Reactions of 2-hydroxybenzophenones with Corey-Chaykovsky reagent

Article abstract of DOI:10.1016/j.tet.2008.01.024

A variety of 2-hydroxybenzophenones on reaction with Corey-Chaykovsky reagent underwent unprecedented rearrangements leading to 3-substituted benzofurans 8 and one-carbon homologated compounds 9 and 12. Compounds 9 could further be quantitatively transfor

Full text of DOI:10.1016/j.tet.2008.01.024

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2586e2595
www.elsevier.com/locate/tet
Reactions of 2-hydroxybenzophenones with CoreyeChaykovsky reagent
Santhosh Kumar Chittimalla a, Tsung-Che Chang a, Ting-Chun Liu a,
a,
Hsing-Pang Hsieh b, , Chun-Chen Liao
*
*
a Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan
b Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Taiwan
Received 15 November 2007; received in revised form 31 December 2007; accepted 8 January 2008
Available online 11 January 2008
Abstract
A variety of 2-hydroxybenzophenones on reaction with CoreyeChaykovsky reagent underwent unprecedented rearrangements leading to
3-substituted benzofurans 8 and one-carbon homologated compounds 9 and 12. Compounds 9 could further be quantitatively transformed to
2-substituted benzofuran derivatives 10.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
compound having a o-hydroxyl substituent led to a novel pro-
tocol for the synthesis of benzofuran derivatives in moderate
to good yields (Scheme 1).5 2-Hydroxyacetophenone (2) pro-
vided 3-methylbenzofuran (5) as a single isolated product in
excellent yield (Scheme 1).5 Based on the isolation of hy-
droxyl intermediate 3 (for various benzaldehydes utilized in
their study) and the CCR ability to form epoxides with car-
bonyl functionalities, one of the possible reaction pathways
for the formation of the observed products might be through
a hydroxy-epoxide intermediate like 6 (Scheme 1). However,
Lowe and Holt pointed out the fact that they did not detect
any hydroxy-epoxide intermediate in these reactions.
Dimethylsulfoxonium methylide, often called as Coreye
Chaykovsky reagent (CCR)1 has proven to be a versatile nu-
cleophilic agent to achieve variety of chemical transformations
and provide new compounds with potential application. In
general trimethylsulfoxonium iodide when reacted with
a strong base such as NaH will generate CCR, which can
then be used as a methylene-transfer reagent. Most often
CCR is employed for the preparation of epoxides2 from car-
bonyl compounds, aziridines from imines,2 cyclopropanes2
from a,b-unsaturated carbonyl compounds, and O-, N-, and
S-alkylated compounds.1e CoreyeChaykovsky reaction is
mostly a reliable strategy in many of the synthetic applications
and was successfully applied for the total synthesis of variety
of natural products with distinct molecular framework and also
for the synthesis of biologically important molecules.3 A num-
ber of modified CCRs were recently utilized for enantioselec-
tive synthesis with excellent selectivities.4 Lowe and Holt
found that CCR on reaction with an aromatic carbonyl
HO
R
O
S
O
O
3
R
-H2O
OH
R
1, 2
O
O
* Corresponding authors. Tel.: þ886 37 246 166x35708; fax: þ886 37
586456 (H.-P.H.); tel.: þ886 3 5715131x3388; fax: þ886 3 5728123
(C.-C.L.).
R
4: R = H, 68%
5: R = CH3, 80%
OH
6
E-mail addresses: hphsieh@nhri.org.tw (H.-P. Hsieh), ccliao@mx.nthu.edu.
tw (C.-C. Liao).
Scheme 1. CCR mediated synthesis of benzofurans.
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.024

S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
2587
Benzo[b]furans and their derivatives have received much
attention in recent years because of their occurrence in natural
substances and their physiological activity.6 These are also
used for organic materials with light-emitting capability,
which can then be used as organic light-emitting devices.7
General routes for the synthesis of benzo[b]furans are widely
described in literature.8 During our study on the design, syn-
thesis, and structureeactivity relationship of novel peroxi-
some-proliferator-activated receptor (PPAR) agonists, we
needed 3-substituted benzofurans as building blocks.9a 3-Phe-
nyl-7-propylbenzofuran-6-ol was found to be a good building
block for providing selective PPAR agonists when attached to
different scaffolds.9b
reaction condition from usual NaH/DMSO to n-BuLi/THF to
generate CCR. After our initial results,9a,10 base dependent
and solvent dependent product distribution in CoreyeChay-
kovsky reaction was also observed by other research groups.11
At the outset the reaction was performed with 2-hydroxy-
benzophenone (7b) under NaH and n-BuLi conditions (Table
1). After several trials we found that 4 equiv of CCR was
required for the completion of the reaction with compound
7b. Sulfoxonium ylide generated utilizing NaH as base in
DMSO on reaction with 7b at 60 ꢀC led to the formation of
3-phenylbenzofuran (8b) in 50% yield with 20% recovery of
starting material (Table 1, entry 1). When solvent was changed
to THF, reaction did not proceed. In an intriguing observation
when n-BuLi was used as base furnished products 3b, 11b,
and 9b in 70% total yield (Table 1, entry 2).
2. Results and discussion
The presence of compounds 3b and 11b could be witnessed
1
from the H NMR of the crude reaction mixtures; however,
In an attempt to obtain 3-phenyl-6-allyloxy-benzofuran
(8a) from 4-allyloxy-2-hydroxybenzophenone (7a) employing
Lowe and Holt sequence led to the serendipitous discovery of
a novel rearrangement product 2-[4-(allyloxy)-2-hydroxy-
phenyl]-1-phenyl-1-ethanone (9a). Compound 9a on subse-
quent cyclization provided 2-phenyl-6-allyloxybenzofuran
(10a, Scheme 2).9a,10 In the view of importance of benzo[b]-
furans, it appeared for us to study the generality of this unprec-
edented reaction.
several attempts to obtain the pure compounds 3b and 11b
by column chromatography were unsuccessful providing mix-
ture of 3b or 11b along with the dehydrated product 3-phenyl-
benzofuran (8b). Consequently, after isolating the one-carbon
homologated compound 9b by column chromatography, the
mixture of 3b, 11b, and 8b was subjected to p-TSA/CH2Cl2
condition to obtain 3-phenylbenzofuran (8b) as the sole prod-
uct. Formation of compounds 3b and 8b is in accord with the
Lowe and Holt’s result.
Consequently, when this reaction was extended to 2-hy-
droxybenzophenone 7c with R4¼OMe furnished 45% of
one-carbon homologated product 9c and 20% of 3-substituted
benzofuran 8c (Table 2). In providing compounds 9a, 9b, 9c
sulfur ylide is effecting a methylene insertion to the benzophe-
none. But this insertion can in principle be at two different
positions of benzophenone. One of the possible reasons for
highly selective methylene insertion product in these cases
O
Ph
Ph
OH
X
R
R
O
R
8a
7a
THF
a) (CH3)3SOI,
n-BuLi,
0 °C - rt
Ph
p-TSA
CH2Cl2
Ph
O
R
OH
O
9a
10a
85% yield based on
Table 1
Unprecedented rearrangements of 2-hydroxybenzophenone on reaction with
CCR
R =
consumed starting material
O
Scheme 2. One-carbon homologation with CCR leading to 2-substituted ben-
zofuran 10a.
HO
Ph
Ph
+
Ph
+
O
O
Initially, compound 8a was of interest. Accordingly, when
the corresponding benzophenone 7a was subjected to sulfoxo-
nium ylide prior generated in the presence of n-BuLi/THF
(Method A), underwent incomplete reaction furnishing
a new compound as indicated by TLC. The newly formed
O
O
8b
OH
3b
9b
Ph
a
O
Ph
OH
Ph
7b
OH
+
+
a) (CH3)3SOI, base
O
OH
12b
O
1
11b
product purified by column chromatography shows in its H
+
Ar
not observed
O
S
NMR spectrum, no peak at around 7.8e8.0 ppm, a diagnostic
value for C-2 proton of benzofuran, instead a singlet at
4.19 ppm accounting for 2 protons. After long standing in
CDCl3 the peak at 4.19 ppm disappeared and a new peak
showed up as a singlet at 6.94 ppm, a diagnostic peak of
C-3 proton of a benzofuran. Careful analysis of all the ob-
Int-1
O
Entry
Method:a
base/solvent
DMSY
(equiv)
Time (h)/
Temp.
