Synthesis of 2-benzoyl-4-(2-hydroxybenzoyl)phenols by catalytic domino 'Michael-retro-Michael-Mukaiyama-aldol' reactions of 1-aryl-1,3-bis(silyloxy)buta-1,3-dienes with 3-formylchromones

Article abstract of DOI:10.1016/j.tet.2007.10.116

The domino reaction of 1-aryl-1,3-bis(silyloxy)buta-1,3-dienes with 3-formylbenzopyrylium triflates, in situ generated from 3-formylchromones, afforded a variety of 2-benzoyl-4-(2-hydroxybenzoyl)phenols.

Full text of DOI:10.1016/j.tet.2007.10.116

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 894e900
www.elsevier.com/locate/tet
Synthesis of 2-benzoyl-4-(2-hydroxybenzoyl)phenols by catalytic domino
‘Michaeleretro-MichaeleMukaiyama-aldol’ reactions of 1-aryl-1,3-
bis(silyloxy)buta-1,3-dienes with 3-formylchromones
Mirza A. Yawer a, Ibrar Hussain a, Christine Fischer b, Helmar Gorls c, Peter Langer a,b,
*
¨
a Institut fu¨r Chemie, Universita¨t Rostock, Albert-Einstein-Strasse 3a, 18059 Rostock, Germany
b Leibniz-Institut fu¨r Katalyse an der Universita¨t Rostock e.V., Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
c Institut fu¨r Anorganische und Analytische Chemie, Universita¨t Jena, August-Bebel-Strasse 2, 07740 Jena, Germany
Received 27 July 2007; received in revised form 26 October 2007; accepted 26 October 2007
Available online 26 November 2007
Abstract
The domino reaction of 1-aryl-1,3-bis(silyloxy)buta-1,3-dienes with 3-formylbenzopyrylium triflates, in situ generated from 3-formylchro-
mones, afforded a variety of 2-benzoyl-4-(2-hydroxybenzoyl)phenols.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
development of new synthetic strategies is of considerable
importance in organic and medicinal chemistries.
Functionalized benzophenones occur in a variety of natural
products and represent important core structures for the devel-
opment of pharmaceuticals.1e3 For example, 2-hydroxy- and
2-aminobenzophenones are promising candidates for antican-
cer therapy, due to their antitubulin activity. Functionalized
benzophenones also represent important technical products.
They are used as photosensitizers4 and as active ingredients
of commercial agents, which protect the skin or color against
UV irradiation.5 Benzophenones are available by reaction of
organometallic reagents with aldehydes and subsequent oxida-
tion. A recent modification of this approach involves the SmI2
mediated reaction of benzaldehydes with benzylhalides and
subsequent oxidation.6 Other benzophenone syntheses rely
on FriedeleCrafts acylations.7 However, these methods often
give unsatisfactory results for the synthesis of functionalized
benzophenones (e.g., containing a hydroxy, halide, or ester
group), due to competing side reactions. Therefore, the
3-Formylchromone represents a useful building block for the
synthesis of a great variety of (2-hydroxybenzoyl)hetarenes.8
These reactions generally proceed by cyclization of 3-formyl-
chromone with a bis(nucleophile), which involves cleavage of
the chromone moiety. Reactions of 3-formylchromone with
carbon nucleophiles are relatively rare. For example, the reac-
tion of 3-formylchromones with enamines was reported to
give (2-hydroxybenzoyl)pyridines.9 The reaction of 3-formyl-
chromone with 1,3-dicarbonyl compounds was reported to
give open-chain products by simple attack of the central carbon
atom of the nucleophile onto the aldehyde (aldol condensa-
tion).10 The employment of acetylacetone resulted in a C,C-
cyclization with concurrent cleavage of the chromone moiety
to give a benzophenone in low yield.11 Besides the low yield,
the reaction proved to be not general. Recently, we reported12
a new approach to 4-(2-hydroxybenzoyl)salicylates based on
a new domino reaction of 1,3-bis-silyl enol ethers13,14 with
3-(formyl)benzopyrylium triflates,15 which are in situ generated
by reaction of 3-formylchromones with trimethylsilyl-trifluoro-
methanesulfonate (Me3SiOTf). Herein, we report the synthesis
of 2-benzoyl-4-(2-hydroxybenzoyl)phenols, which can be re-
garded as functionalized ‘bis(benzophenones)’. These products
* Corresponding author. Fax: þ381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.116

M.A. Yawer et al. / Tetrahedron 64 (2008) 894e900
895
are not readily available by other methods. The reactions
reported herein are carried out under mild conditions using
catalytic amounts of trimethylsilyl-trifluoromethanesulfonate
(Me3SiOTf).
afforded the 2-benzoyl-4-(2-hydroxybenzoyl)phenols 3pe3r,
respectively.
Me3SiO
OSiMe3
The Me3SiOTf catalyzed reaction of 6-methyl-3-formyl-
chromone (2a) with 1-phenyl-1,3-bis(trimethylsilyloxy)-1,3-
butadiene (1a), readily available from benzoylacetone,16
afforded the hydroxylated bis(benzophenone) 3a. The forma-
tion of 3a can be explained by a domino ‘Michaeleretro-Mi-
chaeleMukaiyama-aldol’ reaction (Scheme 1). The reaction
of 6-methyl-3-formylchromone with Me3SiOTf afforded the
benzopyrylium triflate A. The reaction of A with the terminal
carbon atom of 1a gave intermediate B, which underwent
a retro-Michael reaction to give the polyketide C. An intramo-
lecular aldol reaction gave intermediate D, which was trans-
formed into 3a by elimination of siloxane.
O
O
R1
R1
1a-f
R3
R4
R2
R3
R2
i
O
O
OH
OH
R4
+
R5
3a-r
O
R5
2a-f
Scheme 2. Synthesis of 3aer: (i) Me3SiOTf (0.3 equiv), 20 ꢀC, 10 min; (ii) (1)
1aef (1.3 equiv), CH2Cl2, 0/20 ꢀC, 12 h; (2) HCl (10%).
Table 1
Products and yields
O
O
Me
1
2
3
R1
R2
R3
R4
R5
% (3)a
O
O
a
a
a
b
b
b
c
c
c
c
d
d
d
e
e
f
a
b
c
a
b
c
d
e
f
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
Me
iPr
Me
Me
Cl
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
34
37
31
36
34
38
30
27
35
37
38
35
44
39
28
32
34
36
36
O
i
Me
2a
OSiMe3
H
Me3SiO
H
OMe
OH
OH
a
d
e
OMe
OMe
3a
1a
Br
iPr
Cl
b
d
e
g
h
i
H
Me3SiOTf
O
+ H2O
H
F
H
F
Br
Et
SiMe3
O
O
O
O
f
j
H
F
Me3SiO
Me
e
k
l
F
H
H
H
H
H
H
H
H
H
Br
iPr
Cl
Me
b
d
e
F
+
OH
m
n
o
p
q
r
s
F
Me
_
O
OTf
SiMe3
Br
iPr
iPr
Me
Br
Cl
D
A
b
b
a
e
Me
_
e(CH)4e
e(CH)4e
e(CH)4e
e(CH)4e
Me3SiOTf
1a
f
_
+
f
SiMe3
OTf
f
d
O
O
O
O
O
O
Me3SiO
a
Me
Me
Isolated yields.
