Rh(III)-catalyzed aldehyde C-H bond functionalization of salicylaldehydes with arylboronic acids

Article abstract of DOI:10.1016/j.tet.2015.09.053

A Rh(III)-catalyzed aldehyde C-H bond functionalization of salicylaldehydes with arylboronic acids has been developed, with features of mild reaction condition and high efficiency. Furthermore, the functionalized 2-hydroxybenzophenone could be subject to divergent synthesis of heterocycles.

Full text of DOI:10.1016/j.tet.2015.09.053

Tetrahedron 71 (2015) 8511e8516
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Rh(III)-catalyzed aldehyde CeH bond functionalization of
salicylaldehydes with arylboronic acids
Dahai Wang, Sunliang Cui *
Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 July 2015
Received in revised form 18 September 2015
Accepted 22 September 2015
Available online 25 September 2015
A Rh(III)-catalyzed aldehyde CeH bond functionalization of salicylaldehydes with arylboronic acids has
been developed, with features of mild reaction condition and high efficiency. Furthermore, the func-
tionalized 2-hydroxybenzophenone could be subject to divergent synthesis of heterocycles.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
CeH activation
Rh(III) catalysis
Salicylaldehydes
2-Hydroxybenzophenones
Divergent synthesis
1. Introduction
molecules. The classical approach relies on Fries rearrangement of
phenyl ester which is derived from phenol. There also are
4
2
-Hydroxybenzophenones are important building blocks in
transition-metal-catalyzed transformations for access to these
compounds. For example, Chen reported a Pd-catalyzed cross
coupling of salicylaldehyde and diaryliodonium salts for synthesis
synthetic chemistry owing to their high reactivity, particular in the
fields of medicinal chemistry. Due to its prevalence in biologically
active products and synthetic molecules, great efforts have
been devoted to the synthesis of molecules with the 2-
hydroxybenzophenone skeleton, and representative examples are
shown in Fig. 1. These molecules exhibiting a variety of biological
activities, and acted as selective inhibitors of human immunodefi-
ciency virus type 1 reverse transcriptase, antispasmodic agents,
inhibitors of transforming growth factor-kinase. Therefore, there
are many methods reported toward construction of these
5
of 2-hydroxybenzophenones. Meanwhile, Xu also developed a Pd-
catalyzed oxidative coupling of salicylaldehyde with arylboronic
6
acids. Recently, Li reported a Rh-catalyzed rearrangement of 2-
aryloxybenzaldehyde for transforming to 2-hydroxybenzo-
7
phenones. Interestingly, Rao and Dong independently reported
1
2
the Pd-catalyzed ketone-directed hydroxylation of arenes for syn-
3
8
thesis of 2-acylphenols.
Recently, Rh(III)-catalyzed functionalization of aryl CeH bond
has enjoyed tremendous advance owing to their wide applications
to the rapid assembly of various complex molecular structures,
9
particular in the fields of medicinal chemistry. In particular, the
Rh(III)-catalyzed CeH functionalization of aldehyde has been paid
attention. For example, Miura explored the Rh(III)-catalyzed oxi-
dative coupling between salicylaldehydes and internal alkynes,
demonstrating the flexible reactivity of aldehyde in CeH func-
10
11
12
13
tionalization. Inspired by this, Glorius, Radhakrishnan and Li
reported that Rh(III)-catalyzed oxidative coupling of salicylalde-
hydes with electron deficient olefins, diazabicyclic olefins and TIPS-
EBX, respectively. In continuation of our interest in Rh(III)-
catalyzed CeH functionalization for biologically interesting small
molecule synthesis, herein we report a Rh(III)-catalyzed aldehyde
CeH bond functionalization of salicylaldehydes with arylboronic
acids. Moreover, the functionalized 2-hydroxybenzophenones
Fig. 1. Biologically active products containing 2-hydroxybenzophenone skeleton.
14
*
Corresponding author. Tel./fax: þ86 571 8898 1456; e-mail address: slcui@zju.
edu.cn (S. Cui).
http://dx.doi.org/10.1016/j.tet.2015.09.053
0
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

8512
D. Wang, S. Cui / Tetrahedron 71 (2015) 8511e8516
could be subject to various transformations to access divergent
compounds (Scheme 1).
98% yield (Table 1, entry 2). This encouraged us to screen the ad-
ditives, and we found other additives, such as AgOAc, Ag O and
were inferior (Table 1, entries 3e5). When the solvent was
changed to CH CN, the reaction afforded trace product when
Cu(OAc) was used as additive (entry 6). Surprisingly, the combi-
nation of CH CN and Ag O gave the product in 85% yield (entry 7).
2
2 2 8
K S O
3
2
3
2
Further survey of solvents revealed that MeOH, t-amyl alcohol,
trifluoroethanol (TFE) and dioxane were not optimal to produce
trace products (entries 8e11). Moreover, when the temperature
ꢀ
was decreased to 40 C, the reaction would give the product in
a slightly lower yield (entry 12, 76%).
With the optimized reaction condition in hand, we next ex-
panded the scope of this Rh(III)-catalyzed aldehyde functionaliza-
tion using a variety of salicylaldehydes and arylboronic acids. As
depicted in Table 2, various para-substituted arylboronic acids with
valuable functional groups like bromo, chloro, methoxy, methyl,
cyano, hydroxy, phenyl, could react smoothly with 1a in this
process to furnish the products (3be3h) in excellent yields,
thus offering ample opportunity for further derivatization. The
Table 2
a
Rh(III)-catalyzed aldehyde functionalization of salicylaldehydes
Scheme 1. Rh(III)-catalyzed aldehyde CeH functionalization of salicylaldehydes.
