Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840

Article abstract of DOI:10.1016/j.tet.2017.01.030

A three-step protocol toward 1,1,2-triarylethanes 1 starting with β-ketosulfones 2 is developed. A facile process is carried out for the (1) reduction of 2 with NaBH₄, (2) BF₃·OEt₂-mediated Friedel-Crafts reactions of the

Full text of DOI:10.1016/j.tet.2017.01.030

Tetrahedron xxx (2017) 1e8
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Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to
the synthesis of CDP-840
,
, *
Yi-Shan Lin a, Yi-Chun Kuo b, Chun-Hsiung Kuei a **, Meng-Yang Chang c
a Department of Chemistry, National Cheng-Kung University, Tainan 70101, Taiwan
b Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
c Department of Medicinal and Applied Chemistry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
A three-step protocol toward 1,1,2-triarylethanes 1 starting with b-ketosulfones 2 is developed. A facile
Received 5 November 2016
Received in revised form
10 January 2017
Accepted 12 January 2017
Available online xxx
process is carried out for the (1) reduction of 2 with NaBH4, (2) BF3$OEt2-mediated Friedel-Crafts re-
actions of the resulting -hydroxy sulfones 3, and (3) palladium-catalyzed desulfonylative cross-coupling
b
of the corresponding 5 with aryl iodides 4 in the presence of t-BuOK under warming DMF in acceptable
yields. A facile synthesis of CDP-840 (1v) has been studied.
© 2017 Elsevier Ltd. All rights reserved.
Keywords:
1,1,2-Triarylethanes
Desulfonative cross-coupling
CDP-840
1. Introduction
and (iii) palladium-catalyzed a novel desulfonative cross-coupling
of 1,1-diarylethyl sulfones 5 with the aryl iodides 6, as shown in
1,1,2-Triarylethane-based structural units are present in various
biologically active molecules, such as CDP-840 (L-765,527), syn-
thesized by Celltch1a or Merck-Frosst1b as a promising phospho-
diesterase 4 (PDE 4) inhibitor.1 Depending on reports in literature,
CDP-840 can be majorly obtained from transition metal-mediated
routes, such as Pd-catalyzed cross-coupling of arylboronic acid
Scheme 2.
2. Results and discussion
Reduction of a mode substrate
b
-ketosulfone 2a (R ¼ Me;
Ar ¼ Ph) with 1.0 equivalent of NaBH4 in the co-solvent of THF and
MeOH (v/v ¼ 1/1) provided 3a with a nearly quantitative yield.
Without further purification, treatment of the resulting 3a with
anisole (4a, P ¼ Me, n ¼ 1) in the presence of BF3$OEt2 afforded 5a
in an 89% yield under a solvent-free reaction condition.7 The pre-
sent Friedel-Crafts reaction is highly regioselective and only
occurred at the para-position of 4a, relative to the methoxy group.
The reaction was also tried under a CH2Cl2 condition, which gave 5a
in a 63% yield (Scheme 3).
With the conditions, we next explored the substrate scope of the
two-step protocol, and the results are shown in Table 1. All entries
1e14 show that 5a-n were isolated in a range of 75%e90% yields
when Ar and R (R ¼ Me, Tol; Ar ¼ Ph, 4-MeO-C6H4, 4-Ph-C6H4) of
2a-d were the aryl groups. For the oxygenated benzenes 4a-e, the
methoxy group addressed the benzylic carbocation of 3 in the
formation of 5a-n with a diaryl ethyl sulfonyl motif via the
BF3$OEt2-mediated para-regiospecific procedure. Some syntheses
with diaryl vinyl sulfides2a or -arylenals,2b Pd/Cu-catalyzed cross-
b
coupling of styrenes, diboron (B2(pin)2) and aryl iodides,2c Ni-
catalyzed addition of organozincate to vinylsulfoxides,3 or Mn-
catalyzed epoxidation of 1,1,2-triarylethylenes.4 Sulfur ylide medi-
ated metal-free epoxidation of aldehyde provides an access to the
structure of 1,1,2-triarylethanes (see Scheme 1).5
Although the prepared protocols of CDP-840 with a specific
substitution pattern have been developed, newly prepared meth-
odologies are needed. In continuation of our investigation on the
skeleton of
1,1,2-triarylethanes 1 was explored, including (i) NaBH4-mediated
b
-ketosulfones 2,6 a facile three-step route towards
reduction of
reactions of
b
-ketosulfones 2, (ii) BF3$OEt2-mediated Friedel-Crafts
b-hydroxy sulfones 3 with the oxygenated benzenes 4,
* Corresponding author.
** Corresponding author.
E-mail addresses: kuei@mail.ncku.edu.tw (C.-H. Kuei), mychang@kmu.edu.tw
(M.-Y. Chang).
on the useful skeletons with a
b-diarylethyl group were reported by
different methods.8,9
http://dx.doi.org/10.1016/j.tet.2017.01.030
0040-4020/© 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.01.030

2
Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
O
O
OH
3
O
S
With skeleton 5 in hand, 5 mol% of Pd(OAc)2-mediated the
NaBH
BF OEt
4
3
2
S
desulfonylative cross-coupling of mode substrate 5a with iodo-
benzene (6a, Ar1 ¼ Ph, 1.5 eq) provided 1a with a 78% yield in the
presence of t-BuOK (1.1 equiv) under the warming DMF (80 ꢀC)
condition for 25 h (Table 2, entry 1). Next, some Pd-complexes were
studied (entries 2e4), such as Pd(PPh3)4 (60%), Pd(MeCN)Cl2 (45%),
and PdCl2 (38%); however, none of them obtained higher yields of
1a than Pd(OAc)2. Changing bases from t-BuOK to Cs2CO3 or NaH,
we found that Cs2CO3 or NaH provided 50% and 32% yields,
respectively (entries 5e6). The reaction was also tested with DME,
toluene and t-BuOH, instead of DMF. However, these solvents were
not effective in improving the yield of the desulfonylative cross-
coupling reaction (entries 7e10). Other catalytic amounts (10 and
15 mol%) of Pd(OAc)2 were also examined; however, the isolated
yields were similar (72% and 73%). From these observations, we
have concluded that Pd(OAc)2 and t-BuOK in warming DMF provide
an optimal reaction conditions for desulfonylative cross-coupling.
Based on the results, a plausible mechanism with the reasonable
explanation is described in Scheme 4. For this initial step of the
catalytic reaction, an oxidative addition of 5a is formed to afford an
intermediate A having a PdLn-SO2Me complexation (L ¼ OAc or O-t-
Bu). After the cross carbopalladation of A with 6a, removal of
methanesulfinic acid salt (MeSO2K) gives an intermediate B. Sub-
sequently, PdLn is regenerated and 1a is obtained by the reductive
elimination of B under the Mizoroki-Heck conditions. Finally, the
construction of 1,1,2-triarylethane skeleton is furnished via the
novel desulfonylative cross-coupling pathway.