Yield (%)
3b
11b
dc
dd
8b
9b
1b
2
B: NaH/DMSO
A: n-BuLi/THF
4
4
24/60 ꢀC
4/60 ꢀC
dc
dd
50
50
dc
20
tained analytical data (IR, H NMR, 13C NMR and DEPT,
1
HRMS) provided the structures of the newly formed com-
pounds as 9a and 10a, respectively. The slight acid in
CDCl3 solvent caused cyclization of 9a into 10a. This finding
is surprising and contemplated to be due to the change of
a
See Section 4.
20% recovery of SM.
Not observed.
Compounds 3b and 11b could be seen from 1H NMR of the crude sample.
b
c
d

2588
S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
Table 2
Reactions of various 2-hydroxybenzophenones with CCR
The structures of all the new compounds were assigned on
the basis of their IR, 1H NMR and 13C NMR, DEPT, and low-
and high-resolution mass spectral analyses. The 1H NMR data
of the known compounds 8b,12 8c,13 8e,14 9b,15 9e,16 10b,21
10d,17 10e,17 12i18 were compared with the data reported in
literature.
R3
R2
R2
R1
O
R3
R1
O
R1
R2
R3
a
+
R4
R4
OH
R4
R1
R2
O
OH
7
8
9
pTSA
CH2Cl2
R3
or
R1
9
a) (CH3)3SOI, n-BuLi, THF
R2
R4
O
R3
(quantitative)
10
O
ð1Þ
e:R1 = R2 = R4 = H ; R3 = OMe
b:R1 = R2 = R3 = R4 = H
f:R1 = R2 = R4 = H ; R3 = F
c:R1 = R2 = R3 = H; R4 = OMe
d:R1 = R2 = R4 = H ; R3 = Me
g:R1 = R2 = R4 = H ; R3 = CN
h:R1 = R2 = R4 = H ; R3 = CF3
R4
OH
12
Entry
2-Hydroxybenzophenones
Products/yield (%)
To understand the participation of the hydroxyl group in
this CCR mediated reaction, compound 13 was subjected to
standard reaction conditions that provided epoxide 14 in
63% yield (Eq. 2). During a recent study on synthesis of diaz-
onamide A by Nicolaou’s group,19 hydroxyl functionality
in the 2-hydroxybenzophenone was protected and epoxide
formation at the ketone moiety could be carried out in near
quantitative yield.
1
2
3
4
5
6
7
8
9
7b:R1¼R2¼R3¼R4¼H
8b/50þ9b/20
8c/20þ9c/45
8d/45þ9d/20
8e/32þ9e/32
8f/42þ9f/22
8g/42þ9g/12
8h/36þ9h/15
12i/70
7c:R1¼R2¼R3¼H; R4¼OMe
7d:R1¼R2¼R4¼H; R3¼Me
7e:R1¼R2¼R4¼H; R3¼OMe
7f:R1¼R2¼R4¼H; R3¼F
7g:R1¼R2¼R4¼H; R3¼CN
7h:R1¼R2¼R4¼H; R3¼CF3
7i:R1¼R2¼R4¼H; R3¼NO2
7j:R1¼R4¼H; R2¼Me; R3¼NO2
12j/50 (20% SM recovered)
O
O
may be due to electronic factors. Thus, we pursued this reac-
tion with a few selected 2-hydroxybenzophenones to come up
with a probable reaction mechanism and possible scope and
limitation of these novel rearrangements.
Initially, several substituted 2-hydroxybenzophenones were
prepared (see Supplementary data). Thus, electron-rich aryl
groups and electron-deficient aryl groups were connected to
2-hydroxybenzoyl moiety to give 2-hydroxybenzophenones
7, which may provide varying electronic effects during the re-
action with CCR.
When R3 is an electron-donating substituent like methyl- or
methoxy-group furnished the one-carbon homologated prod-
ucts 9d (20%) and 9e (32%) along with 3-substituted benzofu-
rans 8d (45%) and 8e (32%). A weakly electron-withdrawing
substitution like fluorine for R3 gave 22% of 9f, a one-carbon
homologated product, beside 42% of 8f, a 3-substituted benzo-
furan. By changing R3 to cyano- (7g) and trifluoromethyl- (7h)
provided low yields (9g-12% and 9h-15%) of the one-carbon
homologated products and moderate yields of 3-substituted
benzofurans (8g-42% and 8h-36%). In all the cases studied,
products similar to 3b or 11b were not easy to isolate. Thus,
after separating the rearranged product 9 from the crude sam-
ple, the remaining reaction mixture was treated with p-TSA in
CH2Cl2 to obtain 3-phenylbenzofurans 8 as sole products. In
a turn around situation with a nitro substitution for R3 pro-
vided compound 12i as a single product in 70% yield. Here
the methylene insertion took place at the other alternative
position of benzophenone. Compound 7j also gave a similar
rearranged product 12j in 50% yield with 20% recovery of
the starting material.
a
OMe
OMe
ð2Þ
13
14/63%
(17% recovery of SM)
a) (CH3)3SOI, n-BuLi, THF, rt
Although the reaction mechanism involved for the forma-
tion of observed products is not completely understood, we
propose the following pathways. When a 2-hydroxybenzophe-
none substrate is added to the in situ generated ylide, initial
formation of Int-1 takes place. Thus Int-1 is now open for
a number of reaction pathways. If the nucleophilic oxygen
near to the sulfoxonium cation kicks out the dimethyl sulfox-
ide leaving group, it can provide the epoxide Int-2 (Scheme 3,
path I). The phenoxide ion then opens the epoxide ring at car-
bon-1 to give Int-3; subsequent protonation and dehydration
leads to 3-substituted benzofuran 3 (Scheme 3, path I or II).
If the epoxide formed in path I is opened at carbon-2 by the
phenoxide, then formation of Int-4, which upon consequent
cyclization provides Int-7, subsequent protonation (Scheme
3, path II) and further dehydration leads to 3-substituted ben-
zofuran 8. This pathway is proposed based up on the observed
product 11, but we never isolated or detected the intermediate
hydroxyl aldehyde (leading from Int-6). Formation of one-
carbon homologation process is still not clearly understood.
It appears as a cyclopropane type Int-8 (Scheme 3, path III)
that opens up to provide the 2-substituted benzofuran precur-
sor 9. As shown in path IV, migration of a phenyl ring pro-
vides compound 12. The formation of compound 5 can also
be expected to form by the aromatic ring migration depending
upon the substitution pattern on these substrates.
All the one-carbon homologated products 9 on treatment
with p-TSA in CH2Cl2 quantitatively converted to the corre-
sponding 2-aryl substituted benzofurans 10 (Eq. 1).
In order to determine the presence of hydroxy-epoxide
intermediate leading to the formation of 3-substituted

S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
2589
II
Ar
III
substitution on either of the aryl group provided the methylene
insertion to give compound 9. Weakly electron-withdrawing
substitutions provided low yields of the one-carbon homolo-
gated product. Surprisingly, a strongly electron-withdrawing
substitution as in 7i or 7j gave one-carbon homologated prod-
uct with a different regioselectivity. In summary, 2-hydroxy-
benzophenones on reaction with CoreyeChaykovsky reagent
unprecedented rearrangement reactions to provide one-carbon
homologated products, which in turn could be transformed to
2-substituted benzofurans.
O
S
+
O
R1
path III
-
path I
O
Ar
I
Int-1
Ar
O
III
O
1
Li
2
R1
R1
path II
Ar
O
O
Int-8
O
H+
Int-2
R1
2
O
-H2O
Ar
Ar
Ar
Int-3
R1
H
Ar
O
O
O
O
R1
O
Int-9
H+
Li+
O
R1
4. Experimental section
8
Ar
-H2O
H+
Int-4
R1
O
9
4.1. Method A
R1
O
Int-7
OH
Trimethylsulfoxonium iodide in dry THF was placed in
a flask, which was cooled to ꢁ78 ꢀC. To this 1 equiv n-BuLi
was added. After the addition of base, reaction mixture was
brought to rt. Typically it took 10e15 min for the complete
formation of CCR. To this reaction mixture, starting material
(benzophenone) in dry THF was added and heated the reaction
mixture to 60 ꢀC for 4 h. Reaction was quenched with water
and extracted with ether. The combined layers of ether was
dried over anhydrous MgSO4 and evaporated to yield the
crude reaction mixture, which was then subjected to column
chromatography to obtain the pure products.