2
. Results and discussions
We commenced our study by investigating the coupling of sal-
icylaldehyde 1a and phenylboronic acid 2a using [Cp*RhCl
2
]
2
as
ꢀ
catalyst. When the reaction was conducted in DMF at 80 C without
additives, the Rh(III) catalyzed CeH functionalized product was not
observed (Table 1, entry 1). Gratifyingly, equivalent addition of
Cu(OAc)
2
led to the formation of 2-hydroxybenzophenone 3a in
Table 1
a
Optimization of reaction conditions
ꢀ
Yield [%]b
Entry
Additive
None
Solvent
T [ C]
1
2
3
4
5
6
7
8
9
DMF
DMF
DMF
DMF
DMF
80
80
80
80
80
60
60
60
80
60
80
40
0
98
Cu(OAc)
AgOAc
2
Trace
Trace
Trace
Trace
85
Trace
Trace
Trace
Trace
76
2
Ag O
K S O
2 2 8
Cu(OAc)
Ag
2
CH
CH
3
CN
CN
2
O
3
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
2
2
2
2
2
MeOH
t-Amyl alcohol
TFE
Dioxane
DMF
10
11
12
a
a
Reaction conditions: 1a (0.2 mmol), 2a (0.4 mmol), [Cp*RhCl
2
]
2
(4 mol %), ad-
2 2
Reaction Conditions: 1 (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl ] (4 mol %),
o
ditives (2 equiv), solvent (2 mL).
2
Cu(OAc) (2 equiv), DMF (2 mL), 80 C, 8 h.
b
Yields of isolated products.

D. Wang, S. Cui / Tetrahedron 71 (2015) 8511e8516
8513
ortho-substituted and polysubstituted arylboronic acids were also
applicable to furnish the product in moderate to excellent yields
activation of aldehyde occurred to form intermediate A. The
transmetalation of A with arylboronic acid 2a would lead to B, and
reductive elimination furnished the CeC coupling product 3a and
(3ie3l). Additionally, naphthalen-2-ylboronic acid and thiophen-3-
ylboronic acid were amenable to afford the products in moderate to
excellent yields (3me3n). Next, various functionalized salicy-
laldehydes were employed and found suitable in this oxidative
coupling to afford the structural differential 2-hydroxyb-
enzophenones, with diethylamino, chloro and bromo substitution
in the aromatic ring (3oe3t). Furthermore, 2-hydroxy-1-
naphthaldehyde was also applicable to access the corresponding
products in good yields (3u, 3v).
2 2
a Rh(I) species. Reoxidation of Rh(I) to Cp*Rh(OAc) by Cu(OAc)
would enable the catalytic cycle to proceed. Indeed, when benzal-
dehyde was subjected to this reaction condition, the oxidative
coupling was not observed while benzaldehyde was recovered,
thus demonstrating this reaction triggered by the ortho-hydroxy
directed CeH activation.
3. Conclusions
As mentioned before, 2-hydroxybenzophenones were versatile
building block and could be subject to divergent transformations.
The unique features were then studied using 3a as model com-
pound. As shown in Scheme 2, when 3a was treated with ethyl-2-
In conclusion, we have developed a Rh(III)-catalyzed aldehyde
CeH bond functionalization of salicylaldehydes with arylboronic
acids under mild reaction condition. Furthermore, the functional-
ized 2-hydroxybenzophenones could take divergent trans-
formations to access a variety of heterocycles.
(
triphenylphosphoranylidene)acetate in the presence of catalytic
DMAP, the Wittig reaction occurred to form coumarin derivative 4
4
4
. Experimental section
.1. General
All commercially available reagents were used without purifi-
cation unless otherwise noted. Column chromatography was per-
formed using silica gel (200e300 mesh). Visualization of the
compounds was accomplished with UV light (254 nm) and iodine.
1
13
H NMR and C NMR spectra were recorded in CDCl
00 MHz and 100 MHz, respectively. Proton chemical shifts are
reported relative to the residual proton signals of the deuterated
solvent CDCl (7.26 ppm) or TMS. Carbon chemical shifts were in-
ternally referenced to the deuterated solvent signals in CDCl
77.160 ppm). Chemical shifts are reported in (parts per million)
3
operating at
4
3
3
(
d
Scheme 2. Divergent transformations of 3a. Reaction conditions: (a) Ethyl-2-
values. Coupling constants J are reported in Hertz. Proton coupling
patterns were described as singlet (s), doublet (d), triplet (t),
quartet (q), and multiple (m). Mass spectra were measured with
a low-resolution MS instrument using ESI ionization.
(
triphenylphosphoranylidene)acetate (1.07 equiv), DMAP (5.4% mmol), toluene,
reflux, Argon, 10 h; (b) (i) Methyl bromoacetate (1.2 equiv), K CO (1.5 equiv), acetone,
reflux, 2 h; (ii) sodium methanolate (3 equiv), MeOH, reflux, 10 h; (c) ClSO NCO
1 equiv), toluene, reflux, 10 h.
2
3
2
(
General procedure for the synthesis of compounds 3ae3v. A
mixture of salicylaldehyde (0.2 mmol) and arylboronic acid
in 91% yield. 3a could also be transformed into a benzofuran
derivative 5 in 43% yield, when treated with methyl bromoacetate,
2 2
(0.4 mmol) was dissolved in DMF (2 mL) and [Cp*RhCl ] (4.9 mg,
4
mol %) and Cu(OAc)
2
(72.8 mg, 0.4 mmol) was added. Then the
K
2
CO
zophenones can be converted to 4-phenylbenzo[e][1,2,3]oxathia-
zine 2,2-dioxide 6 upon cyclization with ClSO NCO.