Ar
R
Ar
R
(PO) -C H 4
6 6-n
n
THF / MeOH
O
O
2
(PO)
(PO)
n
n
Pd(OAc) , DMF
2
O
S
1
1
Ar
t-BuOK, Ar -I 6
Ar
R
Ar
O
5
1
Scheme 2. Three-step Synthesis of 1,1,2-Triarylethanes 1.
OMe
O
O
OH
O
S
1) NaBH
2) BF OEt
3
4
2
O
S
S
Ph
Me
Ph
Me
MeO-C H
THF / MeOH
(v/v = 1/1)
6
5
Ph
Me
O
O
O
4a
2a
3a (~100%)
solvent-free, 5a (89%)
CH Cl , 5a (63%)
2
2
Scheme 3. Synthesis of 5a.
Table 1
A two-step preparation of 5.a,b
We further explored the substrate scope of the palladium-
catalyzed desulfonative cross-coupling of 1,1-diarylethyl sulfones
5, and the results are shown in Table 3. For the formation of 1,1,2-
triarylethanes 1a-u, the cross-coupling reaction of 5a-c and 5i-m
(Ar ¼ Ph, 4-MeO-C6H4, 4-Ph-C6H4; R ¼ Me, Tol) with a 1.5 equiv-
alent of aryl iodides 6a-c (Ar1 ¼ a, Ph; b, 4-MeO-C6H4; c, 4-F-C6H4)
provided 1a-u in moderate (60%e78%) yields. For the uses of Ar and
R substituents of 6a-c, the electron-donating 4-methoxyphenyl
group (for 6a) and electron-neutral phenyl group (for 6b) were
well tolerated. However, the condition was slightly inappropriate
for 6c having an electron-withdrawing 4-fluorophenyl group which
gave 1f, 1i, 1l, 1o, and 1r in a range of 60%e65% yields. The
involvement of different substituents did not affect the reaction
procedure, as shown in entries 1e21. The formation of 1g was
confirmed by X-ray crystallography (Fig. 1).10
Entry
2, R¼, Ar¼,
4, (PO)n-C6H6-n
5 (%)c
1
2
3
4
5
6
7
8
2a, Me, Ph
2a, Me, Ph
2a, Me, Ph
2b, Tol, Ph
2b, Tol, Ph
2b, Tol, Ph
2b, Tol, Ph
2b, Tol, Ph
2c, Tol, 4-MeO-C6H4
2c, Tol, 4-MeO-C6H4
2c, Tol, 4-MeO-C6H4
2d, Tol, 4-Ph-C6H4
2d, Tol, 4-Ph-C6H4
2d, Tol, 4-Ph-C6H4
4a, MeO-C6H5
4b, 1,2-(MeO)2-C6H4
4c, 1,2,3-(MeO)3-C6H3
4a, MeO-C6H5
4b, 1,2-(MeO)2-C6H4
4d, 1,2-CH2O2-C6H4
4e, 1,3-(MeO)2-C6H4
4c, 1,2,3-(MeO)3-C6H3
4a, MeO-C6H5
4b, 1,2-(MeO)2-C6H4
4c, 1,2,3-(MeO)3-C6H3
4a, MeO-C6H5
5a, 89
5b, 82
5c, 80
5d, 79
5e, 82
5f, 85
5g, 78
5h, 75
5i, 84
5j, 90
5k, 78
5l, 80
5m, 80
5n, 76
9
To examine the synthetic application this three-step route
(Scheme 5), synthesis of CDP-840, was developed. First, BF3$OEt2-
mediated Friedel-Crafts reactions of 3b (prepared from the reduc-
tion of 2b with NaBH4 with excess guaiacol (4f) afforded a mixture
of 5o and 5p with a ratio of 1:1 in an 89% yield. Alkylation of 5o and
10
11
12
13
14
4b, 1,2-(MeO)2-C6H4
4c, 1,2,3-(MeO)3-C6H3
a
The reaction was run on 2 (1.0 mmol), NaBH4 (3.0 eq), MeOH (5 mL), THF (5 mL),
rt, 3 h.
b
c
The reaction was run on the resulting 3, BF3$OEt2 (1.0 equiv), 4 (1.0 g), rt, 20 h.
Isolated yields.
Ni(acac)
MeO
N
N
2
MeO
O
S,S salen Mn(III) complex
(ref 3)
O
5p with K2CO3 and cyclopentyl bromide gave 5q and 5r in 46% and
34% yields, respectively. The formation of 5q was confirmed by X-
ray crystallography (Fig. 2).10 Then, Pd(OAc)2-mediated desulfony-
lative cross-coupling of the resulting isomer 5q with 4-
iodopyridine (6d) in the presence of t-BuOK provided CDP-840
(1v) in a 66% yield.
O
S
Ph
MeO
Tol
(ref 4)
Ph ZnMgCl
3
O
Ph
N
CDP-840
Pd(OAc)
MeO
Pd(PPh )
MeO
2
3 4
N
I
N
B(OH)
2
(this work)
(ref 2a)
N
N
3. Conclusion
O
SO Tol
O
S
2
Ph
Ph
We have developed
triarylethanes 1 starting with
carried out for the (1) reduction of 2 with NaBH4, (2) BF3$OEt2-
a
three-steps protocol toward 1,1,2-
b
-ketosulfones 2. The facile process
Scheme 1. Synthetic routes of CDP-840.
Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.01.030

Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
3
Table 2
Table 3
Reaction conditions.a
Synthesis of 1.a
Entry
5, R¼, Ar¼, (PO)n¼
6, Ar1¼
1, (%)b
Entry
Catalysts (mol %)
Bases
Solvent
1a (%)b
1
5a, Me, Ph, 4-MeO
6a, Ph
1a, 78
1b, 70
1c, 72
1d, 76
1e, 74
1f, 65
1g, 78
1h, 70
1i, 65
1j, 76
1k,70
1l, 62
1m, 72
1n, 73
1o, 60
1p, 73
1q, 68
1r, 60
1s, 78
1t, 76
1u, 72
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
5a, Me, Ph, 4-MeO
5a, Me, Ph, 4-MeO
5b, Me, Ph, 3,4-(MeO)2
5b, Me, Ph, 3,4-(MeO)2
5b, Me, Ph, 3,4-(MeO)2
5c, Me, Ph, 2,3,4-(MeO)3
5c, Me, Ph, 2,3,4-(MeO)3
5c, Me, Ph, 2,3,4-(MeO)3
5i, Tol, 4-MeO-C6H4, 4-MeO
5i, Tol, 4-MeO-C6H4, 4-MeO
5i, Tol, 4-MeO-C6H4, 4-MeO
5j, Tol, 4-MeO-C6H4, 3,4-(MeO)2
5j, Tol, 4-MeO-C6H4, 3,4-(MeO)2
5j, Tol, 4-MeO-C6H4, 3,4-(MeO)2
5k, Tol, 4-MeO-C6H4, 2,3,4-(MeO)3
5k, Tol, 4-MeO-C6H4, 2,3,4-(MeO)3
5k, Tol, 4-MeO-C6H4, 2,3,4-(MeO)3
5l, Tol, 4-Ph-C6H4, 4-MeO
5m, Tol, 4-Ph-C6H4, 3,4-(MeO)2
5n, Tol, 4-Ph-C6H4, 2,3,4-(MeO)3
6b, 4-MeO-C6H4
6c, 4-F-C6H4
6a, Ph
6b, 4-MeO-C6H4
6c, 4-F-C6H4
6a, Ph
6b, 4-MeO-C6H4
6c, 4-F-C6H4
6a, Ph
6b, 4-MeO-C6H4
6c, 4-F-C6H4
6a, Ph
6b, 4-MeO-C6H4
6c, 4-F-C6H4
6a, Ph
6b, 4-MeO-C6H4
6c, 4-F-C6H4
6a, Ph
1
2
3
4
5
6
7
8
Pd(OAc)2 (5)
Pd(PPh3)4 (5)
Pd(MeCN)2Cl2 (5)
PdCl2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (10)
Pd(OAc)2 (15)
t-BuOK
t-BuOK
t-BuOK
t-BuOK
Cs2CO3
NaH
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
DMF
DMF
DMF
DMF
DMF
DMF
DME
toluene
t-BuOH
DMF
78
60
45
38
50
32
48
26
12
72
73
9
10
11
DMF
a
The reaction was run on 5a (1.0 mmol), 6a (1.5 equiv), bases (1.1 equiv), solvent
(7 mL), 80 ꢀC, 25 h.