O
O
O
SiMe3
SiMe3
SiMe3
B
The structure of the products was established by spectro-
C
1
scopic methods. The H NMR spectra showed the presence
of two low field signals assigned to the intramolecular hydro-
gen bonds OeH/O. The structures of bis(benzophenones) 3i
and 3k were independently confirmed by crystal structure
analysis (Figs. 1 and 2).17 All bis(benzophenones) 3aes
show strong UV absorptions (see Section 2) and represent
potentially useful photosensitizers.
In conclusion, we reported the domino reaction of 1-aryl-
1,3-bis(silyloxy)buta-1,3-dienes with 3-formylbenzopyrylium
triflates, which were in situ generated from 3-formylchro-
mones. The products were isolated in only moderate yields.
This can be explained by the fact that not all of the 1,3-bis-
silyl enol ether was converted into product. Noteworthy, the
reactions reported provide a convenient access to a variety
of highly functionalized 2-benzoyl-4-(2-hydroxybenzoyl)phe-
nols under mild conditions. The products are not readily
available by other methods.
Scheme 1. Mechanism of the formation of 3a: (i) Me3SiOTf (0.3 equiv),
20 ꢀC, 10 min; (ii) (1) 1a (1.3 equiv), CH2Cl2, 0/20 ꢀC, 12 h; (2) HCl (10%).
The cyclization of 1,3-bis-silyl enol ether 1a with 6-iso-
propyl-3-formylchromone (2b) and 6,8-dimethyl-3-formylchro-
mone (2c) afforded the 2-benzoyl-4-(2-hydroxybenzoyl)phenols
3b and 3c, respectively (Scheme 2, Table 1). The cyclization
of 1-(2-methoxyphenyl)-1,3-bis(trimethylsilyloxy)buta-1,3-
diene (1b) with 3-formylchromones 2a, 2d, and 2e afforded
the bis(benzophenones) 3def, respectively. The cyclization
of 1-(4-fluorophenyl)- and 1-(2-fluorophenyl)-1,3-bis(tri-
methylsilyloxy)buta-1,3-diene (1c,d) with 3-formylchromones
2b, 2d, 2e, and 2f afforded the fluoro-substituted bis(benzo-
phenones) 3gem. Products 3n and 3o were prepared from 1-
(2-methylphenyl)-1,3-bis(trimethylsilyloxy)buta-1,3-diene (1e).
The cyclization of 1-(1-naphthyl)-1,3-bis(trimethylsilyloxy)-
buta-1,3-diene (1f) with 3-formylchromones 3a, 3b, and 3e

896
M.A. Yawer et al. / Tetrahedron 64 (2008) 894e900
(8 mL) was added, the solution was cooled to 0 ꢀC, and 1,3-
bis-silyl enol ether 1 (1.3 equiv) was added. The mixture
was stirred for 12 h at 20 ꢀC and was subsequently poured
into an aqueous solution of hydrochloric acid (10%). The
organic and the aqueous layers were separated and the latter
was extracted with CH2Cl2 (3ꢁ80 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, n-heptane/CH2Cl2¼
10:1/3:1).
2.2.1. (3-Benzoyl-4-hydroxyphenyl)-(2-hydroxy-5-
methylphenyl)methanone (3a)
Starting with 2a (188 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1a (398 mg, 1.3 mmol),
3a was isolated as a yellow viscous oil (118 mg, 34%). 1H NMR
(300 MHz, CDCl3): d¼2.19 (s, 3H, CH3), 6.85 (d, J¼8.2 Hz,
1H, Ar), 7.09 (d, J¼8.7 Hz, 1H, Ar), 7.16e7.26 (m, 2H, Ar),
7.41e7.44 (m, 2H, Ar), 7.48e7.53 (m, 1H, Ar), 7.60e7.63
(m, 2H, Ar), 7.81 (dd, J¼8.7, 2.1 Hz, 1H, Ar), 7.94e7.95
(m, 1H, Ar), 11.47 (s, 1H, OH), 12.35 (s, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼19.5 (CH3), 95.6 (C), 117.3 (CH),
117.4, 117.63 (C), 117.66, 125.9 (CH), 126.7 (C), 127.5
(CH), 127.7 (C), 128.0 (CH), 131.2 (C), 131.3, 131.5, 136.0,
136.1, 136.2 (CH), 159.9, 165.2 (C), 197.7, 200.2 (C]O). IR
(neat): ~n¼3061 (m), 3038 (m), 2959 (s), 2924 (s), 1630 (s),
1590 (s), 1480 (s), 1486 (m), 1408 (m), 1423 (m), 1350 (s),
1290 (s), 1256 (s), 1135 (m), 978 (m), 924 (w), 826 (s), 791
(s), 636 (m) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼221
(4.33), 257 (4.17), 340 (3.69). GCeMS (CI, 70 eV): m/z
(%)¼333 ([Mþ1]þ, 100), 285 (10), 257 (10), 225 (10), 189
(10), 93 (20). HRMS (CI) Calcd for C21H17O4 ([Mþ1]þ):
333.1121; found: 333.1116.
Figure 1. ORTEP plot of 3i.
Figure 2. ORTEP plot of 3k.
2.2.2. (3-Benzoyl-4-hydroxyphenyl)-(2-hydroxy-5-
2. Experimental section
isopropylphenyl)methanone (3b)
Starting with 2d (147 mg, 0.67 mmol), Me3SiOTf (39 mg,
0.18 mmol), and 1,3-bis-silyl enol ether 1a (270 mg,
0.83 mmol), 3b was isolated as a yellow viscous oil
(81 mg, 37%). 1H NMR (300 MHz, CDCl3): d¼1.05 (d,
J¼7.1 Hz, 6H, CH3), 2.67e2.76 (m, 1H, CH), 6.96 (d,
J¼8.3 Hz, 1H, Ar), 7.13 (d, J¼8.7 Hz, 1H, Ar), 7.27e7.31
(m, 2H, Ar), 7.40e7.45 (m, 2H, Ar), 7.49e7.54 (m, 1H, Ar),
7.60e7.61 (m, 1H, Ar), 7.62e7.63 (m, 1H, Ar), 7.84 (dd,
J¼8.7, 2.1 Hz, 1H, Ar), 8.01 (m, 1H, Ar), 11.55 (s, 1H, OH),
12.44 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼24.3
(2CH3), 33.6 (CH), 118.8 (CH), 118.9, 119.0 (C), 129.0
(2CH), 129.0 (2C), 129.3 (2CH), 130.3, 132.8, 135.0, 136.2
(CH), 137.5 (C), 137.6 (CH), 139.4 (C), 161.5, 166.8 (C),
199.1, 201.8 (C]O). IR (KBr): ~n¼2958 (m), 2922 (m), 2856
(w), 1632 (s), 1598 (s), 1481 (m), 1445 (w), 1355 (s), 1288
(m), 1255 (s), 1115 (w), 981 (w), 949 (w), 840 (w), 794 (m),
635 (w) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼218
(4.50), 263 (4.47), 341 (3.95). GCeMS (EI, 70 eV): m/z
(%)¼360 ([M]þ, 75), 345 (20), 281 (11), 225 (10), 197 (11),
172 (10), 163 (43), 147 (100), 101 (6), 77 (20), 51 (4). HRMS
(EI) Calcd for C23H20O4 ([M]þ): 360.1356; found: 360.1345.