3
and sodium methanolate. Furthermore, 2-hydroxyben-
ꢀ
reaction was conducted in a sealed tube at a temperature of 80 C
for 8 h. The reaction mixture was diluted with ethylacetate (20 mL),
2
washed with H
2
O (3ꢁ10 mL). The organic layer was then dried over
Based on the results and precedents, a plausible mechanism was
depicted in Scheme 3. The initial rhodium diacetate was generated
anhydrous Na SO
2
4
, filtered and concentrate. The crude product was
loaded on a silica gel column and flashed with 5e10% ethyl acetate
in petroleum ether to afford the desired products 3 as solid or
liquid.
2 2 2
from [Cp*RhCl ] and Cu(OAc) , and a carboxylate-assisted CeH
4.2. Compound (3a)
(
2-Hydroxyphenyl)(phenyl)methanone 3a. Pale yellow liquid
1
(
38.8 mg, 98%); H NMR (CDCl
3
, 400 MHz), d: 12.05 (s, 1H),
7
.69e7.67 (m, 2H), 7.62e7.58 (m, 2H), 7.53e7.49 (m, 3H), 7.08 (dd,
13
J
1
¼8.4 Hz, J
2
¼1.2 Hz, 1H), 6.90e6.86 (m, 1H); C NMR (CDCl
3
,
100 MHz),
d
: 201.6, 163.3, 137.9, 136.4, 133.6, 132.0, 129.2, 128.4,
1
19.1, 118.7, 118.4; IR (KBr) v: 3061, 2340, 1626, 1479, 1323, 1238,
ꢂ1
þ
935, 819, 695, 641 cm ; ESI-MS m/z positive 199.3 (MþH) , neg-
ꢂ
ative m/z 197.3 (MꢂH) .
4.3. Compound (3b)
(
4-Bromophenyl)(2-hydroxyphenyl)methanone 3b. Yellow solid
ꢀ
1
(
51.5 mg, 93%); Mp 85e89 C; H NMR (CDCl
3
, 400 MHz),
d: 11.89 (s,
1
6
H), 7.66e7.63 (m, 2H), 7.57e7.50 (m, 4H), 7.07 (d, J¼8.4 Hz, 1H),
13
3
.90e6.86 (m, 1H); C NMR (CDCl , 100 MHz), d: 200.4, 163.3,
Scheme 3. Proposed mechanism.
136.72, 136.68, 133.3, 131.8, 130.9, 127.0, 119.0, 118.9, 118.7; IR (KBr)

8
514
D. Wang, S. Cui / Tetrahedron 71 (2015) 8511e8516
ꢂ1
v: 3480, 2340, 1944, 1804, 1603, 1494, 1214, 912, 811, 749 cm ; ESI-
3
NMR (CDCl , 100 MHz), d: 201.3, 163.3, 145.0, 140.0, 136.7, 136.5,
þ
MS m/z positive 277.2/279.3 (MþH) , negative m/z 275.3/277.3
133.6, 130.0, 129.1, 128.4, 127.4, 127.2, 119.4, 118.8, 118.6; IR (KBr) v:
3418, 2332, 1967, 1610, 1432, 1308, 935, 734, 648 cm ; ESI-MS m/z
positive 275.4 (MþH) , negative m/z 273.4 (MꢂH) .
ꢂ
ꢂ1
(
MꢂH) .
þ
ꢂ
4
.4. Compound (3c)
4
.10. Compound (3i)
(
4-Chlorophenyl)(2-hydroxyphenyl)methanone 3c. Yellow solid
ꢀ
1
(
1
45.6 mg, 98%); Mp 68e72 C; H NMR (CDCl
3
, 400 MHz),
d
: 11.89 (s,
¼8.4 Hz,
, 100 MHz),
00.3, 163.3, 138.5, 136.7, 136.2, 133.3, 130.7, 128.8, 119.0, 118.9,
(2-Hydroxyphenyl)(o-tolyl)methanone
3i.
Yellow
solid
: 12.26
H), 7.65e7.62 (m, 2H), 7.55e7.47 (m, 4H), 7.08 (dd, J
1
ꢀ
1
13
(35.6 mg, 84%); Mp 62e67
C; H NMR (CDCl , 400 MHz),
d
J
2
¼0.8 Hz, 1H), 6.91e6.86 (m, 1H); C NMR (CDCl
3
d:
3
(
(
s,1H), 7.52e7.47 (m,1H), 7.42e7.38 (m,1H), 7.31e7.25 (m, 4H), 7.06
dd, J
2
13
1
¼8.4 Hz, J
2
¼0.8 Hz, 1H), 6.83e6.79 (m, 1H), 2.30 (s, 3H);
C
1
6
2
18.6; IR (KBr) v: 3403, 2937, 2332, 1952, 1843, 1618, 1486, 912, 765,
ꢂ1
þ
NMR (CDCl , 100 MHz),
131.0, 130.3, 127.6, 125.5, 120.0, 119.0, 118.4, 19.7; IR (KBr) v: 3387,
d
: 204.6, 163.4, 138.0, 136.9, 135.6, 133.8,
64 cm ; ESI-MS m/z positive 233.3/235.3 (MþH) , negative m/z
3
ꢂ
31.3/233.3 (MꢂH) .
ꢂ1
2945, 2340, 1998, 1828, 1564, 928, 780, 687 cm ; ESI-MS m/z
þ
ꢂ
positive 213.3 (MþH) , negative m/z 211.4 (MꢂH) .