b
Isolated yields.
mediated Friedel-Crafts reactions of the resulting b-hydroxy sul-
6b, 4-MeO-C6H4
6c, 4-F-C6H4
fones 3, and (3) palladium-catalyzed desulfonylative cross-coupling
of the corresponding 5 with aryl iodides 4 in the presence of t-BuOK
under the warming DMF in acceptable yields. A facile synthesis of
CDP-840 had been studied via this novel desulfonylative cross-
coupling reaction. Further investigation regarding synthetic appli-
a
The reaction was run on 3 (1.0 mmol), t-BuOK (1.1 equiv), DMF (7 mL), 6 (1.5
equiv), Pd(OAc)2 (5 mol%), 80 ꢀC, 25 h.
b
Isolated yields.
cations of
course.
b-ketosulfones will be conducted and published in due
4. Experimental section
4.1. General
All reagents and solvents were obtained from commercial
sources and used without further purification. Reactions were
routinely carried out under an atmosphere of dry nitrogen with
magnetic stirring. Products in organic solvents were dried with
anhydrous magnesium sulfate before concentration in vacuo.
Melting points were determined with a SMP3 melting apparatus.
1H and 13C NMR spectra were recorded on a Varian INOVA-400
spectrometer operating at 400 and at 100 MHz, respectively.
Fig. 1. X-ray structure of 1g.
Chemical shifts (d) are reported in parts per million (ppm) and the
4.2. Compound (3b)11
coupling constants (J) are given in Hertz. High resolution mass
spectra (HRMS) were measured with a mass spectrometer Fin-
nigan/Thermo Quest MAT 95XL. X-ray crystal structures were ob-
tained with an Enraf-Nonius FR-590 diffractometer (CAD4, Kappa
CCD).
NaBH4 (115 mg, 3.0 mmol) was added to a solution of 2b
(274 mg, 1.0 mmol) in the co-solvent of MeOH (5 mL) and THF
(5 mL) at ice bath. The reaction mixture was stirred at rt for 3 h. The
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3 ꢁ 20 mL).
The combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product. Purification on
silica gel (hexanes/EtOAc ¼ 8/1e1/1) afforded 3b. Yield ¼ 99%
(273 mg); Colorless solid; mp ¼ 69e71 ꢀC (recrystallized from
hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for C15H17O3S
Pd(OAc) + t-BuOK
OMe
OMe
2
OMe
Ph
6a
I
PdL
n
PdL
n
L
n
5a
L
n
(L = OAc/O-t-Bu)
Pd
Pd
Ph
Ph
SO Me
Ph
2
Ph
Ph
H
277.0899, found 277.0902; 1H NMR (400 MHz, CDCl3):
d 7.83 (d,
MeSO K
2
A
B
1a
J ¼ 8.0 Hz, 2H), 7.27 (d, J ¼ 8.0 Hz, 2H), 7.33e7.24 (m, 5H), 5.24 (dd,
J ¼ 2.0, 10.0 Hz, 1H), 3.80 (br s, 1H), 3.47 (dd, J ¼ 10.0, 14.4 Hz, 1H),
Scheme 4. Plausible mechanism.
Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.01.030

4
Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
OMe
OMe
OMe
4.3.2. Compound (5b)
Yield ¼ 82% (262 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
17H21O4S 321.1161, found 321.1168; 1H NMR (400 MHz, CDCl3):
7.36e7.22 (m, 5H), 6.86 (dd, J ¼ 2.0, 8.0 Hz, 1H), 6.82 (d, J ¼ 8.0 Hz,
OH
O
O
Pd(OAc)
2
C
d
O
S
O
S
5o
Tol
OH
t-BuOK
N
OMe
4f
Ph
+
Ph
Tol
Ph
I
1H), 6.79 (d, J ¼ 2.0 Hz, 1H), 4.61 (t, J ¼ 7.2 Hz, 1H), 3.84 (s, 6H), 3.75
O
O
N
(dd, J ¼ 2.4, 7.2 Hz, 2H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
5q (46%)
1v (66%)
K CO
2
3
(89%, ~1:1)
6d
3b
+
d
149.26, 148.21, 141.63, 133.83, 129.03 (2x), 127.48 (2x), 127.31,
BF OEt
3
2
C H Br
5 9
119.40, 111.35, 111.12, 60.95, 55.90, 55.81, 45.79, 41.93.
OH
O
OMe
OMe
4.3.3. Compound (5c)
O
S
O
S
Yield ¼ 80% (280 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
5p
18H23O5S 351.1266, found 351.1163; 1H NMR (400 MHz, CDCl3):
Ph
Tol
Ph
Tol
C
O
O
5r (34%)
d
7.32e7.26 (m, 4H), 7.21e7.17 (m, 1H), 6.82 (d, J ¼ 8.8 Hz, 1H), 6.64
(d, J ¼ 8.8 Hz, 1H), 4.88 (t, J ¼ 7.2 Hz, 1H), 3.85 (dd, J ¼ 0.4, 8.0 Hz,
1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.74 (dd, J ¼ 0.4, 8.0 Hz, 1H) 3.67 (s,
Scheme 5. Synthesis of CDP-840 (1v).
3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 153.05, 151.29,
142.38, 141.53, 128.57 (2x), 127.65 (2x), 127.24, 126.83, 122.41,
106.92, 60.48, 60.44, 59.52, 55.73, 41.57, 40.33.