2.1. General
All solvents were dried by standard methods and all reac-
tions were carried out under an inert atmosphere. For 1H
and 13C NMR, the deuterated solvents indicated were used.
Calibration of spectra was carried out on the solvent signals
(CDCl3: d 1H¼7.25, d 13C¼77.0; DMSO-d6: d 1H¼2.50,
d
13C¼39.7). The NMR signals were assigned by DEPT and
two-dimensional 1H,1H COSY, 1H,1H NOESY, and 1H,13C
correlation spectra (HSQC, HMBC). Mass spectrometric
data (MS) were obtained by electron ionization (70 eV),
chemical ionization (CI, H2O), or electrospray ionization
(ESI). For preparative scale chromatography, silica gel (60e
200 mesh) was used. Melting points are uncorrected. Formyl-
chromones 2aef are commercially available.
2.2. General procedure 1 (synthesis of benzophenones)
To 3-formylchromone 2 (1.0 equiv) was added Me3SiOTf
(0.3 equiv) at 20 ꢀC. After stirring for 10 min, CH2Cl2

M.A. Yawer et al. / Tetrahedron 64 (2008) 894e900
897
2.2.3. (3-Benzoyl-4-hydroxyphenyl)-(2-hydroxy-3,5-
dimethylphenyl)methanone (3c)
NMR (75 MHz, CDCl3): d¼55.0 (OCH3), 110.9 (CH),
117.9, 118.6 (C), 119.1, 119.9 (CH), 122.2 (C), 125.8 (CH),
126.8 (C), 127.7 (2CH), 130.5 (C), 131.6, 134.9, 135.2,
136.1 (CH), 155.6, 160.4, 165.3 (C), 196.6, 200.8 (C]O).
IR (KBr): ~n¼3433 (w), 2960 (s), 2924 (s), 2853 (s), 1634
(s), 1590 (m), 1465 (m), 1433 (w), 1354 (m), 1281 (w),
Starting with 5e (139 mg, 0.6 mmol), Me3SiOTf (39 mg,
0.18 mmol), and 1,3-bis-silyl enol ether 1a (239 mg,
0.78 mmol), 3c was isolated as a yellow solid (70 mg, 31%),
mp¼116e118 ꢀC. 1H NMR (300 MHz, CDCl3): d¼2.86
(br s, 6H, CH3), 7.07 (s, 1H, Ar), 7.10 (m, 2H, Ar), 7.39e
7.43 (m, 2H, Ar), 7.47e7.53 (m, 1H, Ar), 7.60e7.63 (m,
2H, Ar), 7.80 (dd, J¼8.5, 1.9 Hz, 1H, Ar), 7.93 (m, 1H, Ar),
11.77 (s, 1H, OH), 12.34 (s, 1H, OH). 13C NMR (75 MHz,
CDCl3): d¼14.5, 19.5 (CH3), 116.9, 117.3 (C), 117.5, 125.9
(CH), 126.0, 126.3 (C), 127.5, 128.0 (CH), 128.1 (2C),
129.0, 131.2, 131.4, 134.6, 136.1, 137.2 (CH), 158.0, 165.1
(C), 198.0, 200.2 (C]O). IR (KBr): ~n¼2960 (m), 2923 (m),
2867 (w), 1633 (s), 1597 (s), 1433 (m), 1445 (w), 1355 (s),
1318 (w), 1288 (s), 1256 (s), 1215 (s), 1139 (m), 1049 (w),
795 (s) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼218
(4.51), 262 (4.40), 340 (4.00). GCeMS (EI, 70 eV): m/z
(%)¼346 ([M]þ, 56), 148 (100), 120 (36), 105 (14), 91 (12),
77 (26), 65 (4). HRMS (EI) Calcd for C22H18O4
([M]þ):346.1199; found: 346.1202.
1260 (s), 1100 (s), 1019 (s), 802 (s), 754 (w), 637 (w) cmꢂ1
.
UVevis (nm, CH3CN): lmax (log 3)¼218 (4.20), 256 (3.97),
337 (3.32). MS (EI, 70 eV): m/z (%)¼384 ([M]þ, [37Cl],
37), 382 ([M]þ, [35Cl], 92), 367 (22), 353 ([37Cl], 51), 351
([35Cl], 100), 249 ([37Cl], 51), 247 ([35Cl], 24), 210 (32),
197 (96), 157 ([37Cl], 19), 155 ([35Cl], 68), 147 (44), 135
(86), 108 (64), 97 (32), 83 (32), 77 (43), 57 (57), 43 (12).
HRMS (EI) Calcd for C21H15O5Cl ([M]þ, 35Cl): 382.0602;
found: 382.0602.
2.2.6. (5-Bromo-2-hydroxyphenyl)[4-hydroxy-3-
(2-methoxybenzoyl)phenyl]methanone (3f)
Starting with 2c (253 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1b (437 mg,
1.3 mmol), 3f was isolated as yellow solid (163 mg, 38%),
mp¼151e152 ꢀC. 1H NMR (250 MHz, CDCl3): d¼3.78
(s, 3H, OCH3), 6.86 (d, J¼8.5 Hz, 1H, Ar), 6.96e6.99
(m, 2H, Ar), 7.10 (d, J¼8.5 Hz, 1H, Ar), 7.26 (dd, J¼7.6,
1.9 Hz, 1H, Ar), 7.38e7.48 (m, 2H, Ar), 7.55e7.56 (m, 1H,
Ar), 7.70e7.71 (m, 1H, Ar), 7.81 (dd, J¼7.4, 2.1 Hz, 1H,
Ar), 11.61 (s, 1H, OH), 12.59 (s, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼56.4 (OCH3), 110.0 (C), 112.4, 119.2
(CH), 119.9, 120.6 (C), 120.9, 121.3 (CH), 127.1, 128.2 (C),
129.1, 133.0, 134.9, 136.6, 137.5, 139.1 (CH), 157.0, 162.2,
166.7 (C), 198.0, 202.2 (C]O). IR (KBr): ~n¼3441 (m),
2958 (m), 2923 (s), 2852 (m), 1637 (s), 1596 (s), 1480 (m),
1464 (s), 1431 (w), 1342 (m), 1320 (s), 1285 (s), 1160 (w),
1102 (m), 1024 (m), 839 (w), 795 (s) cmꢂ1. UVevis (nm,
CH3CN): lmax (log 3)¼218 (3.90), 255 (3.64), 336 (3.19).