4
.5. Compound (3d)
(
2-Hydroxyphenyl)(4-methoxyphenyl)methanone 3d. Pale yel-
1
4.11. Compound (3j)
low liquid (31.9 mg, 70%); H NMR (CDCl
H), 7.73e7.70 (m, 2H), 7.63 (dd, J
m, 1H), 7.06 (dd, J ¼0.8 Hz, 1H), 7.01e6.98 (m, 2H),
¼8.0 Hz, J
3
, 400 MHz),
d: 11.98 (s,
1
(
6
1
5
7
2
1
¼8.0 Hz, J ¼1.6 Hz,1H), 7.51e7.47
2
(3,5-Dimethoxyphenyl)(2-hydroxyphenyl)methanone 3j. Yel-
1
2
1
ꢀ
1
3
low solid (31.5 mg, 61%); Mp 62e65 C; H NMR (CDCl
: 11.97 (s, 1H), 7.64 (dd, J ¼1.6 Hz, 1H), 7.52e7.48 (m,
¼8.0 Hz, J
H), 7.06 (dd, J ¼0.8 Hz, 1H), 6.89e6.85 (m, 1H), 6.78 (d,
¼8.4 Hz, J
J¼2.4 Hz, 2H), 6.66 (t, J¼2.4 Hz, 1H), 3.83 (s, 6H); C NMR (CDCl
100 MHz), : 201.5, 163.3, 160.7, 139.8, 136.6, 133.7, 119.2, 118.8,
18.5, 107.1, 104.1, 55.7; IR (KBr) v: 3464, 2968, 2836, 1603, 1455,
3
, 400 MHz),
.90e6.86 (m,1H), 3.90 (s, 3H); C NMR (CDCl ,100 MHz), : 200.2,
3
d
d
1
2
63.02, 163.01, 135.9, 133.4, 132.0, 130.4, 119.5, 118.6, 118.4, 113.8,
5.6; IR (KBr) v: 2968, 2844, 2355, 1595, 1486, 1339, 1246,1160, 935,
1
1
2
13
ꢂ1
þ
3
,
65, 602 cm ; ESI-MS m/z positive 229.4 (MþH) , negative m/z
ꢂ
d
27.4 (MꢂH) .
1
ꢂ1
ꢂ
1
362, 1168, 1044, 912, 734, 656 cm ; ESI-MS m/z positive 259.3
4
.6. Compound (3e)
þ
(
MþH) , negative m/z 257.3 (MꢂH) .
.12. Compound (3k)
3,5-Dimethylphenyl)(2-hydroxyphenyl)methanone 3k. Pale
(
2-Hydroxyphenyl)(p-tolyl)methanone 3e. Pale yellow liquid
1
(
7
(
3
32.2 mg, 76%); H NMR (CDCl , 400 MHz), d: 12.06 (s, 1H),
4
.63e7.59 (m, 3H), 7.52e7.48 (m, 1H), 7.31 (d, J¼8.0 Hz, 2H), 7.07
1
3
dd, J
NMR (CDCl
1
¼8.4 Hz, J
2
¼0.8 Hz, 1H), 6.90e6.85 (m, 1H), 2.45 (s, 3H);
C
(
3
, 100 MHz),
d
: 201.5, 163.2, 142.9, 136.2, 135.3, 133.7,
1
yellow liquid (44.3 mg, 98%); H NMR (CDCl
3
, 400 MHz),
¼1.6 Hz, 1H), 7.52e7.48 (m, 1H), 7.27 (s,
H), 7.22 (s, 1H), 7.07 (dd, J ¼0.8 Hz, 1H), 6.90e6.86 (m,
¼8.4 Hz, J
H), 2.39 (s, 6H); C NMR (CDCl , 100 MHz), : 202.2, 163.3, 138.2,
38.1, 136.3, 133.8, 133.7, 126.9, 119.4, 118.7, 118.4, 21.4; IR (KBr) v:
d: 12.10 (s,
1
1
(
29.6, 129.1, 119.4, 118.7, 118.5, 21.7; IR (KBr) v: 3030, 2355, 1610,
486, 1331, 1246, 935, 765, 609 cm ; ESI-MS m/z positive 213.3
MþH) , negative m/z 211.3 (MꢂH) .
1
2
1
H), 7.61 (dd, J
1
¼8.0 Hz, J
2
ꢂ1
þ
ꢂ
1
2
13
3
d
1
3
4
.7. Compound (3f)
ꢂ1
046, 2914,1618,1486,1339,1214,1153, 858, 788, 710 cm ; ESI-MS
þ
ꢂ
m/z positive 227.3 (MþH) , negative m/z 225.3 (MꢂH) .
.13. Compound (3l)
2,4-Dimethoxyphenyl)(2-hydroxyphenyl)methanone 3l. Pale
4
-(2-Hydroxybenzoyl)benzonitrile 3f. Yellow solid (37.5 mg,
ꢀ
1
8
7
4%); Mp 117e119 C; H NMR (CDCl , 400 MHz), d: 11.78 (s, 1H),
3
.82e7.80 (m, 2H), 7.77e7.75 (m, 2H), 7.57e7.53 (m, 1H), 7.45 (dd,
¼8.0 Hz, J ¼1.6 Hz, 1H), 7.09 (dd, J ¼8.4 Hz, J ¼0.8 Hz, 1H),
.92e6.87 (m, 1H); C NMR (CDCl , 100 MHz), : 199.9,163.5, 141.6,
37.3, 133.2, 132.3, 129.5, 119.2, 118.9, 118.6, 118.0, 115.4; IR (KBr) v:
480, 2363, 2231, 1626, 1470, 1331, 1230, 920, 842, 772, 687 cm
ESI-MS m/z negative m/z 222.3 (MꢂH) .
