2CH),
130.9, 138.1, 140.0, 140.2, 156.9 (C), 169.8 (C]O). GC–
MS (EI, 70 eV): m/z (%)¼320 ([M]+, [37Cl], 18), 318
([M]+, [35Cl], 54), 274 ([37Cl], 27), 272 ([35Cl], 79), 259
([37Cl], 4), 257 ([35Cl], 13), 237 (81), 219 (100), 165 (42),
115 (6), 77 (5). HRMS (EI) calcd for C18H19ClO3 ([M]+,
[35Cl]): 318.10172; found: 318.101231.
3.1.13. Methyl 5-chloro-2-hydroxy-4-methyl-6-phenyl-
benzoate (11a). Starting with bis-silyl enol ether 4a
(0.429 g, 1.65 mmol), TiCl4 (0.313 g, 1.65 mmol), CH2Cl2
(3 mL), and silyl enol ether 10a (0.403 g, 1.5 mmol), 11a
was isolated (0.204 g, 49%) by column chromatography (sil-
ica gel, n-heptane/EtOAc¼30:1/20:1) as a colorless solid.
1H NMR (CDCl3, 300 MHz): d¼2.28 (s, 3H, CH3), 3.24 (s,
3H, OCH3), 6.82 (s, 1H, Ar), 6.99 (dd, J¼7.4, 1.5 Hz, 2H,
Ar), 7.20–7.23 (m, 2H, Ar), 7.25–7.28 (m, 1H, Ar), 10.67
(s, 1H, OH). 13C NMR (CDCl3, 75 MHz): d¼20.2 (CH3),
54.4 (OCH3), 110.4 (CH), 124.3 (C), 125.5 (CH), 126.1
(2CH), 127.0 (2CH), 139.0, 140.6, 142.2, 158.3 (C), 169.2
(C]O). GC–MS (EI, 70 eV): m/z (%)¼278 ([M]+, [37Cl],
10), 276 ([M]+, [35Cl], 30), 246 ([37Cl], 33), 244 ([35Cl],
100), 216 (22), 181 (10), 152 (27), 76 (14). HRMS (EI) calcd
for C15H13ClO3 ([M]+, [35Cl]): 276.05477; found:
276.05475.
3.1.17. Methyl 6-chloro-40-fluoro-3-hydroxy-5-methyl-
[1,10-biphenyl]-2-carboxylate (11e). Starting with bis-
silyl enol ether 4a (0.429 g, 1.65 mmol), TiCl4 (0.313 g,
1.65 mmol), CH2Cl2 (3 mL), and silyl enol ether 10b
(0.430 g, 1.5 mmol), 11e was isolated (0.125 g, 28%) by col-
umn chromatography (silica gel, n-heptane/EtOAc¼30:1/
20:1) as a colorless solid, mp¼122–124 ꢀC. 1H NMR
(CDCl3, 300 MHz): d¼2.26 (s, 3H, CH3), 3.28 (s, 3H,
OCH3), 6.81 (s, 1H, Ar), 6.93 (m, 2H, Ar), 6.95 (m, 2H,
Ar), 10.70 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d¼20.6 (CH3), 50.9 (OCH3), 110.8 (C), 113.4, 113.7,
118.3 (CH), 124.8 (C), 128.4, 128.6 (CH), 135.3, 139.9,
142.9, 162.5, 162.7 (C), 169.5 (C]O). IR (KBr, cmꢁ1):
~n¼2955 (m), 2853 (w), 1671 (s), 1515 (s), 1362 (s), 1235
(s), 1166 (s), 1014 (m), 809 (s). GC–MS (EI, 70 eV): m/z
(%)¼296 ([M]+, [37Cl], 12), 294 ([M]+, [35Cl], 36), 262
(100), 234 (36), 199 (14), 170 (31), 85 (13). HRMS (EI)
calcd for C15H12ClFO3 ([M]+, [35Cl]): 294.04535; found:
294.045720.
3.1.14. Methyl 6-chloro-3-hydroxy-4,5-dimethyl[1,10-bi-
phenyl]-2-carboxylate (11b). Starting with bis-silyl enol
ether 4f (0.452 g, 1.65 mmol), TiCl4 (0.313 g, 1.65 mmol),
CH2Cl2 (3 mL), and silyl enol ether 10a (0.403 g,
1.5 mmol), 11b was isolated (0.133 g, 31%) by column
chromatography (silica gel, n-heptane/EtOAc¼30:1/
1
20:1) as a colorless solid. H NMR (CDCl3, 300 MHz):
d¼2.19 (s, 3H, CH3), 2.32 (s, 3H, CH3), 3.25 (s, 3H,
OCH3), 6.99–7.02 (m, 2H, Ar), 7.21–7.24 (m, 2H, Ar),
7.26–7.29 (m, 1H, Ar), 11.03 (s, 1H, OH). 13C NMR
(CDCl3, 75 MHz): d¼11.6, 17.1 (CH3), 50.8 (OCH3),
110.0, 124.6, 125.0 (C), 125.7 (CH), 126.4 (2CH), 127.6
(2CH), 137.9, 139.5, 140.7, 156.8 (C), 170.2 (C]O). IR
(KBr, cmꢁ1): ~n¼3063 (w), 3025 (w), 2951 (m), 1655 (s),
1244 (s), 1200 (s), 1175 (s), 1014 (m), 708 (s). GC–MS
(EI, 70 eV): m/z (%)¼292 ([M]+, [37Cl], 11), 290 ([M]+,
[35Cl], 33), 260 ([37Cl], 19), 258 ([35Cl], 57), 223 (100),
195 (10), 165 (21), 82 (8). HRMS (EI) calcd for
C16H15ClO3 ([M]+, [35Cl],): 290.07042; found: 290.07028.
3.1.18. Methyl 6-chloro-40-fluoro-3-hydroxy-4,5-
dimethyl[1,10-biphenyl]-2-carboxylate (11f). Starting
with bis-silyl enol ether 4f (0.452 g, 1.65 mmol), TiCl4
(0.313 g, 1.65 mmol), CH2Cl2 (3 mL), and silyl enol ether
10b (0.430 g, 1.5 mmol), 11f was isolated (0.224 g, 48%)
by column chromatography (silica gel, n-heptane/
EtOAc¼30:1/20:1) as a colorless solid, mp¼65–68 ꢀC.
1H NMR (CDCl3, 300 MHz): d¼2.20 (s, 3H, CH3), 2.33
(s, 3H, CH3), 3.32 (s, 3H, OCH3), 6.97 (m, 2H, Ar), 6.99
(m, 2H, Ar), 11.08 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼11.7, 17.1 (CH3), 50.9 (OCH3), 110.0 (C),
113.3, 113.6 (CH), 125.3 (C), 129.2, 129.3 (CH), 135.8,
136.8, 140.9, 157.0, 159.1, 162.4 (C), 170.1 (C]O). IR
(KBr, cmꢁ1): ~n¼3054 (w), 2960 (m), 1659 (s), 1511 (s),
1470 (s), 1245 (s), 1015 (s), 806 (w). GC–MS (EI, 70 eV):
m/z (%)¼310 ([M]+, [37Cl], 10), 308 ([M]+, [35Cl], 32),
3.1.15. 1-(6-Chloro-3-hydroxy-5-methyl-biphenyl-2-yl)-
ethanone (11c). Starting with 3-chloro-4-phenyl-4-(trime-
thylsilyloxy)but-3-en-2-one (0.748 g, 2.91 mmol), 2,4-bis-
(trimethylsilanyloxy)penta-1,3-diene (0.710 g, 2.91 mmol),
and TiCl4 (0.550 g, 2.91 mmol), 11c (0.324 g, 43%) was ob-
1
tained as yellow crystals, mp 68 ꢀC. H NMR (250 MHz,
CDCl3): d¼11.95 (s, 1H, OH), 7.50–7.43 (m, 3H, ArH),
7.30–7.25 (m, 2H, ArH), 6.95 (s, 1H, Ar–H), 2.42 (s, 3H,
CH3), 1.68 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3):
d¼206.2 (CO), 159.8, 144.4, 141.7, 139.5 (C), 130.4 (2C),
128.9 (3C) (CH–Ph), 125.2, 121.0 (C), 120.2 (CH), 32.0,
22.1 (CH3). IR (Nujol, cmꢁ1): ~n¼3206 (m), 1673 (m),

12568
M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
276 (59), 241 (100), 213 (13), 183 (21), 91 (5). HRMS (EI)
calcd for C16H14ClFO3 ([M]+, [35Cl]): 308.06100; found:
308.060892.
[37Cl], [35Cl], 17), 324 ([M]+, [2ꢂ Cl], 27), 292 (53), 257
35
(100), 229 (11), 165 (25), 99 (5), 82 (12). HRMS (EI) calcd
35
for C16H14Cl2O3: 324.03145 ([M]+, [2ꢂ Cl]); found:
324.031296.
3.1.19. Ethyl 5-chloro-3-ethyl-2-hydroxy-4-methyl-6-(4-
fluorophenyl)benzoate (11g). Starting with bis-silyl enol
ether 4e (0.499 g, 1.65 mmol), TiCl4 (0.313 g, 1.65 mmol)
CH2Cl2 (3 mL), and silyl enol ether 10b (0.430 g,
1.5 mmol), 11g was isolated (0.219 g, 44%) by column chro-
matography (silica gel, n-heptane/EtOAc¼30:1/20:1) as
a light red solid (mp¼73–75 ꢀC). 1H NMR (CDCl3,
300 MHz): d¼0.55 (t, J¼7.2 Hz, 3H, CH3), 0.97 (t,
J¼7.4 Hz, 3H, CH3), 2.24 (s, 3H, CH3), 2.62 (q,
J¼7.5 Hz, 2H, CH2), 3.73 (q, J¼7.2 Hz, 2H, OCH2), 6.86
(m, 2H, Ar), 6.88 (m, 2H, Ar), 11.11 (s, 1H, OH). 13C
NMR (CDCl3, 75 MHz): d¼12.9, 13.1, 17.4 (CH3), 20.4
(CH2), 61.2 (OCH2), 111.3 (C), 114.3, 114.6, 130.3, 130.4
(CH), 132.3, 137.1, 138.0, 141.2, 158.0, 160.3, 163.6 (C),
170.7 (C]O). IR (KBr, cmꢁ1): ~n¼2970 (m), 2927 (m),
1655 (s), 1511 (s), 1376 (s), 1233 (s), 1217 (s), 1187 (s),
810 (w). GC–MS (EI, 70 eV): m/z (%)¼338 ([M]+, [37Cl],
18), 336 ([M]+, [35Cl], 54), 290 (82), 255 (100), 237 (86),
183 (43), 170 (82), 133 (6), 91 (2), 51 (2). HRMS (EI) calcd
for C18H18ClFO3 ([M]+, [35Cl]): 336.09230; found:
336.09188.