MS (EI, 70 eV): m/z (%)¼428 ([M]þ, [81Br], 62), 426
([M]þ, [79Br], 60), 397 ([81Br], 81), 395 ([79Br], 82), 293
([81Br], 12), 291 ([79Br], 13), 197 (100), 173 (7), 147 (31),
135 (57), 108 (37), 77 (27), 57 (19), 43 (15). HRMS (EI)
Calcd for C21H15O5Br ([M]þ, 79Br): 426.0097; found:
426.0088. Anal. Calcd for C21H15O5Br (426.00, 79Br): C
59.21, H 3.55; found: C 59.29, H 3.89.
2.2.4. [4-Hydroxy-3-(2-methoxybenzoyl)phenyl]-
(2-hydroxy-5-methylphenyl)methanone (3d)
Starting with 2a (188 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1b (437 mg, 1.3 mmol),
1
3d was isolated as a yellow viscous oil (131 mg, 36%). H
NMR (300 MHz, CDCl3): d¼2.15 (s, 3H, CH3), 3.72 (s, 3H,
OCH3), 6.84e6.88 (m, 1H, Ar), 6.96 (d, J¼8.5 Hz, 1H, Ar),
7.01 (dd, J¼7.6, 1.5 Hz, 1H, Ar), 7.08 (d, J¼8.8 Hz, 1H,
Ar), 7.18e7.27 (m, 3H, Ar), 7.41 (ddd, J¼8.5, 8.5, 1.8 Hz,
1H, Ar), 7.73 (m, 1H, Ar), 7.80 (dd, J¼8.8, 2.1 Hz, 1H, Ar),
11.54 (s, 1H, OH), 12.53 (s, 1H, OH). 13C NMR (75 MHz,
CDCl3): d¼20.9 (CH3), 56.2 (OCH3), 112.2, 118.6, 118.7
(CH), 119.0, 120.0 (C), 121.1 (CH), 127.3, 128.0 (C), 129.1
(CH), 132.7 (C), 132.8, 132.9, 136.5, 137.5, 137.7 (CH),
157.0, 161.2, 166.2 (C), 199.0, 202.3 (C]O). IR (neat):
~n¼2957 (s), 2934 (s), 2853 (s), 1731 (m), 1670 (w), 1603
(s), 1491 (s), 1446 (s), 1464 (s), 1363 (m), 1286 (m), 1258
(s), 1184 (m), 1163 (m), 1079 (m), 1024 (m), 847 (w), 754
(m), 647 (w) cmꢂ1. MS (EI, 70 eV): m/z (%)¼362 ([M]þ,
71), 347 (5), 331 (27), 227 (18), 197 (23), 167 (8), 149 (23),
135 (100), 77 (18), 57 (14), 43 (12). HRMS (EI) Calcd for
C22H18O5 ([M]þ): 362.1149; found: 362.1139.
2.2.7. [3-(4-Fluorobenzoyl)-4-hydroxyphenyl]-(2-hydroxy-
5-isopropylphenyl)methanone (3g)
2.2.5. (5-Chloro-2-hydroxyphenyl)-[4-hydroxy-3-
(2-methoxybenzoyl)phenyl]methanone (3e)
Starting with 4b (208 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1b (437 mg, 1.3 mmol),
1
6e was isolated as a yellow viscous oil (121 mg, 34%). H
NMR (300 MHz, CDCl3): d¼3.85 (s, 3H, OCH3), 6.92
(d, J¼8.9 Hz, 1H, Ar), 6.97 (d, J¼8.4 Hz, 1H, Ar), 7.11
(d, J¼8.8 Hz, 1H, Ar), 7.19 (s, 1H, Ar), 7.26 (dd, J¼7.5,
2.5 Hz, 1H, Ar), 7.34 (dd, J¼8.9, 2.6 Hz, 1H, Ar), 7.39e
7.45 (m, 2H, Ar), 7.70e7.71 (m, 1H, Ar), 7.83 (dd, J¼8.7,
2.3 Hz, 1H, Ar), 11.60 (s, 1H, OH), 12.58 (s, 1H, OH). 13C
Starting with 2d (216 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1c (421 mg,
1.3 mmol), 3g was isolated as a yellow solid (115 mg, 30%),
1
mp¼134e136 ꢀC. H NMR (300 MHz, CDCl3): d¼1.06 (d,
J¼7.1 Hz, 6H, CH3), 2.72 (m, 1H, CH), 6.92 (d, J¼8.4 Hz,
1H, Ar), 7.08e7.13 (m, 3H, Ar), 7.26 (m, 1H, Ar), 7.30
(dd, J¼8.5, 2.5 Hz, 1H, Ar), 7.64e7.69 (m, 2H, Ar), 7.84
(dd, J¼8.5, 2.1 Hz, 1H, Ar), 7.97e7.98 (m, 1H, Ar), 11.52
(s, 1H, OH), 12.28 (s, 1H, OH). 13C NMR (75 MHz,
CDCl3): d¼22.9 (2CH3), 32.7 (CH), 114.8, 115.1, 117.4,
117.6 (CH), 127.8 (C), 128.8, 130.6, 130.7 (CH), 132.2,

898
M.A. Yawer et al. / Tetrahedron 64 (2008) 894e900
132.3 (C), 133.7, 134.4, 136.2 (CH), 138.0, 160.1, 162.5,
165.2, 165.9 (C), 197.5, 198.6 (C]O). IR (neat): ~n¼3062
(w), 2959 (m), 2871 (m), 1635 (w), 1472 (w), 1201 (w),
1158 (m), 1110 (m), 1073 (m), 871 (m), 852 (m), 793 (m),
638 (m) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼218
(4.65), 263 (4.50), 340 (4.12). MS (EI, 70 eV): m/z (%)¼378
([M]þ, 47), 363 (12), 162 (43), 147 (100), 123 (11), 91 (13),
69 (7), 57 (6). HRMS (EI) Calcd for C23H19O4F: 378.1262;
found: 378.1257.
2.2.10. (5-Ethyl-2-hydroxyphenyl)-[3-(4-fluorobenzoyl)-4-
hydroxyphenyl]methanone (3j)
Starting with 2f (202 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1c (421 mg, 1.3 mmol),
3j was isolated as yellow viscous oil (135 mg, 37%). 1H NMR
(300 MHz, CDCl3): d¼1.06 (t, J¼7.6 Hz, 3H, CH3), 2.48
(q, J¼7.8 Hz, 2H, CH2), 6.89e6.92 (m, 1H, Ar), 7.09e7.14
(m, 3H, Ar), 7.25e7.29 (m, 2H, Ar), 7.65e7.70 (m, 2H,
Ar), 7.82e7.85 (m, 1H, Ar), 7.95e7.96 (m, 1H, Ar), 11.50
(s, 1H, OH), 12.24 (s, 1H, OH). 13C NMR (75 MHz,
CDCl3): d¼16.9 (CH3), 29.2 (CH2), 116.2, 116.5 (CH),
118.8 (C), 118.9, 119.0 (CH), 129.2 (2CH), 131.6, 132.1
(C), 132.2 (CH), 133.6 (C), 134.7 (2CH), 135.7 (CH), 136.6,
137.6, 161.5, 166.5 (C), 199.0, 200.0 (C]O). IR (neat):
~n¼3063 (w), 2964 (m), 2930 (m), 2872 (w), 1631 (s), 1599
(s), 1481 (s), 1409 (w), 1351 (s), 1292 (s), 1255 (s), 1214
(s), 1157 (s), 1073 (w), 882 (w), 844 (s), 612 (w) cmꢂ1. MS
(CI, 70 eV): m/z (%)¼365 ([Mþ1]þ, 100), 340 (10), 303
(7), 243 (8), 177 (20), 149 (25), 133 (20), 96 (10). HRMS
(CI) Calcd for C22H18O4F ([MþH]þ): 365.11836; found:
365.11842.