4
J
1
2
1
2
13
6
1
3
3
d
(
1
yellow liquid (22.7 mg, 44%); H NMR (CDCl
3
, 400 MHz),
H), 7.47e7.39 (m, 2H), 7.28 (d, J¼8.4 Hz, 1H), 7.01 (dd, J
¼0.8 Hz, 1H), 6.82e6.78 (m, 1H), 6.58e6.54 (m, 2H), 3.87 (s, 3H),
d: 12.23 (s,
ꢂ1
;
1
1
¼8.0 Hz,
ꢂ
J
2
13
3
3
.76 (s, 3H); C NMR (CDCl , 125 MHz), d: 201.4, 163.3, 163.0, 158.7,
4
.8. Compound (3g)
136.2, 133.9, 131.1, 120.8, 120.6, 118.6, 118.1, 104.7, 99.0, 55.8, 55.7; IR
(
6
KBr) v: 2937, 2844, 2363, 1610, 1463, 1214, 1145, 1021, 935, 757,
(
2-Hydroxyphenyl)(4-hydroxyphenyl)methanone 3g. Yellow
ꢂ1
þ
09 cm ; ESI-MS m/z positive 259.3 (MþH) , negative m/z 257.2
ꢀ
1
ꢂ
solid (19.3 mg, 45%); Mp 144e147 C; H NMR (CDCl
3
, 400 MHz),
d
:
:
(MꢂH) .
1
1
2
1.98 (s,1H), 7.68e7.62 (m, 3H), 7.52e7.48 (m, 1H), 7.07 (d, J¼8.0 Hz,
13
3
H), 6.94e6.88 (m, 3H), 6.06 (s, 1H); C NMR (CDCl , 100 MHz),
d
00.3, 163.0, 159.7, 136.1, 133.5, 132.3, 130.5, 119.5, 118.8, 118.5,
4.14. Compound (3m)
1
15.4; IR (KBr) v: 3434, 2363, 1579, 1494, 1432, 1323, 1207, 912, 765,
ꢂ1
þ
6
09 cm ; ESI-MS m/z positive 215.4 (MþH) , negative m/z 213.3
(2-Hydroxyphenyl)(naphthalen-2-yl)methanone 3m. Yellow
ꢂ
ꢀ
1
(
MꢂH) .
solid (48.6 mg, 98%); Mp 77e81 C; H NMR (CDCl
2.09 (s, 1H), 8.18 (s, 1H), 7.98e7.92 (m, 3H), 7.79 (dd, J
¼1.6 Hz,1H), 7.68 (dd, J ¼8.0 Hz, J ¼1.6 Hz,1H), 7.65e7.52 (m, 3H),
.13 (dd, J ¼0.8 Hz, 1H), 6.92e6.88 (m, 1H); C NMR
¼8.4 Hz, J
(CDCl , 100 MHz), : 201.6, 163.3, 136.4, 135.2, 134.9, 133.8, 132.3,
3
, 400 MHz),
d:
1
1
¼8.4 Hz,
4
.9. Compound (3h)
J
2
1
2
13
7
1
2
0
[
1,1 -Biphenyl]-4-yl(2-hydroxyphenyl)methanone 3h. Yellow
3
d
ꢀ
1
solid (23.6 mg, 43%); Mp 87e90 C; H NMR (CDCl
3
, 400 MHz),
d:
130.6, 129.3, 128.5, 128.3, 128.0, 127.1, 125.4, 119.4, 118.8, 118.5; IR
ꢂ1
ꢂ
1
2.07 (s, 1H), 7.76 (m, 4H), 7.70e7.66 (m, 3H), 7.56e7.49 (m, 3H),
(KBr) v: 3472, 2355, 1633, 1595, 1486, 1308, 1191, 795, 718 cm
;
13
þ
7.45e7.41 (m, 1H), 7.11 (d, J¼8.0 Hz, 1H), 6.94e6.90 (m, 1H);
C
ESI-MS m/z positive 249.4 (MþH) , negative m/z 247.4 (MꢂH) .

D. Wang, S. Cui / Tetrahedron 71 (2015) 8511e8516
8515
4
.15. Compound (3n)
2-Hydroxyphenyl)(thiophen-3-yl)methanone 3n. Pale yellow
4.21. Compound (3t)
(
(5-Bromo-2-hydroxyphenyl)(phenyl)methanone 3t. Yellow
solid (50.4 mg, 91%); Mp 105e107 C; H NMR (CDCl
11.93 (s, 1H), 7.70e7.66 (m, 3H), 7.64e7.57 (m, 2H), 7.55e7.52 (m,
1
ꢀ
1
liquid (15.5 mg, 38%); H NMR (CDCl
.96 (dd, J
m, 1H), 7.20 (t, J
3
, 400 MHz),
¼1.6 Hz, 1H), 7.75 (d, J ¼4.4 Hz, 2H), 7.54e7.50
¼4.4 Hz, 1H), 7.07 (dd, J ¼8.4 Hz, J ¼0.8 Hz, 1H),
, 100 MHz), : 191.3, 162.7, 142.4,
d
: 11.62 (s, 1H),
3
, 400 MHz), d:
7
(
1
¼8.0 Hz, J
2
1
13
1
1
2
2H), 6.99 (d, J¼9.2 Hz, 1H); C NMR (CDCl
3
, 100 MHz), d: 200.6,
1
3
6
.98e6.93 (m, 1H); C NMR (CDCl
3
d
162.2, 139.1, 137.3, 135.5, 132.5, 129.3, 128.7, 120.6, 120.5, 110.4; IR
ꢂ1
136.1, 134.7, 134.1, 132.0, 128.1, 119.6, 119.1, 118.6; IR (KBr) v: 2967,
(KBr) v: 3449, 2922, 2355, 1595, 1479, 1331, 935, 780, 664 cm
ESI-MS negative m/z 275.3/277.3 (MꢂH) .