3.1.22. Ethyl 40,6-dichloro-4-ethyl-3-hydroxy-5-methyl-
[1,10-biphenyl]-2-carboxylate (11j). Starting with bis-
silyl enol ether 4e (0.659 g, 2.18 mmol), TiCl4 (0.413 g,
2.18 mmol), CH2Cl2 (3 mL), and silyl enol ether 10c
(0.606 g, 2.00 mmol), 11j was isolated (0.335 g, 47%)
by column chromatography (silica gel, n-heptane/
EtOAc¼30:1/20:1) as a colorless solid, mp¼94–96 ꢀC.
1H NMR (CDCl3, 300 MHz): d¼0.67 (t, J¼7.2 Hz, 3H,
CH3), 1.09 (t, J¼7.4 Hz, 3H, CH3), 2.36 (s, 3H, CH3),
2.74 (q, J¼7.4 Hz, 2H, CH2), 3.85 (q, J¼7.2 Hz, 2H,
OCH2), 6.97–6.99 (m, 2H, Ar), 7.26–7.29 (m, 2H, Ar),
11.25 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz): d¼12.8,
13.0, 17.4 (CH3), 20.3 (CH2), 61.2 (OCH2), 110.9, 125.7
(C), 127.7 (2CH), 130.1 (2CH), 132.4, 132.6, 137.7, 139.6,
141.2, 158.0 (C), 170.6 (C]O). IR (KBr, cmꢁ1): ~n¼3431
(w), 2966 (m), 2929 (m), 1672 (s), 1382 (s), 1305 (s),
1219 (s), 1101 (m), 186 (m). MS (EI, 70 eV): m/z
37
(%)¼356 ([M]+, [2ꢂ Cl], 3), 354 ([M]+, [37Cl], [35Cl],
16), 352 ([M]+, [2ꢂ Cl], 25), 306 (35), 271 (100), 199
35
(4), 165 (15), 152 (4), 82 (2). HRMS (EI) calcd for
35
C18H18Cl2O3 ([M]+, [2ꢂ Cl]): 352.06275; found:
3.1.20. Methyl 40,6-dichloro-3-hydroxy-5-methyl[1,10-bi-
phenyl]-2-carboxylate (11h). Starting with bis-silyl enol
ether 4a (0.567 g, 2.18 mmol), TiCl4 (0.413 g, 2.18 mmol)
CH2Cl2 (3 mL), and silyl enol ether 10c (0.606 g,
2.00 mmol), 11h was isolated (0.275 g, 44%) by column
chromatography (silica gel, n-heptane/EtOAc¼30:1/
20:1) as a colorless solid, mp¼80–82 ꢀC. 1H NMR
(CDCl3, 300 MHz): d¼2.29 (s, 3H, CH3), 3.32 (s, 3H,
OCH3), 6.85 (m, 1H, Ar), 6.93–6.96 (m, 2H, Ar), 7.24–
7.27 (m, 2H, Ar), 10.76 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼21.5 (CH3), 51.9 (OCH3), 111.5 (C), 119.4
(CH), 125.6 (C), 127.8 (2CH), 129.8 (2CH), 132.8, 138.8,
140.6, 144.0, 159.8 (C), 170.3 (C]O). IR (KBr, cmꢁ1):
~n¼2952 (m), 2923 (w), 1671 (s), 1452 (s), 1229 (s), 1190
(s), 1018 (s), 820 (w). GC–MS (EI, 70 eV): m/z (%)¼314
352.06340.
3.1.23. Methyl 6-chloro-3-hydroxy-20,5-dimethyl[1,10-bi-
phenyl]-2-carboxylate (11k). Starting with bis-silyl enol
ether 4a (0.286 g, 1.10 mmol), TiCl4 (0.208 g, 1.10 mmol),
CH2Cl2 (2 mL), and silyl enol ether 10d (0.282 g,
1.00 mmol), 11k was isolated (0.74 g, 26%) by column
chromatography (silica gel, n-heptane/EtOAc¼30:1/
20:1) as a yellow oil. 1H NMR (CDCl3, 300 MHz):
d¼1.95 (s, 3H, CH3), 2.33 (s, 3H, CH3), 3.30 (s, 3H,
OCH3), 6.82 (d, J¼7.3 Hz, 1H, Ar), 6.87 (m, 1H, Ar),
7.09–7.13 (m, 1H, Ar), 7.75–7.77 (m, 2H, Ar), 10.89 (s,
1H, OH). 13C NMR (CDCl3, 75 MHz): d¼20.0, 22.0
(CH3), 52.4 (OCH3), 111.8 (C), 119.4, 125.6 (CH), 126.1
(C), 127.6, 128.2, 129.5 (CH), 135.8, 140.6, 142.1, 144.5,
160.5 (C), 171.0 (C]O). IR (neat, cmꢁ1): ~n¼3421 (w),
3064 (w), 2949 (w), 1668 (s), 1441 (s), 1349 (s), 1323 (s),
1228 (s), 1036 (w), 734 (s), 706 (s). GC–MS (EI, 70 eV):
m/z (%)¼292 ([M]+, [37Cl], 13), 290 ([M]+, [35Cl], 38),
258 (100), 223 (14), 195 (22), 165 (26), 152 (24), 82 (11).
HRMS (EI) calcd for C16H15ClO3 ([M]+, [35Cl]):
290.07042; found: 290.070510.
37
([M]+, [2ꢂ Cl], 3), 312 ([M]+, [37Cl], [35Cl], 18), 310
35
([M]+, [2ꢂ Cl], 28), 278 (100), 250 (13), 215 (15), 187
(8), 152 (9), 93 (8), 76 (9). HRMS (EI) calcd for
35
C15H12Cl2O3 ([M]+, [2ꢂ Cl]): 310.01580; found:
310.01625.
3.1.21.
Methyl
40,6-dichloro-3-hydroxy-4,5-
dimethyl[1,10-biphenyl]-2-carboxylate (11i). Starting
with bis-silyl enol ether 4f (0.598 g, 2.18 mmol), TiCl4
(0.413 g, 2.18 mmol), CH2Cl2 (3 mL), and silyl enol ether
10c (0.606 g, 2.00 mmol), 11i was isolated (0.220 g, 34%)
by column chromatography (silica gel, n-heptane/
EtOAc¼30:1/20:1) as a light yellow solid, mp¼95–
3.1.24. Methyl 6-chloro-3-hydroxy-20,4,5-trimethyl[1,10-
biphenyl]-2-carboxylate (11l). Starting with bis-silyl enol
ether 4f (0.302 g, 1.10 mmol), TiCl4 (0.208 g, 1.10 mmol),
CH2Cl2 (3 mL), and silyl enol ether 10d (0.282 g,
1.00 mmol), 11l was isolated (0.123 g, 40%) by column
chromatography (silica gel, n-heptane/EtOAc¼30:1/
20:1) as a yellow oil. 1H NMR (CDCl3, 300 MHz):
d¼1.95 (s, 3H, CH3), 2.33 (s, 3H, CH3), 2.35 (s, 3H, CH3),
3.29 (s, 3H, OCH3), 6.81 (d, J¼7.3 Hz, 1H, Ar), 7.08–7.12
(m, 1H, Ar), 7.13–7.17 (m, 2H, Ar), 11.24 (s, 1H, OH).
13C NMR (CDCl3, 75 MHz): d¼13.1, 18.6, 20.0 (CH3),
52.4 (OCH3), 111.0 (C), 125.5, 125.6 (CH), 126.1, 126.3
(C), 128.4, 129.5 (CH), 136.0, 139.0, 141.2, 142.4, 158.7
(C), 171.6 (C]O). IR (neat, cmꢁ1): ~n¼3060 (m), 2951 (s),
1
97 ꢀC. H NMR (CDCl3, 300 MHz): d¼2.23 (s, 3H, CH3),
2.35 (s, 3H, CH3), 3.34 (s, 3H, OCH3), 6.96–6.99 (m, 2H,
Ar), 7.27–7.29 (m, 2H, Ar), 11.12 (s, 1H, OH). 13C NMR
(CDCl3, 75 MHz): d¼13.1, 18.6 (CH3), 52.4 (OCH3),
111.2, 126.0, 126.9 (C), 128.2 (2CH), 130.5 (2CH), 131.1,
138.0, 139.8, 142.4, 158.5 (C), 171.4 (C]O). IR (KBr,
cmꢁ1): ~n¼3053 (w), 2957 (m), 2927 (w), 1660 (s), 1441
(s), 1244 (s), 1202 (s), 1016 (s), 809 (m). GC–MS (EI,
37
70 eV): m/z (%)¼328 ([M]+, [2ꢂ Cl], 4), 326 ([M]+,

M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
12569
2856 (m), 1667 (s), 1439 (s), 1384 (s), 1320 (m), 1202 (s),
1013 (s), 807 (s), 703 (s). GC–MS (EI, 70 eV): m/z
(%)¼306 ([M]+, [37Cl], 14), 304 ([M]+, [35Cl], 44), 272
(72), 257 (100), 237 (29), 165 (32), 115 (5), 89 (11).
HRMS (EI) calcd for C17H17ClO3 ([M]+, [35Cl]):
304.08607; found: 304.08662.