2.2.8. (5-Chloro-2-hydroxyphenyl)-[3-(4-fluorobenzoyl)-4-
hydroxyphenyl]methanone (3h)
Starting with 2b (208 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1c (421 mg, 1.3 mmol),
3h was isolated as a yellow viscous oil (101 mg, 27%).
1H NMR (300 MHz, CDCl3): d¼6.95 (d, J¼8.7 Hz, 1H, Ar),
7.06e7.09 (m, 1H, Ar), 7.11e713 (m, 1H, Ar), 7.17 (d,
J¼7.1 Hz, 1H, Ar), 7.38 (dd, J¼8.7, 2.5 Hz, 1H, Ar), 7.49e
7.50 (m, 1H, Ar), 7.63e7.68 (m, 1H, Ar), 7.72e7.75
(m, 1H, Ar), 7.84 (dd, J¼8.6, 2.1 Hz, 1H, Ar), 7.96e7.97
(m, 1H, Ar), 11.51 (s, 1H, OH), 12.39 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼113.5, 113.9 (CH), 117.5 (C),
118.0 (CH), 118.5 (C), 119.2 (2CH), 122.3, 126.9, 127.4
(C), 131.7 (2CH), 134.7, 135.05 (CH), 135.08 (C), 135.9
(CH), 160.3, 165.6 (C), 195.5, 199.1 (C]O). IR (KBr):
~n¼2960 (w), 2925 (w), 1626 (s), 1581 (s), 1468 (m), 1255
(s), 1217 (s), 841 (s), 796 (m) cmꢂ1. UVevis (nm, CH3CN):
lmax (log 3)¼218 (4.30), 259 (4.06), 338 (3.64). MS
(CI, 70 eV): m/z (%)¼373 ([Mþ1]þ, [37Cl], 10), 371
([Mþ1]þ, [35Cl], 20), 342 ([37Cl], 14), 340 ([35Cl], 28), 285
(18), 229 (20), 177 (100), 111 (8), 85 (12), 69 (20). HRMS
(CI) Calcd for C20H12O4ClF ([Mþ1]þ, 35Cl): 371.3142;
found: 371.3143.
2.2.11. (5-Bromo-2-hydroxyphenyl)-[3-(2-fluorobenzoyl)-4-
hydroxyphenyl]methanone (3k)
Starting with 2c (253 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1d (421 mg,
1.3 mmol), 3k was isolated as yellow solid (155 mg, 38%),
mp¼105 ꢀC. 1H NMR (300 MHz, CDCl3): d¼6.86 (d,
J¼8.3 Hz, 1H, Ar), 7.14 (d J¼8.7 Hz, 1H, Ar), 7.18e7.23
(m, 1H, Ar), 7.25e7.28 (m, 1H, Ar), 742e7.46 (m, 1H, Ar),
7.47 (m, 1H, Ar), 7.49e7.51 (m, 1H, Ar), 7.65e7.66
(m, 1H, Ar), 7.74e7.76 (m, 1H, Ar), 7.88 (dd, J¼8.5,
2.3 Hz, 1H, Ar), 11.55 (s, 1H, OH), 12.36 (s, 1H, OH). 13C
NMR (75.5 MHz, CDCl3): d¼110.6 (C), 116.8, 117.1 (CH),
119.2 (C), 119.7 (CH), 120.5 (C), 120.9, 125.6 (CH), 128.5,
130.5 (C), 134.9, 136.2, 136.3, 138.0, 139.2 (CH), 139.3,
162.2, 166.8 (C), 197.8, 198.6 (C]O). IR (neat): ~n¼3054
(w), 2956 (s), 2924 (s), 2852 (s), 1629 (s), 1590 (s), 1465
(s), 1418 (s), 1418 (s), 1304 (m), 1253 (s), 1208 (s), 1122
(s), 927 (m), 844 (s), 763 (s), 629 (m) cmꢂ1. UVevis (nm,
CH3CN): lmax (log 3)¼218 (4.50), 256 (4.23), 340 (3.79).
MS (EI, 70 eV): m/z (%)¼416 ([M]þ, [81Br], 97), 414
([M]þ, [79Br], 97), 397 ([81Br], 6), 395 ([79Br], 6), 216
([81Br], 71), 214 ([79Br], 71), 199 ([81Br], 100), 197 ([79Br],
100), 147 (47), 123 (51), 95 (22), 57 (11). HRMS (EI) Calcd
for C20H12O4BrF ([M]þ, 79Br): 413.9897; found: 413.9891.
2.2.9. (5-Bromo-2-hydroxyphenyl)-[3-(4-fluorobenzoyl)-4-
hydroxyphenyl]methanone (3i)
Starting with 2c (253 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1c (421 mg,
1.3 mmol), 3i was isolated as yellow solid (146 mg, 35%),
mp¼118e120 ꢀC. 1H NMR (300 MHz, CDCl3): d¼6.89
(d, J¼8.9 Hz, 1H, Ar), 7.14e7.19 (m, 3H, Ar), 7.50 (dd,
J¼8.9, 2.4 Hz, 1H, Ar), 7.65 (m, 1H, Ar), 7.67e7.72
(m, 2H, Ar), 7.86 (dd, J¼8.5, 2.1 Hz, 1H, Ar), 7.90e7.91
(m, 1H, Ar), 11.50 (s, 1H, OH), 12.33 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼110.6 (C), 116.3, 116.6 (CH),
118.5 (C), 119.8 (CH), 120.6 (C), 121.1 (CH), 128.3 (C),
132.1, 132.2 (CH), 133.4, 133.5 (C), 135.0, 136.0, 137.5,
139.2 (CH), 162.2, 167.1 (C), 197.9, 199.8 (C]O). IR
(KBr): ~n¼3069 (w), 2956 (m), 2900 (w), 1627 (s), 1585 (s),
1466 (s), 1341 (m), 1287 (m), 1253 (s), 1213 (s), 1072 (m),
843 (s), 610 (w) cmꢂ1. UVevis (nm, CH3CN): lmax
(log 3)¼218 (4.30), 259 (4.06), 338 (3.64). MS (EI, 70 eV):
m/z (%)¼416 ([M]þ, [81Br], 100), 414 ([M]þ, [79Br], 100),
319 (7), 243 (12), 216 ([81Br], 80), 214 ([79Br], 80), 200
([81Br], 96), 198 ([79Br], 96), 172 (10), 147 (67), 123 (75),
95 (55), 57 (25). HRMS (EI) Calcd for C20H12O4BrF ([M]þ,
79Br): 413.9897; found: 413.9897.
