Transition-Metal-Free Arylation and Alkylation of Diarylmethyl p-Tolyl Sulfones with Zinc Reagents

Article abstract of DOI:10.1021/acs.joc.8b01428

The transition-metal-free synthesis of unsymmetrical and highly functionalized triarylmethanes through arylation of the situ generated o-QMs from diarylmethyl p-tolyl sulfones with aryl zinc reagents is described. Alkyl zinc reagents are also well tolerated in this reaction. Additionally, the straightforward synthesis of the analogue of the antituberculosis agent A and the key precursor of the anti-breast-cancer agent B are achieved by this strategy.

Full text of DOI:10.1021/acs.joc.8b01428

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Note
Transition-Metal Free Arylation and Alkylation of
Diarylmethyl p-Tolyl Sulfones with Zinc Reagents
Maozhong Miao, Wenguang Yin, Lei Wang, Zhengkai Chen, Jianfeng Xu, and Hongjun Ren
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01428 • Publication Date (Web): 01 Aug 2018
Downloaded from http://pubs.acs.org on August 1, 2018
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Transition-Metal Free Arylation and Alkylation of Diarylmethyl
p-Tolyl Sulfones with Zinc Reagents
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Maozhong Miao*, Wenguang Yin, Lei Wang, Zhengkai Chen, Jianfeng Xu, and Hongjun Ren*
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Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018 (P. R. China)
mmzok@zstu.edu.cn；renhj@zstu.edu.cn
Abstract: The transitionꢀmetal free synthesis of unsymmetrical and highly functionalized
triarylmethanes through arylation of the situ generated oꢀQMs from diarylmethyl pꢀtolyl sulfones
with aryl zinc reagents is described. Alkyl zinc reagents are also well tolerated in this reaction.
Additionally, the straightforward synthesis of the analogue of the antiꢀtuberculosis agent A and the
key precursor of the antiꢀbreast cancer agent B are achieved by this strategy.
The triarylmethanes, a class of structurally unique molecules, are widespread in material science and
medicinal chemistry.1 For example, several triarylmethane compounds have been utilized as
pharmacological agents for treating bacterial infection (A, Chart 1),2 breast cancer (B)3 and diabetes
(C).4 Triarylmethane dyes are synthetic organic compounds containing triphenylmethane backbones,
which have been widely used in material sciences due to their special photochemical and
photophysical properties.5 Although quite rare, the triarylmethane units have been found in natural
products such as cassigarol B and muchimangin B (D).6
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Chart 1. Biologically pertinent triarylmethanes.
The synthesis of unsymmetrical triarylmethanes is a challenge because of their unique structures
with three aryl groups attached to the central sp3ꢀhybridized methide carbon. Conventionally,
triarylmethanes are prepared through typical Friedel–Crafts alkylation of diarylcarbinols in the
presence of either Brönsted or Lewis acids (Scheme 1),7 however, these reactions are limited to
electronꢀrich arenes and have poor regioselectivies. Despite the cross coupling and CꢀH activation
based strategies addressing these synthesis most require expensive palladium salts and ligands
(Scheme 1).8 Hence, the development of environmentally benign, practical, transitionꢀmetal free
protocols for the efficient synthesis of unsymmetrically functionalized triarylmethanes are highly
desired. 9
Orthoꢀquinone methides (oꢀQMs), are useful building blocks in modern chemical
transformations.11 Pioneering synthesis are availuable for generating oꢀQMs in situ from the
corresponding substituted benzylsulfones.12 We envisaged that the appropriately substituted
benzylsulfones might undergo elimination to form transient oꢀQMs with the assistance of aryl zinc
reagents,13 the resulting oꢀQMs could be trapped by the excess aryl zinc reagents to afford the
triarylmethanes. In this process, the zinc reagents play dual roles, as bases generating oꢀQM
intermediates and attacking the oꢀQMs as nucleophiles (Scheme 1).
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Scheme 1. Synthetic Approaches to Triarylmethanes
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a) Friedel−Crafts reaction, b) Pd or Ni catalyzed crossꢀcoupling reaction, c) transitionꢀmetal
catalyzed CꢀH functionalization. d) This work: transitionꢀmetal free [1,4] or [1,6] addition (R1, R2,
R3 = substituted groups, EDG = ElectronꢀDonating Group, LG = Leaving Group).
With
this
idea
in
mind,
we
started
our
investigation
by
using
2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a as a model substrate which was prepared according to
a modified literature method.11a The typical results are summarized in Table 1. The reaction of 1a
with phenyl Grignard reagent (Knochel type Grignard with LiCl) catalyzed by CuI (5 mol %) in
o
tetrahydrofuran (THF) at ꢀ78 C for 12 hours detected the desired arylation product 2a in trace
amount (Table 1, entry 1). Elevating the temperature to 0 oC gave only trace product (entry 2). When
the phenyl zinc reagent was employed, the desired arylation product 2a was isolated in 22% yield
(entry 3). To our delight, after some experimentation, we found that the arylation product 2a could be
obtained in 20 % yield in the absence of CuI at 0 oC (entry 4). Decreasing the temperature to ꢀ 30 oC
decreased the yield (entry 5) but the yield was dramatically improved when the reaction temperature
o
o
was raised to 60 C (entry 6). By contrast, the phenyl Grignard reagent gave a poor result at 60 C
(entry 7). Under optimal conditions using 3.0 equivalent of phenyl zinc reagent at 60 oC for 12 hours,
the yield was further improved to 82% (entry 8). Furthermore, the reaction was carried out using 1
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equivalent of bases such as K2CO3 and Et3N together with 1 equivalent of zinc reagent at 60 C,
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7
however, poor results were obtained (entries 9 and 10). These results indicated that excess zinc
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reagents were necessary.
Table 1. Optimization of the Reaction Conditionsa
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entry
reagent (equiv)
catalyst
temp. (oC)
yield (%)b
1
2
PhMgBr—LiCl (2.5)
PhMgBr—LiCl (2.5)
PhZnBr—LiCl (2.5)
PhZnBr—LiCl (2.5)
PhZnBr—LiCl (2.5)
PhZnBr—LiCl (2.5)
PhMgBr—LiCl (2.5)
PhZnBr—LiCl (3.0)
PhZnBr—LiCl (1.0)c
PhZnBr—LiCl (1.0)d
CuI
ꢀ78
0
trace
trace
22
CuI
3
CuI
0
4
/
/
/
/
/
/
/
0
20
5
6
ꢀ30
60
60
60
60
60
trace
78
7
trace
82
8
9
0
10
trace
aConditions: 1a (0.5 mmol), PhMgBr—LiCl (2.5 equiv) or PhZnBr—LiCl (2.5 or 3.0 equiv),
in solvent of THF under N2. b Isolated yield. c K2CO3 (1 equiv) was used. d Et3N (1 equiv) was used. (THF = tetrahydrofuran).
With the optimized conditions, the generality of arylation reaction for the synthesis of
triarylmethane derivatives 2 from various tosylmethyl phenols 1 and functionalized aryl zinc
reagents was next investigated (2b−x, Scheme 2). paraꢀSubstituted aryl zinc reagents with groups
such
as
pꢀphenyl,
pꢀtꢀBu,
pꢀOMe,
and
pꢀchloro
reacted
with
2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a to afford the corresponding desulfonylation arylation
products 2b−e in good yields (69ꢀ90%). paraꢀ, metaꢀ and orthoꢀ Methyl substituted phenyl zinc
reagents were well tolerated, whereas oꢀmethyl phenyl zinc reagent gave the slightly lower yield
presumably because of steric effect (2g−i). With respect to tosylmethyl phenols 1, products (2j−l)
were isolated in up to 95% yield. Furthermore, heterocycles such as thiophene could be tolerated in
this reaction (2m). In the case of βꢀnaphthol substrates, the desulfonylation products were obtained
in good to excellent yields (2n−s). In particular, heterocyclic zinc reagents such as thiophenyl and
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carbazolyl zinc reagents could be used in this transformation to provide the unsymmetrical
triarylmethanes containing heterocycles with high potential in material science (2r−s). Tosylmethyl
naphthols with heterocyclic structures were also compatible with the desulfonylation arylation
method (2t−u). Functionalized zinc reagents with CN and Br substitutents at orthoꢀ and paraꢀ
position of benzene ring were suitable substrates to affording triarylmethanes in reasonable yield
(2v−w). However, the zinc reagent with strong electronꢀwithdrawing group ꢀCOOEt at paraꢀ
position of benzene ring failed to give the desired product. The bulky zinc reagent
phenanthrenꢀ9ꢀylzinc(II) bromide reacted with 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a to
provide the arylation product 2x in 91% yield, which is an analogue of the antiꢀbreastꢀcancer agent
B.
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Scheme 2. Generality of the Reaction with Aryl Zinc Reagentsa,b
R2
R2
O
ArZnBr (3.0 equiv)
S
Ar
OH
THF, 60 oC, 12 h
R1
R1
O
OH
CH3
2bꢀx, 41ꢀ99%
1
OMe
OMe
OMe
OMe
R
Cl
Cl
OH
OH
OH
OH
R
2f: 39%
2g: R = oꢀMe, 60%;
2h: R = mꢀMe, 81%;
2j: 76%
2b: R = Ph, 90%
2c: R = tBu, 87%
2i
: R= pꢀMe, 84%.
2d
: R = OMe, 79%
: R = Cl, 69%
OMe
2e
X
OMe
S
CH3
OH
R
OH
2o
2p
2q
: R = H, 82 %
: R = Ph, 97%
: R = OMe, 96%
OH
OH
2n
2m
: 70%
2k
2l
: X = F, 76%
: X = Cl, 95%
: 99%
OMe
OMe
X
OH
S
N
CH3
OH
2t: X = O, 88%
2u
OH
: X = S, 99%
2s: 55%
2r: 89%
MeO
S
S
CN
HO
OH
OH
2w: 73%
Br
2v: 47%
2x
: 91%
a Conditions: 1 (0.5 mmol), Zinc reagents (3.0 equiv), in THF at 60 oC in under N2; b Isolated yield.
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We extended the above protocol using alkyl zinc reagents. Under the standard reaction condition,
the substrate of 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a was treated with various simple alkyl
zinc reagents, such as ethyl, iꢀpropyl, and tꢀbutyl zinc reagents to afford the corresponding
functionalized diaryl compounds in 32−78% yields. More sterically crowded reagents afforded the
products in lower yields (Scheme 3, 3a−d). In the case of tosylmethyl naphthol substrates, the
ethylation and isopropylation went well to provide the corresponding products in 89% and 72%
yields, respectively (3e−f). Functionalized alkyl zinc reagents, such as (4ꢀacetoxybutyl)zinc(II)
bromide and (5ꢀethoxyꢀ5ꢀoxopentyl)zinc(II) bromide were also suitable to this transformation and
provided the products in yield of 73% and 60%, respectively (3g−h). Interestingly, when
Reformatsky enolate was introduced, both the intermolecular desulfonylation alkylation and the
intramolecular esterification occurred to furnish the 1,2ꢀdihydro benzo[f]chromenꢀ3ꢀone derivatives
in good yields (3i−j).