;
ꢂ1
ꢂ
2
929, 2355, 1579, 1409, 1246, 757, 648 cm ; ESI-MS m/z positive
þ
ꢂ
2
05.3 (MþH) , negative m/z 203.3 (MꢂH) .
4.22. Compound (3u)
4
.16. Compound (3o)
(
2-Hydroxynaphthalen-1-yl)(phenyl)methanone 3u. Yellow
2
-Hydroxy-3-methoxyphenyl)(phenyl)methanone 3o. Yellow
ꢀ
1
solid (46.6 mg, 94%); Mp 136e139 C; H NMR (CDCl
1.20 (s, 1H), 7.91 (d, J¼8.8 Hz, 1H), 7.73 (d, J¼8.0 Hz, 1H), 7.63e7.61
m, 2H), 7.56e7.52 (m, 1H), 7.38 (t, J¼8.0 Hz, 2H), 7.30e7.22 (m, 3H),
3
, 400 MHz), d:
1
liquid (39.2 mg, 86%); H NMR (CDCl
.69e7.66 (m, 2H), 7.60e7.56 (m, 1H), 7.50e7.46 (m, 2H), 7.18 (dd,
¼8.0 Hz, J ¼1.2 Hz, 1H), 7.09 (d, J¼7.6 Hz, 1H), 6.81 (t, J¼8.0 Hz,
H), 3.93 (s, 3H); C NMR (CDCl
38.1, 132.1, 129.3, 128.4, 124.9, 119.4, 118.1, 117.1, 56.4; IR (KBr) v:
929, 2363, 1595, 1447, 1347, 1254, 982, 741, 695 cm ; ESI-MS m/z
positive 228.9 (MþH) , negative m/z 226.8 (MꢂH) .
3
, 400 MHz), d: 12.24 (s, 1H),
1
(
7
1
1
7
(
7
J
1
2
13
.16e7.12 (m, 1H); C NMR (CDCl
3
, 100 MHz), d: 200.5, 161.4, 140.4,
13
1
1
2
3
, 100 MHz), d: 201.9, 153.5, 149.1,
36.4, 132.8, 132.5, 129.5, 128.7, 128.5, 126.8, 126.4, 123.8, 119.3,
14.5; IR (KBr) v: 3387, 2347, 1642, 1564, 1424, 1238, 966, 819,
ꢂ1
ꢂ1
þ
02 cm ; ESI-MS m/z positive 249.4 (MþH) , negative m/z 247.4
þ
ꢂ
ꢂ
MꢂH) .
4
.17. Compound (3p)
4.23. Compound (3v)
(
4-(Diethylamino)-2-hydroxyphenyl)(phenyl)methanone
3p.
: 12.99 (s,
H), 7.62e7.60 (m, 2H), 7.53e7.44 (m, 3H), 7.37 (d, J¼9.2 Hz, 1H),
1
(4-Bromophenyl)(2-hydroxynaphthalen-1-yl)methanone
3v.
3
,
3
Yellow gel (37.7 mg, 70%); H NMR (CDCl , 400 MHz), d
ꢀ
1
Yellow solid (53.0 mg, 81%); Mp 151e155 C; H NMR (CDCl
400 MHz),
: 11.08 (s, 1H), 7.92 (d, J¼8.8 Hz, 1H), 7.75e7.73 (m, 1H),
.53e7.47 (m, 4H), 7.29e7.26 (m, 2H), 7.24e7.17 (m, 2H); C NMR
CDCl , 100 MHz), : 199.1, 161.5, 139.0, 136.6, 132.2, 132.0, 131.1,
1
6
13
d
.17e6.13 (m, 2H), 3.41 (q, J¼7.2 Hz, 4H), 1.21 (t, J¼7.2 Hz, 6H);
, 100 MHz), : 198.1, 166.4, 154.0, 139.1, 135.7, 130.8,
28.8, 128.2, 109.1, 103.7, 97.4, 44.8, 12.8; IR (KBr) v: 2967, 2921,
C
13
7
(
NMR (CDCl
3
d
3
d
1
1
2
ꢂ1
618, 1525, 1339, 1230, 1129, 795, 694 cm ; ESI-MS m/z positive
128.8, 128.5, 127.9, 127.1, 126.2, 124.0, 119.3, 114.2; IR (KBr) v: 3364,
ꢂ1
þ
ꢂ
1642, 1579, 1517, 1424, 1277, 1075, 904, 811, 749, 609 cm ; ESI-MS
70.4 (MþH) , negative m/z 268.4 (MꢂH) .
þ
m/z positive 327.4/329.4 (MþH) , negative m/z 325.4/327.3
ꢂ
(
MꢂH) .