4.3.4. Compound (5d)
Yield ¼ 79% (289 mg); Colorless solid; mp ¼ 121e123 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H23O3S 367.1368, found 367.1372; 1H NMR (400 MHz, CDCl3):
d
7.53 (d, J ¼ 8.4 Hz, 2H), 7.21e7.11 (m, 7H), 7.04 (d, J ¼ 8.8 Hz, 2H),
6.72 (d, J ¼ 8.8 Hz, 2H), 4.57 (t, J ¼ 7.2 Hz, 1H), 3.7 (d, J ¼ 7.2 Hz, 2H),
3.73 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3):
158.35,
d
144.05, 141.81, 136.62, 133.44, 129.41 (2x), 128.60 (2x), 128.56 (2x),
127.91 (2x), 127.41 (2x), 126.67, 113.97 (2x), 61.67, 55.13, 45.31,
21.44.
4.3.5. Compound (5e)
Yield ¼ 82% (325 mg); Colorless solid; mp ¼ 125e127 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H25O4S 397.1474, found 397.1481; 1H NMR (400 MHz, CDCl3):
Fig. 2. X-ray structure of 5q.
d
7.49 (d, J ¼ 8.0 Hz, 2H), 7.20e7.08 (m, 7H), 6.50 (d, J ¼ 1.2 Hz, 2H),
3.31 (dd, J ¼ 1.6, 10.0 Hz, 1H), 2.46 (s, 3H); 13C NMR (100 MHz,
6.57 (br s, 1H), 4.55 (t, J ¼ 7.2 Hz, 1H), 3.90 (dd, J ¼ 7.6, 14.8 Hz, 1H),
3.85 (dd, J ¼ 7.6, 14.8 Hz, 1H), 3.78 (s, 3H), 3.74 (s, 3H), 2.33 (s, 3H);
CDCl3):
d 145.17, 140.67, 136.11, 130.02 (2x), 128.66 (2x), 128.21,
13C NMR (100 MHz, CDCl3):
d 148.72, 147.76, 143.97, 141.56, 136.48,
127.94 (2x), 125.58 (2x), 68.39, 63.92, 21.60.
133.61, 129.22 (2x), 128.50 (2x), 127.79 (2x), 127.27 (2x), 126.61,
119.50, 111.01, 110.86, 61.57, 55.67, 55.56, 45.68, 21.30.
4.3. A representative two-step synthetic procedure of skeleton 5 is
as follows
4.3.6. Compound (5f)
Yield ¼ 85% (323 mg); Colorless solid; mp ¼ 126e128 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H21O4S 381.1161, found 381.1166; 1H NMR (400 MHz, CDCl3):
NaBH4 (115 mg, 3.0 mmol) was added to a solution of 2a
(274 mg, 1.0 mmol) in the co-solvent of MeOH (5 mL) and THF
(5 mL) at ice bath. The reaction mixture was stirred at rt for 3 h. The
solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3 ꢁ 20 mL).
The combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product. Without further
purification, BF3$OEt2 (140 mg, 1.0 mmol) was added to a solution
of crude 3 in the presence of excess 4 (1.0 g) was stirred at rt for
20 h. The reaction mixture was diluted with NaHCO3(aq) (10 mL) and
the mixture was extracted with CH2Cl2 (3 ꢁ 20 mL). The combined
organic layers were washed with brine, dried, filtered and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc ¼ 8/1e1/1) afforded skeleton 5.
d
7.53 (d, J ¼ 8.4 Hz, 2H), 7.22e7.09 (m, 7H), 6.63 (d, J ¼ 1.2 Hz, 2H),
6.52 (s, 1H), 5.87 (d, J ¼ 1.6 Hz, 1H), 3.85 (d, J ¼ 1.6 Hz, 1H), 4.52 (t,
J ¼ 7.2 Hz, 1H), 3.83 (d, J ¼ 7.2 Hz, 2H), 2.38 (s, 3H); 13C NMR
(100 MHz, CDCl3):
d 147.73, 146.41, 144.16, 141.62, 136.62, 135.23,
129.44 (2x), 128.71 (2x), 127.98 (2x), 127.34 (2x), 126.86, 120.95,
108.27, 107.92, 101.00, 61.58, 45.82, 21.50.
4.3.7. Compound (5g)
Yield ¼ 78% (309 mg); Colorless solid; mp ¼ 82e84 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H25O4S 397.1474, found 397.1480; 1H NMR (400 MHz, CDCl3):
d
7.51 (d, J ¼ 8.4 Hz, 2H), 7.20e7.10 (m, 7H), 6.89 (d, J ¼ 8.4 Hz, 1H),
4.3.1. Compound (5a)
6.31 (dd, J ¼ 2.4, 8.4 Hz, 1H), 6.24 (d, J ¼ 2.4 Hz, 1H), 4.77 (t,
J ¼ 7.2 Hz, 1H), 4.05 (dd, J ¼ 7.6, 14.8 Hz, 1H), 3.80 (dd, J ¼ 7.6,
14.8 Hz, 1H), 3.73 (s, 3H), 3.66 (s, 3H), 2.37 (s, 3H); 13C NMR
Yield ¼ 89% (258 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
16H19O3S 291.1055, found 291.1061; 1H NMR (400 MHz, CDCl3):
d
7.33e7.22 (m, 7H), 6.87 (d, J ¼ 8.8 Hz, 2H), 4.63 (t, J ¼ 7.2 Hz, 1H),
(100 MHz, CDCl3): d 159.89, 157.40, 143.79, 141.19, 136.60, 129.34,
129.16 (2x), 128.28 (2x), 128.01 (2x), 127.83 (2x), 126.40, 121.79,
104.09, 98.67, 59.96, 55.23, 55.09, 40.53, 21.46; Anal. Calcd for
3.78 (s, 3H), 3.74 (d, J ¼ 7.2 Hz, 2H), 2.31 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 158.76, 141.85, 133.41, 129.07 (2x), 128.74 (2x), 127.52 (2x),
127.29, 114.44 (2x), 61.04, 55.24, 45.45, 42.00.
C23H24O4S: C, 69.67; H, 6.10. Found: C, 69.82; H, 6.25.
Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
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Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
5
4.3.8. Compound (5h)
4.62 (t, J ¼ 7.2 Hz,1H), 3.92 (dd, J ¼ 3.2, 6.8 Hz, 2H), 3.82 (s, 3H), 3.79
(s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3):
148.92, 147.95,
144.09, 140.44, 139.72, 136.62, 133.74, 129.34 (3x), 128.71 (3x),
127.94 (2x), 127.87 (2x), 127.29 (2x), 126.87 (2x), 119.50, 111.14,
110.92, 61.74, 55.81, 55.74, 45.53, 21.44.
Yield ¼ 75% (320 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
d
C
24H27O5S 427.1579, found 427.1582; 1H NMR (400 MHz, CDCl3):
d
7.57 (d, J ¼ 8.4 Hz, 2H), 7.22e7.11 (m, 7H), 6.73 (d, J ¼ 8.8 Hz, 1H),
6.47 (d, J ¼ 8.8 Hz, 1H), 4.83 (t, J ¼ 7.2 Hz, 1H), 3.96 (dd, J ¼ 7.6,
14.4 Hz, 1H), 3.83 (dd, J ¼ 6.8, 14.4 Hz, 1H), 3.79 (s, 3H), 3.75 (s, 3H),
3.62 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
152.81,
4.3.14. Compound (5n)
151.24, 143.94, 141.56, 136.78, 129.80, 128.38 (2x), 128.40 (2x),
128.02 (2x), 127.71 (2x), 127.28, 126.53, 122.66, 106.69, 60.51, 60.46,
60.44, 55.84, 40.15, 21.50.