(CH), 110.5 (C), 119.1 (CH), 125.3 (C), 127.4, 128.7
(CH), 129.4, 130.8, 134.8, 140.0, 155.5, 157.0 (C), 169.9
(C]O). IR (KBr, cmꢁ1): ~n¼2971 (m), 2958 (m), 2871
(m), 1649 (s), 1299 (s), 1233 (s), 1114 (s), 1030 (s), 811
(w). GC–MS (EI 70, eV): m/z (%)¼350 ([M]+, [37Cl], 15),
348 ([M]+, [35Cl], 46), 302 (74), 287 (19), 271 (100), 249
(16), 224 (7), 181 (11), 165 (12), 115 (4), 77 (2). HRMS
(EI) calcd for C19H21ClO4 ([M]+, [35Cl]): 348.11229; found:
348.11171.
3.1.25. Methyl 6-chloro-3-hydroxy-20-methoxy-5-methyl-
[1,10-biphenyl]-2-carboxylate (11m). Starting with bis-
silyl enol ether 4a (0.573 g, 2.20 mmol), TiCl4 (417 g,
2.20 mmol), CH2Cl2 (4 mL), and silyl enol ether 10e
(0.597 g, 2.00 mmol), 11m was isolated (0.285 g, 47%) by
3.1.28. Methyl 6-chloro-3-hydroxy-20-methoxy-5-
propyl[1,10-biphenyl]-2-carboxylate (11p). Starting with
bis-silyl enol ether 4a (0.573 g, 2.20 mmol), TiCl4 (417 g,
2.20 mmol), CH2Cl2 (4 mL), and silyl enol ether 10f
(0.653 g, 2.00 mmol), 11p was isolated (0.229 g, 34%) by
column
chromatography
(silica
gel,
n-heptane/
EtOAc¼30:1/20:1) as a slightly yellow oil. 1H NMR
(CDCl3, 300 MHz): d¼2.28 (s, 3H, CH3), 3.28 (s, 3H,
OCH3), 3.61 (s, 3H, OCH3), 6.80 (m, 1H, Ar), 6.81–6.83
(m, 1H, Ar), 6.84 (m, 1H, Ar), 6.85–6.86 (m, 1H, Ar),
7.18–7.24 (m, 1H, Ar), 10.76 (s, 1H, OH). 13C NMR
(CDCl3, 75 MHz): d¼20.68 (CH3), 50.8, 54.7 (OCH3),
109.4 (CH), 111.0 (C), 118.0 (CH), 118.1 (C), 119.1 (CH),
125.1 (C), 127.7, 128.6 (CH), 137.8, 142.8, 155.2, 158.8
(C), 169.6 (C]O). GC–MS (EI, 70 eV): m/z (%)¼308
([M]+, [37Cl], 12), 306 ([M]+, [35Cl], 37), 274 (100), 245
(8), 231 (8), 211 (8), 183 (7), 168 (11), 139 (10), 91 (3),
76 (6). HRMS (EI) calcd for C16H15ClO4 ([M]+, [35Cl]):
306.06534; found: 306.06620.
column chromatography (silica gel,
n-heptane/
EtOAc¼30:1/20:1) as a slightly yellow oil. 1H NMR
(CDCl3, 300 MHz): d¼0.87 (t, J¼7.4 Hz, 3H, CH3),
1.50–1.62 (m, 2H, CH2), 2.52–2.65 (m, 2H, CH2), 3.27
(m, 3H, OCH3), 3.60 (s, 3H, OCH3), 6.79 (s, 1H, Ar),
6.82 (m, 1H, Ar), 6.83–6.85 (m, 2H, Ar), 7.17–7.23 (m,
1H, Ar), 10.73 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d¼12.9 (CH3), 21.2, 35.7 (CH2), 50.8, 54.7 (OCH3),
109.4 (CH), 111.1 (C), 117.2 (CH), 117.3 (C), 119.1
(CH), 124.7 (C), 127.6, 128.7 (CH), 138.0, 146.6, 155.3,
158.8 (C), 169.6 (C]O). GC–MS (EI, 70 eV): m/z
(%)¼336 ([M]+, [37Cl], 12), 334 ([M]+, [35Cl], 37), 302
(100), 274 (43), 230 (10), 181 (5), 152 (9), 139 (8).
HRMS (EI) calcd for C18H19ClO4 ([M]+, [35Cl):
334.09664; found: 334.09699.
3.1.26. Methyl 6-chloro-3-hydroxy-20-methoxy-4,5-
dimethyl[1,10-biphenyl]-2-carboxylate (11n). Starting
with bis-silyl enol ether 4f (0.604 g, 2.20 mmol), TiCl4
(417 g, 2.20 mmol), CH2Cl2 (4 mL), and silyl enol ether
10e (0.597 g, 2.00 mmol), 11n was isolated (0.319 g, 50%)
by column chromatography (silica gel, n-heptane/
EtOAc¼30:1/20:1) as a colorless solid, mp¼78–80 ꢀC.
1H NMR (CDCl3, 300 MHz): d¼2.16 (s, 3H, CH3), 2.30
(s, 3H, CH3), 3.27 (s, 3H, OCH3), 3.61 (s, 3H, OCH3),
6.79–6.82 (m, 1H, Ar), 6.83–6.87 (m, 2H, Ar), 7.16–7.22
(m, 1H, Ar), 11.10 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼11.7, 17.2 (CH3), 50.8, 54.7 (OCH3), 109.3
(CH), 110.2 (C), 119.1 (CH), 125.0, 125.1 (C), 127.5,
128.7 (CH), 129.1, 134.7, 140.8, 155.3, 157.0 (C), 170.2
(C]O). IR (KBr, cmꢁ1): ~n¼3063 (w), 2953 (m), 2923
(m), 1668 (s), 1436 (s), 1293 (s), 1200 (s), 1015 (m), 744
(s). GC–MS (EI, 70 eV): m/z (%)¼322 ([M]+, [37Cl], 17),
320 ([M]+, [35Cl], 56), 288 (100), 273 (32), 257 (97), 181
(19), 165 (13), 152 (13), 115 (5), 76 (7). HRMS (EI) calcd
for C17H17ClO4 ([M]+, [35Cl]): 320.08099; found:
320.081273.
3.1.29. Methyl 6-chloro-3-hydroxy-20-methoxy-4-methyl-
5-propyl[1,10-biphenyl]-2-carboxylate (11q). Starting
with bis-silyl enol ether 4f (0.604 g, 2.20 mmol), TiCl4
(417 g, 2.20 mmol) CH2Cl2 (4 mL), and silyl enol ether
10f (0.653 g, 2.00 mmol), 11q was isolated (0.325 g, 47%)
by column chromatography (silica gel, n-heptane/
1
EtOAc¼30:1/20:1) as a slightly yellow viscous oil. H
NMR (CDCl3, 300 MHz): d¼0.90 (t, J¼7.4 Hz, 3H, CH3),
1.41–1.49 (m, 2H, CH2), 2.17 (s, 3H, CH3), 2.67–2.74 (m,
2H, CH2), 3.25 (m, 3H, OCH3), 3.59 (s, 3H, OCH3), 6.78
(d, J¼8.1 Hz, 1H, Ar), 6.82–6.83 (m, 2H, Ar), 7.14–7.20
(m, 1H, Ar), 11.07 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼4.8, 14.2 (CH3), 16.3, 38.0 (CH2), 53.7, 57.6
(OCH3), 112.3 (CH), 113.3 (C), 122.0 (CH), 127.6, 127.8
(C), 130.4, 131.7 (CH), 132.1, 137.9, 147.7, 158.3, 160.2
(C), 173.1 (C]O). IR (neat, cmꢁ1): ~n¼3000 (w), 2958 (s),
2931 (m), 2872 (m), 1663 (s), 1249 (s), 1218 (s), 1104
(m), 1028 (s), 808 (m). MS (EI, 70 eV): m/z (%)¼350
([M]+, [37Cl], 13), 348 ([M]+, [35Cl], 37), 316 (100), 301
(15), 285 (14), 257 (21), 181 (11), 165 (7), 69 (13). HRMS
(EI) calcd for C19H21ClO4 ([M]+, [35Cl]): 348.11229; found:
348.11170.
3.1.27. Ethyl 6-chloro-4-ethyl-3-hydroxy-20-methoxy-5-
methyl[1,10-biphenyl]-2-carboxylate (11o). Starting with
bis-silyl enol ether 4e (0.665 g, 2.20 mmol), TiCl4 (417 g,
2.20 mmol), CH2Cl2 (4 mL), and silyl enol ether 10e
(0.597 g, 2.00 mmol), 11o was isolated (0.290 g, 42%) by
column
chromatography
(silica
gel,
n-heptane/
3.1.30. Ethyl 6-chloro-4-ethyl-3-hydroxy-20-methoxy-5-
propyl[1,10-biphenyl]-2-carboxylate (11r). Starting with
bis-silyl enol ether 4e (0.665 g, 2.20 mmol), TiCl4
(417 g, 2.20 mmol) CH2Cl2 (4 mL), and monosilyl enol
ether 10f (0.654 g, 2.00 mmol), 11r was isolated
(0.384 g, 51%) by column chromatography (silica gel,
EtOAc¼30:1/20:1) as a colorless solid, mp¼90–92 ꢀC.