4
.18. Compound (3q)
Procedure for the synthesis of compounds 4. A mixture of 3a
20 mg, 0.1 mmol) was dissolved in toluene (2 mL), ethyl-2-
(
(
4-Chlorophenyl)(4-(diethylamino)-2-hydroxyphenyl)
meth-
ꢀ
1
(triphenylphosphoranylidene)acetate (37 mg, 0.107 mmol) DMAP
0.7 mg, 5.4% mmol) was added. Then the reaction mixture was
heated at reflux under Argon for 10 h. The resulting reaction mix-
ture was loaded on a silica gel column and flashed with 10% ethyl
acetate in petroleum ether to afford the desired products 4 as solid.
anone 3q. Yellow solid (37.6 mg, 62%); Mp 104e108 C; H NMR
CDCl
(
(
3
, 400 MHz), d: 12.86 (s, 1H), 7.56e7.54 (m, 2H), 7.44e7.42 (m,
2
1
H), 7.31 (d, J¼9.6 Hz, 1H), 6.15e6.13 (m, 2H), 3.43 (q, J¼6.8 Hz, 4H),
13
.20 (t, J¼7.2 Hz, 6H); C NMR (CDCl
54.1, 137.4, 137.0, 135.3, 130.2,128.5,108.9, 103.8, 97.4, 44.8, 12.7; IR
KBr) v: 3472, 2960, 2929, 2347, 2347, 1610, 1432, 1067, 835,
3
, 100 MHz), d: 196.5, 166.4,
1
(
6
ꢂ1
þ
72 cm ; ESI-MS m/z positive 304.4/306.4 (MþH) , negative m/z
4.24. Compound (4)
ꢂ
3
02.4/304.4 (MꢂH) .
4
-Phenyl-2H-chromen-2-one 4. Pale yellow solid (20.2 mg,
ꢀ
1
4
.19. Compound (3r)
91%); Mp 83e86 C; H NMR (CDCl
H), 7.25e7.21 (m, 1H), 6.38 (s, 1H); C NMR (CDCl , 125 MHz),
3
, 400 MHz),
d: 7.58e7.40 (m,
1
3
8
3
d:
(
2-Hydroxy-5-methylphenyl)(phenyl)methanone 3r. Yellow
160.9,155.8,154.3,135.3,132.1, 129.8,129.0,128.6,127.1,124.3, 119.1,
ꢀ
1
solid (41.6 mg, 98%); Mp 78e80 C; H NMR (CDCl
1.88 (s, 1H), 7.69e7.66 (m, 2H), 7.62e7.58 (m, 1H), 7.53e7.49 (m,
3
, 400 MHz),
d:
117.5, 115.3; IR (KBr) v: 3069, 2914, 2852, 1735, 1603, 1432, 1261,
ꢂ1
þ
1
2
(
1
1
(
1036, 935, 873, 749 cm ; ESI-MS m/z positive 222.9 (MþH) .
13
H), 7.37e7.31 (m, 2H), 6.99 (d, J¼8.4 Hz, 1H), 2.26 (s, 3H); C NMR
, 100 MHz), : 201.7, 161.3, 138.2, 137.5, 133.3, 131.9, 129.2,
28.5, 127.9, 118.9, 118.3, 20.6; IR (KBr) v: 3449, 2363, 1626, 1595,
Procedure for the synthesis of compounds 5. A mixture of 3a
CDCl
3
d
(100 mg, 0.5 mmol) was dissolved in acetone (10 mL), K
2
CO
3
(104 mg, 0.75 mmol) and methyl bromoacetate (91.8 mg, 56.7
mL,
ꢂ1
479, 1331, 1223, 951, 749, 710 cm ; ESI-MS m/z positive 213.3
MþH) , negative m/z 211.4 (MꢂH) .
0.6 mmol) was then added. The reaction mixture was heated under
reflux for 2 h. The reaction mixture was then diluted with ethyl-
þ
ꢂ
acetate (20 ml), washed with H
then dried over anhydrous Na
afford the crude product.
2
O (3ꢁ10 mL). The organic layer was
4
.20. Compound (3s)
2
SO , filtered and concentrated to
4
(
5-Chloro-2-hydroxyphenyl)(phenyl)methanone 3s. Yellow
The crude product was dissolved in MeOH (5 mL), sodium
methanolate (81 mg, 1.5 mmol) was added. Then the reaction
mixture was stirred for 10 h at 60 C. The reaction mixture was
ꢀ
1
3
solid (45.6 mg, 98%); Mp 89e92 C; H NMR (CDCl , 400 MHz), d:
1.92 (s, 1H), 7.69e7.66 (m, 2H), 7.65e7.60 (m, 1H), 7.56e7.51 (m,
ꢀ
1
3
1
3
H), 7.45 (dd, J
, 100 MHz),
28.7, 123.5, 120.2, 119.9; IR (KBr) v: 3434, 3085, 2378, 1905, 1820,
1
¼8.8 Hz, J
2
d
¼2.8 Hz, 1H), 7.04 (d, J¼8.8 Hz, 1H);
C
diluted with ethylacetate (20 ml), washed with H
organic layer was then dried over anhydrous Na
2
O (3ꢁ10 mL). The
NMR (CDCl
3
: 200.7, 161.8, 137.3, 136.3, 132.5, 129.3,
2
SO , filtered and
4
1
1
(
concentrate. The crude product was loaded on a silica gel column
and flashed with 10% ethyl acetate in petroleum ether to afford the
desired products 5 as solid.
ꢂ1
572, 1470, 1339, 928, 827, 741 cm ; ESI-MS m/z positive 233.4
MþH) , negative m/z 231.3/233.3 (MꢂH) .
þ
ꢂ

8516
D. Wang, S. Cui / Tetrahedron 71 (2015) 8511e8516
4
.25. Compound (5)
Methyl 3-phenylbenzofuran-2-carboxylate 5. White solid
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.09.053.