Yield ¼ 76% (382 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
30H31O5S 503.1892, found 503.1887; 1H NMR (400 MHz, CDCl3):
d
7.59e7.56 (m, 2H), 7.53e7.50 (m, 2H), 7.43e7.39 (m, 4H),
7.34e7.30 (m, 1H), 7.22 (d, J ¼ 8.4 Hz, 2H), 7.15 (d, J ¼ 8.4 Hz, 2H),
6.62 (d, J ¼ 8.8 Hz,1H), 6.50 (d, J ¼ 8.8 Hz,1H), 4.90 (t, J ¼ 7.2 Hz,1H),
3.98 (dd, J ¼ 7.2, 14.4 Hz, 1H), 3.90 (dd, J ¼ 7.2, 14.4 Hz, 1H), 3.80 (s,
3H), 3.78 (s, 3H), 3.71 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz,
4.3.9. Compound (5i)
Yield ¼ 84% (333 mg); Colorless solid; mp ¼ 144e146 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H25O4S 397.1474, found 397.1477; 1H NMR (400 MHz, CDCl3):
CDCl3):
d 152.88, 151.21, 143.94, 142.21, 140.58, 140.45, 139.42,
d
7.51 (d, J ¼ 8.0 Hz, 2H), 7.14 (d, J ¼ 8.0 Hz, 2H), 7.02 (d, J ¼ 8.8 Hz,
4H), 6.71 (d, J ¼ 8.8 Hz, 4H), 4.51 (t, J ¼ 7.2 Hz,1H), 3.82 (d, J ¼ 7.2 Hz,
2H), 3.73 (s, 6H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3):
158.32
136.82, 129.37 (2x), 128.68 (2x), 128.18 (2x), 128.02 (2x), 127.31,
127.18, 127.04 (2x), 126.86 (2x), 122.54, 106.81, 60.60, 60.52, 60.48,
55.85, 39.87, 21.46.
d
(2x), 144.00, 136.74, 133.86 (2x), 129.41 (2x), 128.48 (4x), 127.95
(2x), 113.99 (4x), 61.92, 55.18 (2x), 44.54, 21.47; Anal. Calcd for
4.4. Compounds (5o) and (5p)
C
23H24O4S: C, 69.67; H, 6.10. Found: C, 69.89; H, 6.34.
BF3$OEt2 (140 mg, 1.0 mmol) was added to a solution of 3b
(276 mg, 1.0 mmol) in the presence of guaiacol (4f) (1.0 g) was
stirred at rt for 20 h. The reaction mixture was diluted with NaH-
CO3(aq) (10 mL) and the mixture was extracted with CH2Cl2
(3 ꢁ 20 mL). The combined organic layers were washed with brine,
dried, filtered and evaporated to afford crude product. Purification
on silica gel (hexanes/EtOAc ¼ 4/1e2/1) afforded a mixture of 5o
and 5p in a ratio of 1:1. Yield ¼ 89% (340 mg); Colorless oil; HRMS
(ESI, Mþþ1) calcd for C22H23O4S 383.1317, found 383.1322; 1H NMR
4.3.10. Compound (5j)
Yield ¼ 90% (383 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
24H27O5S 427.1579, found 427.1581; 1H NMR (400 MHz, CDCl3):
d
7.49 (d, J ¼ 8.4 Hz, 2H), 7.11 (d, J ¼ 8.4 Hz, 2H), 7.02 (d, J ¼ 8.8 Hz,
2H), 6.71 (d, J ¼ 8.8 Hz, 2H), 6.66 (d, J ¼ 8.4 Hz, 1H), 6.63 (dd, J ¼ 2.0,
8.4 Hz, 1H), 6.56 (d, J ¼ 2.0 Hz, 1H), 4.50 (t, J ¼ 7.2 Hz, 1H), 3.83 (dd,
J ¼ 2.0, 7.2 Hz, 2H), 3.79 (s, 3H), 3.75 (s, 3H), 3.72 (s, 3H), 2.35 (s,
3H); 13C NMR (100 MHz, CDCl3):
d 158.29, 148.82, 147.78, 143.96,
136.66, 134.12, 133.63, 129.27 (2x), 128.38 (2x), 127.86 (2x), 119.41,
113.92 (2x), 111.08, 110.88, 61.89, 55.74, 55.65, 55.09, 44.93, 21.37;
Anal. Calcd for C24H26O5S: C, 67.58; H, 6.14. Found: C, 67.68; H, 6.35.
(400 MHz, CDCl3): d 7.54e7.48 (m, 2H), 7.22e7.09 (m, 7H),
6.73e6.54 (m, 3H), 5.53e5.50 (m, 1H), 4.56e4.47 (m, 1H),
3.87e3.83 (m, 2H), 3.81 (s, 3/2H), 3.76 (s, 3/2H), 2.37 (s, 3H).
4.3.11. Compound (5k)
4.5. A representative synthetic procedure of skeleton 1 is as follows
Yield ¼ 78% (356 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
25H29O6S 457.1685, found 457.1688; 1H NMR (400 MHz, CDCl3):
t-BuOK (123 mg, 1.1 mmol) was added to a stirred solution of
skeleton 5 (1.0 mmol) in DMF (5 mL) at rt. The reaction mixture was
stirred at 80 ꢀC for 4 h. 6 (1.5 mmol) in DMF (1 mL) was added to the
reaction mixture at rt. After 10 min, Pd(OAc)2 (11 mg, 0.05 mmol) in
DMF (1 mL) was added to the reaction mixture at rt. The reaction
mixture was refluxed for 25 h, cooled to rt, and the solvent was
concentrated. The residue was diluted with water (10 mL) and the
mixture was extracted with CH2Cl2 (3 ꢁ 20 mL). The combined
organic layers were washed with brine, dried, filtered and evapo-
rated to afford crude product. Purification on silica gel (hexanes/
EtOAc ¼ 4/1e2/1) afforded skeleton 1.
d
7.55 (d, J ¼ 8.0 Hz, 2H), 7.16 (d, J ¼ 8.0 Hz, 2H), 7.06 (d, J ¼ 8.4 Hz,
2H), 6.73 (d, J ¼ 8.8 Hz, 2H), 6.69 (d, J ¼ 8.4 Hz, 1H), 6.46 (d,
J ¼ 8.8 Hz, 1H), 4.78 (t, J ¼ 7.2 Hz, 1H), 3.92 (dd, J ¼ 7.6, 14.8 Hz, 1H),
3.79 (dd, J ¼ 7.6, 14.8 Hz, 1H), 3.78 (s, 3H), 3.76 (s, 3H), 3.73 (s, 3H),
3.64 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3):
d 158.14,
152.70, 151.12, 143.84, 142.14, 136.81, 133.50, 129.33 (2x), 128.72
(2x), 127.98 (2x), 127.61, 122.43, 113.72 (2x), 106.70, 60.63, 60.54,
60.44, 55.81, 55.12, 39.34, 21.44; Anal. Calcd for C25H28O6S: C,
65.77; H, 6.18. Found: C, 65.93; H, 6.49.