5
Ar
Ar
R1
OLi
R1
O
O
O
Int-6
Int-5
Ar
O
O
O
O
Ar
S
Ar
-
+
path IV
H+
O
R1
R1
R1
OH
O
Int-10
Int-1
10
Scheme 3. Plausible reaction mechanisms for the formation of observed
products.
4.2. Method B
benzofuran, epoxide 15 was synthesized (Scheme 4). Com-
pound 15 under (CH3)3SOI, n-BuLi, THF condition trans-
formed to product 8b (trace amount of 3b was observed in
1H NMR of crude reaction mixture). Though, this proves the
presence of hydroxy-epoxide intermediate, other possible reac-
tion mechanisms leading to compound 8b cannot be ruled out.
A weighed amount of NaH (60% mineral oil dispersion)
was washed with hexane to remove the mineral oil.
This was dispersed in dry DMSO. Trimethyloxosulfonium
iodide (1 equiv) in dry DMSO was added and stirred for
10e15 min during which time formation of DMSY took
place. Now the starting material (benzophenones) in dry
DMSO was added and heated the reaction mixture to 60 ꢀC
until the disappearance of starting material. Reaction was
quenched with water and extracted with ether. The combined
layers of ether was dried over anhydrous MgSO4 and evapo-
rated to yield the crude reaction mixture, which was then
subjected to column chromatography to obtain the pure
products.
O
O
a
O
O
Li
TBDMS
TBDMS
15
16
I
O
path II
8b
O
Benzophenones 7a, 7b, 7c, and 7e are commercially avail-
able. 3-Methyl-4-nitrobenzaldehyde (23) was prepared from
commercially available 3-methyl-4-nitrobenzoic acid in two
steps (Scheme 5). In a general synthetic sequence, Grignard
reaction of a substituted benzaldehyde X with 2-methoxyphe-
nylmagnesium bromide furnished crude diaryl carbinol after
usual workup. Thus obtained diaryl carbinol required no fur-
ther purification and on subsequent PDC oxidation20 gave
the corresponding benzophenone derivatives 15e22 in good
yield. Demethylation of the 2-methoxybenzophenones 15e
22 in the presence of BBr321 afforded the 2-hydroxybenzophe-
nones 7d, 7fe7j required for the present study. Most of the
substituted benzaldehydes were bought from commercial
sources.
Li
a) (CH3)3SOI, n-BuLi, THF
Scheme 4. Presence of hydroxy-epoxide intermediate in CCR mediated
reactions.
3. Summary
In conclusion, though the reaction offered mixture of prod-
ucts, the novel rearrangement reaction observed here to pro-
vide the one-carbon homologated products, which were
subsequently transformed to 2-substituted benzofuran deriva-
tives is noteworthy and unprecedented. Electron-releasing

2590
S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
(i) B2H6-DMS
THF
3H), 6.98 (d, J¼8.4 Hz, 1H), 7.03 (t, J¼7.6 Hz, 1H), 7.22
HO2C
Me
OHC
Me
(d, J¼8.0 Hz, 2H), 7.33 (dd, J¼1.6, 7.6 Hz, 1H), 7.45 (ddd,
J¼1.6, 7.6, 8.4 Hz, 1H), 7.73 (d, J¼8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 21.5 (CH3), 55.5 (CH3), 111.4 (CH),
120.3 (CH), 128.8 (2ꢂCH), 129.2 (CH), 129.9 (2ꢂCH),
131.4 (CH), 135.2 (C), 143.6 (2ꢂC), 157.1 (C), 195.9 (C);
MS (EI, 70 eV) m/z (relative intensity) 226 (Mþ, 88), 209
(32), 135 (100), 91 (65), 77 (41), 65 (37); HRMS (EI) calcd
for C15H14O2 (Mþ) 226.0993, found 226.1003.
(ii) PCC
CH2Cl2
NO2
NO2
23
(i)
X
THF
0 °C-rt, 3 h
PDC
CH2Cl2
rt, 2 h
Mg
MgBr
OMe
Br
THF
(ii)
reflux
R4
R4
OMe
O
O
BBr3
CH2Cl2
0 °C, 4 h
Ar
Ar
4.4.2. (4-Fluorophenyl)(2-methoxyphenyl)methanone (18)
IR (neat) n 3074 (m), 3066 (w), 2944 (m), 2839 (m), 1677
(s), 1598 (s), 1488 (s), 1305 (s), 1295 (s), 1261 cmꢁ1; 1H NMR
(400 MHz, CDCl3) d 3.68 (s, 3H), 7.08e6.95 (m, 4H), 7.33e
7.31 (m, 1H), 7.46e7.41 (m, 1H), 7.81e7.78 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 55.4 (CH3), 111.4 (CH), 115.2
(d, J¼22.9 Hz, 2ꢂCH), 120.5 (CH), 128.5 (C), 129.3 (CH),
131.9 (CH), 132.2 (d, J¼9.2 Hz, 2ꢂCH), 134.2 (C), 157.1
(C), 165.6 (d, J¼253.5 Hz, CF), 194.7 (C); MS (EI, 70 eV)
m/z (relative intensity) 230 (Mþ, 69), 185 (14), 135 (100),
123 (79), 95 (97), 92 (45); HRMS (EI) calcd for C14H11FO2
(Mþ) 230.0743, found 230.0741.
R4
R4
OMe
OH
15-22
7d, 7f-7j
R1
R2
R3
X:
OHC
h:R1 = R2 = R4 = H; R3 = CF3
i:R1 = R2 = R4 = H; R3 = NO2
j:R1 = R4 = H; R2 = Me; R3 = NO2
d:R1 = R2 = R4 = H; R3 = Me
f:R1 = R2 = R4 = H; R3 = F
g:R1 = R2 = R4 = H; R3 = CN
Scheme 5. Synthesis of 2-hydroxybenzophenones.
4.3. General procedure for the preparation of
2-methoxybenzophenones
4.4.3. 4-(2-Methoxybenzoyl)benzonitrile (19)
IR (neat) n 3455 (br), 2834 (w), 2230 (m), 1658 (s), 1598
Place in the flask 1.5 mmol of Mg turnings and 10 mL of
dry THF. To this 2-bromoanisoles (1.2 mmol) are added and
allowed to gently reflux while stirring until most of the Mg
turnings are utilized for the reaction. The reaction flask was
cooled to 0 ꢀC and corresponding benzaldehydes (1.0 mmol)
in dry THF are dropwise added and allowed to stir for 3 h.
Reaction was quenched by adding crushed ice and the precip-
itated magnesium compounds by the addition of 10% aq
hydrochloric acid with stirring until the precipitate has disap-
peared. Extraction was performed using ethylacetate and the
extracts were dried over MgSO4. This crude reaction mixture
in CH2Cl2 is added to a stirred solution of PDC (2.0 mmol)
(s), 1487 (s), 1404 (m), 1311 (s), 1296 (s), 1259 (s) cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 3.67 (s, 3H), 6.98 (dd, J¼0.8,
7.6 Hz, 1H), 7.06 (ddd, J¼0.8, 7.6, 8.4 Hz, 1H), 7.41 (dd,
J¼2.0, 7.6 Hz, 1H), 7.51 (ddd, J¼2.0, 7.6, 8.4 Hz, 1H), 7.70
(dd, J¼2.0, 8.4 Hz, 2H), 7.84 (dd, J¼2.0, 8.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3) d 55.5 (CH3), 111.5 (CH), 115.7
(C), 118.2 (C), 120.9 (CH), 127.4 (C), 129.8 (CHꢂ2), 130.1
(CH), 132.0 (CHꢂ2), 133.1 (CH), 141.4 (C), 157.6 (C),
195.0 (C); MS (EI, 70 eV) m/z (relative intensity) 237 (Mþ,
50), 206 (5), 135 (100), 130 (16), 107 (3), 102 (30); HRMS
(EI) calcd for C15H11NO2 237.0799, found 237.0790.
˚
and 4 A molecular sieves in CH2Cl2 and the reaction is stirred
until completion, then filtered through Celite and concentrated
under reduced pressure. Purification by column chromatogra-
phy furnished 2-methoxybenzophenones.