1H NMR (CDCl3, 300 MHz): d¼0.63 (t, J¼7.1 Hz, 3H,
CH3), 1.09 (t, J¼7.4 Hz, 3H, CH3), 2.36 (s, 3H, CH3),
2.73 (q, J¼7.4 Hz, 2H, CH2), 3.66 (m, 3H, OCH3), 3.83
(q, J¼7.1 Hz, 2H, OCH2), 6.82–6.85 (m, 1H, Ar), 6.86–
6.88 (m, 2H, Ar), 7.21–7.27 (m, 1H, Ar), 11.24 (s, 1H,
OH). 13C NMR (CDCl3, 75 MHz): d¼11.9, 12.1, 16.4
(CH3), 19.4 (CH2), 54.6 (OCH3), 59.9 (OCH2), 109.3
n-heptane/EtOAc¼30:1/20:1) as
a colorless solid,
1
mp¼79–81 ꢀC. H NMR (CDCl3, 300 MHz): d¼0.64 (t,
J¼7.2 Hz, 3H, CH3), 0.97 (t, J¼7.4 Hz, 3H, CH3), 1.13

12570
M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
(t, J¼7.4 Hz, 3H, CH3), 1.47–1.54 (m, 2H, CH2), 2.67–
2.69 (m, 2H, CH2), 2.72–2.76 (m, 2H, CH2), 3.67 (s, 3H,
OCH3), 3.83 (q, J¼7.2 Hz, 2H, OCH2), 6.84 (d,
J¼8.1 Hz, 1H, Ar), 6.87–6.89 (m, 2H, Ar), 7.22–7.28 (m,
1H, Ar), 11.19 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d¼11.9, 13.2, 13.5 (CH3), 19.3, 21.9, 32.4 (CH2), 54.7
(OCH3), 59.9 (OCH2), 109.4 (CH), 110.7 (C), 119.1
(CH), 124.9 (C), 127.4, 128.8 (CH), 129.5, 130.5, 135.1,
144.1, 155.5, 157.3 (C), 169.8 (C]O). IR (KBr, cmꢁ1):
~n¼3421 (w), 2959 (s), 2932 (s), 2870 (m), 1652 (s), 1392
(s), 1243 (s), 1185 (s), 1049 (m), 801 (w). MS (EI,
70 eV): m/z (%)¼378 ([M]+, [37Cl], 14), 376 ([M]+,
[35Cl], 42), 330 (100), 299 (84), 287 (7), 271 (8), 181 (9),
165 (6), 131 (8), 69 (19), 43 (12). HRMS (EI) calcd
for C21H25ClO4 ([M]+, [35Cl]): 376.14359; found:
376.142978.
100), 259 (7), 239 (16), 211 (7), 181 (6), 165 (6), 152 (8),
115 (4), 76 (5). HRMS (EI) calcd for C15H11ClO3 ([M]+,
[35Cl]): 274.03912; found: 274.03900.
3.2.3. 10-Chloro-8-ethyl-7-hydroxy-9-methyl-6H-benzo-
[c]chromen-6-one (12c). Starting with 11o (0.110 g,
0.31 mmol) in CH2Cl2 (5 mL), BBr3 (0.315 g, 1.26 mmol),
and KOtBu (10 mL, 0.1 M aqueous solution), 12c was iso-
lated as a colorless solid (0.060 g, 60%). 1H NMR (CDCl3,
300 MHz): d¼1.06 (t, J¼7.4 Hz, 3H, CH3), 2.40 (s, 3H,
CH3), 2.71 (q, J¼7.4 Hz, 2H, CH2), 7.17–7.18 (m, 1H,
Ar), 7.21 (m, 1H, Ar), 7.32–7.37 (m, 1H, Ar), 9.08–9.11
(m, 1H, Ar), 12.12 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼13.4, 18.6 (CH3), 20.8 (CH2), 105.4 (C),
117.8 (CH), 118.5, 121.8 (C), 124.6, 128.0 (CH), 128.8
(C), 130.5 (CH), 132.9, 146.8, 150.5, 159.5 (C), 165.9
(C]O). IR (KBr, cmꢁ1): ~n¼2969 (m), 2928 (m), 1663 (s),
1393 (s), 1242 (s), 1166 (s), 1116 (m), 758 (m). GC–MS
(EI, 70 eV): m/z (%)¼290 ([M]+, [37Cl], 16), 288 ([M]+,
[35Cl], 49), 273 (100), 245 (3), 181 (7), 165 (6), 152 (7),
126 (3), 76 (5). HRMS (EI) calcd for C16H13ClO3 ([M]+,
[35Cl]): 288.05477; found: 288.05465.
3.2. General procedure for synthesis of benzo[c]chro-
men-6-ones 12a–f by lactonization with BBr3
To a CH2Cl2 solution of 6 was added BBr3 at 0 ꢀC. The so-
lution was allowed to warm to 20 ꢀC for 18 h. To the solution
was added an aqueous solution of KOtBu (0.1 M) and the so-
lution was stirred for 15 min. The organic and the aqueous
layers were separated and the latter was extracted with
CH2Cl2. The combined organic layers were dried
(Na2SO4), filtered, and the filtrate was concentrated in va-
cuo. The product was purified by chromatography (silica
gel, n-hexane/EtOAc¼20:1) as a colorless solid.
3.2.4. 10-Chloro-7-hydroxy-9-propyl-6H-benzo[c]chro-
men-6-one (12d). Starting with 11p (0.107 g, 0.32 mmol)
in CH2Cl2 (5 mL), BBr3 (0.320 g, 1.27 mmol), and KOtBu
(10 mL, 0.1 M aqueous solution), 12d was isolated as a col-
orless crystalline (0.078 g, 88%), mp¼115–117 ꢀC. 1H
NMR (CDCl3, 300 MHz): d¼0.95 (t, J¼7.4 Hz, 3H, CH3),
1.56–1.68 (m, 2H, CH2), 2.69–2.75 (m, 2H, CH2), 6.89 (s,
1H, Ar), 7.21–7.22 (m, 1H, Ar), 7.25 (m, 1H, Ar), 7.36–
7.42 (m, 1H, Ar), 9.18–9.21 (m, 1H, Ar), 11.73 (s, 1H,
OH). 13C NMR (CDCl3, 75 MHz): d¼14.3 (CH3), 22.7,
37.9 (CH2), 106.3 (C), 117.9 (CH), 118.5 (C), 118.9 (CH),
121.0 (C), 124.7, 128.2, 131.1 (CH), 131.8, 150.0, 153.0,
161.4 (C), 165.4 (C]O). IR (KBr, cmꢁ1): ~n¼2965 (m),
2931 (m), 2876 (m), 1675 (s), 1606 (m), 1421 (s), 1232
(s), 1216 (s), 1105 (w), 765 (s). GC–MS (EI, 70 eV): m/z
(%)¼290 ([M]+, [37Cl], 33), 288 ([M]+, [35Cl], 100), 260
(94), 253 (16), 225 (38), 197 (13), 181 (10), 168 (14), 152
(18), 139 (23), 126 (6), 75 (5). HRMS (EI) calcd for
C16H13ClO3 ([M]+, [35Cl]): 288.05477; found: 288.05478.
3.2.1. 10-Chloro-7-hydroxy-9-methyl-6H-benzo[c]chro-
men-6-one (12a). Starting with 11m (0.104 g, 0.31 mmol)
in CH2Cl2 (5 mL), BBr3 (0.339 g, 1.35 mmol), and KOtBu
(10 mL, 0.1 M aqueous solution), 12a was isolated as a col-
orless solid (0.063 g, 73%), mp¼107–110 ꢀC. 1H NMR
(CDCl3, 300 MHz): d¼2.45 (s, 3H, CH3), 6.96 (s, 1H, Ar),
7.27–7.30 (m, 2H, Ar), 7.41–7.46 (m, 1H, Ar), 9.24–9.27
(m, 1H, Ar), 11.78 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼21.0 (CH3), 104.0 (C), 115.7 (CH), 116.1
(C), 117.2 (CH), 119.1 (C), 122.5, 125.8, 128.8 (CH),
129.3, 147.0, 148.5, 159.1 (C), 163.2 (C]O). IR (KBr,
cmꢁ1): ~n¼3026 (w), 2957 (w), 2924 (w), 1667 (s), 1265
(s), 1218 (s), 1102 (s), 1031 (s), 763 (s). GC–MS (EI,
70 eV): m/z (%)¼262 ([M]+, [35Cl], 33), 260 ([M]+, [35Cl],
100), 225 (26), 197 (13), 169 (8), 139 (10), 112 (14), 69
(5). HRMS (EI) calcd for C14H9ClO3 ([M]+, [35Cl]):
260.02347; found: 260.02249.
3.2.5. 10-Chloro-7-hydroxy-8-methyl-9-propyl-6H-ben-
zo[c]chromen-6-one (12e). Starting with 11q (0.129 g,
0.37 mmol) in CH2Cl2 (5 mL), BBr3 (0.320 g, 1.27 mmol),
and KOtBu (10 mL, 0.1 M aqueous solution), 12e was iso-
lated as a light brown solid (0.060 g, 54%), mp¼98–
100 ꢀC. 1H NMR (CDCl3, 300 MHz): d¼1.01 (t,
J¼7.4 Hz, 3H, CH3), 1.49–1.54 (m, 2H, CH2), 2.26 (s, 3H,
CH3), 2.83–2.89 (m, 2H, CH2), 7.23–7.24 (m, 1H, Ar),
7.27 (m, 1H, Ar), 7.36–7.42 (m, 1H, Ar), 9.20 (d,
J¼8.9 Hz, 1H, Ar), 12.20 (s, 1H, OH). 13C NMR (CDCl3,
75 MHz): d¼11.4, 13.4 (CH3), 20.6, 33.1 (CH2), 104.0
(C), 116.4 (CH), 117.3, 119.8 (C), 123.2, 126.8 (CH),
127.3, 127.7 (C), 129.1 (CH), 149.2, 149.9, 158.6 (C),
164.6 (C]O). IR (KBr, cmꢁ1): ~n¼2968 (m), 2925 (m),
2861 (m), 1671 (s), 1598 (m), 1394 (s), 1259 (s), 1221
(m), 1166 (s), 774 (s). GC–MS (EI, 70 eV): m/z (%)¼304
([M]+, [37Cl], 33), 302 ([M]+, [35Cl], 100), 274 (52), 267
(22), 239 (44), 181 (16), 152 (17), 115 (5), 76 (5). HRMS
(EI) calcd for C17H15ClO3 ([M]+, [35Cl]): 302.07042; found:
302.07123.
3.2.2. 10-Chloro-7-hydroxy-8,9-dimethyl-6H-benzo[c]-
chromen-6-one (12b). Starting with 11n (0.129 g,
0.37 mmol) in CH2Cl2 (5 mL), BBr3 (0.374 g, 1.49 mmol),
and KOtBu (10 mL, 0.1 M aqueous solution), 12b was iso-
lated as a colorless solid (0.080 g, 78%), mp¼154–156 ꢀC.