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Scheme 3. Generality of the Reaction with Alkyl Zinc Reagentsa,b
a Conditions: 1 (0.5 mmol), Zinc reagents (3.0 equiv), in THF at 60 oC in under N2; b Isolated yield.
To show the utility of the modular approach to unsymmetrically functionalized triarylmethanes,
the applications for the synthesis of antiꢀtuberculosis agent A and antiꢀbreastꢀcancer agent B
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analogues were carried out (Scheme 4). Gratifying, the desulfonylation arylation proceed smoothly
when substrate paraꢀphenol sulfone 4a was utilized instead of orthoꢀphenol sulfone 1a. Treatment of
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paraꢀphenol sulfone 4a with (3ꢀchlorophenyl)zinc(II) bromide at 60 C gave the desulfonylation
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arylation product 5a in 92% yield. Various tosylmethyl phenols 4 with different substituents were
well tolerated in this reaction to afford 5b−d in high yields. Moreover, switching to
phenanthrenꢀ9ꢀylzinc(II) bromide led to the key precursor of antiꢀbreastꢀcancer agent B in 57% yield
(Scheme 4). The reaction of 2,6ꢀdimethylꢀ4ꢀ(phenyl(tosyl)methyl)phenol 4f and thiophenꢀ2ꢀylzinc(II)
bromide furnished 5f, an analogue of the antiꢀtuberculosis agent A, in 76% yield (Scheme 4).
Scheme 4. Synthesis of the Anti-tuberculosis Agent Analogue A and the Key Precursor of the
Anti-breast-cancer Agent B.
In summary, we have realized the first arylation of an orthoꢀquinone methides (oꢀQMs) from the
readily available 2ꢀtosylalylphenol with functionalized zinc reagents, providing several types of
unsymmetrical and functionalized triarylmethanes, including those are difficult to access via
transition metalꢀcatalyzed reactions, in good to excellent yields. This strategy can be applied to
prepare the key precursor of the antiꢀbreastꢀcancer agent B and the analogues of the antiꢀtuberculosis
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agent A in a straightforward manner. In particular, the alkylation with functionalized alkyl zinc
reagents also successfully lead to the functionalized diaryl compounds. Moreover, the reaction of
Reformatsky enolate gave 1,2ꢀdihydro benzo[f]chromenꢀ3ꢀone derivatives in good yields.
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EXPERIMENTAL SECTION
1. General Methods.
1
The H NMR (400 MHz) chemical shifts were reported in parts per million (δ) relative to internal
standard TMS (7.26 ppm). The coupling constants, J values are reported in Hertz (Hz). The 13C
NMR (100 MHz) chemical shifts were referenced to the internal solvent signals (central peak is 77.0
ppm in CDCl3). Highꢀresolution mass spectra (HRMS) were recorded by ESI ionization. Infrared
spectra (IR) were recorded by an ATR module and absorption bands are given in wavenumbers
(cmꢀ1). Melting points were not corrected. All commercial reagents were used without additional
purification and solvents were dried by standard methods when necessary. Petroleum ether refers to
the fraction with boiling point in the range 60−90 °C. All reactions were monitored by TLC with GF
254 silica gel coated plates. Flash column chromatography was carried out using 200−300 mesh
silica gel. The substrates 111a, 12c were prepared according to the literature procedure.
2. Procedure and experiment data for triarylmethanes 2
(1) General procedure for the synthesis of triarylmethanes 2
Method A: In a 25 mL Schlenk tube, aryl Grignard reagent in THF (3.0 equiv) was added to a
solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 oC under N2 atmosphere. After 15 min, the
mixture was treated with substrate 1 (0.5 mmol, 1.0 equiv) at room temperature. After the addition
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was completed, the reaction mixture was stirred at 60 °C for 12 h. Then the mixture was quenched by
adding 5 mL of NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was
washed with H2O (3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified by
flash silica gel chromatography to afford 2.
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Method B: In a 25 mL Schlenk tube, aryl halides (3.0 equiv) in dry THF (2 mL) was added dropwise
nꢀBuLi (0.6 mL, 3.0 equiv, 2.5 M in hexane) at 0 oC under N2 atmosphere. The reaction mixture was
stirred for 1ꢀ2 h. Suspension of ZnBr2 solution (1.5 mL, 1.0 M in THF, 3.0 equiv) was added, After
15 min at 0°C, the mixture was treated with substrate 1 (0.5 mmol, 1.0 equiv) at room temperature.
After the addition was completed, the reaction mixture was stirred at 60 °C for 12 h. After
completion of the reaction, the mixture was quenched by adding 5 mL of NH4Cl and extracted with
EtOAc (3×10 mL). The combined organic phase was washed with H2O (3×10 mL), dried over
anhydrous Na2SO4, concentrated in vacuo and purified by flash silica gel chromatography to afford
2.
Method C: In a 25 mL Schlenk tube, aryl halides in dry THF (2 mL) was added dropwise
isopropylmagnesium chloride (3.0 equiv, 2.5 M in THF, 0.6 mL) at ꢀ30°C under N2 atmosphere. The
reaction mixture was stirred for 3.5 h. Suspension of ZnBr2 solution (1.5 mL, 1.0 M in THF, 3.0
equiv) was added, After 15 min stir at 0 °C, the mixture was treated with substrate 1 (0.5 mmol, 1.0
equiv) at room temperature. After the addition was completed, the reaction mixture was stirred at
60 °C for 12 h. After completion of the reaction, the mixture was quenched by adding 5 mL of
NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was washed with H2O
(3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified by flash silica gel
chromatography to afford 2.
Experiment data
2-((4-methoxyphenyl)(phenyl)methyl)phenol (2a)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 °C for 12 h. Purification by flash column chromatography provided
1
2a (118.9 mg, 91%) as yellow oil; Rf = 0.51 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz,
CDCl3): δ 7.31 ( t, J =7.2 Hz, 2H), 7.22ꢀ7.24 (m, 1H), 7.17ꢀ7.12 (m, 3H), 7.05 (d, J =8.4 Hz, 2H),
6.86ꢀ6.80 (m, 5H), 5.67 (s, 1H), 4.74 (s, 1H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.3,
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153.4, 142.7, 134.4, 130.5, 130.4, 130.3, 129.3, 128.5, 127.8, 126.6, 120.7, 116.0, 113.9, 55.2, 50.1;
HRMS (ES+ꢀTOF) calcd for C20H19O2 ([M+H]+): 291.1380, found 291.1375. IR: 3405, 1589, 1507,
1454, 1236, 1180, 1091, 1027, 841, 807, 752.
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2-([1,1'-biphenyl]-4-yl(4-methoxyphenyl)methyl)phenol (2b)
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According to Method A with [1,1'ꢀbiphenyl]ꢀ4ꢀylmagnesium bromide (1.5 mmol, 0.66 M in THF, 3.0
equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5
mmol, 1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography
provided 2b (164.7 mg, 90%) as white solid; m.p 70ꢀ71 oC (Petroleum ether/EtOAc); Rf = 0.64
1
(Petroleum ether/EtOAc = 3/1); H NMR (400 MHz, CDCl3): δ 7.62ꢀ7.56 (m, 4H), 7.47ꢀ7.43 (m,
3H), 7.36ꢀ7.26 (m, 1H), 7.24ꢀ7.22 (m, 2H), 7.13 (d, J = 8.4 Hz, 2H), 6.91ꢀ6.79 (m, 5H), 5.77 (s, 1H),
4.95 (s, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.3, 153.4, 142.0, 140.7, 139.3, 134.5,
130.5, 130.4, 130.3, 129.6, 128.7, 128.3, 127.9, 127.1, 127.0, 126.7, 126.6, 120.7, 116.0, 115.6,
114.0, 55.2, 49.7; HRMS (ES+ꢀTOF) calcd for C26H22O2Na([M+Na]+): 389.1512, found 389.1516.
IR: 3416, 1608, 1508, 1486, 1454, 1245, 1177, 1034, 834, 757, 697.
2-((4-(tert-butyl)phenyl)(4-methoxyphenyl)methyl)phenol (2c)
According to Method A with (4ꢀ(tertꢀbutyl)phenyl)magnesium bromide (1.5 mmol, 0.65 M in THF,
3.0 equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a
o
(0.5 mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column
chromatography provided 2c (150.5, 62%) as yellow oil; Rf = 0.73 (Petroleum ether/EtOAc = 3/1);
1H NMR (400 MHz, CDCl3): δ 7.33ꢀ7.31 (m, 2H), 7.16ꢀ7.05 (m, 5H), 6.86ꢀ6.81 (m, 5H), 5.62 (s,
1H), 4.76 (s, 1H), 3.79 (s, 3H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 158.2, 153.5, 149.4,
139.4, 134.5, 130.7, 130.3, 130.2, 128.8, 127.8, 125.5, 120.7, 116.2, 113.9, 55.2, 49.8, 34.4, 31.3;
HRMS (ES+ꢀTOF) calcd for C24H27O2 ([M+H]+): 347.2006, found 347.2010. IR: 3425, 1595, 1512,
1454, 1238, 1178, 1088, 1027, 841, 810, 753.
2-(bis(4-methoxyphenyl)methyl)phenol (2d)
According to Method A with (4ꢀmethoxyphenyl)magnesium bromide (1.5 mmol, 1.4 M in THF, 3.0
equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5
mmol, 1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography
provided 2d (126.4 mg, 79%) as yellow oil; Rf = 0.54 (Petroleum ether/EtOAc = 3/1); 1H NMR (400
MHz, CDCl3): δ 7.17ꢀ7.14 (m, 1H), 7.06 (d, J = 8.8 Hz, 4H), 6.88ꢀ6.80 (m, 7H), 5.62 (s, 1H), 4.92 (s,
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1H), 3.79 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 158.2, 153.4, 134.8, 130.8, 130.24, 130.20, 127.8,
120.6, 116.0, 113.9, 55.2, 49.3; HRMS (ES+ꢀTOF) calcd for C21H20O3Na ([M+Na]+): 343.1305,
found 343.1321. IR: 3418, 1608, 1508, 1454, 1245, 1176, 1033, 833, 755.