4.3.12. Compound (5l)
Yield ¼ 80% (354 mg); Colorless solid; mp ¼ 178e180 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C28H27O3S 443.1681, found 443.1685; 1H NMR (400 MHz,
4.5.1. Compound (1a)12
Yield ¼ 78% (225 mg); Colorless solid; mp ¼ 82e84 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C21H21O 289.1592, found 289.1593; 1H NMR (400 MHz, CDCl3):
CDCl3):
d 7.53e7.48 (m, 4H), 7.43e7.37 (m, 4H), 7.35e7.31 (m, 1H),
7.17 (d, J ¼ 8.0 Hz, 2H), 7.12 (d, J ¼ 8.0 Hz, 2H), 7.08 (d, J ¼ 8.4 Hz, 2H),
d
7.30e7.13 (m,10H), 7.05e7.03 (m, 2H), 6.82 (d, J ¼ 8.8 Hz, 2H), 4.22
6.75 (d, J ¼ 8.4 Hz, 2H), 4.61 (t, J ¼ 7.2 Hz, 1H), 3.95e3.84 (m, 2H),
(t, J ¼ 8.0 Hz, 1H), 3.78 (s, 3H), 3.37 (d, J ¼ 8.0 Hz, 2H); 13C NMR
3.75 (s, 3H), 2.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
d
158.49,
(100 MHz, CDCl3): d 157.85, 144.85, 140.33, 136.56, 129.05 (2x),
144.09, 140.66, 140.56, 139.71, 136.71, 133.52, 129.44 (2x), 128.72
(2x), 128.58 (2x), 127.99 (2x), 127.93 (2x), 127.33 (2x), 127.27, 126.93
(2x), 114.12 (2x), 61.74, 55.21, 45.12, 21.49.
128.92 (2x), 128.28 (2x), 128.00 (2x), 127.90 (2x), 126.05, 125.80,
113.65 (2x), 55.13, 52.20, 42.25.
4.5.2. Compound (1b)
4.3.13. Compound (5m)
Yield ¼ 70% (223 mg); Colorless solid; mp ¼ 94e96 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C22H23O2 319.1698, found 319.1702; 1H NMR (400 MHz, CDCl3):
Yield ¼ 80% (378 mg); Colorless solid; mp ¼ 130e132 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C29H29O4S 473.1787, found 473.1789; 1H NMR (400 MHz, CDCl3):
d
7.27e7.09 (m, 7H), 6.91 (d, J ¼ 8.8 Hz, 2H), 6.80 (d, J ¼ 8.8 Hz, 2H),
d
7.52e7.49 (m, 4H), 7.44e7.39 (m, 4H), 7.36e7.31 (m, 1H), 7.18 (d,
6.72 (d, J ¼ 8.8 Hz, 2H), 4.14 (t, J ¼ 7.6 Hz, 1H), 3.76 (s, 3H), 3.75 (s,
J ¼ 8.0 Hz, 2H), 7.11 (d, J ¼ 8.0 Hz, 2H), 6.70 (br s, 2H), 6.30 (s, 1H),
3H), 3.27 (d, J ¼ 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 157.83,
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6
Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
157.67, 144.95, 136.67, 132.44, 129.94 (2x), 128.95 (2x), 128.28,
127.93 (2x), 126.02 (2x), 113.65 (2x), 113.41 (2x), 55.15, 55.12, 52.46,
41.38.
C
d
24H27O4 379.1909, found 379.1911; 1H NMR (400 MHz, CDCl3):
7.26e7.20 (m, 4H), 7.16e7.12 (m, 1H), 7.04 (d, J ¼ 8.4 Hz, 1H), 6.95
(d, J ¼ 8.8 Hz, 2H), 6.73 (d, J ¼ 8.4 Hz, 2H), 6.66 (d, J ¼ 8.8 Hz, 1H),
4.57 (t, J ¼ 7.6 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.74 (s, 3H), 3.47 (s,
3H), 3.25 (dd, J ¼ 2.4, 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
4.5.3. Compound (1c)
Yield ¼ 72% (220 mg); Colorless solid; mp ¼ 93e95 ꢀC (recrys-
d 157.65, 151.95, 151.61, 144.96, 142.18, 132.62, 130.72, 129.93 (2x),
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
128.06 (4x), 125.79, 122.13, 113.36 (2x), 106.90, 60.53, 60.42, 55.81,
55.08, 45.59, 40.80; Anal. Calcd for C24H26O4: C, 76.17; H, 6.92.
Found: C, 76.38; H, 7.06.
C
21H20FO 307.1498, found 307.1500; 1H NMR (400 MHz, CDCl3):
d
7.29e7.25 (m, 2H), 7.21e7.16 (m, 3H), 7.12 (d, J ¼ 8.8 Hz, 2H),
6.96e6.93 (m, 2H), 6.89e6.79 (m, 4H), 4.14 (t, J ¼ 7.6 Hz,1H), 3.77 (s,
3H), 3.10 (d, J ¼ 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
161.21 (d,
4.5.9. Compound (1i)
J ¼ 241.8 Hz), 157.92, 144.58, 136.29, 135.96 (d, J ¼ 3.1 Hz), 130.38 (d,
J ¼ 8.3 Hz, 2x), 128.90 (2x), 128.34 (2x), 127.87 (2x), 126.15, 114.76
(d, J ¼ 20.4 Hz, 2x), 113.70 (2x), 55.15, 52.40, 41.43.
Yield ¼ 65% (238 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
23H24FO3 367.1710, found 367.1713; 1H NMR (400 MHz, CDCl3):
d
7.27e7.13 (m, 5H), 7.02 (d, J ¼ 8.8 Hz, 2H), 6.99e6.95 (m, 1H),
6.89e6.83 (m, 2H), 6.66 (d, J ¼ 8.8 Hz, 1H), 4.55 (t, J ¼ 8.0 Hz, 1H),
3.84 (s, 3H), 3.83 (s, 3H), 3.48 (s, 3H), 3.28 (dd, J ¼ 2.8, 8.0 Hz, 2H);
4.5.4. Compound (1d)
Yield ¼ 76% (242 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
13C NMR (100 MHz, CDCl3):
d
161.18 (d, J ¼ 241.8 Hz), 152.08, 151.59,
C
22H23O2 319.1698, found 319.1701; 1H NMR (400 MHz, CDCl3):
144.58, 142.20, 136.16 (d, J ¼ 3.1 Hz), 130.36 (d, J ¼ 7.6 Hz, 2x),
130.36, 128.12 (2x), 128.02 (2x), 125.92, 122.07, 114.68 (d,
J ¼ 20.5 Hz, 2x), 106.92, 60.51, 60.41, 55.81, 45.64, 40.82; Anal. Calcd
for C23H23FO3: C, 75.39; H, 6.33. Found: C, 75.46; H, 6.62.
d
7.29e7.13 (m, 8H), 7.02e6.99 (m, 2H), 6.76 (br s, 2H), 6.64 (br s,
1H), 4.18 (t, J ¼ 8.0 Hz,1H), 6.84 (s, 3H), 3.77 (s, 3H), 3.33 (dd, J ¼ 2.4,
7.2 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
148.55, 147.29, 144.67,
140.30, 136.98, 129.08 (2x), 128.30 (2x), 128.03 (2x), 127.88 (2x),
126.14, 125.85, 119.78, 111.66, 110.92, 55.78, 55.73, 52.59, 42.30.