4.4.4. (2-Methoxyphenyl)[4-(trifluoromethyl)phenyl]-
methanone (20)
IR (neat) n 3335 (w), 3069 (m), 3017 (m), 2972 (m), 2839
(w), 1675 (s), 1603 (s), 1510 (s), 1451 (s), 1326 (s), 1295 (s),
1
1245 (s) cmꢁ1; H NMR (400 MHz, CDCl3) d 3.69 (s, 3H),
4.4. General procedure for demethylation to provide
2-hydroxybenzophenones
6.98 (dd, J¼1.2, 8.0 Hz, 1H), 7.05 (ddd, J¼1.2, 6.8, 7.2 Hz,
1H), 7.40 (dd, J¼1.8, 7.2 Hz, 1H), 7.49 (ddd, J¼1.8, 6.8,
7.2 Hz, 1H), 7.67 (dd, J¼0.8, 8.0 Hz, 2H), 7.87 (dd, J¼0.8,
8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 55.2 (CH3),
A solution of 1.0 mmol of 2-methoxybenzophenones in
6 mL of CH2Cl2 was added during 5 min to a well-stirred so-
lution of 1.5 mmol of BBr3 (1.0 M in CH2Cl2) at 0 ꢀC. The re-
action mixture was then quenched by the addition of crushed
ice and NH4Cl (aq). Extraction was performed using ethylace-
tate, the extracts were dried over MgSO4 and concentrated
under reduced pressure. Purification by column chromatogra-
phy furnished the required 2-hydroxybenzophenones.
1
111.3 (CH), 120.6 (CH), 123.6 (q, J¼270.1 Hz, CF3), 125.0
(q, 3J¼3.8 Hz, CHꢂ2), 127.7 (C), 129.6 (CHꢂ2), 129.8
(CH), 132.6 (CH), 133.6 (q, 2J¼32.2 Hz, C), 140.8 (C),
157.4 (C), 195.1 (C); MS (EI, 70 eV) m/z (relative intensity)
280 (Mþ, 43), 211 (12), 173 (17), 145 (38), 135 (100), 107
(7); HRMS (EI) calcd for C15H11F3O2 280.0711, found
280.0713.
4.4.1. (2-Methoxyphenyl)(4-methylphenyl)methanone (16)
IR (neat) n 3027 (w), 2944 (w), 2858 (w), 1664 (s), 1601
(s), 1488 (s), 1459 (s), 1435 (s), 1297 (s), 1262 (s), 1244 (s)
4.4.5. (2-Methoxyphenyl)(4-nitrophenyl)methanone (21)
IR (neat) n 3105 (m), 2937 (m), 2838 (m), 1674 (s), 1602
1
1
cmꢁ1; H NMR (400 MHz, CDCl3) d 2.40 (s, 3H), 3.71 (s,
(s), 1488 (m), 1465 (m), 1354 (s), 1261 (s) cmꢁ1; H NMR

S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
2591
(400 MHz, CDCl3) d 3.64 (s, 3H), 6.97 (d, J¼8.0 Hz, 1H),
7.04 (t, J¼8.0 Hz, 1H), 7.42 (dd, J¼1.6, 7.6 Hz, 1H), 7.49
(ddd, J¼1.6, 7.6, 8.0 Hz, 1H), 7.86 (d, J¼8.8 Hz, 2H), 8.21
(d, J¼8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 55.3
(CH3), 111.5 (CH), 120.8 (2ꢂCH), 123.2 (2ꢂCH), 127.3
(CH), 130.1 (2ꢂCH), 133.1 (CH), 143.0 (C), 149.8 (C),
157.5 (C), 194.5 (C); MS (EI, 70 eV) m/z (relative intensity)
257 (Mþ, 28), 240 (18), 210 (16), 185 (9), 135 (100);
HRMS (EI) calcd for C14H11NO4 (Mþ) 257.0688, found
257. 0675.
7.54 (dd, J¼1.6, 8.0 Hz, 1H), 7.67e7.71 (m, 2H), 11.88 (s,
1H); 13C NMR (100 MHz, CDCl3) d 115.4 (d, J¼22.4 Hz,
2ꢂCH), 118.4 (CH), 118.9 (C), 131.7 (d, J¼7.6 Hz, 2ꢂCH),
133.1 (CH), 134.0 (C), 136.3 (CH), 163.1 (C), 165.9 (d,
J¼252 Hz, C), 199.8 (C); MS (EI, 70 eV) m/z (relative inten-
sity) 216 (Mþ, 100), 133 (4), 123 (53), 120 (34), 75 (14);
HRMS (EI) calcd for C13H9FO2 (Mþ) 216.0588, found
216.0597.
4.4.10. 4-(2-Hydroxybenzoyl)benzonitrile (7g)
IR (neat) n 2967 (w), 2930 (w), 2858 (w), 2233 (m), 1626
(s), 1590 (s), 1482 (s), 1439 (s), 1335 (s), 1244 (s), 1221
4.4.6. (2-Methoxyphenyl)(3-methyl-4-nitrophenyl)-
methanone (22)
IR (neat) n 3074 (w), 2937 (m), 2839 (m), 1674 (s), 1599
1
(s) cmꢁ1; H NMR (400 MHz, CDCl3) d 6.88 (ddd, J¼0.8,
7.2, 8.0 Hz, 1H), 7.08 (dd, J¼0.8, 8.4 Hz, 1H), 7.43 (dd,
J¼1.6, 8.0 Hz, 1H), 7.54 (ddd, J¼1.6, 7.2, 8.4 Hz, 1H), 7.74
(dd, J¼2.0, 8.4 Hz, 2H), 7.80 (dd, J¼2.0, 8.4 Hz, 2H), 11.77
(s, 1H); 13C NMR (100 MHz, CDCl3) d 115.2 (C), 117.8
(C), 118.4 (C), 118.7 (CH), 119.0 (CH), 129.4 (CHꢂ2),
132.2 (CHꢂ2), 137.2 (CH), 141.5 (C), 163.3 (C), 199.7 (C);
MS (EI, 70 eV) m/z (relative intensity) 223 (Mþ, 98), 222
(100), 197 (6), 130 (23), 121 (91), 102 (35), 93 (15); HRMS
(EI) calcd for C14H9NO2 223.0633, found 223.0632.
1
(s), 1578 (s), 1483 (s), 1349 (s), 1297 (s), 1257 (s) cmꢁ1; H
NMR (400 MHz, CDCl3) d 2.58 (s, 3H), 3.67 (s, 3H), 6.98
(dd, J¼0.8, 8.4 Hz, 1H), 7.04 (ddd, J¼0.8, 7.6, 7.6 Hz, 1H),
7.40 (dd, J¼2.0, 7.6 Hz, 1H), 7.49 (ddd, J¼2.0, 7.6, 8.4 Hz,
1H), 7.63 (dd, J¼1.2, 8.4 Hz, 1H), 7.74 (d, J¼1.2 Hz, 1H),
7.91 (d, J¼8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) d 20.1
(CH3), 55.4 (CH3), 111.4 (CH), 120.7 (CH), 124.3 (CH),
127.3 (C), 127.9 (CH), 130.0 (CH), 133.0 (CH), 133.3 (C),
133.3 (CH), 141.2 (C), 151.1 (C), 157.4 (C), 194.8 (C); MS
(EI, 70 eV) m/z (relative intensity) 271 (Mþ, 33), 256 (3),
164 (6), 136 (10), 135 (100), 121 (29), 77 (27); HRMS (EI)
calcd for C15H13NO4 271.0845, found 271.0842.
4.4.11. (2-Hydroxyphenyl)[4-(trifluoromethyl)phenyl]-
methanone (7h)
IR (neat) n 3078 (w), 2926 (w), 1628 (s), 1612 (s), 1576 (s),
;
1483 (s), 1408 (s), 1324 (s), 1245 (s) cmꢁ1 1H NMR
4.4.7. 3-Methyl-4-nitrobenzaldehyde (23)
IR (neat) n 3104 (w), 2854 (m), 2748 (w), 1703 (s), 1686
(400 MHz, CDCl3) d 6.87 (ddd, J¼1.2, 7.2, 8.0 Hz, 1H),
7.07 (dd, J¼1.2, 8.4 Hz, 1H), 7.48 (dd, J¼1.6, 8.0 Hz, 1H),
7.52 (ddd, J¼1.6, 7.2, 8.4 Hz, 1H), 7.79 (m, 4H), 11.86 (s,
1H); 13C NMR (100 MHz, CDCl3) d 118.6 (CH), 118.7 (C),
118.9 (CH), 123.6 (q, 1J¼270.9 Hz, CF3), 125.39 (q,
3J¼3.8 Hz, CHꢂ2), 129.3 (CHꢂ2), 133.2 (CH), 133.3 (q,
2J¼32.9 Hz, C), 136.9 (CH), 141.0 (C), 163.4 (C), 200.3
(C); MS (EI, 70 eV) m/z (relative intensity) 266 (Mþ, 82),
265 (50), 173 (22), 145 (35), 121 (100); HRMS (EI) calcd
for C14H9F3O2 266.0555, found 266.0555.