2.2.12. [3-(2-Fluorobenzoyl)-4-hydroxyphenyl]-(2-hydroxy-
5-isopropylphenyl)methanone (3l)
Starting with 2d (216 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1d (421 mg,
1.3 mmol), 3l was isolated as a yellow solid (130 mg, 35%),
1
mp¼105e107 ꢀC. H NMR (300 MHz, CDCl3): d¼0.86 (d,
J¼7.1 Hz, 6H, CH3), 2.25 (m, 1H, CH), 6.75 (d, J¼8.5 Hz,
1H, Ar), 6.95e6.98 (m, 1H, Ar), 7.01e7.07 (m, 3H, Ar),
7.12 (dd, J¼8.5, 2.3 Hz, 1H, Ar), 7.23e7.28 (m, 1H, Ar),
7.33e7.38 (m, 1H, Ar), 7.70e7.72 (m, 2H, Ar), 11.34 (s,

M.A. Yawer et al. / Tetrahedron 64 (2008) 894e900
899
1H, OH), 12.30 (s, 1H, OH). 13C NMR (75 MHz, CDCl3):
d¼24.9, 25.0 (CH3), 34.2 (CH), 117.3, 117.6, 119.4, 120.0
(CH), 120.5 (C), 124.0 (CH), 125.0 (C), 125.7 (CH), 126.4,
126.7, 130.1 (C), 131.0, 135.6, 136.5, 139.9 (CH), 140.1,
161.6, 167.0 (C), 199.4, 199.6 (C]O). IR (KBr): ~n¼3431
(w), 2960 (m), 2924 (w), 2868 (w), 1634 (s), 1612 (s), 1588
(s), 1483 (s), 1357 (s) 1251 (s), 1212 (s), 840 (m), 765 (s),
634 (m) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼218
(4.30), 258 (3.95), 339 (3.33). MS (EI, 70 eV): m/z (%)¼378
([M]þ, 13), 343 (5), 163 (25), 162 (29), 147 (100), 123 (68),
121 (7), 91 (31), 69 (14), 57 (19), 41 (19). HRMS (EI) Calcd
for C23H19O4F ([M]þ): 378.1262; found: 378.1257.
(w) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼252 (4.52),
330 (4.18). MS (EI, 70 eV): m/z (%)¼412 ([M]þ, [81Br],
52), 410 ([M]þ, [79Br], 51), 397 ([81Br], 16), 395 ([79Br],
17), 340 (2), 267 (15), 237 (11), 211 (100), 199 ([81Br], 33),
197 ([79Br], 31), 194 (22), 161 (10), 147 (22), 119 (52), 91
(63), 69 (22). HRMS (EI) Calcd for C21H15O4Br ([M]þ,
79Br): 410.0148; found: 410.0140.
2.2.15. (2-Hydroxy-5-isopropylphenyl)-[4-hydroxy-3-
(2-methylbenzoyl)phenyl]methanone (3o)
Starting with 2d (216 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1d (416 mg,
1.3 mmol), 3o was isolated as a yellow solid (105 mg, 28%),
2.2.13. (5-Chloro-2-hydroxyphenyl)-[3-(2-fluorobenzoyl)-4-
hydroxyphenyl]methanone (3m)
1
mp¼138e140 ꢀC. H NMR (300 MHz, CDCl3): d¼1.04 (d,
J¼7.1 Hz, 6H, CH3), 2.26 (s, 3H, CH3), 2.61e2.75
(m, 1H, CH), 6.88 (d, J¼8.5 Hz, 1H, Ar), 7.12 (d, J¼8.7 Hz,
1H, Ar), 7.17 (m, 1H, Ar), 7.18e7.19 (m, 2H, Ar), 7.22
(s, 1H, Ar), 7.24e7.25 (m, 1H, Ar), 7.27e7.31 (m, 1H, Ar),
7.68 (m, 1H, Ar) 7.84 (dd, J¼8.5, 2.1 Hz, 1H, Ar), 11.56 (s,
1H, OH), 12.65 (s, 1H, OH). 13C NMR (75.5 MHz, CDCl3):
d¼20.0 (CH3), 24.3 (2CH3), 33.6 (CH), 118.8, 119.2 (CH),
119.5 (C), 125.9, 127.7 (CH), 129.3 (C), 130.3, 131.0,
131.6, 135.0 (CH), 135.1, 136.0 (C), 136.2 (CH), 137.2 (C),
138.1 (CH), 139.4, 161.6, 166.8 (C), 199.0, 204.6 (C]O).
IR (KBr): ~n¼3430 (w), 3055 (w), 3029 (w), 2961 (m), 2924
(m), 2872 (w), 1632 (s), 1593 (s), 1483 (s), 1356 (s), 1316
(s), 1256 (s), 1211 (s), 1140 (w), 1118 (w), 1097 (w), 981
(w), 900 (w), 846 (w), 794 (s), 636 (m) cmꢂ1. UVevis (nm,
CH3CN): lmax (log 3)¼255 (4.20), 339 (3.80). MS (EI,
70 eV): m/z (%)¼374 ([M]þ, 78), 359 (19), 316 (3), 139 (5),
211 (16), 172 (8), 163 (48), 162 (46), 147 (100), 119 (10),
97 (8), 91 (26), 83 (10), 69 (18), 57 (16). HRMS (EI) Calcd
for C24H22O4 ([M]þ): 374.1513; found: 374.1505.
Starting with 2b (208 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1d (421 mg, 1.3 mmol),
3m was isolated as a yellow solid (163 mg, 44%), mp¼123e
1
125 ꢀC. H NMR (300 MHz, CDCl3): d¼6.91 (d, J¼8.9 Hz,
1H, Ar), 7.14 (d, J¼8.7 Hz, 1H, Ar), 7.18e7.19 (m, 1H,
Ar), 7.22e7.25 (m, 1H, Ar), 7.35 (dd, J¼8.9, 2.6 Hz, 1H,
Ar), 7.42e7.45 (m, 1H, Ar), 7.46e7.50 (m, 1H, Ar), 7.53
(m, 1H, Ar), 7.75e7.77 (m, 1H, Ar), 7.89 (dd, J¼8.9,
2.1 Hz, 1H, Ar), 11.53 (s, 1H, OH), 12.34 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼117.5, 117.8 (CH), 119.9, 120.0
(C), 120.6, 121.3, 124.6 (CH), 126.4, 126.6, 129.3 (C),
131.1, 132.8 (CH), 134.9 (C), 135.0, 137.2, 138.8 (CH),
162.5, 167.5 (C), 198.5, 199.3 (C]O). IR (neat): ~n¼3077
(w), 2956 (s), 2924 (s), 2853 (s), 1675 (s), 1633 (s), 1598
(s), 1466 (s), 1417 (s), 1253 (s), 1208 (s), 1140 (s), 1097
(m), 950 (m), 844 (s), 763 (s) cmꢂ1. UVevis (nm, CH3CN):
lmax (log 3)¼221 (4.41), 258 (4.27), 340 (3.82). MS (EI,
70 eV): m/z (%)¼372 ([M]þ, [37Cl], 38), 370 ([M]þ, [37Cl],
100), 340 ([37Cl], 8), 338 ([35Cl], 10), 267 (26), 243 (10),
216 (51), 197 (20), 177 (19), 155 (96), 147 (33), 123 (42),
95 (25), 57 (27). HRMS (EI) Calcd for C20H12O4ClF ([M]þ,
35Cl): 370.0403; found: 370.0402.