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2-((4-chlorophenyl)(4-methoxyphenyl)methyl)phenol (2e)
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According to Method A with (4ꢀchlorophenyl)magnesium bromide (1.5 mmol, 0.55 M in THF, 3.0
equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5
mmol, 1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography
provided 2e (111.8 mg, 69%) as yellow oil; Rf = 0.69 (Petroleum ether/EtOAc = 3/1); 1H NMR (400
MHz, CDCl3): δ 7.30ꢀ7.20 (m, 2H), 7.18ꢀ7.14 (m, 2H), 7.07ꢀ7.03 (m, 3H), 6.90ꢀ6.86 (m, 3H),
6.81ꢀ6.78 (m, 2H), 5.72 (s, 1H) 5.00 (s, 1H), 3.81 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.3,
153.2, 145.4, 134.3, 133.9, 130.3, 130.2, 130.0, 129.6, 129.3, 128.0, 127.5, 126.6, 120.8, 115.9,
114.0, 55.2, 49.4; HRMS (ES+ꢀTOF) calcd for C20H18ClO2 ([M+H]+): 325.0990, found 325.0995. IR:
3404, 1592, 1509, 1454, 1246, 1178, 1033, 788.
2-((3-chlorophenyl)(4-methoxyphenyl)methyl)phenol (2f)
According to Method A with (3ꢀmethoxyphenyl)magnesium bromide (1.5 mmol, 0.65 M in THF, 3.0
equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5
mmol, 1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography
1
provided 2f (63.2 mg, 39%) as yellow oil; Rf = 0.58 (Petroleum ether/EtOAc = 3/1); H NMR (400
MHz, CDCl3): δ 7.23ꢀ7.22 (m, 2H), 7.17ꢀ7.13 (m, 2H), 7.06ꢀ7.02 (m, 3H), 6.89ꢀ6.86 (m, 3H),
6.82ꢀ6.78 (m, 2H), 5.71 (s, 1H), 4.94 (s, 1H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.2,
153.2, 141.7, 134.3, 132.1, 130.6, 130.3, 130.2, 129.4, 128.7, 128.5, 127.9, 127.8, 120.7, 116.6,
115.8, 114.0, 113.9, 55.2, 49.0; HRMS (ES+ꢀTOF) calcd for C20H17ClO2Na([M+Na]+): 347.0809,
found 347.0817. IR: 3396, 1608, 1509, 1454, 1245, 1178, 1089, 1014, 831, 755.
2-((4-methoxyphenyl)(o-tolyl)methyl)phenol (2g)
According to Method A with oꢀtolylmagnesium bromide (1.5 mmol, 0.76 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
1
2g (91.2 mg, 60%) as yellow oil; Rf = 0.71 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz,
CDCl3): δ 7.20ꢀ7.17 (m, 4H), 7.04ꢀ7.02 (m, 2H), 6.87ꢀ6.85 (m, 4H), 6.82ꢀ6.79 (m, 1H), 6.75ꢀ6.73 (m,
1H), 5.78 (s, 1H), 4.86 (s, 1H), 3.81 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.2,
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153.4, 141.2, 136.8, 133.9, 130.6, 130.5, 130.2, 130.1, 128.8, 127.7, 126.7, 125.9, 120.7, 115.9,
113.9, 55.2, 46.7, 19.6; HRMS (ES+ꢀTOF) calcd for C21H20O2Na([M+Na]+): 327.1356, found
327.1357. IR: 3415, 1608, 1509, 1454, 1245, 1178, 1034, 836, 751.
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2-((4-methoxyphenyl)(m-tolyl)methyl)phenol (2h)
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According to Method A with mꢀtolylmagnesium bromide (1.5 mmol, 0.53 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
1
2h (123.2 mg, 81%) as yellow oil; Rf = 0.70 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz,
CDCl3): δ 7.25ꢀ7.15 (m, 2H), 7.10ꢀ7.08 (m, 3H), 7.01 (s, 1H), 6.97ꢀ6.81 (m, 6H), 5.68 (s, 1H), 4.95
(s, 1H), 3.82 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.2, 153.4, 142.7, 138.1, 134.5,
130.6, 130.4, 130.3, 130.0, 128.4, 127.8, 127.4, 126.3, 120.6, 116.0, 113.9, 55.2, 50.0, 21.4; HRMS
(ES+ꢀTOF) calcd for C21H20O2Na ([M+Na]+): 305.1536, found 305.1529. IR: 3426, 1610, 1516, 1454,
1255, 1172, 1036, 840, 752.
2-((4-methoxyphenyl)(p-tolyl)methyl)phenol (2i)
According to Method A with pꢀtolylmagnesium bromide (1.5 mmol, 0.85 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
2i (127.7 mg, 84%) as yellow solid; m.p. 121ꢀ122oC (Petroleum ether/EtOAc); Rf = 0.65 (Petroleum
ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.13ꢀ7.07 ( m, 3H), 7.14ꢀ7.09 (m, 4H), 6.99ꢀ6.92
(m, 4H), 6.83 (d, J =7.6 Hz, 1H), 5.72 (s, 1H), 5.08 (s, 1H), 3.83 (s, 3H), 2.40 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 158.1, 153.4, 139.8, 136.1, 134.7, 130.7, 130.3, 130.2, 129.2, 129.1, 127.7, 120.6,
116.0, 113.9, 55.2, 49.6, 21.0; HRMS (ES+ꢀTOF) calcd for C21H21O2 ([M+H]+): 305.1536, found
305.1539. IR: 3405, 1589, 1507, 1454, 1236, 1180, 1091, 1027, 841, 807, 752.
4-chloro-2-((4-methoxyphenyl)(phenyl)methyl)phenol (2j)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 4ꢀchloroꢀ2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1b
o
(0.5 mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column
chromatography provided 2j (123.3 mg, 76%) as yellow oil; Rf = 0.51 (Petroleum ether/EtOAc =
3/1); 1H NMR (400 MHz, CDCl3): δ 7.33 (t, J = 8.4 Hz, 2H), 7.27ꢀ7.28 (m, 1H), 7.13ꢀ7.08 (m, 3H),
7.05 (d, J = 8.4 Hz, 2H), 6.88ꢀ6.85 (m, 2H), 6.78 (d, J = 2.0 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 5.63
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(s, 1H), 5.05 (s, 1H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 158.4, 152.1, 142.0, 133.7, 132.5,
130.2, 130.0, 129.1, 128.7, 127.7, 126.8, 125.6, 117.3, 114.1, 55.2, 50.0; HRMS (ES+ꢀTOF) calcd for
C20H17ClO2Na([M+Na]+): 347.0809, found 347.0802. IR: 3404, 1608, 1509, 1412, 1247, 1177, 1109,
1031, 806, 700, 650.
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2-((4-fluorophenyl)(phenyl)methyl)phenol (2k)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀfluorophenyl)(tosyl)methyl)phenol 1c (0.5 mmol, 1.0
equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided 2k
o
(105.7 mg, 76%) as white solid; m.p. 75ꢀ76 C (Petroleum ether/EtOAc); Rf = 0.74 (Petroleum
ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.35ꢀ7.25 (m, 3H), 7.19ꢀ7.09 (m, 5H), 7.00 (t, J
= 8.6 Hz, 2H), 6.90ꢀ6.86 (m, 1H), 6.80 (d, J = 8.4 Hz, 2H), 5.77(s, 1H), 4.78 (s, 1H); 13C NMR (100
MHz, CDCl3): δ 162.7, 160.3, 153.2, 142.5, 138.4, 138.3, 130.8 (d, J = 7.3 Hz), 130.4, 130.2, 129.2,
129.1, 128.6, 128.5, 128.0, 126.7, 120.8, 115.9, 115.4, 115.1, 49.8; HRMS (ES+ꢀTOF) calcd for
C19H15FONa ([M+Na]+): 301.0999, found 301.0992. IR: 3524, 1604, 1505, 1452, 1329, 1222, 1156,
1087, 837, 748, 700.
2-((4-chlorophenyl)(phenyl)methyl)phenol (2l)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀchlorophenyl)(tosyl)methyl)phenol 1d (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
1
2l (154.7 mg, 95%) as yellow oil; Rf = 0.62 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz,
CDCl3): δ 7.34ꢀ7.26 (m, 5H), 7.17ꢀ7.06 (m, 5H), 6.89ꢀ6.85 (m, 1H), 6.79 (d, J = 8.8 Hz, 2H) 5.75 (s,
1H), 4.81 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 153.2, 142.2, 141.4, 132.3, 130.7, 130.4, 129.9,
129.3, 128.6, 128.5, 128.0, 126.7, 120.8, 115.9, 44.9; HRMS (ES+ꢀTOF) calcd for C19H16ClO
([M+H]+): 295.0884, found 295.0891. IR: 3416, 1597, 1488, 1453, 1234, 1089, 1014, 754, 700.
2-(phenyl(thiophen-2-yl)methyl)phenol (2m)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ(thiophenꢀ2ꢀyl(tosyl)methyl)phenol 1e (0.5 mmol, 1.0
equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided 2m
o
(93.1 mg, 70%) as yellow solid; m.p. 77ꢀ78 C (Petroleum ether/EtOAc); Rf = 0.28 (Petroleum
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ether/EtOAc = 3/1); H NMR (400 MHz, CDCl3): δ7.37ꢀ7.34 (m, 2H), 7.31ꢀ7.27 (m, 4H), 7.19ꢀ7.17
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(m, 1H), 7.02ꢀ6.98 (m, 2H), 6.91 (t, J = 7.2 Hz, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.76 (d, J = 2.4 Hz,
1H), 5.98 (s, 1H), 4.85 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 153.1, 146.6, 142.6, 130.3, 129.8,
128.7, 128.5, 128.1, 126.9, 126.7, 126.5, 124.8, 120.8, 116.0, 45.9; HRMS (ES+ꢀTOF) calcd for
C17H14OSNa ([M+Na]+): 289.0658, found 289.0663. IR: 3507, 1594, 1497, 1452, 1325, 1273, 1183,
1086, 757, 700.
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1-((4-methoxyphenyl)(o-tolyl)methyl)naphthalen-2-ol (2n)
According to Method A with oꢀtolylmagnesium bromide (1.5 mmol, 0.76 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f
o
(0.5 mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column
chromatography provided 2n (175.2 mg, 99%) as yellow oil; Rf = 0.61 (Petroleum ether/EtOAc =
1
3/1); H NMR (400 MHz, CDCl3): δ 7.85 (d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.72 (d, J =
8.4 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.31 (t, J = 14.4 Hz, 1H), 7.25ꢀ7.19 (m, 2H), 7.15ꢀ7.09 (m, 3H),
7.05ꢀ6.99 (m, 2H), 6.86 (d, J = 8.4 Hz, 2H), 6.30 (s, 1H), 5.38 (s, 1H), 3.79 (s, 3H), 2.19 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 158.7, 153.4, 140.2, 137.3 , 133.2, 133.0, 131.1, 130.0, 129.6, 129.5,
128.7, 128.5, 127.4, 126.9, 123.1, 122.5, 119.8, 118.9, 114.7, 55.2, 46.1, 19.7; HRMS (ES+ꢀTOF)
calcd for C25H23O2 ([M+H]+): 355.1693, found 355.1682. IR: 3475, 1621, 1508, 1250, 1176, 1032,
815, 744.