(s), 1519 (s), 1507 (s), 1459 (m), 1381 (s), 1358 (s) cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 2.63 (s, 3H), 7.82e7.84 (m,
2H), 8.02 (d, J¼8.4 Hz, 1H), 10.05 (s, 1H); 13C NMR
(100 MHz, CDCl3) d 19.9 (CH3), 125.2 (CH), 127.8 (CH),
133.8 (CH), 134.2 (C), 138.5 (C), 190.4 (CH); MS (EI,
70 eV) m/z (relative intensity) 165 (Mþ, 13), 148 (100), 120
(17), 91 (40), 77 (17); HRMS (EI) calcd for C8H7NO3
165.0426, found 165.0424.
4.4.8. (2-Hydroxyphenyl)(4-methylphenyl)methanone (7d)
IR (neat) n 3029 (br), 2912 (m), 2857 (m), 1624 (s), 1602
4.4.12. (2-Hydroxyphenyl)(4-nitrophenyl)methanone (7i)
IR (neat) n 3105 (br), 3076 (s), 2937 (s), 2838 (s), 1674 (s),
1
1
(s), 1483 (s), 1331 (m), 1304 (m), 1243 (s) cmꢁ1; H NMR
1602 (s), 1488 (m), 1465 (s), 1354 (s), 1261 cmꢁ1; H NMR
(400 MHz, CDCl3) d 2.42 (s, 3H), 6.82e6.86 (m, 1H), 7.04
(d, J¼8.0 Hz, 1H), 7.27 (d, J¼7.6 Hz, 2H), 7.46 (t,
J¼8.0 Hz, 1H), 7.57 (d, J¼7.6 Hz, 2H), 7.60 (d, J¼1.6 Hz,
1H), 12.07 (s, 1H); 13C NMR (100 MHz, CDCl3) d 21.4
(CH3), 118.1 (CH), 118.3 (CH), 119.0 (C), 128.8 (2ꢂCH),
129.3 (2ꢂCH), 133.3 (CH), 134.9 (C), 135.9 (CH), 142.5
(C), 162.9 (C), 201.1 (C); MS (EI, 70 eV) m/z (relative inten-
sity) 212 (Mþ, 87), 211 (72), 197 (100), 121 (47), 120 (38),
119 (48); HRMS (EI) calcd for C14H12O2 (Mþ) 212.0837,
found 212.0845.
(400 MHz, CDCl3) d 6.88 (ddd, J¼0.8, 7.6, 8.0 Hz, 1H),
7.09 (dd, J¼0.8, 8.0 Hz, 1H), 7.42 (dd, J¼1.6, 8.0 Hz, 1H),
7.55 (ddd, J¼1.6, 7.6, 8.0 Hz, 1H), 7.81 (d, J¼8.8 Hz, 2H),
8.35 (d, J¼8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d 118.5 (C), 118.8 (CH), 119.0 (CH), 123.6 (2ꢂCH), 129.8
(2ꢂCH), 133.0 (CH), 137.3 (CH), 143.1 (C), 149.5 (C),
163.4 (C), 199.5 (C); MS (EI, 70 eV) m/z (relative intensity)
243 (Mþ, 100), 226 (54), 196 (89), 151 (12), 121 (98), 102
(12), 92 (7); HRMS (EI) calcd for C13H9NO4 (Mþ)
243.0532, found 243.0528.
4.4.9. (2-Hydroxyphenyl)(4-fluorophenyl)methanone (7f)
IR (neat) n 3076 (br), 3053 (w), 1676 (w), 1627 (s), 1603
4.4.13. (2-Hydroxyphenyl)(3-methyl-4-nitrophenyl)
methanone (7j)
1
(s), 1590 (s), 1483 (s), 1446 (s), 1244 (s) cmꢁ1; H NMR
IR (neat) n 3083 (w), 3043 (w), 2935 (w), 2864 (w), 1628
(s), 1605 (s), 1583 (s), 1522 (s), 1483 (s), 1446 (s), 1337 (s),
(400 MHz, CDCl3) d 6.86 (td, J¼7.2, 1.2 Hz, 1H), 7.05 (d,
1
J¼8.0 Hz, 1H), 7.14e7.18 (m, 2H), 7.46e7.50 (m, 1H),
1310 (s), 1247 (s) cmꢁ1; H NMR (400 MHz, CDCl3) d 2.65

2592
S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
1
(s, 3H), 6.88 (ddd, J¼1.2, 8.0, 9.2 Hz, 1H), 7.08 (dd, J¼0.8,
8.4 Hz, 1H), 7.45 (dd, J¼1.2, 8.0 Hz, 1H), 7.54 (ddd, J¼1.6,
8.0, 9.2 Hz, 1H), 7.58 (dd, J¼1.6, 8.0 Hz, 1H), 7.61 (d,
J¼0.8 Hz, 1H), 8.05 (d, J¼8.4 Hz, 1H), 11.78 (s, 1H); 13C
NMR (100 MHz, CDCl3) d 20.3 (CH3), 118.6 (C), 118.7
(CH), 119.1 (CH), 124.6 (CH), 127.3 (CH), 133.0 (CH), 133.1
(CH), 133.9 (C), 137.2 (CH), 141.6 (C), 150.7 (C), 163.4 (C),
199.7 (C); MS (EI, 70 eV) m/z (relative intensity) 257 (Mþ,
97), 242 (100), 240 (22), 211 (12), 197 (12), 121 (56);
HRMS (EI) calcd for C14H11NO4 257.0688, found 257.0678.
123.3 (CH), 124.2 (q, J¼270.2 Hz, CF3), 124.9 (CH), 125.9
3
2
(q, J¼3.8 Hz, CHꢂ2), 127.5 (CHꢂ2), 129.4 (q, J¼32.5 Hz,
C), 135.8 (C), 142.0 (CH), 155.8 (C); MS (EI, 70 eV) m/z (rel-
ative intensity) 263 (Mþþ1, 11), 262 (Mþ, 100), 165 (28);
HRMS (EI) calcd for C15H9F3O 262.0605, found 262.0607.
4.4.18. 2-[4-(Allyloxy)-2-hydroxyphenyl]-1-phenyl-1-
ethanone (9a)
IR (film) n 3150 (m), 3041 (w), 1690 (s), 1640 (m), 1589
;
(m), 743 (s), 693 (s) cmꢁ1 1H NMR (400 MHz, CDCl3)
d 4.19 (s, 2H), 4.46 (d, J¼4.8 Hz, 2H), 5.24 (dd, J¼1.2,
8.4 Hz, 1H), 5.35 (dd, J¼1.2, 14.0 Hz, 1H), 5.97e6.04 (m,
1H), 6.44 (dd, J¼2.8, 8.8 Hz, 1H), 6.53 (d, J¼2.4 Hz, 1H),
7.03 (d, J¼8.0 Hz, 1H), 7.48 (t, J¼8.0 Hz, 2H), 7.60 (t,
J¼7.2 Hz, 1H), 8.07 (d, J¼7.2 Hz, 2H); 13C NMR
(125 MHz, CDCl3) d 40.3 (CH2), 68.8 (CH2), 104.0 (CH),
107.4 (CH), 113.3 (C), 117.6 (CH2), 128.8 (2ꢂCH), 129.0
(2ꢂCH), 131.3 (CH), 133.1 (CH), 134.0 (CH), 135.7 (C),
156.5 (C), 159.3 (C), 201.4 (C); MS (EI, 70 eV) m/z (relative
intensity) 268 (27), 250 (24), 210 (15), 209 (86), 163 (86), 152
(10), 105 (28); HRMS (EI) calcd for C17H16O3 (Mþ)
268.1099, found 268.1101.