ꢀ
1
(
54.2 mg, 43%); Mp 88e92 C; H NMR (CDCl , 400 MHz), d:
3
7
.65e7.58 (m, 4H), 7.53e7.44 (m, 4H), 7.34e7.30 (m, 1H), 3.89 (s,
13
3
H); C NMR (CDCl
29.7, 128.6, 128.31, 128.29, 128.2, 123.9, 122.2, 112.4, 52.2; IR (KBr)
v: 3434, 2922, 2852, 2347, 1719, 1572, 1277, 1137, 990, 749,
3
, 100 MHz), d: 160.3, 154.6, 139.8, 130.5, 130.0,
1
References and notes
ꢂ1
þ
7
02 cm ; ESI-MS m/z positive 253.4 (MþH) .
1. Wyatt, P. G.; Bethell, R. C.; Cammack, N.; Charon, D.; Dodic, N.; Dumaitre, B.;
Evans, D. N.; Green, D. V. S.; Hopewell, P. L. J. Med. Chem. 1995, 38, 1657.
Procedure for the synthesis of compounds 6. A mixture of 3a
2
3
4
. Rubinstein, K.; Elming, N.; Fakstorp, J.; Hermansen, K.; Pedersen, J. G. A.; Natvig,
J. T. J. Med. Chem. 1966, 9, 804.
(
(
100 mg, 0.5 mmol) was dissolved in toluene (10 mL), ClSO
2
NCO
70.8 mg, 43.4 L, 0.5 mmol) was added. Then the reaction mixture
m
. Shimizu, T.; Kimura, K.; Sakai, T.; Kawakami, K.; Miyazaki, T.; Nakouji, M.;
Ogawa, A.; Ohuchi, H.; Shimizu, K. J. Med. Chem. 2008, 51, 3326.
. For recent reviews, see: (a) Reddy, V. P.; Prakash, G. K. S. In Chemistry of Phenols;
Rappoport, Z., Ed.; John Wiley & Sons: Chichester, UK, 2003; Vol. 1, p 605; (b)
Martin, R. Org. Prep. Proced. Int. 1992, 24, 369.
was heated at reflux for 10 h. The reaction mixture was washed
with H O (10 mL). The organic layer was then dried over anhydrous
Na SO , filtered and concentrated. The crude product was loaded
2
2
4
on a silica gel column and flashed with 20% ethyl acetate in pe-
troleum ether to afford the desired products 6 as solid.
5. Chen, D.-J.; Chen, Z.-C. Synthesis 2000, 1175.
. Weng, F.; Wang, C.; Xu, B. Tetrahedron Lett. 2010, 51, 2593.
. Rao, H.; Li, C.-J. Angew. Chem., Int. Ed. 2011, 50, 8936.
6
7
8
. (a) Shan, G.; Yang, X.; Ma, L.; Rao, Y. Angew. Chem., Int. Ed. 2012, 51, 13070; (b)
Mo, F.; Trzepkowski, L. J.; Dong, G. Angew. Chem., Int. Ed. 2012, 51, 13075.
. For reviews, see: (a) Satoh, T.; Ueura, K.; Miura, M. Pure Appl. Chem. 2008, 80,
4
.26. Compound (6)
-Phenylbenzo[e][1,2,3]oxathiazine 2,2-dioxide 6. White solid
9
1127; (b) Satoh, T.; Miura, M. Synthesis 2010, 3395; (c) Zhu, C.; Wang, R.; Falck,
4
J. R. Chem.dAsian J. 2012, 7, 1502; (d) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev.
2012, 41, 3651; (e) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica
Acta 2012, 45, 31.
ꢀ
1
(
7
7
1
98.4 mg, 76%); Mp 105e110 C; H NMR (CDCl
.78e7.74 (m, 3H), 7.69e7.64 (m, 2H), 7.56 (t, J¼7.6 Hz, 2H),
.41e7.37 (m, 2H); 13C NMR (CDCl
, 100 MHz), : 176.5, 154.6, 137.1,
33.6, 133.3, 131.9, 130.6, 128.9, 125.9, 119.4, 116.5; IR (KBr) v: 3441,
3
, 400 MHz), d:
10. Shimizu, M.; Tsurugi, H.; Satoh, T.; Miura, M. Chem.dAsian J. 2008, 3, 881.
3
d
11. Shi, Z.; Schr c¸ der, N.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 8092.
12. Jijy, E.; Prakash, P.; Shimi, M.; Pihko, P. M.; Josepha, N.; Radhakrishnan, K. V.
Chem. Commun. 2013, 7349.
13. Wang, H.; Xie, F.; Qi, Z.; Li, X. Org. Lett. 2015, 17, 920.
ꢂ1
2
340, 1991, 1595, 1517, 1393, 1184, 935, 819, 734 cm ; ESI-MS m/z
þ
ꢂ
positive 260.4 (MþH) , negative m/z 258.4 (MꢂH) .
14. (a) Cui, S.; Zhang, Y.; Wu, Q. Chem. Sci. 2013, 4, 3421; (b) Cui, S.; Zhang, Y.; Wang,
D.; Wu, Q. Chem. Sci. 2013, 4, 3912; (c) Zhang, Y.; Wu, Q.; Cui, S. Chem. Sci. 2014, 5,
297; (d) Zhang, Y.; Zheng, J.; Cui, S. J. Org. Chem. 2014, 79, 6490; (e) Zheng, J.;
Zhang, Y.; Cui, S. Org. Lett. 2014, 16, 3560; (f) Zhang, Y.; Shen, M.; Cui, S.; Hou, T.
Bioorg. Chem. Med. Lett. 2014, 24, 5470; (g) Zhang, Y.; Wang, D.; Cui, S. Org. Lett.
Acknowledgements
The authors are grateful for financial supports from NSFC of
2015, 17, 2494; (h) Wang, D.; Cui, S. Tetrahedron 2015, http://dx.doi.org/10.1016/j.
China (21202143, 21472163).
tet.2015.06.024