1-((4-methoxyphenyl)(phenyl)methyl)naphthalen-2-ol (2o)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f
o
(0.5 mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column
chromatography provided 2o (139.4 mg, 82%) as yellow oil; Rf = 0.72 (Petroleum ether/EtOAc
=3/1); 1H NMR (400 MHz, CDCl3): δ 8.07 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 8.4 Hz 1H), 7.80 (d, J =
8.4 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.41ꢀ7.32 (m, 6H), 7.26ꢀ7.23 (m, 2H), 7.15 (d, J = 8.8 Hz, 1H),
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6.93 (d, J = 8.4 Hz, 2H), 6.44 (s, 1H), 5.45 (s, 1H), 3.81 (s, 3H) ; C NMR (100 MHz, CDCl3): δ
158.6, 152.7, 141.9, 133.34, 133.30, 130.0, 129.5, 129.0, 128.9, 128.6, 127.0, 126.7, 123.1, 122.8,
120.2, 119.7, 115.2, 114.4, 55.1, 47.7; HRMS (ES+ꢀTOF) calcd for C24H20O2Na([M+Na]+): 363.1356,
found 363.1342. IR: 3473, 1621, 1508, 1249, 1177, 1031, 812, 700.
1-([1,1'-biphenyl]-4-yl(4-methoxyphenyl)methyl)naphthalen-2-ol (2p)
According to Method A with [1,1'ꢀbiphenyl]ꢀ4ꢀylmagnesium bromide (1.5 mmol, 0.66 M in THF, 3.0
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oC for 12 h. Purification by flash column chromatography provided 2p (199.7 mg, 96%) as yellow
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solid; m.p. 68ꢀ69oC (Petroleum ether/EtOAc); Rf = 0.57 (Petroleum ether/EtOAc = 3/1); H NMR
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(400 MHz, CDCl3): δ 8.07 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H),
7.63ꢀ7.60 (m, 4H), 7.44ꢀ7.41 (m, 3H), 7.40ꢀ7.37 (m, 4H), 7.21 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 8.8
Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.40 (s, 1H), 5.33 (s, 1H), 3.80 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 158.7, 152.8, 140.8, 140.5, 139.9, 133.33, 133.29, 130.0, 129.65, 129.6, 129.4, 128.7,
127.7, 127.3, 127.0, 126.8, 123.2, 122.7, 120.1, 119.8, 115.4, 114.6, 55.3, 47.5; HRMS (ES+ꢀTOF)
calcd for C30H24O2Na([M+Na]+): 439.1669, found 439.1670. IR: 3470, 1599, 1508, 1487, 1247,
1178, 833, 757, 697.
1-(bis(4-methoxyphenyl)methyl)naphthalen-2-ol (2q)
According to Method A with (4ꢀmethoxyphenyl)magnesium bromide (1.5 mmol, 1.40 M in THF, 3.0
equiv),
ZnBr2
(1.5
mL,
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M
in
THF,
3.0
equiv),
1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f (0.5 mmol, 1.0 equiv) in 2 mL of THF at 60
oC for 12 h. Purification by flash column chromatography provided 2q (177.6 mg, 96%) as yellow
o
1
solid; m.p. 94ꢀ95 C (Petroleum ether/EtOAc); Rf = 0.63 (Petroleum ether/EtOAc = 3/1); H NMR
(400 MHz, CDCl3): δ 8.00 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H),
7.43 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 7.4 Hz, 1H), 7.18 (d, J = 8.8 Hz, 4H), 7.09 (d, J = 8.8 Hz, 1H),
6.88 (d, J = 8.8 Hz, 4H), 6.31 (s, 1H), 5.39 (s, 1H), 3.79 (s, 6H); 13C NMR (100 MHz, CDCl3): δ
158.6, 152.7, 133.6, 133.3, 129.9, 129.5, 128.7, 123.1, 122.7, 120.3, 119.8, 115.9, 114.5, 55.2,46.9;
HRMS (ES+ꢀTOF) calcd for C25H23O3 ([M+H]+): 371.1642, found 371.1634. IR: 3420, 1604, 1508,
1438, 1246, 1176, 1034, 810, 751.
1-((4-methoxyphenyl)(5-methylthiophen-2-yl)methyl)naphthalen-2-ol (2r)
According to Method B: In a 25 mL Schlenk tube, 2,5ꢀdimethylthiophene (1.5 mmol, 3.0 equiv) in
dry THF (2 mL) was added dropwise nꢀBuLi (0.6 mL, 3.0 equiv, 2.5 M in hexane) at 0 °C under N2
atmosphere. The reaction mixture was stirred for 1 h. Suspension of ZnBr2 solution (1.5 mL, 1.0 M
in THF, 3.0 equiv) was added, After 15 min stir at 0°C, the mixture was treated with substrate 1f (0.5
mmol, 1.0 equiv) at room temperature. After the addition was completed, the reaction mixture was
stirred at 60 °C for 12 h. Purification by flash column chromatography provided 2r (160.2 mg, 89%)
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as yellow solid; m.p. 129ꢀ130 oC (Petroleum ether/EtOAc); Rf = 0.65 (Petroleum ether/EtOAc = 3/1);
1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.74 (d, J = 8.8 Hz,
1H),7.44 (t, J = 7.6 Hz, 1H), 7.35ꢀ7.28 (m, 3H), 7.11 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H),
6.60 (s, 2H), 6.41 (s, 1H), 5.77 (s, 1H), 3.79 (s, 3H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
158.7, 152.9, 143.9, 140.7, 133.0, 132.7, 129.7, 129.5, 129.4, 128.7, 126.8, 126.78, 124.8, 123.2,
122.4, 119.8, 119.7, 114.3, 55.2, 43.3, 15.4; HRMS (ES+ꢀTOF) calcd for C23H21O2S ([M+H]+):
361.1257, found 361.1224. IR: 3450, 1600, 1510, 1463, 1249, 1177, 1033, 812, 739.
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1-((9-ethyl-9H-carbazol-3-yl)(4-methoxyphenyl)methyl)naphthalen-2-ol (2s)
According to Method B: In a 25 ml Schlenk tube, 2ꢀBromoindazole (1.5 mmol, 3.0 equiv) in dry
THF (2 mL) was added dropwise nꢀBuLi (0.6 mL, 3.0 equiv, 2.5 M in hexane) at ꢀ78 °C under N2
atmosphere. The reaction mixture was stirred for 2 h. Suspension of ZnBr2 solution (1.5 mL, 1.0 M
in THF, 3.0 equiv) was added, After 15 min stir at 0°C, the mixture was treated with substrate 1f (0.5
mmol, 1.0 equiv) at room temperature. After the addition was completed, the reaction mixture was
stirred at 60 °C for 12 h. Purification by flash column chromatography provided 2s (125.7 mg, 55%)
o
as brown solid; m.p. 81ꢀ82 C (Petroleum ether/EtOAc); Rf = 0.55 (Petroleum ether/EtOAc = 3/1);
1H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.93 (s, 1H), 7.80
(d, J = 8.0 Hz, 1H), 7.76 (d, J = 9.2 Hz, 1H), 7.46ꢀ7.38 (m, 3H), 7.37ꢀ7.31 (m, 3H), 7.26ꢀ7.23 (m,
3H), 7.18 (t, J = 7.2 Hz, 1H), 7.10 (d, J = 8.8 Hz, 1H), 6.90 (d, J = 8.4 Hz, 2H), 6.55 (s, 1H), 5.49 (s,
1H), 4.35 (q, J = 7.2 Hz, 2H), 3.81 (s, 3H), 1.43 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
158.6, 153.0, 140.3, 139.0, 133.9 133.4, 132.0, 130.2, 129.5, 128.7, 126.8, 126.5, 125.9, 123.4, 123.1,
122.7, 122.5, 120.63, 120.60, 120.5, 120.0, 118.8, 114.5, 109.2, 108.5, 55.2, 47.9, 37.6, 13.8; HRMS
(ES+ꢀTOF) calcd for C32H27NO2Na ([M+Na]+):480.1934, found 480.1932. IR: 3458, 1600, 1508,
1469, 1384, 1331, 1249, 1177, 1032, 814, 746.
1-(furan-2-yl(phenyl)methyl)naphthalen-2-ol (2t)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 1ꢀ(furanꢀ2ꢀyl(tosyl)methyl)naphthalenꢀ2ꢀol 1g (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
2t (132.0 mg , 88%) ; as brown oil; (Petroleum ether/EtOAc); Rf = 0.63 (Petroleum ether/EtOAc =
1
3/1); H NMR (400 MHz, CDCl3): δ 7.94 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.0 Hz, 2H), 7.72 (d, J =
9.2 Hz, 1H), 7.43ꢀ7.39 (m, 2H), 7.33ꢀ7.28 (m, 4H), 7.24ꢀ7.21 (m, 3H), 7.09 (d, J = 8.8 Hz, 1H), 6.40
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(s, 1H), 6.33ꢀ6.32 (m, 1H), 6.09 (d, J = 3.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 155.3, 152.8,
142.7, 139.9, 133.0, 129.8, 129.5, 128.9, 128.7, 128.1, 127.2, 126.8, 123.1, 122.6, 119.4, 117.7,
110.4, 108.9, 42.1; HRMS (ES+ꢀTOF) calcd for C21H17O2 ([M+H]+): 301.1223, found 301.1211. IR:
3499, 1621, 1491, 1432, 1256, 1034, 964, 810, 752, 696.
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1-(phenyl(thiophen-2-yl)methyl)naphthalen-2-ol (2u)
According to Method A with phenylmagnesium bromide (1.5 mmol, 1.74 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 1ꢀ(thiophenꢀ2ꢀyl(tosyl)methyl)naphthalenꢀ2ꢀol 1h (0.5
o
mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column chromatography
provided 2u (156.4 mg , 99%) ; as brown oil; (Petroleum ether/EtOAc); Rf = 0.62 (Petroleum
ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 8.02 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.0 Hz, 1H),
7.76 (d, J = 9.2 Hz, 1H), 7.44 (t, J = 7.2 Hz, 1H), 7.39ꢀ7.33 (m, 5H), 7.31ꢀ7.29 (m, 2H), 7.11 (d, J =
8.8 Hz, 1H), 6.98ꢀ6.96 (m, 1H), 6.84 (d, J = 7.6 Hz, 1H), 6.58 (s, 1H), 5.51 (s, 1H); 13C NMR (100
MHz, CDCl3): δ 152.8, 145.9, 141.4, 132.8, 129.9, 129.5, 129.0, 128.8, 128.4, 127.4, 127.0, 126.9,
126.8, 126.0, 123.3, 122.5, 119.9, 119.8, 43.9; HRMS (ES+ꢀTOF) calcd for C21H16OSNa ([M+Na]+):
339.0814, found 339.0815. IR: 3496, 1623, 1491, 1434, 1253, 1034, 964, 803, 755, 710.