4.4.14. 3-(4-Methylphenyl)benzo[b]furan (8d)
IR (neat) n 3025 (w), 2919 (w), 2854 (w), 1578 (s), 1508
(s), 1451 (s), 1341 (s) cmꢁ1 1H NMR (400 MHz, CDCl3)
;
d 2.50 (s, 3H), 7.35e7.45 (m, 4H), 7.62e7.65 (m, 3H), 7.83
(s, 1H), 7.93 (dd, J¼1.2, 7.2 Hz, 1H); 13C NMR (100 MHz,
CDCl3) d 21.1 (CH3), 111.6 (CH), 120.3 (CH), 122.1 (C),
122.8 (CH), 124.4 (CH), 126.6 (C), 127.6 (C), 127.3
(2ꢂCH), 129.0 (C), 129.6 (2ꢂCH), 137.1 (C), 140.9 (CH),
155.8 (C); MS (EI, 70 eV) m/z (relative intensity) 208 (Mþ,
100), 207 (12), 115 (11), 102 (4); HRMS (EI) calcd for
C15H12O (Mþ) 208.0888, found 208.0884.
4.4.15. 4-(1-Benzofuran-3-yl)benzonitrile (8g)
4.4.19. 2-(2-Hydroxy-4-methoxyphenyl)-1-phenyl-1-
ethanone (9c)
IR (neat) n 3378 (s), 2909 (s), 2837 (s), 1677 (s), 1619 (s),
IR (neat) n 3448 (br), 3103 (w), 2233 (m), 2226 (s), 1611
(s), 1577 (m), 1449 (s), 1343 (w), 1276 (w), 1219 (s), 1109
1
(s) cmꢁ1; H NMR (400 MHz, CDCl3) d 7.33 (ddd, J¼1.2,
1596 (s), 1465 (m), 1447 (s) cmꢁ1 1H NMR (400 MHz,
;
7.2, 7.2 Hz, 1H), 7.38 (ddd, J¼1.6, 7.2, 7.2 Hz, 1H), 7.56
(dd, J¼1.2, 7.2 Hz, 1H), 7.72 (m, 4H), 7.79 (dd, J¼1.6,
7.2 Hz, 1H), 7.85 (s, 1H); 13C NMR (100 MHz, CDCl3)
d 110.8 (C), 112.0 (CH), 118.8 (C), 119.9 (CH), 120.8 (C), 123.5
(CH), 125.1 (CH), 125.4 (C), 127.6 (CHꢂ2), 132.7 (CHꢂ2),
136.9 (C), 142.5 (CH), 155.8 (C); MS (EI, 70 eV) m/z (relative
intensity) 220 (Mþ1, 22), 219 (Mþ, 100), 190 (53); HRMS
(EI) calcd for C15H9NO 219.0684, found 219.0688.
CDCl3) d 3.72 (s, 3H), 4.19 (s, 2H), 6.42 (dd, J¼2.8, 8.4 Hz,
1H), 6.51 (d, J¼2.4 Hz, 1H), 7.03 (d, J¼8.4 Hz, 1H), 7.45e
7.49 (m, 2H), 7.57e7.60 (m, 1H), 8.05e8.07 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 40.4 (CH2), 55.3 (CH3), 103.3
(CH), 106.8 (CH), 113.1 (C), 128.8 (2ꢂCH), 129.0 (2ꢂCH),
131.4 (CH), 134.0 (CH), 135.8 (C), 156.7 (C), 160.5 (C),
201.4 (C); MS (EI, 70 eV) m/z (relative intensity) 242 (Mþ,
26), 151 (15), 137 (100), 105 (45), 77 (42); HRMS (EI) calcd
for C15H14O3 (Mþ) 242.0943, found 242.0954.
4.4.16. 3-(4-Fluorophenyl)benzo[b]furan (8f)
IR (neat) n 3056 (w), 1596 (m), 1570 (m), 1505 (s), 1452
4.4.20. 2-(2-Hydroxyphenyl)-1-(4-methylphenyl)-1-
ethanone (9d)
1
(s), 1341 (m), 1271 (s), 1108 (s) cmꢁ1; H NMR (400 MHz,
CDCl3) d 7.19 (m, 2H), 7.32e7.41 (m, 2H), 7.58e7.62 (m,
2H), 7.75 (s, 1H), 7.81 (ddd, J¼0.8, 0.8, 7.6 Hz, 1H); 13C
IR (neat) n 3424 (br), 3024 (w), 2961 (w), 2915 (w), 1675
(s), 1608 (m), 1596 (m), 1456 (m), 1341 (m), 1268 (w), 1224
(w) cmꢁ1; 1H NMR (400 MHz, CDCl3) d 2.40 (s, 3H), 4.24 (s,
2H), 6.85 (t, J¼7.6 Hz, 1H), 6.93 (d, J¼7.6 Hz, 1H), 7.14 (t,
J¼7.6 Hz, 2H), 7.27 (d, J¼8.4 Hz, 2H), 7.98 (d, J¼8.4 Hz,
2H); 13C NMR (100 MHz, CDCl3) d 21.6 (CH3), 40.8
(CH2), 117.5 (CH), 120.6 (CH), 121.2 (C), 128.8 (CH),
129.1 (2ꢂCH), 129.4 (2ꢂCH), 130.8 (CH), 133.3 (C), 145.0
(C), 155.6 (C), 200.7 (C); MS (EI, 70 eV) m/z (relative inten-
sity) 226 (Mþ, 14), 121 (100), 95 (27); HRMS (EI) calcd for
C15H14O2 (Mþ) 226.0993, found 226.1004.
NMR (100 MHz, CDCl3)
d
111.7 (CH), 115.8 (d,
J¼21.4 Hz, 2ꢂCH), 120.0 (CH), 121.3 (C), 123.0 (CH),
124.6 (CH), 126.3 (C), 128.0 (C), 129.0 (d, J¼7.6 Hz,
2ꢂCH), 141.1 (CH), 155.7 (C), 162.2 (d, J¼244 Hz, CF);
MS (EI, 70 eV) m/z (relative intensity) 212 (Mþ, 100), 184
(6), 183 (42), 182 (4); HRMS (EI) calcd for C14H9OF (Mþ)
212.0637, found 212.0647.
4.4.17. 3-[4-(Trifluoromethyl)phenyl]-1-benzofuran (8h)
IR (neat) n 3120 (w), 3057 (w), 1912 (w), 1683 (m), 1652 (s),
1622 (s), 1558 (m), 1506 (m), 1451 (s), 1413 (s), 1327 (s), 1265
4.4.21. 1-(4-Fluorophenyl)-2-(2-hydroxyphenyl)-1-
ethanone (9f)
IR (neat) n 3424 (s), 2538 (s), 1677 (s), 1598 (s), 1454 (s),
1
(s), 1219 (s) cmꢁ1; H NMR (400 MHz, CDCl3) d 7.33 (ddd,
J¼1.2, 7.2, 7.2 Hz, 1H), 7.38 (ddd, J¼1.6, 7.2, 7.2 Hz, 1H),
7.57 (dd, J¼1.2, 7.2 Hz, 1H), 7.71e7.76 (m, 4H), 7.81 (dd,
J¼1.6, 7.2 Hz, 1H), 7.84 (s, 1H); 13C NMR (100 MHz,
CDCl3) d 111.3 (C), 111.9 (CH), 120.1 (CH), 121.1 (C),
1
1464 (m), 1344 (m), 1217 (m) cmꢁ1; H NMR (400 MHz,
CDCl3) d 4.24 (s, 2H), 6.86 (dd, J¼7.2, 7.6 Hz, 1H), 6.93 (d,
J¼7.6 Hz, 1H), 7.18e7.13 (m, 4H), 8.13e8.09 (m, 2H); 13C

S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
2593
NMR (100 MHz, CDCl3) d 40.8 (CH2), 116.0 (CH), 116.4 (d,
J¼22.9 Hz, 2ꢂCH), 120.5 (CH), 123.0 (C), 129.2 (CH), 132.0
(CH), 132.4 (d, J¼9.2 Hz, 2ꢂCH), 134.7 (C), 156.2 (C),
167.0 (d, J¼250.4 Hz, CF), 199.3 (C); MS (EI, 70 eV) m/z (rel-
ativeintensity) 230 (Mþ, 30), 123 (100), 107 (9), 95 (30); HRMS
(EI) calcd for C14H11FO2 (Mþ) 230.0743, found 230.0736.