4.5.10. Compound (1j)13
Yield ¼ 76% (242 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
4.5.5. Compound (1e)
C
22H23O2 319.1698, found 319.1707; 1H NMR (400 MHz, CDCl3):
Yield ¼ 74% (258 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
d
7.21e7.10 (m, 7H), 7.03e7.01 (m, 2H), 6.80 (d, J ¼ 8.8 Hz, 4H), 4.16
C
23H25O3 349.1804, found 349.1811; 1H NMR (400 MHz, CDCl3):
(t, J ¼ 7.6 Hz, 1H), 3.77 (s, 6H), 3.31 (d, J ¼ 7.6 Hz, 2H); 13C NMR
d
7.28e7.15 (m, 5H), 6.91 (d, J ¼ 8.8 Hz, 2H), 6.78e6.71 (m, 4H), 6.65
(100 MHz, CDCl3): d 157.79 (2x), 140.45, 136.99 (2x), 129.07 (2x),
(d, J ¼ 1.2 Hz, 1H), 4.12 (t, J ¼ 8.0 Hz, 1H), 3.83 (s, 3H), 3.78 (s, 3H),
128.81 (4x), 127.99 (2x), 125.77, 113.64 (4x), 55.15 (2x), 51.33, 42.46.
3.75 (s, 3H), 3.27 (dd, J ¼ 1.6, 8.8 Hz, 2H); 13C NMR (100 MHz,
CDCl3):
d
157.72, 148.55, 147.26, 144.76, 137.08, 132.38, 129.96 (2x),
4.5.11. Compound (1k)
128.30 (2x), 127.90 (2x), 126.11, 119.81, 113.42 (2x), 111.64, 110.91,
55.78, 55.74, 55.13, 52.83, 41.41.
Yield ¼ 70% (244 mg); Colorless solid; mp ¼ 86e88 ꢀC
(recrystallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd
for C23H25O3 349.1804, found 349.1809; 1H NMR (400 MHz, CDCl3):
4.5.6. Compound (1f)
d
7.12 (d, J ¼ 8.8 Hz, 4H), 6.93 (d, J ¼ 8.4 Hz, 2H), 6.81 (d, J ¼ 8.4 Hz,
Yield ¼ 65% (218 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
4H), 6.74 (d, J ¼ 8.8 Hz, 2H), 4.11 (t, J ¼ 7.6 Hz, 1H), 3.78 (s, 6H), 3.76
C
22H22FO2 337.1604, found 337.1610; 1H NMR (400 MHz, CDCl3):
(s, 3H), 3.26 (d, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 157.75
d
7.29e7.25 (m, 2H), 7.21e7.16 (m, 3H), 6.96e6.92 (m, 2H),
(2x),157.63,137.08 (2x),132.52,129.93 (2x),128.81 (4x),113.61 (4x),
113.38 (2x), 55.12 (2x), 55.08, 51.56, 41.55.
6.89e6.84 (m, 2H), 6.78 (d, J ¼ 8.0 Hz, 1H), 6.74 (dd, J ¼ 2.4, 8.0 Hz,
1H), 6.64 (d, J ¼ 2.4 Hz, 1H), 4.12 (t, J ¼ 7.6 Hz, 1H), 3.84 (s, 3H), 3.78
(s, 3H), 3.10 (d, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d
161.22
4.5.12. Compound (1l)
(d, J ¼ 241.8 Hz), 148.62, 147.37, 144.38, 136.71, 135.92 (d, J ¼ 3.0 Hz),
130.38 (d, J ¼ 7.6 Hz, 2x), 128.34 (2x), 127.83 (2x), 126.22, 119.75,
114.76 (d, J ¼ 20.4 Hz, 2x), 111.55, 110.94, 55.76, 55.74, 52.77, 41.44.
Yield ¼ 62% (208 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
d
22H22FO2 337.1604, found 337.1606; 1H NMR (400 MHz, CDCl3):
7.09 (d, J ¼ 8.8 Hz, 4H), 6.95e6.92 (m, 2H), 6.88e6.83 (m, 2H), 6.80
(d, J ¼ 8.4 Hz, 4H), 4.08 (t, J ¼ 8.0 Hz, 1H), 3.77 (s, 6H), 3.26 (d,
4.5.7. Compound (1g)
J ¼ 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
161.19 (d, J ¼ 241.8 Hz),
d
Yield ¼ 78% (271 mg); Colorless solid; mp ¼ 76e78 ꢀC (recrys-
157.86 (2x), 136.71 (2x), 136.07 (d, J ¼ 3.0 Hz), 130.39 (d, J ¼ 7.6 Hz,
2x), 128.78 (4x), 114.75 (d, J ¼ 20.5 Hz, 2x), 113.68 (4x), 55.16 (2x),
51.55, 41.63.
tallized from hexanes and EtOAc); HRMS (ESI, Mþþ1) calcd for
C
23H25O3 349.1804, found 349.1812; 1H NMR (400 MHz, CDCl3):
d
7.29e7.16 (m, 8H), 7.10e7.07 (m, 3H), 6.69 (d, J ¼ 8.8 Hz, 1H), 4.67
(t, J ¼ 8.0 Hz, 1H), 3.86 (s, 6H), 3.50 (s, 3H), 3.36 (dd, J ¼ 1.6, 8.0 Hz,
4.5.13. Compound (1m)
2H); 13C NMR (100 MHz, CDCl3):
d
151.95, 151.57, 144.85, 142.14,
Yield ¼ 72% (251 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
140.48, 130.57, 129.10 (2x), 128.03 (2x), 127.99 (2x), 127.91 (2x),
125.80, 125.71,122.11,106.87, 60.46, 60.33, 55.75, 45.38, 41.65; Anal.
Calcd for C23H24O3: C, 79.28; H, 6.94. Found: C, 79.53; H, 6.76.