2-((2-hydroxynaphthalen-1-yl)(thiophen-2-yl)methyl)benzonitrile (2v)
According to Method C with 2ꢀiodobenzonitrile(1.5 mmol, 3.0 equiv), isopropylmagnesium chloride
(0.82
M
in THF, 3.0 equiv), ZnBr2 (1.5 mL, 1.0
M
in THF, 3.0 equiv),
o
1ꢀ(thiophenꢀ2ꢀyl(tosyl)methyl)naphthalenꢀ2ꢀol 1h in 2mL of THF at 60 C for 12 h. Purification by
flash column chromatography provided 2v (80.2 mg, 47%); as yellow solid; m.p. 212ꢀ213oC
(Petroleum ether/EtOAc); Rf = 0.30 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ
7.89 (d, J = 8.4 Hz, 1H), 7.79 (t, J = 6.4 Hz, 2H), 7.73 (d, J = 7.2 Hz, 1H), 7.54ꢀ7.43 (m, 3H),
7.41ꢀ7.33 (m, 3H), 7.10 (d, J = 8.8 Hz, 1H), 6.99ꢀ6.97 (m, 1H), 6.89 (s, 1H), 6.68 (d, J = 3.6 Hz, 1H),
5.67 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 153.3, 145.4, 144.7, 133.4, 133.3, 132.6, 130.6, 129.6,
129.5, 128.9, 127.8, 127.3, 127.0, 123.6, 122.3, 119.6, 118.2, 117.4, 113.0, 42.8; HRMS (ES+ꢀTOF)
calcd for C22H16NOS ([M+H]+): 342.0947, found 342.0956. IR: 3403, 2225, 1626, 1515, 1438, 1284,
968, 812, 766, 744, 697.
1-((4-bromophenyl)(thiophen-2-yl)methyl)naphthalen-2-ol (2w)
According to Method C with 1ꢀbromoꢀ4ꢀiodobenzene (1.5 mmol, 3.0 equiv), isopropylmagnesium
chloride (0.82 M in THF, 3.0 equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv),
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1ꢀ(thiophenꢀ2ꢀyl(tosyl)methyl)naphthalenꢀ2ꢀol 1h in 2 mL of THF at 60 oC for 12 h. Purification by
flash column chromatography provided 2w (143.8 mg, 73%); as yellow solid; m.p. 112ꢀ113oC
(Petroleum ether/EtOAc); Rf = 0.65 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ
7.94 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 4.49ꢀ7.44 (m, 3H),
7.39ꢀ7.33 (m, 2H), 7.29ꢀ7.28 (m, 2H), 7.14ꢀ7.11 (d, J = 8.8 Hz, 1H), 6.99 (t, J = 4.4 Hz, 1H),
6.86ꢀ6.85 (m, 1H), 6.55 (s, 1H), 5.46 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 152.6, 145.6, 140.5,
132.6, 132.0, 130.2, 130.1, 129.6, 128.9, 127.0, 126.9, 126.3, 123.4, 122.5, 121.2, 119.6, 119.4, 43.3;
HRMS (ES+ꢀTOF) calcd for C21H16BrOS ([M+H]+): 395.0100, found 395.0090. IR: 3532, 1622,
1508, 1486, 1260, 1010, 819, 751, 702.
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2-((4-methoxyphenyl)(phenanthren-9-yl)methyl)phenol (2x)
According to Method A withphenanthrenꢀ9ꢀylmagnesium bromide (3.7 mL, 0.41 M in THF, 3.0
equiv), ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a in 2
o
mL of THF at 60 C for 12 h. Purification by flash column chromatography provided 2x (193.1 mg,
o
99%); as white solid; m.p.85ꢀ86 C (Petroleum ether/EtOAc); Rf = 0.68 (Petroleum ether/EtOAc =
1
3/1); H NMR (400 MHz, CDCl3): δ8.74 (d, J = 8.0 Hz, 1H), 8.67 (d, J = 8.0 Hz, 1H), 8.03 (d, J =
8.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.64ꢀ7.61 (m, 2H), 7.53 (q, J = 8.1 Hz, 2H), 7.23 (s, 1H),
7.20ꢀ7.13 (s, 3H), 6.88ꢀ6.85 (m, 3H), 6.83ꢀ6.82 (m, 2H) 6.39 (s, 1H), 4.81 (s, 1H), 3.81 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 158.4, 153.1, 137.3, 134.0, 131.4, 131.0, 130.9, 130.6, 130.2, 129.9,
128.7, 128.0, 127.9, 126.8, 126.6, 126.5, 126.3, 125.1, 123.0, 122,4, 120.9, 116.1, 114.1, 55.2, 46.5;
HRMS (ES+ꢀTOF) calcd for C28H23O2 ([M+H]+):391.1693, found. 391.1685. IR: 3419, 1607, 1508,
1454, 1245, 1177, 1090, 1033, 748.
3. Synthesis of diarylmethanes 3 from 1
Method A: In a 25 ml Schlenk tube, alkyl Grignard reagent (3.0 equiv) was added to a solution of
o
ZnBr2 (1.5 mL, 1.0 M, 3.0 equiv) at 0 C under N2 atmosphere. After 15 min stir, the mixture was
treated with substrate 1 (0.5 mmol, 1.0 equiv) at room temperature. After the addition was completed,
the reaction mixture was stirred at 60°C for 12 h. After completion of the reaction, the mixture was
quenched by adding 5 mL of NH4Cl and extracted with EtOAc (3×10 mL). The combined organic
phase was washed with H2O (3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and
purified with flash silica gel chromatography to afford 3.
Method D: Zinc powder (156 mg, 2.4 mmol, 1.2 equiv) was suspended in anhydrous THF (3 mL)
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under N2, and then 1,2ꢀdibromoethane (22 ꢁL, 0.3 mmol, 15 mol%) was added. The mixture was
heated at 65 °C for 10 min. After the mixture was cooled to room temperature, TMSCl (13 ꢁL, 0.1
mmol, 5 mol%) was added, and the mixture was stirred for another 15 min before a solution of
Halogenated hydrocarbons (2 mmol, 1.0 equiv) in anhydrous THF (5 mL) was added dropwise. The
resulting mixture was stirred for 24 h at 40 °C. In another 25 mL Schlenk tube, substrate 1 (0.5 mmol,
1.0 equiv) was dissolved in 2 mL of dry THF under N2 atmosphere. Then formed RZnX (2 mmol, 4.0
equiv) were added to this mixture was heated at 60 °C for 12 h.. After completion of the reaction, the
mixture was quenched by adding 5 mL of NH4Cl and extracted with EtOAc (3×10 mL). The
combined organic phase was washed with H2O (3×10 mL), dried over anhydrous Na2SO4,
concentrated in vacuo and purified with flash silica gel chromatography to afford 3.
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2-(1-(4-methoxyphenyl)propyl)phenol (3a)
According to Method A with ethylmagnesium bromide (1.5 mmol, 0.69 M in THF, 3.0 equiv), ZnBr2
(1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol, 1.0
o
equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column chromatography provided 3a
(94.4 mg, 78%) as colorless oil; (Petroleum ether/EtOAc); Rf = 0.75 (Petroleum ether/EtOAc = 3/1);
1H NMR (400 MHz, CDCl3): δ 7.28 (d, J = 7.6 Hz, 1H), 7.19 (d, J = 8.4 Hz, 2H), 7.13ꢀ7.08 (m, 1H),
6.97ꢀ6.93 (m, 1H), 6.86 (d, J = 11.6 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 4.88 (s, 1H), 4.04 (t, J = 15.2
Hz, 1H), 3.79 (s, 3H), 2.14ꢀ1.73 (m, 2H), 0.94 (t, J = 14.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
158.0, 153.4, 136.1, 131.2, 129.0, 127.8, 127.2, 120.7, 115.9, 113.9, 55.2, 45.3, 27.7, 12.6; HRMS
(ES+ꢀTOF) calcd for C16H18O2Na([M+Na]+): 265.1199, found 265.1199. IR: 3403, 1600, 1514, 1462,
1383, 1232, 1126, 1023, 833, 752.
2-(1-(4-methoxyphenyl)-2-methylpropyl)phenol (3b)
According to Method A with isopropylmagnesium bromide (1.5 mmol, 0.82 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
o
3b (74.3 mg, 58%); as red solid; m.p. 103ꢀ104 C (Petroleum ether/EtOAc); Rf = 0.75 (Petroleum
ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.34 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H),
7..03 (t, J = 7.6 Hz, 1H), 6.92 (t, J = 7.4 Hz, 1H), 6.80 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.0 Hz, 1H),
4.72 (s, 1H), 3.79 (s, 1H), 3.76 (s, 3H), 2.51ꢀ2.45 (m, 1H), 0.94 (d, J =6.4 Hz, 3H), 0.87 (d, J =6.4
Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 157.8, 153.3, 136.1, 131.2, 129.3, 129.2, 127.9, 126.8,
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120.9, 128.0, 115.9, 113.7, 55.2, 51.4, 31.1, 21.7; HRMS (ES+ꢀTOF) calcd for C17H21O2 ([M+H]+):
257.1536, found 257.1552. IR: 3403, 1608, 1510, 1462, 1383, 1233, 1129, 1023, 833, 753.
2-(1-(4-methoxyphenyl)-2,2-dimethylpropyl)phenol (3c)
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According to Method A with tertꢀbutylmagnesium bromide (1.5 mmol, 0.99 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 2ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 1a (0.5 mmol,
1.0 equiv) in 2 mL of THF at 60 oC for 12 h. Purification by flash column chromatography provided
3c (43.2 mg, 32%); as red oil; (Petroleum ether/EtOAc); Rf = 0.71 (Petroleum ether/EtOAc = 3/1);
1H NMR (400 MHz, CDCl3): δ 7.63 (d, J = 7.6 Hz, 1H), 7.21 (d, J = 8.8 Hz, 2H), 7.04 (t, J = 7.6 Hz,
1H), 6.90 (t, J = 7.2 Hz, 1H), 6.80 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.8 Hz, 1H), 4.77 (s, 1H), 4.27 (s,
1H), 3.77 (s, 3H), 1.07 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 157.8, 153.4, 134.8, 131.2, 130.4,
129.8, 126.7, 120.3, 115.8, 113.3, 55.1, 52.3, 35.2, 29.2; HRMS (ES+ꢀTOF) calcd for C18H23O2
([M+H]+): 271.1693, found 271.1701. IR: 3403, 1610, 1510, 1454, 1380, 1233, 1126, 1023, 831,
750.