1H NMR (CDCl3, 300 MHz): d¼2.23 (s, 3H, CH3), 2.41
(s, 3H, CH3), 7.22–7.24 (m, 1H, Ar), 7.26 (m, 1H, Ar),
7.36–7.42 (m, 1H, Ar), 9.17 (dd, J¼8.4, 2.1 Hz, 1H, Ar),
12.18 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz): d¼10.9,
16.9 (CH3), 102.9 (C), 115.5 (CH), 116.2, 119.3 (C), 123.3
(CH), 124.7 (C), 125.8 (CH), 126.4 (C), 128.2 (CH),
145.1, 148.2, 157.3 (C), 163.6 (C]O). IR (KBr, cmꢁ1):
~n¼3446 (w), 2925 (m), 2851 (m), 1669 (s), 1597 (s), 1397
(s), 1254 (s), 1168 (s), 1113 (m), 780 (s). GC–MS (EI,
70 eV): m/z (%)¼276 ([M]+, [37Cl], 33), 274 ([M]+, [35Cl],

M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
12571
3.2.6. 10-Chloro-8-ethyl-7-hydroxy-9-propyl-6H-ben-
zo[c]chromen-6-one (12f). Starting with 11r (0.200 g,
0.51 mmol) in CH2Cl2 (5 mL), BBr3 (0.513 g, 2.12 mmol),
and KOtBu (10 mL, 0.1 M aqueous solution), 12f was iso-
lated as a light red solid (0.080 g, 48%), mp¼98–100 ꢀC.
1H NMR (CDCl3, 300 MHz): d¼1.03 (t, J¼7.4 Hz, 3H,
CH3), 1.13 (t, J¼7.4 Hz, 3H, CH3), 1.55–1.60 (m, 2H,
CH2), 2.75 (q, J¼7.4 Hz, 2H, CH2), 2.83–2.88 (m, 2H,
CH2), 7.24–7.25 (m, 1H, Ar), 7.27–7.28 (m, 1H, Ar),
7.37–7.42 (m, 1H, Ar), 9.20–9.23 (m, 1H, Ar), 12.19 (s,
1H, OH). 13C NMR (CDCl3, 75 MHz): d¼14.1, 14.9
(CH3), 20.8, 23.1, 34.1 (CH2), 105.7 (C), 117.8 (CH),
118.7, 121.4 (C), 124.6, 128.3 (CH), 129.4 (C), 130.6
(CH), 132.8, 150.6, 150.8, 160.0 (C), 166.1 (C]O). IR
(KBr, cmꢁ1): ~n¼2955 (m), 2928 (m), 2869 (m), 1677 (s),
1597 (w), 1383 (s), 1243 (s), 1215 (s), 1116 (s), 753 (s).
GC–MS (EI, 70 eV): m/z (%)¼314 ([M]+, [35Cl], 33), 316
([M]+, [35Cl], 100), 302 (8), 301 (40), 273.1 (51), 205 (7),
165 (4), 76 (4). HRMS (EI) calcd for C18H17ClO3 ([M]+,
[35Cl]): 316.08607; found: 316.08636.
(CDCl3, 300 MHz): d¼0.24 (s, 9H, CH3), 2.01 (s, 3H,
CH3), 7.29 (m, 2H, Ar), 7.62–7.65 (m, 2H, Ar). 13C NMR
(CDCl3, 75 MHz): d¼0.8, 0.9, 2.0, 21.6 (CH3), 111.6 (C),
128.6 (2CH), 130.8 (2CH), 136.3, 138.9, 158.6 (C), 190.9
(C]O).
3.2.10. 3-Chloro-4-(2-methylphenyl)-4-[(trimethylsilyl)-
oxy]-3-buten-2-one (10d). To a stirred benzene solution
(13.8 mL) of 9d (1.16 g, 5.5 mmol) was added triethylamine
(1.23 mL, 8.84 mmol). After the solution was stirred for 2 h,
trimethylchlorosilane (1.25 mL, 9.9 mmol) was added. Af-
ter the solution was stirred for 72 h, the solvent was removed
in vacuo and hexane (50 mL) was added to the residue to
give a suspension. The latter was filtered under argon atmo-
sphere. The filtrate was concentrated in vacuo to give 10d as
reddish yellow oil (1.13 g, 72%). 1H NMR (CDCl3,
300 MHz): d¼0.20 (s, 9H, CH3), 2.14 (s, 3H, CH3), 2.57
(s, 3H, CH3), 728 (m, 1H, Ar), 7.35 (m, 1H, Ar), 7.47 (m,
1H, Ar), 7.48 (m, 1H, Ar). 13C NMR (CDCl3, 75 MHz):
d¼0.4, 1.1, 2.1, 25.7 (CH3), 108.4 (C), 125.6, 127.5,
130.1, 130.5 (CH), 134.8, 135.4, 182.6 (C), 195.3 (C]O).
3.2.7. 3-Chloro-4-phenyl-4-[(trimethylsilyl)oxy]-3-
buten-2-one (10a). To a stirred benzene solution (120 mL)
of 9a (9.50 g, 48.3 mmol) was added triethylamine
(10.71 mL, 77.3 mmol). After the solution was stirred for
2 h, trimethylchlorosilane (10.98 mL, 86.9 mmol) was
added. After the solution was stirred for 72 h, the solvent
was removed in vacuo and hexane (75 mL) was added to
the residue to give a suspension. The latter was filtered under
argon atmosphere. The filtrate was concentrated in vacuo to
3.2.11. 3-Chloro-4-(2-methoxyphenyl)-4-[(trimethylsilyl)-
oxy]-3-buten-2-one (10e). To a stirred benzene solution
(35.3 mL) of 9f (2.67 g, 11.7 mmol) was added triethyl-
amine (2.64 mL, 18.8 mmol). After the solution was stirred
for 2 h, trimethylchlorosilane (2.67 mL, 21.19 mmol) was
added. After the solution was stirred for 72 h, the solvent
was removed in vacuo and hexane (75 mL) was added to
the residue to give a suspension. The latter was filtered under
argon atmosphere. The filtrate was concentrated in vacuo to
1
give 10a as a dark yellow oil (10.10 g, 90%). H NMR
1
(CDCl3, 300 MHz): d¼0.26 (s, 9H, CH3), 1.99 (s, 3H,
CH3), 7.33–7.36 (m, 2H, Ar), 7.40–7.43 (m, 1H, Ar),
7.70–7.73 (m, 2H, Ar). 13C NMR (CDCl3, 75 MHz):
d¼0.5, 0.7, 1.9, 21.4 (CH3), 111.6 (CCl), 128.1 (2CH),
129.1 (2CH), 132.4 (CH), 137.7, 157.4 (C), 191.8 (C]O).
give 10e as reddish yellow oil (2.70 g, 76%). H NMR
(CDCl3, 300 MHz): d¼0.02 (s, 9H, CH3), 1.96 (s, 3H,
CH3), 3.72 (s, 3H, OCH3), 6.85–6.88 (m, 1H, Ar), 7.10–
7.12 (m, 1H, Ar), 7.30–7.33 (m, 1H, Ar), 7.70–7.81 (m,
1H, Ar). 13C NMR (CDCl3, 75 MHz): d¼0.2 (3CH3), 28.8
(CH3), 54.9 (OCH3), 110.7 (CH), 117.8 (C), 120.3 (CH),
122.8, 124.9 (C), 129.9, 131.4 (CH), 156.2 (C), 192.8
(C]O).
3.2.8. 3-Chloro-4-(4-fluorophenyl)-4-[(trimethylsilyl)-
oxy]-3-buten-2-one (10b). To a stirred benzene solution
(45 mL) of 9b (3.25 g, 15.11 mmol) was added triethyl-
amine (3.38 mL, 24.17 mmol). After the solution was stirred
for 2 h, trimethylchlorosilane (3.43 mL, 27.2 mmol) was
added. After the solution was stirred for 72 h, the solvent
was removed in vacuo and hexane (75 mL) was added to
the residue to give a suspension. The latter was filtered under
argon atmosphere. The filtrate was concentrated in vacuo to
3.2.12. 2-Chloro-1-(2-methoxyphenyl)-1-[(trimethylsilyl)-
oxy]-1-hexen-3-one (10f). To a stirred benzene solution
(43.8 mL) of 9f (3.72 g, 14.6 mmol) was added triethyl-
amine (3.28 mL, 23.4 mmol). After the solution was
stirred for 2 h, trimethylchlorosilane (3.32 mL,
26.3 mmol) was added. After the solution was stirred for
72 h, the solvent was removed in vacuo and hexane
(75 mL) was added to the residue to give a suspension.
The latter was filtered under argon atmosphere. The filtrate
was concentrated in vacuo to give 10f as reddish yellow oil
1
give 10b as reddish yellow oil (3.50 g, 80%). H NMR
(CDCl3, 300 MHz): d¼0.24 (s, 9H, CH3), 1.91 (s, 3H,
CH3), 7.00–7.03 (m, 2H, Ar), 7.72–7.76 (m, 2H, Ar). 13C
NMR (CDCl3, 75 MHz): d¼0.6, 0.8, 1.9, 21.4 (CH3),
111.4 (C), 115.2, 115.5, 131.9, 132.1 (CH), 157.9, 163.7,
167.3 (C), 188.4 (C]O).
1
(4.05 g, 84%). H NMR (CDCl3, 300 MHz): d¼0.02 (s,
9H, CH3), 0.74 (t, J¼7.4 Hz, 3H, CH3), 1.38–1.50 (m,
2H, CH2), 2.38 (t, J¼7.2 Hz, 2H, CH2), 3.73 (s, 3H,
OCH3), 6.86–6.87 (m, 1H, Ar), 6.90–6.92 (m, 1H, Ar),
7.10 (dd, J¼7.4, 1.7 Hz, 1H, Ar), 7.29–7.31 (m, 1H, Ar).
13C NMR (CDCl3, 75 MHz): d¼0.4, 0.8, 0.9, 13.6 (CH3),
17.6, 42.7 (CH2), 55.1 (OCH3), 110.8 (CH), 117.6 (C),
120.4 (CH), 125.8 (C), 130.1, 131.1 (CH), 155.2, 156.3
(C), 196.3 (C]O).