1H), 7.40e7.44 (m, 3H), 7.80e7.82 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 55.7 (CH3), 95.9 (CH), 101.1 (CH),
111.9 (CH), 120.9 (CH), 122.6 (C), 124.4 (2ꢂCH), 128.0
(CH), 128.7 (2ꢂCH), 130.7 (C), 155.2 (C), 156.0 (C), 158.1
(C); MS (EI, 70 eV) m/z (relative intensity) 224 (Mþ, 82)
209 (100), 153 (33), 77 (15); HRMS (EI) calcd for
C14H12O4 (Mþ) 224.0837, found 224.0825. Anal. Calcd for
C14H12O4: C, 80.34; H, 5.39. Found: C, 80.46; H, 5.44.
4.4.22. 4-[(2-Hydroxyphenyl)acetyl]benzonitrile (9g)
IR (neat) n 3431 (s), 3068 (w), 2924 (w), 2852 (w), 2242
(m), 1683 (s), 1558 (s), 1506 (s), 1457 (s), 1401 (s), 1339
4.4.26. 2-(4-Fluorophenyl)benzo[b]furan (10f)
IR (neat) n 3066 (w), 2928 (w), 2853 (w), 1600 (s), 1504
1
(s), 1268 (m), 1213 (m) cmꢁ1; H NMR (400 MHz, CDCl3)
1
d 4.28 (s, 2H), 6.43 (br, 1H), 6.87 (dd, J¼1.2, 7.6 Hz, 1H),
6.99 (ddd, J¼1.2, 7.2, 7.6 Hz, 1H), 7.14 (dd, J¼1.6, 7.2 Hz,
1H), 7.17 (ddd, J¼1.6, 7.6, 7.6 Hz, 1H), 7.77 (dd, J¼2.0,
6.4 Hz, 2H), 8.14 (dd, J¼2.0, 6.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 40.9 (CH2), 116.8 (C), 117.0 (CH),
117.8 (C), 120.3 (C), 121.2 (CH), 129.2 (CHꢂ2), 129.2
(CH), 131.1 (CH), 132.6 (CHꢂ2), 139.1 (C), 154.6 (C),
198.5 (C); MS (EI, 70 eV) m/z (relative intensity) 238
(Mþ1, 12), 237 (Mþ, 72), 130 (100), 107 (36), 102 (16);
HRMS (EI) calcd for C15H11NO2 237.0790, found 237.0778.
(s), 1452 (s), 1300 (m), 1234 (m), 1097 (m) cmꢁ1; H NMR
(400 MHz, CDCl3) d 6.93 (s, 1H), 7.10e7.15 (m, 2H),
7.21e7.30 (m, 2H), 7.50 (d, J¼8.0 Hz, 1H), 7.57 (dd,
J¼0.8, 8.0 Hz, 1H), 7.80e7.84 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 101.0 (CH), 111.1 (CH), 115.8 (d,
J¼22.9 Hz, 2ꢂCH), 120.8 (CH), 123.0 (CH), 124.2 (CH),
126.7 (d, J¼7.6 Hz, 2ꢂCH), 129.2 (C), 154.9 (C), 155.0
(C), 162.9 (d, J¼247.3 Hz, C); MS (EI, 70 eV) m/z (relative
intensity) 212 (Mþ, 100), 183 (34), 157 (4), 106 (3); HRMS
(EI) calcd for C14H12O4 (Mþ) 212.0637, found 212.0629.
4.4.23. 2-(2-Hydroxyphenyl)-1-[4-(trifluoromethyl)phenyl]-
ethanone (9h)
4.4.27. 4-(1-Benzofuran-2-yl)benzonitrile (10g)
IR (neat) n 2226 (m), 1734 (m), 1684 (s), 1653 (s), 1558 (s),
IR (neat) n 3435 (s), 1682 (s), 1596 (m), 1458 (m), 1405
(m), 1341 (m), 1327 (m), 1312 (m), 1259 (m), 1118
1506 (s) cmꢁ1 1H NMR (400 MHz, CDCl3) d 7.16 (d,
;
J¼0.8 Hz, 1H), 7.25 (ddd, J¼0.8, 7.2, 7.6 Hz, 1H), 7.34
(ddd, J¼1.2, 7.2, 8.4 Hz, 1H), 7.52 (dd, J¼0.8, 8.4 Hz, 1H),
7.61 (ddd, J¼0.8, 1.2, 7.6 Hz, 1H), 7.70 (dd, J¼1.6, 8.0 Hz,
2H), 7.92 (dd, J¼1.6, 8.0 Hz, 2H); 13C NMR (100 MHz,
CDCl3) d 104.3 (CH), 111.4 (CH), 111.5 (C), 118.7 (C),
121.5 (CH), 123.4 (CH), 125.1 (CHꢂ2), 125.5 (CH), 128.6
(C), 132.6 (CHꢂ2), 134.4 (C), 153.5 (C), 155.2 (C); MS
(EI, 70 eV) m/z (relative intensity) 220 (Mþ1, 24), 219 (Mþ,
100), 190 (68), 164 (19), 163 (11); HRMS (EI) calcd for
C15H9NO 219.0684, found 219.0697.
1
(s) cmꢁ1; H NMR (400 MHz, CDCl3) d 4.29 (s, 2H), 6.83
(br, 1H), 6.86e6.90 (m, 2H), 7.14e7.18 (m, 2H), 7.73 (dd,
J¼0.8, 8.0 Hz, 2H), 8.16 (dd, J¼0.8, 8.0 Hz, 2H); 13C NMR
(100 MHz, CDCl3) d 40.9 (CH2), 117.1 (CH), 120.5 (C),
121.1 (CH), 123.5 (q, 1J¼270.9 Hz, CF3), 125.8 (q,
3J¼3.8 Hz, CHꢂ2), 129.1 (CH), 129.2 (CHꢂ2), 131.0 (CH),
2
134.9 (q, J¼32.5 Hz, C), 138.7 (C), 154.8 (C), 199.3 (C);
MS (EI, 70 eV) m/z (relative intensity) 280 (Mþ, 26), 173
(100), 145 (41), 107 (57), 77 (29); HRMS (EI) calcd for
C15H11F3O2 280.0711, found 280.0714.
4.4.28. 2-[4-(Trifluoromethyl)phenyl]-1-benzofuran (10h)
IR (neat) n 2919 (w), 2851 (w), 1681 (w), 1652 (w), 1610
(w), 1506 (m), 1472 (m), 1412 (m), 1326 (m), 1294 (m), 1163
4.4.24. 6-Allyloxy-2-phenyl-1-benzofuran (10a)
IR (film) n 3082 (m), 2915 (w), 1619 (s), 1566 (m) cmꢁ1
;
1H NMR (400 MHz, CDCl3) d 4.60 (d, J¼5.2 Hz, 2H), 5.33
(dd, J¼1.2, 5.2 Hz, 1H), 5.47 (dd, J¼1.2, 8.8 Hz, 1H),
6.07e6.16 (m, 1H), 6.91 (dd, J¼2.4, 4.4 Hz, 1H), 6.94 (s,
1H), 7.09 (d, J¼1.2 Hz, 1H), 7.32 (dt, J¼0.4, 7.2 Hz, 1H),
7.41e7.45 (m, 3H), 7.82 (d, J¼4.0 Hz, 2H); 13C NMR
(125 MHz, CDCl3) d 69.4 (CH2), 97.1 (CH), 101.1 (CH),
112.6 (CH), 117.7 (CH2), 121.0 (CH), 122.8 (C), 124.5
(2ꢂCH), 128.0 (CH), 128.7 (2ꢂCH), 130.7 (C), 133.3 (CH),
155.2 (C), 155.8 (C), 157.0 (C); MS (EI, 70 eV) m/z (relative
intensity) 250 (24), 209 (100), 153 (15.3), 152 (33.2), 128
(64), 105 (14.2); HRMS (EI) calcd for C17H14O2 (Mþ)
250.0994, found 250.0986.