2.2.16. (2-Hydroxy-5-isopropylphenyl)-[4-hydroxy-3-
(1-naphthoyl)phenyl]methanone (3p)
Starting with 2d (216 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1f (463 mg, 1.3 mmol),
3p was isolated as a yellow viscous oil (130 mg, 32%).
1H NMR (300 MHz, CDCl3): d¼0.90 (d, J¼6.9 Hz, 6H,
CH3), 2.44e2.56 (m, 1H, CH), 7.11 (m, 1H, Ar), 7.16e7.18
(m, 1H, Ar), 7.19e7.22 (m, 1H, Ar), 7.41e7.44 (m, 1H,
Ar), 7.45 (m, 1H, Ar), 7.47 (m, 2H, Ar), 7.48e7.52 (m, 1H,
Ar), 7.74e7.75 (m, 1H, Ar), 7.82e7.84 (m, 1H, Ar), 7.85e
7.86 (m, 1H, Ar), 7.87e7.89 (m, 1H, Ar), 7.92 (dd, J¼7.6,
1.2 Hz, 1H, Ar), 11.52 (s, 1H, OH), 12.73 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼24.9 (2CH3), 33.4 (CH), 118.7,
119.3 (CH), 120.0 (C), 124.7, 125.2, 126.7, 127.2, 128.0,
129.0 (CH), 129.3 (C), 130.2 (CH), 130.6 (C), 131.8 (CH),
134.1, 134.9 (C), 135.0, 136.3, 138.2 (CH), 139.6, 161.5,
166.9, 189.6 (C), 198.8, 204.0 (C]O). IR (neat): ~n¼3058
(m), 2959 (s), 2926 (m), 2870 (m), 1630 (s), 1589 (s), 1508
(m), 1480 (s), 1354 (s), 1296 (m), 1252 (s), 1211 (s), 1146 (m),
2.2.14. (5-Bromo-2-hydroxyphenyl)-[4-hydroxy-3-
(2-methylbenzoyl)phenyl]methanone (3n)
Starting with 2c (253 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1e (416 mg,
1.3 mmol), 3n was isolated as a yellow solid (160 mg, 39%),
mp¼119e121 ꢀC. 1H NMR (300 MHz, CDCl3): d¼2.25
(s, 3H, CH3), 6.84 (d, J¼8.7 Hz, 1H, Ar), 7.13 (d, J¼7.7 Hz,
1H, Ar), 7.17 (m, 1H, Ar), 7.25e7.26 (m, 1H, Ar), 7.28
(m, 1H, Ar), 7.30e7.33 (m, 1H, Ar), 7.44 (dd, J¼8.9,
2.5 Hz, 1H, Ar), 7.52e7.53 (m, 1H, Ar), 7.64e7.65 (m, 1H,
Ar), 7.83 (dd, J¼8.5, 2.3 Hz, 1H, Ar), 11.54 (s, 1H, OH),
12.68 (s, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼20.5
(CH3), 110.5, 119.4 (C), 119.6 (CH), 120.5 (CH), 121.0,
126.0, 127.8 (CH), 128.3 (C), 131.2, 131.7, 134.9 (CH),
136.2, 136.5, 136.9 (C), 137.8, 139.1 (CH), 162.2, 167.2
(C), 197.8, 204.4 (C]O). IR (KBr): ~n¼3431 (w), 3064 (w),
3022 (w), 2957 (w), 2924 (w), 2854 (w), 1632 (s), 1597 (s),
1463 (s), 1381 (m), 1319 (s), 1255 (s), 1237 (m), 1209 (s),
1101 (w), 992 (w), 931 (m), 769 (m), 769 (s), 708 (w), 652
1129 (w), 1045 (w), 908 (m), 843 (s), 793 (s), 733 (s) cmꢂ1
.
GCeMS (EI, 70 eV): m/z (%)¼410 ([M]þ, 86), 395 (16),
247 (14), 197 (17), 163 (49), 147 (100), 127 (30), 91 (19),

900
M.A. Yawer et al. / Tetrahedron 64 (2008) 894e900
65 (5). HRMS (EI) Calcd for C27H22O4 ([M]þ): 410.1513;
found: 410.1512.
7.15e7.16 (m, 1H, Ar), 7.18 (s, 1H, Ar),), 7.28 (dd, J¼8.9,
2.5 Hz, 1H, Ar), 7.35 (m, 1H, Ar), 7.44e7.47 (m, 2H, Ar),
7.51e7.52 (m, 1H, Ar), 7.53 (s, 1H, Ar), 7.71e7.72 (m, 1H,
Ar), 7.81e7.83 (m, 1H, Ar), 7.85e7.86 (m, 1H, Ar), 7.91e
7.95 (m, 1H, Ar), 11.45 (s, 1H, OH), 12.73 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼119.6 (CH), 119.8, 120.0 (C),
120.5 (CH), 123.6 (C), 124.7, 125.2 (CH), 127.3 (2CH),
128.1 (CH), 128.3 (C), 129.0 (CH), 130.6 (C), 131.9, 132.1
(CH), 134.2, 134.6 (C), 136.3, 136.6, 137.9 (CH), 161.7,
167.3 (C), 197.9, 203.6 (C]O). MS (CI, 70 eV): m/z
(%)¼405 ([Mþ1]þ, [37Cl], 50), 403 ([Mþ1]þ, [37Cl], 100),
285 (10), 257 (12), 229 (10), 177 (13), 125 (14), 97 (15), 85
(20), 69 (21). HRMS (CI) Calcd for C24H16O4Cl ([Mþ1]þ,
35Cl): 403.0732; found: 403.0731.
2.2.17. (2-Hydroxy-5-methylphenyl)-[4-hydroxy-3-(1-
naphthoyl)phenyl]methanone (3q)
Starting with 2a (188 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1f (463 mg,
1.3 mmol), 3q was isolated as a yellow solid (130 mg, 34%),
1
mp¼112e114 ꢀC. H NMR (300 MHz, CDCl3), d¼2.00 (s,
3H, CH3), 6.77 (d, J¼8.4 Hz, 1H, Ar), 7.06e7.07 (m, 1H,
Ar), 7.08e7.11 (m, 1H, Ar), 7.13 (m, 1H, Ar), 7.41e7.42
(m, 1H, Ar), 7.43 (m, 1H, Ar), 7.44e7.47 (m, 2H, Ar),
7.68e7.69 (m, 1H, Ar), 7.78e7.80 (m, 1H, Ar), 7.81e7.82
(m, 1H, Ar), 7.83e7.85 (m, 1H, Ar), 7.89 (dd, J¼7.6,
1.5 Hz, 1H, Ar), 11.42 (s, 1H, OH), 12.65 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼19.3 (CH3), 117.2 (CH), 117.3
(C), 117.7 (CH), 118.6 (C), 123.2, 123.8, 125.4, 125.8,
126.6, 127.5 (CH), 127.7, 129.1 (C), 130.4, 131.2 (CH),
132.2, 133.5 (C), 135.0, 136.1, 136.7 (CH), 159.8, 165.4,
188.1 (C), 197.3, 202.4 (C]O). UVevis (nm, CH3CN):
lmax (log 3)¼222 (4.88), 256 (4.32), 341 (4.02). GCeMS
(CI, 70 eV): m/z (%)¼383 ([Mþ1]þ, 100), 305 (5), 267 (4),
229 (3), 177 (5), 122 (3), 88 (3). HRMS (CI) Calcd for
C25H19O4 ([Mþ1]þ): 383.1278: found: 383.1297.