3.2.9. 3-Chloro-4-(4-chlorophenyl)-4-[(trimethylsilyl)-
oxy]-3-buten-2-one (10c). To a stirred benzene solution
(33 mL) of 9c (2.607 g, 11.27 mmol) was added triethyl-
amine (2.52 mL, 18.0 mmol). After the solution was stirred
for 2 h, trimethylchlorosilane (2.56 mL, 20.3 mmol) was
added. After the solution was stirred for 72 h, the solvent
was removed in vacuo and hexane (75 mL) was added to
the residue to give a suspension. The latter was filtered under
argon atmosphere. The filtrate was concentrated in vacuo to
3.2.13. 2-Chloro-1-(4-flourophenyl)butane-1,3-dione
(9b). A mixture of 8b (4.11 g, 22.8 mmol) and NCS
(3.09 g, 22.8 mmol) in CCl4 (50 mL) was heated at reflux
1
give 10c as reddish yellow oil (2.51 g, 73%). H NMR

12572
M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
for 4 h. After cooling, the precipitate of succinimide was fil-
tered off and water was added, the layers were separated, and
the aqueous layer was extracted with CH2Cl2 (3ꢂ150 mL).
The combined organic layers were dried (Na2SO4) and fil-
tered, and the solvent was removed in vacuo. The residue
was purified by chromatography (silica gel, n-heptane/
EtOAc 30:1/20:1) to give 9b as dark yellow oil (3.25 g,
filtered off and water was added, the layers were separated,
and the aqueous layer was extracted with CH2Cl2
(3ꢂ150 mL). The combined organic layers were dried
(Na2SO4) and filtered, and the solvent was removed in va-
cuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc 30:1/20:1) to give 9e as yellow oil
1
(2.67 g, 47%). H NMR (CDCl3, 300 MHz): d¼2.26 (s,
1
66%). H NMR (CDCl3, 300 MHz): d¼2.29 (s, 3H, CH3),
3H, CH3), 3.78 (s, 3H, OCH3), 5.56 (s, 1H, CH), 6.88 (d,
J¼8.4 Hz, 1H, Ar), 6.91–6.96 (m, 1H, Ar), 7.40–7.46 (m,
1H, Ar), 7.74 (dd, J¼7.6, 1.9 Hz, 1H, Ar). 13C NMR
(CDCl3, 75 MHz): d¼26.0 (CH3), 54.5 (OCH3), 66.9
(CH), 110.8, 120.4 (CH), 123.4 (C), 130.4, 134.3 (CH),
157.4 (C), 189.3, 196.3 (C]O). GC–MS (EI, 70 eV): m/z
(%)¼228 ([M]+, [37Cl], 3), 226 ([M]+, [35Cl], 1), 197
(37Cl, 8), 195 (35Cl, 24), 135 (100), 108 (7), 92 (9), 77
(21), 63 (5). HRMS (EI) calcd for C10H9ClO2 ([M]+,
[35Cl]): 226.03912; found: 226.03926.
5.46 (s, 1H, CH), 7.06–7.09 (m, 2H, Ar), 7.92–7.97 (m,
2H, Ar). 13C NMR (CDCl3, 75 MHz): d¼25.6 (CH3), 63.2
(CH), 115.1, 115.3, 131.2, 131.3 (CH), 163.7, 167.7 (C),
187.3, 197.6 (C]O). GC–MS (EI 70 eV): m/z (%)¼216
([M]+, [37Cl], 12), 214 ([M]+, [35Cl], 4), 199 (4), 172
(114), 123 (100), 95 (39), 75 (13), 43 (19). HRMS (EI) calcd
for C10H8ClFO2 ([M]+, [35Cl]): 214.01914; found:
214.01824.
3.2.14. 3-Chloro-4-(4-chlorophenyl)butane-1,3-dione
(9c). A mixture of 8c (4.38 g, 22.3 mmol) and NCS
(3.02 g, 22.3 mmol) in CCl4 (49 mL) was heated at reflux
for 4 h. After cooling, the precipitate of succinimide was fil-
tered off and water was added, the layers were separated, and
the aqueous layer was extracted with CH2Cl2 (3ꢂ150 mL).
The combined organic layers were dried (Na2SO4) and fil-
tered, and the solvent was removed in vacuo. The residue
was purified by chromatography (silica gel, n-heptane/
EtOAc 30:1/20:1) to give 9c as yellowish oil (2.60 g,
3.2.17. 2-Chloro-1-(2-methoxyphenyl)hexane-1,3-dione
(9f). A mixture of 8f (4.00 g, 18 mmol) and NCS (2.41 g,
18 mmol) in CCl4 (40 mL) was heated at reflux for 4 h. After
cooling, the precipitate of succinimide was filtered off and
water was added, the layers were separated, and the aqueous
layer was extracted with CH2Cl2 (3ꢂ150 mL). The com-
bined organic layers were dried (Na2SO4) and filtered, and
the solvent was removed in vacuo. The residue was purified
by chromatography (silica gel, n-heptane/EtOAc 30:1/
1
1
52%). H NMR (CDCl3, 300 MHz): d¼2.31 (s, 3H, CH3),
20:1) to give 9f as yellowish oil (3.72 g, 81%). H NMR
5.43 (s, 1H, CH), 7.42 (m, 2H, CH3), 7.84–7.87 (m, 2H,
CH3). 13C NMR (CDCl3, 75 MHz): d¼27.0 (CH3), 64.5
(CH), 128.7 (C), 129.7 (2CH), 131.1 (2CH), 141.6 (C),
189.1, 198.9 (C]O). GC–MS (EI, 70 eV): m/z (%)¼234
(CDCl3, 300 MHz): d¼0.80 (t, J¼7.4 Hz, 3H, CH3), 1.48–
1.58 (m, 2H, CH2), 2.51–2.58 (m, 2H, CH2), 3.73 (s, 3H,
OCH3), 5.64 (s, 1H, CH), 6.83–6.86 (m, 1H, Ar), 6.87–
6.92 (m, 1H, Ar), 7.36–7.42 (m, 1H, Ar), 7.71 (dd, J¼7.8,
1.7 Hz, 1H, Ar). 13C NMR (CDCl3, 75 MHz): d¼11.6
(CH3), 15.0, 39.5 (CH2), 55.6 (OCH3), 65.8, 110.0, 119.3
(CH), 122.6 (C), 129.5, 133.5 (CH), 156.5 (C), 188.5,
197.6 (C]O). IR (KBr, cmꢁ1): ~n¼2957 (w), 2926 (w),
1665 (s), 1618 (w), 1440 (s), 1344 (s), 1177 (s), 1094 (m),
805 (s). GC–MS (EI, 70 eV): m/z (%)¼256 ([M]+, [37Cl],
6), 254 ([M]+, [35Cl], 12), 223 (79), 184 (59), 135 (100),
92 (46), 77 (76), 43 (64). HRMS (EI) calcd for
C13H15ClO3 ([M]+, [35Cl]): 254.07042; found: 254.07013.
37
([M]+, [2ꢂ Cl], 1), 232 ([M]+, [37Cl], [35Cl], 6), 230
35
([M]+, [2ꢂ Cl], 10), 215 (3), 188 (13), 139 (100), 111
(38), 75 (21), 43 (26). HRMS (EI) calcd for C10H8Cl2O2
35
([M]+, [2ꢂ Cl]): 229.98959; found: 229.98919.
3.2.15. 2-Chloro-1-o-tolylbutane-1,3-dione (9d). A mix-
ture of 8d (2.21 g, 12.5 mmol) and NCS (1.67 g,
12.5 mmol) in CCl4 (27.6 mL) was heated at reflux for 4 h.
After cooling, the precipitate of succinimide was filtered off
and water was added, the layers were separated, and the aque-
ous layer was extracted with CH2Cl2 (3ꢂ150 mL). The com-
bined organic layers were dried (Na2SO4) and filtered, and the
solvent was removed in vacuo. The residue was purified by
chromatography (silica gel, n-heptane/EtOAc 30:1/20:1)
3.2.18. 4-(4-Fluorophenyl)-4-hydroxy-3-buten-2-one
(8b). To a stirred solution of LDA (75 mmol) in THF
(62 mL) was added acetone (2.904 g, 50.0 mmol) at
ꢁ78 ꢀC. After the solution was stirred for 1 h, 4-fluoroben-
zoyl chloride (9.51 g, 60.0 mmol) was added. The tempera-
ture of the solution was allowed to rise to 20 ꢀC for 12 h. A
saturated solution of NH4Cl was added, the layers were sep-
arated, and the aqueous layer was extracted with ethylacetate
(3ꢂ150 mL). The combined organic layers were dried
(Na2SO4) and filtered, and the solvent was removed in va-
cuo. The residue was purified by chromatography (silica
gel, n-hexane/EtOAc 30:1/20:1) to give 8b as a colorless
solid (3.9 g, 36%), mp¼48–49 ꢀC. 1H NMR (300 MHz,
CDCl3): d¼2.11 (s, 3H, CH3), 6.04 (s, 1H, CH), 7.04 (m,
2H, CH), 7.81 (m, 2H, CH), 16.07 (br s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼24.4 (CH3), 95.3 (CH), 114
1
to give 9d as a yellow oil (1.16 g, 44%). H NMR (CDCl3,
300 MHz): d¼2.27 (s, 3H, CH3), 2.35 (s, 3H, CH3), 7.16
(m, 1H, Ar), 7.19–7.20 (m, 2H, Ar), 7.24 (m, 1H, Ar),
15.46 (s, 1H, OH). 13C NMR (CDCl3, 75 MHz): d¼19.6,
26.0 (CH3), 108.6 (C), 125.8, 127.7, 130.4 (CH), 135.5,
135.7, 182.9 (C), 195.6 (C]O). IR (neat, cmꢁ1): ~n¼3389
(w), 3066 (m), 2929 (m), 2870 (m), 1684 (m), 1570 (m),
1201 (m), 1037 (m), 903 (m), 738 (w). GC–MS (EI,
70 eV): m/z (%)¼212 ([M]+, [37Cl], 3), 210 ([M]+, [35Cl],
7), 195 (100), 175 (6), 160 (11), 119 (92), 103 (15), 77
(12), 65 (19), 43 (21). HRMS (EI) calcd for C11H11ClO2
([M]+, [35Cl]): 210.04421; found: 210.04370.