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1-(1-(4-methoxyphenyl)propyl)naphthalen-2-ol (3d)
According to Method A with ethylmagnesium bromide (1.5 mmol, 0.69 M in THF, 3.0 equiv), ZnBr2
(1.5 mL, 1.0 M in THF, 3.0 equiv), 1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f (0.5
o
mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column chromatography
provided 3d (129.9 mg, 89%) as yellow solid; m.p. 65ꢀ66oC (Petroleum ether/EtOAc); Rf = 0.62
(Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.0 Hz, 1H), 7.80 (d, J =
8.0 Hz, 1H),7.68 (d, J = 8.8 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.36ꢀ7.29 (m, 3H), 7.01 (d, J = 8.8 Hz,
1H), 6.86 (d, J = 8.4 Hz, 2H), 5.04ꢀ5.02 (m, 1H), 4.93ꢀ4.89 (m, 1H), 3.78 (s, 3H), 2.47ꢀ2.39 (m, 1H),
2.28ꢀ2.21 (m, 1H), 0.91 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 158.2, 151.8, 148.1,
134.9, 133.8, 129.6, 128.8, 128.7, 128.5, 126.4, 123.0, 122.5, 119.3, 114.3, 55.2, 41.3, 24.6, 12.7;
HRMS (ES+ꢀTOF) calcd for C20H20O2Na([M+Na]+): 315.1356, found 315.1376. IR: 3398, 1622,
1510, 1465, 1250, 1181, 1030, 801, 748.
1-(1-(4-methoxyphenyl)-2-methylpropyl)naphthalen-2-ol (3e)
According to Method A with isopropylmagnesium bromide (1.5 mmol, 0.82 M in THF, 3.0 equiv),
ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv), 1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f
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(0.5 mmol, 1.0 equiv) in 2 mL of THF at 60 C for 12 h. Purification by flash column
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chromatography provided 3e (79.6 mg, 52%) as yellow solid; m.p. 123ꢀ124 C (Petroleum
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ether/EtOAc); Rf = 0.64 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 8.30 (d, J =
8.4 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.53ꢀ7.49 (m, 1H), 7.43 (d, J = 8.8 Hz,
2H), 7.34 (t, J = 7.4 Hz, 1H), 6.95 (d, J = 8.8 Hz, 1H), 6.83 (d, J = 8.8 Hz, 2H), 5.22 (s, 1H), 4.58 (d,
J = 10.4 Hz, 1H), 3.75 (s, 3H), 3.11ꢀ3.06 (m, 1H), 1.18 (d, J = 6.4 Hz, 3H), 0.80 (d, J = 6.4 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 157.7, 151.1, 135.0, 133.9, 129.6, 129.4, 128.8, 128.4, 126.4, 123.4,
123.2, 122.9, 119.0, 113.8, 55.1, 49.0, 28.6, 23.0, 21.5; HRMS (ES+ꢀTOF) calcd for C21H23O2
([M+H]+): 307.1693, found 307.1690. IR: 3412, 1621, 1509, 1432, 1263, 1179, 1025, 810, 740, 525.
5-(2-hydroxynaphthalen-1-yl)-5-(4-methoxyphenyl)pentyl acetate (3f)
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According to Method D with (5ꢀmethoxyꢀ5ꢀoxopentyl)zinc(II) iodide (2 mmol, 4.0 equiv),
1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f (0.5 mmol, 1.0 equiv), 2 mL of THF at 60 oC
for 12 h. Purification by flash column chromatography provided 3f (128.6 mg, 68%) as yellow oil;
(Petroleum ether/EtOAc); Rf = 0.41 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ
8.05 (s, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 7.35ꢀ7.28 (m, 3H), 7.02
(d, J = 8.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 2H), 5.38 (s, 1H), 4.99 (t, J = 7.4 Hz, 1H), 3.98 (t, J = 6.8 Hz,
1H), 3.77 (m, 3H) , 2.41ꢀ2.31 (m, 2H), 1.97 (s, 3H), 1.72ꢀ1.60 (m, 2H), 1.43ꢀ1.41 (m, 1H), 1.28ꢀ1.22
(m, 1H); 13C NMR (100 MHz, CDCl3): δ 171.2, 158.0, 151.8, 135.2, 133.6, 129.6, 128.8, 128.6,
128.4, 126.4, 123.1, 122.9, 122.5, 119.0, 114.1, 64.4, 55.2, 39.8, 31.4, 28.7, 24.4, 20.9; HRMS
(ES+ꢀTOF) calcd for C24H26O4Na([M+Na]+): 401.1723, found 401.1724. IR: 3445, 1733, 1610, 1512,
1241, 1177, 1030, 813, 750.
ethyl 6-(2-hydroxynaphthalen-1-yl)-6-(4-methoxyphenyl)hexanoate (3g)
According to Method D with (5ꢀethoxyꢀ5ꢀoxopentyl)zinc(II) iodide (2 mmol, 4.0 equiv),
1ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)naphthalenꢀ2ꢀol 1f (0.5 mmol, 1.0 equiv), 2 mL of THF at 60 oC
for 12 h. Purification by flash column chromatography provided 3g (117.6 mg, 60%) as yellow oil;
(Petroleum ether/EtOAc); Rf = 0.46 (Petroleum ether/EtOAc = 20/1); 1H NMR (400 MHz, CDCl3): δ
8.05 (s, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.44 (s, 1H), 7.34ꢀ7.27 (m, 3H), 7.01
(d, J = 8.8 Hz, 1H), 6.83 (d, J = 8.8 Hz, 2H), 5.19 (s, 1H), 4.99ꢀ4.96 (m, 1H), 4.05 (q, J = 7.2 Hz,
2H), 3.77 (s, 3H), 2.37ꢀ2.19 (m, 4H); 1.70ꢀ1.60 (m, 4H), 1.18 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3): δ 174.0, 158.0, 151.8, 133.5, 129.6, 128.8, 128.6, 128.4, 126.3, 122.9, 122.6, 119.1,
114.1, 60.2, 55.2, 39.7, 34.2, 31.5, 27.6, 25.2, 14.1; HRMS (ES+ꢀTOF) calcd for C25H28O4Na
([M+Na]+): 415.1880, found 415.1882. IR: 3445, 1731, 1625, 1510, 1247, 1179, 1033, 813, 747.
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1-(4-methoxyphenyl)-1,2-dihydro-3H-benzo[f]chromen-3-one (3h)
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According to Method D with Zinc powder (156 mg, 2.4 mmol, 1.2 equiv) was suspended in
anhydrous THF (3 mL) under N2, and then 1,2ꢀdibromoethane (22 ꢁL, 0.3 mmol, 15 mol%) was
added. The mixture was heated at 65 °C for 10 min. After the mixture was cooled to room
temperature, TMSCl (13 ꢁL, 0.1 mmol, 5 mol%) was added, and the mixture was stirred for another
15 min before a solution of ethyl bromoacetate (2 mmol, 1.0 equiv) in anhydrous THF (5 mL) was
added dropwise. The resulting mixture was stirred for 24 h at 40 °C. In another 25 mL Schlenk tube,
substrate 1f (0.5 mmol, 1.0 equiv) was dissolved in 2 mL of dry THF under N2 atmosphere. Then
formed (2ꢀethoxyꢀ2ꢀoxoethyl)zinc(II) bromide (2 mmol, 4.0 equiv) were added to this mixture was
heated at 60 °C for 12 h. Purification by flash column chromatography provided 3h (109.5 mg, 72%)
as white solid; m.p.49.1ꢀ50.7 oC (Petroleum ether/EtOAc); Rf = 0.43 (Petroleum ether/EtOAc = 3/1);
1H NMR (400 MHz, CDCl3): δ 7.88 (d, J = 8.8 Hz, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.50ꢀ7.42 (m, 2H),
7.34 (d, J = 8.8 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 4.92ꢀ4.91 (m, 1H), 3.73
(s, 3H), 3.18ꢀ3.15 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 167.3, 158.6, 149.6, 132.5, 131.0, 130.9,
129.8, 128.7, 128.0, 127.4, 125.2, 123.0, 117.9, 117.5, 114.5, 55.2, 37.7, 36.8; HRMS (ES+ꢀTOF)
calcd for C20H17O3([M+H]+): 305.1172, found 305.1181. IR: 3447, 1763, 1611, 1509, 1244, 1176,
1138, 1031, 969, 851, 817, 746.
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1-(thiophen-2-yl)-1,2-dihydro-3H-benzo[f]chromen-3-one (3i)
According to Method D with Zinc powder (156 mg, 2.4 mmol, 1.2 equiv) was suspended in
anhydrous THF (3 mL) under N2, and then 1,2ꢀdibromoethane (22 ꢁL, 0.3 mmol, 15 mol%) was
added. The mixture was heated at 65 °C for 10 min. After the mixture was cooled to room
temperature, TMSCl (13 ꢁL, 0.1 mmol, 5 mol%) was added, and the mixture was stirred for another
15 min before a solution of ethyl bromoacetate (2 mmol, 1.0 equiv) in anhydrous THF (5 mL) was
added dropwise. The resulting mixture was stirred for 24 h at 40 °C. In another 25 mL Schlenk tube,
substrate 1h (0.5 mmol, 1.0 equiv) was dissolved in 2 mL of dry THF under N2 atmosphere. Then
formed (2ꢀethoxyꢀ2ꢀoxoethyl)zinc(II) bromide (2 mmol, 4.0 equiv) were added to this mixture was
heated at 60 °C for 12 h. Purification by flash column chromatography provided 3i (128.8 mg, 92%)
as white solid; m.p.78ꢀ79 oC (Petroleum ether/EtOAc); Rf = 0.52 (Petroleum ether/EtOAc = 3/1); 1H
NMR (400 MHz, CDCl3): δ 7.93ꢀ7.86 (m, 3H), 7.56 (t, J = 7.6 Hz, 1H), 7.48 (t, J = 7.4 Hz, 1H), 7.17
(d, J = 8.8 Hz, 1H), 7.15 (d, J = 4.8 Hz, 1H), 6.85 (t, J = 8.8 Hz, 1H), 6.68ꢀ6.67 (m, 1H), 5.19 (d, J =
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6.0 Hz, 1H), 3.3 (d, J = 14.8 Hz, 1H), 3.20 (dd, J1 = 16.0 Hz, J2 = 6.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3): δ 166.8, 149.3, 143.6, 131.0, 130.6, 130.1, 128.8, 127.6, 127.2, 125.4, 125.0, 124.9, 122.9,
117.9, 117.7, 37.6, 32.8; HRMS (ES+ꢀTOF) calcd for C17H13O2S([M+H]+): 281.0631, found
281.0638. IR: 3446, 1771, 1627, 1516, 1224, 1174, 1109, 819, 710.
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4. Application of triarylmethanes derivatives
(S)-4-((3-chlorophenyl)(4-methoxyphenyl)methyl)phenol (5a)
In a 25 mL Schlenk tube, (3ꢀchlorophenyl)magnesium bromide (2.3 mL, 0.65 M in THF, 3.0 equiv)
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was added to a solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 C under N2 atmosphere.