(s), 1108 (s) cmꢁ1; H NMR (400 MHz, CDCl3) d 7.12 (d,
1
J¼0.8 Hz, 1H), 7.24 (ddd, J¼0.8, 7.2, 7.6 Hz, 1H), 7.32 (ddd,
J¼1.2, 7.2, 8.4 Hz, 1H), 7.53 (dd, J¼0.8, 8.4 Hz, 1H), 7.60
(ddd, J¼0.8, 1.2, 7.6 Hz, 1H), 7.68 (dd, J¼0.8, 8.0 Hz, 1H),
7.95 (dd, J¼0.8, 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 103.2 (CH), 111.3 (CH), 121.3 (CH), 123.3 (CH), 124.1 (q,
1J¼270.1 Hz, CF3), 124.9 (CHꢂ2), 125.1 (CH), 125.8 (q,
3J¼3.8 Hz, CHꢂ2), 128.8 (C), 130.1 (q, 2J¼32.2 Hz, C),
133.7 (C), 154.2 (C), 155.1 (C); MS (EI, 70 eV) m/z (relative
intensity) 263 (Mþ1, 18), 262 (Mþ, 100), 165 (36), 106 (10);
HRMS (EI) calcd for C15H9F3O 262.0605, found 262.0602.
4.4.29. 1-(2-Hydroxyphenyl)-2-(3-methyl-4-nitrophenyl)-
ethanone (12j)
4.4.25. 6-Methoxy-2-phenylbenzo[b]furan (10c)
IR (neat) n 3113 (w), 3007 (w), 2965 (w), 2838 (w), 1615
IR (neat) n 3056 (br), 2973 (w), 2931 (w), 2856 (w), 1636
(s), 1612 (s), 1581 (m), 1520 (s), 1487 (s), 1447 (s), 1340 (s),
1
(s), 1560 (s), 1488 (s), 1450 (s), 1298 (s) cmꢁ1; H NMR
1
(400 MHz, CDCl3) d 3.86 (s, 3H), 6.86 (dd, J¼2.0, 8.4 Hz,
1273 (m) cmꢁ1; H NMR (400 MHz, CDCl3) d 2.59 (s, 3H),
1H), 6.94 (s, 1H), 7.07 (d, J¼2.0 Hz, 1H), 7.29e7.33 (m,
4.35 (s, 2H), 6.92 (ddd, J¼1.2, 7.6, 8.0 Hz, 1H), 6.99 (dd,

2594
S.K. Chittimalla et al. / Tetrahedron 64 (2008) 2586e2595
J¼1.2, 8.4 Hz, 1H), 7.21e7.23 (m, 2H), 7.49 (ddd, J¼1.6, 7.6,
8.4 Hz, 1H), 7.81 (dd, J¼1.6, 8.0 Hz, 1H), 7.96 (d, J¼8.4 Hz,
1H), 11.99 (s, 1H); 13C NMR (100 MHz, CDCl3) d 20.6
(CH3), 44.4 (CH2), 118.7 (C), 118.8 (CH), 119.2 (CH),
125.1 (CH), 128.1 (CH), 130.0 (CH), 134.0 (CH), 134.2 (C),
137.0 (CH), 139.5 (C), 148.1 (C), 162.8 (C), 202.3 (C); MS
(EI, 70 eV) m/z (relative intensity) 271 (Mþ, 3), 121 (100),
93 (10), 65 (14); HRMS (EI) calcd for C15H13NO4
271.0845, found 271.0850.
References and notes
1. (a) Johnson, A. W.; Lacount, R. B. J. Am. Chem. Soc. 1961, 417; (b)
Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1962, 84, 867; (c) Trost,
B. M.; Melvin, L. S. Sulfur Ylides: Emerging Synthetic Intermediates;
Blomquist, A. T., Wasserman, H. H., Eds.; Organic Chemistry A Series
of Monographs; Academic: New York, NY, 1975; Vol. 31, Chapter 5;
(d) Ng, J.-S.; Liu, C. Encyclopedia of Reagents in Organic Synthesis;
Paquette, L. A., Ed.; Wiley: New York, NY, 1995; pp 2159e2165; (e)
Gololobov, Y. G.; Nesmeyanov, A. N.; Lysenko, V. P.; Boldesku, I. E.
Tetrahedron 1987, 12, 2609; (f) Donaldson, W. A. Tetrahedron 2001,
57, 8589.
4.4.30. tert-Butyl(dimethyl)[2-(1-phenylvinyl)phenoxy]-
silane (24)
IR (neat) n 3059 (m), 3028 (m), 2956 (s), 2929 (s), 2884
(m), 2857 (s), 1942 (w), 1800 (w), 1612 (m), 1596 (s), 1574
(m), 1495 (s), 1486 (s), 1448 (s), 1276 (s), 1249 (s) cmꢁ1
1H NMR (400 MHz, CDCl3) d 0.03 (s, 6H), 1.69 (s, 9H),
5.27, 5.30 (abq, J¼1.2 Hz, 2H), 6.80 (dd, J¼0.8, 8.4 Hz,
1H), 6.95 (ddd, J¼1.2, 7.2, 7.2 Hz, 1H), 7.19e7.29 (m, 7H);
13C NMR (100 MHz, CDCl3) d 17.9 (C), 25.4 (CH3ꢂ5),
115.2 (CH2), 119.2 (CH), 121.0 (CH), 126.5 (CHꢂ2), 127.3
(CH), 128.0 (CHꢂ2), 128.7 (CH), 131.7 (CH), 133.3 (C),
140.6 (C), 147.5 (C), 153.1 (C); MS (EI) m/z (relative inten-
sity) 254 (Mꢁ56, 21), 53 (Mꢁ57, 100), 151 (11), 57 (8);
HRMS (EI) calcd for C20H26OSi 310.1753, found 253.1046
(Mꢁ57).
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3. (a) Thompson, S. K.; Heathcock, C. H. J. Org. Chem. 1990, 55, 3004;
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4. Aggarwal, V. K.; Richardson, J. Chem. Commun. 2003, 2644.
5. Holt, B.; Lowe, P. A. Tetrahedron Lett. 1966, 7, 683.
6. (a) Cagniant, P.; Cagniant, D. Adv. Heterocycl. Chem. 1975, 18, 337; (b)
Ohemeng, K. A.; Apollina, M. A.; Nguyen, V. N.; Schwender, C. F.;
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4.4.31. tert-Butyl(dimethyl)[2-(2-phenyloxiran-2-yl)-
phenoxy]silane (15)
IR (neat) n 3068 (m), 3041 (m), 2960 (s), 2933 (s), 2891
(m), 2856 (s), 1728 (w), 1597 (m), 1574 (m), 1493 (s), 1460
1
(s), 1450 (s), 1276 (s), 1253 (s), 1097 (m) cmꢁ1; H NMR
(400 MHz, CDCl3) d 0.14 (s, 3H), 0.19 (s, 3H), 0.76 (s, 9H),
3.19, 3.26 (abq, J¼5.6 Hz, 2H), 6.84 (dd, J¼0.8, 8.0 Hz,
1H), 6.96 (ddd, J¼1.2, 7.2, 7.2 Hz, 1H), 7.16e7.25 (m, 6H),
7.40 (dd, J¼1.6, 7.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 17.9 (C), 25.4 (CH3ꢂ5), 57.5 (CH2), 59.2 (C), 117.8 (CH),
120.7 (CH), 126.0 (CHꢂ2), 127.4 (CH), 127.9 (CHꢂ2),
129.2 (CH), 129.7 (C), 130.2 (CH), 140.1 (C), 154.2 (C);
MS (EI) m/z (relative intensity) 326 (Mþ, 16), 270 (23), 269
(100), 195 (2), 77 (3); HRMS (EI) calcd for C20H26O2Si
326.1702, found 326.1718.
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Acknowledgements
Financial support by the National Science Council, Taiwan
is sincerely acknowledged. (Grant No: NSC-95-2113-M-400-
001-MY3 and NSC- 95-2752-B-007 for HPH; NSC-95-
2113-M-007-027-MY3 for CCL.) One of the authors S.K.C.
thanks National Science Council, Taiwan for postdoctoral
fellowship.
10. (a) Chittimalla, S. K. Ph.D. Thesis, National Tsing Hua University, 2004;
(b) Chang, T.-C. Master Dissertation, National Tsing Hua University,
2005.
Supplementary data
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J.-H.; Li, W.-D. Z. Tetrahedron 2006, 62, 1209; (b) Date, S. M.; Singh,
R.; Ghosh, S. K. Org. Biomol. Chem. 2005, 3, 3369.
Copies of 1H and 13C NMR spectra were provided. Supple-
mentary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2008.01.024.
12. Kashulin, I. A.; Nifant’ev, I. E. J. Org. Chem. 2004, 69, 5476.

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