3
2
(d, J¼21.8 Hz, 2CH), 128.4 (d, J¼8.9 Hz, 2CH), 130.3
4
1
3.2.16. 2-Chloro-1-(2-methoxyphenyl)butane-1,3-dione
(9e). A mixture of 8e (4.80 g, 25.0 mmol) and NCS
(3.33 g, 25 mmol) in CCl4 (55 mL) was heated at reflux
for 4 h. After cooling, the precipitate of succinimide was
(d, J¼2.9 Hz, C), 164.3 (d, J¼252.0 Hz, CF), 181.9 (C),
191.8 (C]O). IR (KBr, cmꢁ1): ~n¼1603 (s), 1507 (s), 1297
(m), 1246 (s), 1159 (m), 1095 (m), 1014 (w), 849 (s), 786
(s), 506 (w). MS (EI, 70 eV): m/z (%)¼180 ([M]+, 64),

M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
12573
165 (66), 138 (6), 123 (100), 109 (6), 95 (48), 85 (11), 75
(20), 69 (50), 50 (5), 43 (23). HRMS (EI) calcd for
C10H9FO2 ([M]+): 180.05811; found: 180.05765.
gel, n-heptane/EtOAc 30:1/20:1) to give 13a as yellow
1
solid (70 mg, 40%). H NMR (300 MHz, CDCl3): d¼2.27
(s, 3H, CH3), 6.57 (s, 1H, Ar), 7.18–7.25 (m, 1H, Ar),
7.38–7.44 (m, 1H, Ar), 7.55 (d, J¼7.2 Hz, 1H, Ar), 8.03
(d, J¼7.6 Hz, 1H, Ar), 8.43 (s, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼21.3 (CH3), 117.5 (C), 120.5 (CH),
122.0 (C), 124.4, 124.8, 129.6 (CH), 135.0 (C), 135.1
(CH), 139.9, 143.3, 147.9, 156.0 (C), 195.2 (C]O). GC–
MS (EI, 70 eV): m/z (%)¼246 ([M]+, [37Cl], 50), 244
([M]+, [35Cl], 100), 216 (10), 181 (21), 152 (37), 126 (3),
90 (7), 76 (17). HRMS (EI) calcd for C14H9ClO2 ([M]+,
[35Cl]): 244.02856; found: 244.02847.
3.2.19. 4-(4-Chlorophenyl)-4-hydroxy-3-buten-2-one
(8c). To a stirred solution of LDA (75 mmol) in THF
(62 mL) was added acetone (2.904 g, 50.0 mmol) at
ꢁ78 ꢀC. After the solution was stirred for 1 h, 4-chloroben-
zoyl chloride (10.5 g, 60.0 mmol) was added. The tempera-
ture of the solution was allowed to rise to 20 ꢀC for 12 h. A
saturated solution of NH4Cl was added, the layers were sep-
arated, and the aqueous layer was extracted with ethylacetate
(3ꢂ150 mL). The combined organic layers were dried
(Na2SO4) and filtered, and the solvent was removed in va-
cuo. The residue was purified by chromatography (silica
gel, n-hexane/EtOAc 30:1/20:1) to give 8c as a light
yellow solid (3.762 g, 38%), mp¼66–68 ꢀC. 1H NMR
(300 MHz, CDCl3): d¼2.12 (s, 3H, CH3), 6.06 (s, 1H,
CH), 7.33 (m, 1H, CH), 7.35 (m, 1H, CH), 7.72 (m, 1H,
CH), 7.75 (m, 1H, CH), 16.01 (br s, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼26.1 (CH3), 96.9 (CH), 128.7 (2CH),
129.3 (2CH), 133.7, 138.9, 182.6 (C), 194.1 (C]O). IR
(KBr, cmꢁ1): ~n¼3075 (m), 2847 (m), 1594 (s), 1547 (s),
1486 (s), 1284 (m), 1113 (m), 1093 (s), 1012 (s), 840 (m),
779 (s), 437 (m). MS (EI, 70 eV): m/z (%)¼198 ([M]+,
[37Cl], 34), 196 ([M]+, [35Cl], 69), 181 (87), 161 (26), 154
(8), 139 (100), 111 (44), 101 (5), 89 (13), 85 (25), 75 (36),
69 (79), 63 (6), 50 (11), 43 (36). HRMS (EI) calcd for
C10H9ClO2 ([M]+, [35Cl]): 196.02856; found: 196.02870.
3.2.22. 4-Chloro-1-hydroxy-2,3-dimethyl-9H-fluoren-9-
one (13b). Concd sulfuric acid (3.1 mL) was added to 11b
(74 mg, 0.27 mmol) and the solution was stirred for 1 h.
Then water was added and the aqueous solution was ex-
tracted with CH2Cl2 (3ꢂ50 mL). The organic layers were
dried (Na2SO4) and filtered, and the solvent was removed
in vacuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc 30:1/20:1) to give 13b as yellow
1
solid (60 mg, 86%). H NMR (250 MHz, CDCl3): d¼2.07
(s, 3H, CH3), 2.22 (s, 3H, CH3), 7.11–7.22 (m, 1H, Ar),
7.36–7.42 (m, 1H, Ar), 7.50–7.53 (m, 1H, Ar), 7.96–7.99
(m, 1H, Ar), 8.76 (s, 1H, OH). 13C NMR (62 MHz,
CDCl3): d¼11.8, 17.1 (CH3), 116.0, 122.0 (C), 123.8,
124.1 (CH), 127.9 (C), 128.7 (CH), 134.3 (C), 134.5 (CH),
136.5, 143.3, 144.9, 154.3 (C), 195.5 (C]O). GC–MS (EI,
70 eV): m/z (%)¼260 ([M]+, [37Cl], 50), 258 ([M]+, [35Cl],
100), 243 (12), 223 (29), 195 (11), 176 (9), 165 (27), 152
(12), 139 (6), 115 (5), 82 (8). HRMS (EI) calcd for
C15H11ClO2 ([M]+, [35Cl]): 258.04421; found: 258.04414.
3.2.20. 4-Hydroxy-4-(2-methylphenyl)-3-buten-2-one
(8d). To a stirred solution of LDA (75 mmol) in THF
(62 mL) was added acetone (2.904 g, 50.0 mmol) at
ꢁ78 ꢀC. After the solution was stirred for 1 h, 2-methylben-
zoyl chloride (9.25 g, 60.0 mmol) was added. The tempera-
ture of the solution was allowed to rise to 20 ꢀC for 12 h. A
saturated solution of NH4Cl was added, the layers were sep-
arated, and the aqueous layer was extracted with ethylacetate
(3ꢂ150 mL). The combined organic layers were dried
(Na2SO4) and filtered, and the solvent was removed in va-
cuo. The residue was purified by chromatography (silica
gel, n-hexane/EtOAc 30:1/20:1) to give 8d as a yellowish
3.2.23. 4-Chloro-7-fluoro-1-hydroxy-3-methyl-9H-fluo-
ren-9-one (13c). Concd sulfuric acid (2.31 mL) was added
to 11e (57 mg, 0.19 mmol) and the solution was stirred for
1 h. Then water was added and the aqueous solution was ex-
tracted with CH2Cl2 (3ꢂ50 mL). The organic layers were
dried (Na2SO4) and filtered, and the solvent was removed
in vacuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc 30:1/20:1) to give 13c as yellow
1
solid (30 mg, 61%). H NMR (300 MHz, CDCl3): d¼2.29
1
oil (3.5 g, 33%). H NMR (300 MHz, CDCl3): d¼2.05 (s,
(s, 3H, CH3), 6.58 (s, 1H, Ar), 7.06–7.13 (m, 1H, Ar), 7.09
(dd, J¼7.2, 2.4 Hz, 1H, Ar), 8.01–8.05 (m, 1H, Ar), 8.33
(s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼19.9 (CH3),
110.5 (CH), 116.3, 118.9 (C), 119.7, 120.4, 124.7 (CH),
135.9, 137.6, 137.9, 147.1, 154.7 (C), 162.5 (d, 1J¼
251.1 Hz, CF), 192.2 (C]O). GC–MS (EI, 70 eV): m/z
(%)¼264 ([M]+, [37Cl], 50), 262 ([M]+, [35Cl], 100), 234
(15), 199 (13), 152 (7), 132 (7), 110 (8), 99 (11), 84 (11).
HRMS (EI) calcd for C14H8ClFO2 ([M]+, [35Cl]):
262.01914; found: 262.01903.
3H, CH3), 2.39 (s, 3H, CH3Ar), 5.74 (s, 1H, CH), 7.12 (d,
3J¼7.2 Hz, 2H, CH), 7.22 (m, 1H, CH), 7.35 (dd,
3J¼7.4 Hz, 4J¼1.9 Hz, 1H, CH), 15.90 (br s, 1H, OH). 13
C
NMR (75 MHz, CDCl3): d¼21.0 (CH3), 25.9 (CH3), 101.1
(CH), 126.1, 128.6, 131.2, 132.0 (CH), 136.3, 139.7, 188.5
(C), 193.3 (C]O). IR (neat, cmꢁ1): ~n¼2967 (w), 1717
(m), 1606 (s), 1457 (s), 1264 (s), 1159 (m), 1069 (w), 769
(w), 735 (s), 662 (w). GC–MS (EI, 70 eV): m/z (%)¼176
([M]+, 13), 161 (100), 143 (3), 132 (6), 119 (35), 91 (41),
85 (10), 77 (8), 69 (30), 65 (17), 51 (6), 43 (21), 39 (7).
HRMS (EI) calcd for C11H12O2 ([M]+): 176.08318; found:
176.08266.
3.2.24. 4-Chloro-7-fluoro-1-hydroxy-2,3-dimethyl-9H-
fluoren-9-one (13d). Concd sulfuric acid (3.06 mL) was
added to 11f (79 mg, 0.25 mmol) and the solution was stirred
for 1 h. Then water was added and the aqueous solution was
extracted with CH2Cl2 (3ꢂ50 mL). The organic layers were
dried (Na2SO4) and filtered, and the solvent was removed in
vacuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc 30:1/20:1) to give 13d as yellow
3.2.21. 4-Chloro-1-hydroxy-3-methyl-9H-fluoren-9-one
(13a). Concd sulfuric acid (8.5 mL) was added to 11a
(195 mg, 0.71 mmol) and the solution was stirred for 1 h.