After 15 min, the mixture was treated with 4ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 4a (0.5 mmol,
1.0 equiv) at room temperature. After the addition was completed, the reaction mixture was stirred at
60 °C for 12 h. After completion of the reaction, the mixture was quenched by adding 5 mL of
NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was washed with H2O
(3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified with flash silica gel
chromatography to afford 5a (149.6 mg, 92%) as yellow oil; Rf = 0.52 (Petroleum ether/EtOAc =
3/1); 1H NMR (400 MHz, CDCl3): δ 7.28ꢀ7.26 (m, 2H), 7.07ꢀ7.03 (m, 4H), 6.97 (d, J = 8.4 Hz, 2H),
6.87 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.4 Hz, 2H), 5.68 (s, 1H), 5.43 (s, 1H), 3.82 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 157.9, 154.0, 143.0, 136.0, 135.9, 131.9, 130.6, 130.3, 130.2, 128.3, 115.2,
113.8, 55.2, 54.4; HRMS (ES+ꢀTOF) calcd for C20H18ClO2 ([M+H]+): 325.0990, found 325.0991. IR:
3404, 1610, 1509, 1471, 1246, 1174, 1034, 830, 706, 580.
4-benzhydryl-2-methoxyphenol (5b)
In a 25 mL Schlenk tube, phenylmagnesium bromide (0.93 mL, 1.61 M in THF, 3.0 equiv) was
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added to a solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 C under N2 atmosphere. After
15 min, the mixture was treated with 2ꢀmethoxyꢀ4ꢀ(phenyl(tosyl)methyl)phenol 4b (0.5 mmol, 1.0
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equiv) at room temperature. After the addition was completed, the reaction mixture was stirred at
60°C for 12 h. After completion of the reaction, the mixture was quenched by adding 5 mL of NH4Cl
and extracted with EtOAc (3×10 mL). The combined organic phase was washed with H2O (3×10
mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified with flash silica gel
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chromatography to afford 5b (107 mg, 74%) as white solid; m.p.98ꢀ99 C (Petroleum ether/EtOAc);
Rf = 0.62 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.29ꢀ7.25 (m, 4H), 7.21 (d,
J = 6.8 Hz, 2H), 7.11 (d, J = 7.6 Hz, 4H), 6.82 (d, J = 8 Hz, 1H), 6.62 (2, 1H), 6.56 (d, J = 8 Hz, 1H),
5.49 (d,J = 7.6 Hz, 2H), 3.75 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 146.5, 144.3, 144.2, 136.0,
129.5, 128.4, 126.4, 122.4, 114.2, 112.2, 56.6, 56.0 ; HRMS (ES+ꢀTOF) calcd for C20H18ClO2
([M+H]+): 325.0990, found 325.0991. IR: 2515, 1593, 1509, 1487, 1445, 1425, 1274, 1227, 1025,
807, 713, 689, 535 .
4-benzhydryl-2,6-dimethoxyphenol (5c)
In a 25 mL Schlenk tube, phenylmagnesium bromide (0.93 mL, 1.61 M in THF, 3.0 equiv) was
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added to a solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 C under N2 atmosphere. After
15 min, the mixture was treated with 2,6ꢀdimethoxyꢀ4ꢀ(phenyl(tosyl)methyl)phenol 4c (0.5 mmol,
1.0 equiv) at room temperature. After the addition was completed, the reaction mixture was stirred at
60 °C for 12 h. After completion of the reaction, the mixture was quenched by adding 5 mL of
NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was washed with H2O
(3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified with flash silica gel
chromatography to afford 5c (111 mg, 69%) as yellow solid; m.p.126ꢀ127 oC (Petroleum
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(m, 4H), 7.22ꢀ7.19 (m, 2H), 7.11 (d, J = 8.4 Hz, 4H), 6.35 (s, 2H), 5.47 (s, 1H), 5.41 (s, 1H), 3.75 (s,
6H) ; 13C NMR (100 MHz, CDCl3): δ 147.0, 144.1, 135.1, 133.4, 129.4, 128.4, 126.4, 106.6, 56.9,
56.4 ; HRMS (ES+ꢀTOF) calcd for C20H18ClO2 ([M+H]+): 325.0990, found 325.0991. IR: 3481, 1618,
1514, 1450, 1422, 1207, 1106, 740, 701.
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4-benzhydryl-2,6-dibromophenol (5d)
In a 25 mL Schlenk tube, phenylmagnesium bromide (0.93 mL, 1.61 M in THF, 3.0 equiv) was
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added to a solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 C under N2 atmosphere. After
15 min, the mixture was treated with 2,6ꢀdibromoꢀ4ꢀ(phenyl(tosyl)methyl)phenol 4d (0.5 mmol, 1.0
equiv) at room temperature. After the addition was completed, the reaction mixture was stirred at
60 °C for 12 h. After completion of the reaction, the mixture was quenched by adding 5 mL of
NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was washed with H2O
(3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified with flash silica gel
chromatography to afford 5d (127 mg, 61%) as white solid; m.p.120ꢀ121 oC (Petroleum
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ether/EtOAc); Rf = 0.71 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz, CDCl3): δ 7.31ꢀ7.28
(m, 4H), 7.24ꢀ7.23 (m, 2H), 7.18 (s, 2H), 7.07 (d, J = 7.2 Hz, 4H), 5.79 (s, 1H), 5.42 (s, 1H) ; 13C
NMR (100 MHz, CDCl3): δ 148.0, 142.8, 138.9,132.8, 132.8, 129.3, 128.7, 126.9, 109.9, 55.6 ;
HRMS (ES+ꢀTOF) calcd for C20H18ClO2 ([M+H]+): 325.0990, found 325.0991. IR: 3491, 1605, 1492,
1472, 1168, 728, 696, 590.
(S)-4-((4-methoxyphenyl)(phenanthren-9-yl)methyl)phenol (5e)
In a 25 mL Schlenk tube, phenanthrenꢀ9ꢀylmagnesium bromide (3.7 mL, 0.41 M in THF, 3.0 equiv)
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was added to a solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 C under N2 atmosphere.
After 15 min, the mixture was treated with 4ꢀ((4ꢀmethoxyphenyl)(tosyl)methyl)phenol 4a (0.5 mmol,
184.0 mg, 1.0 equiv) at room temperature. After the addition was completed, the reaction mixture
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was stirred at room temperature for 18 h. After completion of the reaction, the mixture was quenched
by adding 5 mL of NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was
washed with H2O (3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified with
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(Petroleum ether/EtOAc); Rf = 0.52 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ
8.73 (d, J = 8.4 Hz, 1H), 8.66 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H),
7.63ꢀ7.59 (m, 2H), 7.55ꢀ7.48 (m, 2H), 7.16 (s, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H),
6.84 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.4 Hz, 2H), 6.15 (s, 1H), 5.02ꢀ4.95 (m, 1H), 3.79 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 158.0, 154.0, 138.8, 136.0, 135.9, 131.4, 131.2, 130.8, 130.6, 129.8,
128.7, 128.3, 126.6, 126.5, 126.4, 126.1, 125.2, 123.0, 122,3, 115.3, 113.8, 55.2, 51.8; HRMS
(ES+ꢀTOF) calcd for C28H23O2 ([M+H]+):391.1693, found. 391.1687. IR: 3396, 1609, 1508, 1449,
1245, 1172, 1034, 800, 748, 723.
2,6-dimethyl-4-(phenyl(thiophen-2-yl)methyl)phenol (5f)
In a 25 mL Schlenk tube, thiophenꢀ2ꢀylmagnesium bromide (2.1 mL, 0.72 M in THF, 3.0 equiv) was
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added to a solution of ZnBr2 (1.5 mL, 1.0 M in THF, 3.0 equiv) at 0 C under N2 atmosphere. After
15 min, the mixture was treated with 2,6ꢀdimethylꢀ4ꢀ(phenyl(tosyl)methyl)phenol 4f (0.5 mmol,
183.0 mg, 1.0 equiv) at room temperature. After the addition was completed, the reaction mixture
was stirred at 60 °C for 12 h. After completion of the reaction, the mixture was quenched by adding 5
mL of NH4Cl and extracted with EtOAc (3×10 mL). The combined organic phase was washed with
H2O (3×10 mL), dried over anhydrous Na2SO4, concentrated in vacuo and purified with flash silica
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gel chromatography to afford 5f (111.7 mg, 76%) as white solid; m.p.105ꢀ106 C (Petroleum
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ether/EtOAc); Rf = 0.78 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz, CDCl3): δ 7.34ꢀ7.30
(m, 2H), 7.26ꢀ7.21 (m, 4H), 6.95 (t, J = 8.4 Hz, 1H), 6.85 (s, 2H), 6.70 (d, J = 3.2 Hz, 1H), 5.57 (s,
1H), 4.58 (s, 1H), 2.21 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 150.9, 148..6, 144.2, 135.4, 128.9,
128.7, 128.3, 126.5, 126.4, 126.1, 124.3, 122.8, 51.4, 16.0; HRMS (ES+ꢀTOF) calcd for
C19H18OSNa([M+Na]+): 317.0971, found 317.0973. IR: 3580, 1600, 1487, 1300, 1204, 1029, 823,
701.
5. Synthesis of starting materials
General procedure A:
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A solution of Grignard reagents 6 (25 mmol) was added to orthoꢀhydroxybenzaldehyde 5 (10.0
mmol) in THF (10 mL) under N2. After being stirred at room temperature for 3 h, the reaction
mixture was quenched by a saturated NH4Cl (20 mL) and extracted with CH2Cl2. The combined
organic phases were washed with brine, then dried over Na2SO4, filtered and concentrated. The crude
mixture was purified through a short silica gel column (hexane/ethyl acetate) to afford
2ꢀ(hydroxy(phenyl)methyl)phenols 7. TolSO2Na (2.047 g, 11.5 mmol) and TsOH (3.360 g, 17.5
mmol) were placed in a dried Schlenk tube, and dry CH2Cl2 (40 mL) was added. The mixture was
stirred at room temperature for 5 min. Then, a solution 30 mL of 2ꢀ(hydroxy(phenyl)methyl)phenols
7 (10 mmol) in CH2Cl2 was added and stirred for 1.5 h, the reaction mixture was quenched and
adjusted to pH = 8 by saturated NaHCO3. After extracted with CH2Cl2, the combined organic phases
were washed with 1N HCl and brine, then dried over Na2SO4, filtered and concentrated. The crude
mixture was purified through a short silica gel column (hexane/ethyl acetate) to afford
2ꢀ(phenyl(tosyl)methyl)phenol 1.