Acknowledgements
Financial support by the State of Pakistan (HEC scholar-
ships for M.A.Y. and I.H.) is gratefully acknowledged.
References and notes
1. Liou, J.-P.; Chang, J.-Y.; Chang, C.-W.; Chang, C.-Y.; Mahindroo, N.;
Kuo, F.-M.; Hsieh, H.-P. J. Med. Chem. 2004, 47, 2897.
2. Liou, J.-P.; Chang, C.-W.; Song, J. S.; Yang, Y. S.; Yeh, C. F.; Tseng,
H. Y.; Lo, Y. K.; Chang, C.-L.; Chang, C.-M.; Hsieh, H.-P. J. Med.
Chem. 2002, 45, 2556.
2.2.18. (5-Bromo-2-hydroxyphenyl)-[4-hydroxy-3-
(1-naphthoyl)phenyl]methanone (3r)
Starting with 2c (253 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1f (463 mg,
1.3 mmol), 3r was isolated as a yellow solid (166 mg, 36%),
mp¼125e127 ꢀC. 1H NMR (300 MHz, CDCl3): d¼6.79
(d, J¼8.9 Hz, 1H, Ar), 7.14e7.15 (m, 1H, Ar), 7.17 (s, 1H,
Ar) 7.38 (m, 1H, Ar), 7.41e7.43 (m, 1H, Ar), 7.44e7.45
(m, 1H, Ar), 7.49e750 (m, 1H, Ar), 7.52e7.53 (m, 1H, Ar),
7.71e7.72 (m, 1H, Ar), 7.80e7.82 (m, 1H, Ar), 7.83e7.84
(m, 1H, Ar), 7.85e7.88 (m, 1H, Ar), 7.92 (dd, J¼7.3,
1.9 Hz, 1H, Ar), 11.46 (s, 1H, OH), 12.74 (s, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼109.1 (C), 118.2 (CH), 118.5,
119.0 (C), 119.5, 123.3, 123.8, 125.7, 125.8, 126.6 (CH),
126.8 (C), 127.6 (CH), 129.2 (C), 130.7 (CH), 132.8, 133.1
(C), 133.5, 135.1, 136.5, 137.7 (CH), 160.7, 165.9 (C),
196.4, 202.2 (C]O). IR (KBr): ~n¼3047 (w), 2957 (w),
2924 (w), 2853 (w), 1626 (s), 1588 (s), 1507 (w), 1464 (s),
1336 (s), 1251 (s), 1209 (s), 1045 (w), 915 (s), 777
(s) cmꢂ1. UVevis (nm, CH3CN): lmax (log 3)¼257 (3.89),
339 (3.48). GCeMS (EI, 70 eV): m/z (%)¼448 ([M]þ,
[81Br], 89), 446 ([M]þ, [79Br], 90), 368 (6), 249 ([81Br], 89),
247 ([79Br], 89), 231 (13), 155 (35), 128 (100), 63 (10).
HRMS (EI) Calcd for C24H15O4Br: 446.0148 ([M]þ, 79Br):
found: 446.0161.
3. Pettit, G. R.; Toki, B.; Herald, D. L.; Verdier-Pinard, P.; Boyd, M. R.;
Hamel, E.; Pettit, R. K. J. Med. Chem. 1998, 41, 1688.
4. Cai, X.; Sakamoto, M.; Fujitsuka, M.; Majima, T. Chem.dEur. J. 2005,
11, 6471 and references cited therein.
5. Langhals, H.; Fuchs, K. Chem. Unserer Zeit 2004, 38, 98 and references
cited therein.
6. Shiue, J.-S.; Lin, M.-H.; Fang, J.-M. J. Org. Chem. 1997, 62, 4643.
7. Buchta, E.; Egger, H. Chem. Ber. 1957, 90, 2760.
8. For reviews on 3-formylchromone, see: (a) Ellis, G. P. The Chemistry of
Heterocyclic Compounds; Weisberger, A., Ed.; Interscience: New York,
NY, 1977; Vol 35, p 921; (b) Ghosh, C. K.; Ghosh, C. Indian J. Chem.
1997, 36B, 968.
9. Heber, D. Synthesis 1978, 691.
10. (a) Ghosh, C. K.; Khan, S. Synthesis 1981, 903; (b) Hass, G.; Stanton,
J. L.; von Sprecher, A.; Wenk, P. J. Heterocycl. Chem. 1981, 18, 607;
(c) Prousek, J. Collect. Czech. Chem. Commun. 1991, 1361; (d) Ghosh,
C. K.; Bandyopadhyay, C.; Biswas, S.; Chakravarty, A. K. Indian
J. Chem., Sect. B 1990, 29, 814.
11. Bandyopadhyay, C.; Sur, K. R.; Patra, R. J. Chem. Res., Synop. 1998, 12,
802.
12. (a) Langer, P.; Appel, B. Tetrahedron Lett. 2003, 7921; (b) Appel, B.;
Rotzoll, S.; Reinke, H.; Langer, P. Eur. J. Org. Chem. 2006, 3638.
13. For a review on 1,3-bis-silyl enol ethers, see: Langer, P. Synthesis 2002,
441.
14. For a review on domino reactions of 1,3-bis-silyl enol ethers with benzo-
pyrylium triflates, see: Langer, P. Synlett 2007, 1016.
15. Lee, Y.-G.; Ishimaru, K.; Iwasaki, H.; Ohkata, K.; Akiba, K. J. Org.
Chem. 1991, 56, 2058.
2.2.19. (5-Chloro-2-hydroxyphenyl)-[4-hydroxy-3-
(1-naphthoyl)phenyl]methanone (3s)
Starting with 2d (208 mg, 1.0 mmol), Me3SiOTf (66 mg,
0.3 mmol), and 1,3-bis-silyl enol ether 1f (463 mg, 1.3 mmol),
3s was isolated as a yellow viscous oil (144 mg, 36%).
1H NMR (300 MHz, CDCl3): d¼6.84 (d, J¼8.1 Hz, 1H, Ar),
16. Molander, G. A.; Cameron, K. O. J. Am. Chem. Soc. 1993, 115, 830.
17. CCDC-650038 (3i) and CCDC-650039 (3k) contain all crystallographic
details of this publication and is available free of charge at www.ccdc.
cam.ac.uk/conts/retrieving.html or can be ordered from the following
address: Cambridge Crystallographic Data Centre, 12 Union Road,
GB-Cambridge CB21EZ; fax: þ44 1223 336 033; or deposit@
ccdc.cam.ac.uk.