Then water was added and aqueous solution was extracted
with CH2Cl2 (3ꢂ50 mL). The organic layers were dried
(Na2SO4) and filtered, and the solvent was removed in va-
cuo. The residue was purified by chromatography (silica
1
solid (38 mg, 55%). H NMR (300 MHz, CDCl3): d¼2.04
(s, 3H, CH3), 2.19 (s, 3H, CH3), 6.98–7.05 (m, 1H, Ar),

12574
M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
J. Chem. Soc., Perkin Trans. 1 1983, 413; (d) Elix, J. A.;
Jenie, U. A.; Arvidsson, L.; Joergensen, P. M.; James, P. W.
Aust. J. Chem. 1986, 39, 719; (e) Nielsen, J.; Nielsen, P. H.;
Frisvad, J. C. Phytochemistry 1999, 50, 263.
7.13–7.18 (m, 1H, Ar), 7.85–7.89 (m, 1H, Ar), 8.58 (s, 1H,
OH). 13C NMR (75 MHz, CDCl3): d¼9.8, 15.2 (CH3),
109.6 (CH), 114.3 (C), 118.3 (CH), 119.6 (C), 123.5 (CH),
125.8, 133.9, 134.8, 136.9, 148.4, 152.4 (C), 161.5 (d,
1J¼251.0 Hz, CF), 191.7 (C]O). GC–MS (EI, 70 eV): m/z
(%)¼278 ([M]+, [37Cl], 50), 276 ([M]+, 100), 261 (16),
241 (31), 213 (12), 183 (25), 170 (11), 138 (6), 91 (7).
HRMS (EI) calcd for C15H10ClFO2 ([M]+, [35Cl]):
276.03479; found: 276.03433.
2. (a) Sakata, K.; Masago, H.; Sakurai, A.; Takahashi, N.
Tetrahedron Lett. 1982, 23, 2095; (b) Tomozane, H.;
Takeuchi, Y.; Choshi, T.; Kishida, S.; Yamato, M. Chem.
Pharm. Bull. 1990, 38, 925; (c) Belofsky, G. N.; Gloer,
K. B.; Gloer, J. B.; Wicklow, D. T.; Dowd, P. F. J. Nat. Prod.
1998, 61, 1115.
3. Steyn, P.; Vleggaar, G. J. Chem. Soc., Perkin Trans. 1 1974,
2250.
4. See for example 6-demethylchlortetracyclin: Olack, G.;
Morrison, H. J. Org. Chem. 1991, 56, 4969.
5. Nozawa, K.; Nakajima, S.; Yamada, M.; Kawai, K.-i. Chem.
Pharm. Bull. 1980, 28, 1622.
6. (a) Wei, S.; Chu, J. Experientia 1974, 30, 174; (b) Sasaki, H.;
Hosokawa, T.; Sawada, M.; Ando, K. J. Antibiot. 1973, 26,
676; (c) Hunter, R.; Mellows, G. Tetrahedron Lett. 1978, 19,
5051.
7. (a) Kwon, H. J.; Yoshida, M.; Abe, K.; Horinouchi, S.; Beppu,
T. Biosci. Biotechnol. Biochem. 1992, 56, 538; (b) Lampilas,
M.; Lett, R. Tetrahedron Lett. 1992, 33, 777; (c) Elix, J. A.;
Barclay, C. E.; Lumbsch, H. T.; Wardlaw, J. H. Aust. J.
Chem. 1997, 50, 971; Bazzanin: (d) Martin, U.; Zapp, J.;
Becker, H. Phytochemistry 1998, 47, 89.
8. Zhang, H.-W.; Huang, W.-Y.; Song, Y.-C.; Chen, J.-R.; Tan,
R.-X. Helv. Chim. Acta 2005, 88, 2861.
9. Flambamycin: (a) Ollis, W. D.; Smith, C.; Wrigth, D. E.
Tetrahedron 1979, 35, 105; Everninomicin: (b) Schering Co.,
Kenilworth, N.J. (USA). U.S. Patent 3,920,629, 1975; Chem.
Abstr. 1975, 84, 90526.
3.2.25. 4,7-Dichloro-1-hydroxy-3-methyl-9H-fluoren-9-
one (13e). Concd sulfuric acid (3.3 mL) was added to 11h
(85 mg, 0.27 mmol) and the solution was stirred for 1 h.
Then water was added and the aqueous solution was ex-
tracted with CH2Cl2 (3ꢂ50 mL). The organic layers were
dried (Na2SO4) and filtered, and the solvent was removed
in vacuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc 30:1/20:1) to give 13e as yellow
1
solid (65 mg, 84%). H NMR (300 MHz, CDCl3): d¼2.31
(s, 3H, CH3), 6.63 (s, 1H, Ar), 7.44 (dd, J¼8.1, 2.1 Hz, 1H,
Ar), 7.53 (m, 1H, Ar), 8.00 (d, J¼8.0 Hz, 1H, Ar), 8.35 (s,
1H, OH). 13C NMR (75 MHz, CDCl3): d¼21.3 (CH3),
117.4 (C), 120.8 (CH), 122.2 (C), 124.7, 125.8, 135.4 (CH),
135.9, 136.6, 139.2, 141.4, 148.5, 156.2 (C), 193.7 (C]O).
37
GC–MS (EI, 70 eV): m/z (%)¼282 ([M]+, [2ꢂ Cl], 15),
280 ([M]+, [37Cl], [35Cl], 65), 278 ([M]+, [2ꢂ Cl] 100),
35
251 (11), 215 (12), 186 (24), 152 (57), 137 (8/), 123 (12),
107 (21), 93 (17), 75 (9). HRMS (EI) calcd for C14H8Cl2O2
35
([M]+, [2ꢂ Cl]): 277.98959; found: 277.98973.
3.2.26. 4,7-Dichloro-1-hydroxy-2,3-dimethyl-9H-fluoren-
9-one (13f). Concd sulfuric acid (2.76 mL) was added to 11i
(74 mg, 0.23 mmol) and the solution was stirred for 1 h.
Then water was added and the aqueous solution was ex-
tracted with CH2Cl2 (3ꢂ50 mL). The organic layers were
dried (Na2SO4) and filtered, and the solvent was removed
in vacuo. The residue was purified by chromatography (silica
gel, n-heptane/EtOAc 30:1/20:1) to give 13f as yellow
10. Oda, T.; Yamaguchi, Y.; Sato, Y. Chem. Pharm. Bull. 1986, 34,
858.
11. 4-O-Methylarmillaridin: (a) Donnelly, D. M. X.; Hutchinson,
R. M. Phytochemistry 1990, 29, 179; Melledonal B: (b)
Arnone, A.; Cardillo, R.; Nasini, G.; Meille, S. V. J. Chem.
Soc., Perkin Trans. 1 1988, 503.
1
12. (a) Jinno, S.; Hata, K.; Shimidzu, N.; Okita, T. J. Antibiot.
1998, 51, 508; (b) Jinno, S.; Okita, T. Chem. Pharm. Bull.
1998, 46, 1688; (c) Papendorf, O.; Koenig, G. M.; Wright,
A. D. Phytochemistry 1998, 49, 2383; (d) Bohlmann, F.;
Knauf, W.; Misra, L. N. Tetrahedron 1984, 40, 4987;
Methoxymicareic acid: (e) Elix, J. A.; Jones, A. J.; Lajide,
L.; Coppins, B. J.; James, P. W. Aust. J. Chem. 1984, 37, 2349.
13. Falch, B. S.; Koenig, G. M.; Wright, A. D.; Sticher, O. J. Org.
Chem. 1993, 58, 6570.
14. Metal-Catalyzed Cross-Coupling Reactions; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, 2004.
15. (a) Harkal, S.; Kumar, K.; Michalik, D.; Zapf, A.; Jackstell, R.;
Rataboul, F.; Riermeier, T.; Monsees, A.; Beller, M.
Tetrahedron Lett. 2005, 46, 3237 and references cited therein;
(b) Harkal, S.; Rataboul, F.; Zapf, A.; Fuhrmann, C.; Riermeier,
T. H.; Monsees, A.; Beller, M. Adv. Synth. Catal. 2004, 346,
1742.
solid (50 mg, 74%). H NMR (300 MHz, CDCl3): d¼2.11
(s, 3H, CH3), 2.27 (s, 3H, CH3), 7.36 (dd, J¼8.1, 2.1 Hz,
1H, Ar), 7.49–7.50 (m, 1H, Ar), 7.94–7.97 (m, 1H, Ar),
8.58 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼12.3,
17.6 (CH3), 116.5, 123.1 (C), 124.6, 125.7 (CH), 128.8
(C), 134.4 (C), 135.3, 136.3, 136.5, 141.8, 145.9, 154.9
(C), 194.4 (C]O).GC–MS (EI, 70 eV): m/z (%)¼296
37
([M]+, [2ꢂ Cl], 15), 294 ([M]+, [37Cl], [35Cl], 65), 292
35
([M]+, [2ꢂ Cl], 277 (10), 257 (15), 229 (9), 199 (5), 165
(11), 150 (6), 111 (7), 82 (10).
Acknowledgements
Financial support from the state of Pakistan (HEC scholar-
ship for M.A.Y., I.H., and I.I.), and from the state of
Mecklenburg-Vorpommern (scholarship for Z.A.) is grate-
fully acknowledged.
16. (a) Savard, J.; Brassard, P. Tetrahedron Lett. 1979, 20, 4911;
(b) Corral, C.; Lissavetzky, J.; Manzanares, I. Synthesis
1997, 29.
References and notes
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18. For a review of 1,3-bis(silyl enol ethers), see: Langer, P.
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1. (a) Sala, T.; Sargent, M. V. J. Chem. Soc., Perkin Trans. 1 1981,
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M. A. Yawer et al. / Tetrahedron 63 (2007) 12562–12575
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20. Ahmed, Z.; Langer, L. Tetrahedron Lett. 2006, 47, 417.
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25. CCDC-654466 (11a), CCDC-654467 (11c), and CCDC-
652984 (12d) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
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