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General procedure B:
o
At 0 C under N2, to a flameꢀdried flask charged with a solution of bromoꢀhydrocarbons (25 mmol)
in dry THF (15 mL) was added nꢀBuLi (25 mmol, 2.5 M in THF, 10 mL) dropwise. The reaction was
stirred for 30 min at the same temperature and then a solution of the aldehyde (10 mmol) in THF (6
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mL) was added by syringe. The reaction mixture was then warmed to 60 C and stirred overnight.
Upon completion, the reaction mixture was cooled to 0 oC. A saturated aqueous NH4Cl solution (20
mL) was added dropwise. The organic layer was separated. The aqueous layer was extracted with
Et2O (3× 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and
concentrated. The residue was purified by silica gel chromatography to afford the desired alcohol 7.
TolSO2Na (2.047 g, 11.5 mmol) and TsOH (3.360 g, 17.5 mmol) were placed in a dried Schlenk tube,
and dry CH2Cl2 (40 mL) was added, and the mixture was stirred at room temperature for 5 min. Then,
the solution 30 mL of 2ꢀ(hydroxy(phenyl)methyl)phenols 7 (10 mmol) in CH2Cl2 was added and
stirred for 1.5 h, the reaction mixture was quenched and adjusted to pH = 8 by saturated NaHCO3.
After extracted with CH2Cl2, the combined organic phases were washed with 1N HCl and brine, then
dried over Na2SO4, filtered and concentrated. The crude mixture was purified through a short silica
gel column (hexane / ethyl acetate) to afford 2ꢀ(phenyl(tosyl)methyl)phenol 1.
2-((4-methoxyphenyl)(tosyl)methyl)phenol (1a)
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According to general procedure A: 1a (2.39 g, 65%); as white solid; (Petroleum ether/EtOAc); Rf
= 0.31 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.67ꢀ7.64 (M , 1H), 7.54 (d, J
= 8.0 Hz , 2H) , 7.43 (d, J = 8.8 Hz , 2H), 7.16ꢀ7.09 (m, 3H), 6.90 (t, J = 3.6 Hz ,1H), 6.82ꢀ6.74 (m,
4H), 5.87 (m, 1H), 3.76 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.7, 154.2, 144.5,
135.0, 131.5, 130.5, 129.9, 129.3, 128.8, 124.2, 121.0, 120.2, 117.4, 114.0, 69.2, 55.2, 21.6.
4-chloro-2-((4-methoxyphenyl)(tosyl)methyl)phenol (1b)
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According to general procedure A: 4e (2.17 g, 67%); as white solid; m.p. 164ꢀ165oC (Petroleum
ether/EtOAc); Rf = 0.32 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.61 (d, J =
2.4 Hz , 1H), 7.54 (d, J = 8.0 Hz , 2H), 7.44 (d, J = 8.8 Hz , 2H), 7.18 (d, J = 8.8 Hz , 2H), 7.09ꢀ7.06
(m, 1H)，6.81 (d, J = 8.8 Hz , 2H), 6.70 (d, J = 8.8 Hz , 1H), 5.79 (s, 1H), 3.77 (s, 3H), 2.36 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 159.9, 153.0, 144.9, 134.6, 131.4, 130.1, 129.9, 129.4, 128.8, 125.9,
123.6, 121.9, 118.8, 114.1, 69.0, 55.2, 21.6; HRMS(ES+ꢀTOF) calcd for C21H19ClO4SNa ([M+Na+]):
425.0585, found 425.0587. IR: 3415, 1599, 1510, 1416, 1253, 1178, 1140, 1086, 1030, 820, 725, 665,
585, 538.
4-fluoro-2-((4-methoxyphenyl)(tosyl)methyl)phenol (1c)
According to general procedure A: 4g (2.06 g, 58%); 1H NMR (400 MHz, CDCl3): δ 7.67ꢀ7.65 (m ,
1H), 7.55ꢀ7.49 (m, 4H) , 7.17ꢀ7.12 (m , 3H),6.99ꢀ6.91 (m , 3H), 6.77ꢀ6.75 (m, 1H)，6.55 (s , 1H),5.90
(m , 1H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 164.0, 161.5, 154.1, 144.8, 134.9, 132.0 (d, J
= 9.3 Hz), 130.4, 130.1, 129.4, 128.8, 128.2, 121.2, 119.9, 117.3, 115.7, 115.4, 68.8, 21.6.
2-((4-chlorophenyl)(tosyl)methyl)phenol (1d)
According to general procedure A: 4f (2.75 g, 74%); as white solid; m.p. 183ꢀ184oC (Petroleum
ether/EtOAc); Rf = 0.24 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz, CDCl3): δ 7.60ꢀ7.55
(m , 3H), 7.47 (d, J = 8.8 Hz, 2H) , 7.29ꢀ7.28 (m , 1H), 7.27ꢀ7.26 (m, 1H)，7.21ꢀ7.17 (m, 3H)，6.93 (t,
J = 8.0 Hz, 1H)，6.81 (d, , J = 8.0 Hz, 1H)，5.85 (s , 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 154.0, 144.9, 134.9, 134.8, 131.6, 130.9, 130.6, 130.3, 129.4, 128.9, 128.8, 121.4, 119.8, 117.7,
69.3, 21.6; HRMS (ES+ꢀTOF) calcd for C20H18ClO3S ([M+H]+): 373.0660, found: 373.0673. IR:
3374, 1596, 1490, 1458, 1312, 1274, 1145, 1085, 1015, 814, 760, 714, 649, 577.
2-(thiophen-2-yl(tosyl)methyl)phenol (1e)
According to general procedure B: 4j (2.82 g, 73%); as purple solid; m.p. 148ꢀ149oC (Petroleum
ether/EtOAc); Rf = 0.30 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.61 (d, J =
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8.0 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 5.2 Hz, 1H), 7.25ꢀ7.24 (m, 1H), 7.20ꢀ7.17 (m, 3H),
6.98ꢀ6.96 (m, 1H), 6.93ꢀ6.91(m, 1H), 6.80 (d, J = 8.0 Hz, 1H), 6.18 (s, 1H), 2.37 (s, 3H);13C NMR
(100 MHz, CDCl3): δ 154.2, 144.8, 134.2, 133.3, 130.8, 130.4, 129.9, 129.3, 129.1, 127.1, 126.9,
121.2, 119.6, 117.4, 65.3, 21.6; HRMS (ES+ꢀTOF) calcd for C18H17O3S2 ([M+H]+): 345.0614, found
345.0630. IR: 3369, 1596, 1458, 1354, 1294, 1134, 1078, 814, 756, 712, 587.
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1-((4-methoxyphenyl)(tosyl)methyl)naphthalen-2-ol (1f)
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According to general procedure A: 4i (6.41g, 76%) as yellow solid; m.p. 158ꢀ159 C (Petroleum
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ether/EtOAc); Rf = 0.52 (Petroleum ether/EtOAc = 3/1); H NMR (400 MHz, CDCl3): δ 7.72ꢀ7.58
(m, 7H), 7.33 (t, J = 7.4 Hz, 1H), 7.26ꢀ7.19 (m, 2H), 7.04 (d, J = 7.6 Hz, 2H), 6.86 (d, J = 8.4 Hz,
2H), 6.44 (s, 1H), 3.77 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.9, 154.4, 145.0,
134.3, 132.9, 131.6, 131.3, 129.3, 128.9, 128.5, 127.1, 123.2, 122.4, 120.9, 120.6, 114.2, 110.8, 69.8,
55.2, 21.5; HRMS (ES+ꢀTOF) calcd for C25H23O4S ([M+H]+): 419.1312, found 419.1313. IR: 3318,
1626, 1504, 1437, 1361, 1186, 1138, 1081, 1033, 966, 775, 751, 662, 520.
1-(furan-2-yl(tosyl)methyl)naphthalen-2-ol (1g)
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According to general procedure B: 4d (1.74 g, 46%); as green solid; m.p. 114ꢀ115 C (Petroleum
ether/EtOAc); Rf = 0.30 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 7.74 (d, J =
9.2 Hz, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0 Hz, 3H),7.38 (t, J = 7.4 Hz, 2H), 7.29ꢀ7.27 (m,
1H), 7.29ꢀ7.22 (m, 2H), 7.12 (d, J = 8.0 Hz, 2H), 6.83 (s, 1H), 6.53 (s, 1H), 3.39ꢀ6.38 (m, 1H), 2.30
(s, 3H); 13C NMR (100 MHz, CDCl3): 154.9, 145.3, 144.4, 143.4, 134.2, 132.9. 131.9, 129.5, 129.3,
128.9, 128.7, 127.2, 124.7, 123.3, 120.8, 112.7, 111.2, 108.9, 64.6, 21.4; HRMS (ES+ꢀTOF) calcd for
C22H19O4S ([M+H]+): 275.1436, found 275.1443. IR: 3406, 1600, 1517, 1439, 1274, 1142, 1085,
1016, 812, 749, 653, 577.
1-(thiophen-2-yl(tosyl)methyl)naphthalen-2-ol (1h)
According to general procedure A: 4c (1.97 g, 50%); as yellow solid; m.p.147ꢀ148oC (Petroleum
ether/EtOAc); Rf = 0.24 (Petroleum ether/EtOAc = 3/1); 1H NMR (400 MHz, CDCl3): δ 8.72 (s, 1H),
7.74 (d, J = 9.2 Hz, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.62 (d, J = 8.0 Hz, 1H), 7.55 (s, 1H), 7.35ꢀ7.31
(m, 3H), 7.25ꢀ7.23 (m, 1H), 7.04 (d, J = 8.0 Hz, 2H), 6.99ꢀ6.97 (m, 1H), 6.64 (s, 1H), 2.24 (s,
3H);13C NMR (100 MHz, CDCl3): δ 154.8, 145.4, 132.6, 132.0, 131.3, 130.1, 129.4, 129.2, 128.9,
128.8, 128.7, 127.7, 127.3, 126.8, 123.3, 121.1, 120.2, 110.6, 66.1, 21.5; HRMS (ES+ꢀTOF) calcd for
C22H18O3S2 ([M+H]+): 395.0770, found 395.0789. IR: 3360, 1624, 1513, 1438, 1280, 1135, 1078,
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