Single-crystal X-Ray diagram: crystal of compound 1g was grown
by slow diffusion of EtOAc into a solution of compound 1g in CH2Cl2
to yield colorless prisms. The compound crystallizes in the triclinic
crystal system, space group P - 1, a ¼ 7.6352(4) Å, b ¼ 11.1162(6) Å,
c ¼ 12.1743(6) Å, V ¼ 935.46(8) Å3, Z ¼ 2, dcalcd ¼ 1.237 mg/cm3,
C
d
23H25O3 349.1804, found 349.1812; 1H NMR (400 MHz, CDCl3):
7.21e7.11 (m, 5H), 7.02e7.00 (m, 2H), 6.81 (d, J ¼ 8.8 Hz, 2H), 6.76
(d, J ¼ 8.4 Hz, 1H), 6.73 (dd, J ¼ 1.6, 8.4 Hz, 1H), 6.63 (d, J ¼ 1.6 Hz,
1H), 4.14 (t, J ¼ 8.0 Hz, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 3.77 (s, 3H),
3.30 (dd, J ¼ 2.0, 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 157.83,
148.52, 147.20, 140.40, 137.41, 136.79, 129.09 (2x), 128.78 (2x),
125.80 (2x), 125.80, 119.62, 113.64 (2x), 111.54, 110.88, 55.77, 55.71,
55.15, 51.72, 42.49.
F(000) ¼ 372, 2
q
range 1.996e26.586ꢀ, R indices (all data)
R1 ¼ 0.0566, wR2 ¼ 0.1139.
4.5.14. Compound (1n)
Yield ¼ 73% (276 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
4.5.8. Compound (1h)
C
d
24H27O4 379.1909, found 379.1912; 1H NMR (400 MHz, CDCl3):
Yield ¼ 70% (265 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
7.12 (d, J ¼ 8.4 Hz, 2H), 6.92 (d, J ¼ 8.4 Hz, 2H), 6.83e6.71 (m, 6H),
Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.01.030

Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
7
6.65 (d, J ¼ 1.6 Hz, 1H), 4.09 (t, J ¼ 7.6 Hz, 1H), 3.84 (s, 3H), 3.78 (s,
3H), 3.77 (s, 3H), 3.75 (s, 3H), 3.24 (d, J ¼ 7.6 Hz, 2H); 13C NMR
4.5.20. Compound (1t)
Yield ¼ 76% (299 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
28H27O2 395.2011, found 395.2014; 1H NMR (400 MHz, CDCl3):
7.69e7.66 (m, 2H), 7.62 (d, J ¼ 8.0 Hz, 2H), 7.53e7.49 (m, 2H),
(100 MHz, CDCl3):
d
157.79, 157.66, 148.53, 147.18, 137.51, 136.87,
C
d
132.46, 129.94 (2x), 128.78 (2x), 119.66, 113.61 (2x), 113.39 (2x),
111.56, 110.91, 55.75, 55.71, 55.12, 55.09, 51.94, 41.58; Anal. Calcd for
7.44e7.39 (m, 3H), 7.32e7.22 (m, 3H), 7.17e7.15 (m, 2H), 6.90 (dd,
J ¼ 1.6, 8.0 Hz, 1H), 6.87 (d, J ¼ 8.0 Hz, 1H), 6.79 (d, J ¼ 1.6 Hz, 1H),
4.34 (t, J ¼ 7.6 Hz, 1H), 3.92 (s, 3H), 3.87 (s, 3H), 3.53e3.43 (m, 2H);
C
24H26O4: C, 76.17; H, 6.92. Found: C, 76.31; H, 7.14.
13C NMR (100 MHz, CDCl3):
d 148.55, 147.31, 143.75, 140.72, 140.16,
4.5.15. Compound (1o)
138.86, 136.79, 129.02 (2x), 128.60 (2x), 128.19 (2x), 127.99 (2x),
126.97, 126.92 (2x), 126.82 (2x), 125.81, 119.75, 111.64, 110.97, 55.66
(2x), 52.18, 42.22.
Yield ¼ 60% (220 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
23H24FO3 337.1710, found 337.1713; 1H NMR (400 MHz, CDCl3):
d
7.10 (d, J ¼ 8.8 Hz, 2H), 6.95e6.91 (m, 2H), 6.89e6.79 (m, 4H), 6.76
(d, J ¼ 8.4 Hz, 1H), 6.72 (dd, J ¼ 2.0, 8.0 Hz, 1H), 6.62 (d, J ¼ 2.0 Hz,
1H), 4.06 (t, J ¼ 8.0 Hz, 1H), 3.84 (s, 3H), 3.78 (s, 3H), 3.77 (s, 3H),
4.5.21. Compound (1u)
Yield ¼ 72% (305 mg); Colorless gum; HRMS (ESI, Mþþ1) calcd
3.26 (d, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 161.20 (d,
for C29H29O3 425.2117, found 425.2122; 1H NMR (400 MHz, CDCl3):
J ¼ 241.9 Hz), 157.89, 148.60, 147.29, 137.14, 136.50, 136.02 (d,
J ¼ 3.0 Hz), 130.40 (d, J ¼ 7.5 Hz, 2x), 128.75 (2x), 119.60, 114.74 (d,
J ¼ 21.2 Hz, 2x), 113.67 (2x), 111.45, 110.91, 55.78, 55.73, 55.15, 51.92,
41.65.
d
7.57e7.55 (m, 2H), 7.48 (d, J ¼ 8.4 Hz, 2H), 7.43e7.39 (m, 2H),
7.33e7.26 (m, 3H), 7.20e7.11 (m, 4H), 7.07e7.04 (m, 2H), 6.66 (d,
J ¼ 8.4 Hz, 1H), 4.65 (t, J ¼ 8.0 Hz, 1H), 3.84 (s, 3H), 3.81 (s, 3H), 3.47
(s, 3H), 3.33 (d, J ¼ 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 152.08,
151.65, 144.11, 142.25, 140.94, 140.53, 138.65, 130.55, 129.11 (2x),
128.66 (2x), 128.43 (2x), 128.03 (2x), 126.98, 126.91 (2x), 126.82
(2x), 122.23, 125.83, 107.02, 60.58, 60.51, 55.87, 45.09, 41.71.
4.5.16. Compound (1p)
Yield ¼ 73% (276 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
24H27O4 379.1909, found 379.1912; 1H NMR (400 MHz, CDCl3):
d
7.19e7.09 (m, 5H), 7.04e6.98 (m, 3H), 6.77 (d, J ¼ 8.8 Hz, 2H), 6.64
4.6. Compound (1v, CDP-840)
(d, J ¼ 8.8 Hz, 1H), 4.54 (t, J ¼ 8.0 Hz, 1H), 3.83 (s, 3H), 3.81 (s, 3H),
3.75 (s, 3H), 3.46 (s, 3H), 3.25 (dd, J ¼ 3.2, 8.0 Hz, 2H); 13C NMR
K2CO3 (400 mg, 2.9 mmol) was added to a solution of 5o and 5p
(1.0 mmol) in acetone (10 mL) at rt. The reaction mixture was
stirred at rt for 10 min. Cyclopenty bromide (450 mg, 3.0 mmol)
was added to the reaction mixture at rt. The reaction mixture was
stirred at reflux for 8 h. The reaction mixture was cooled to rt and
the solvent was concentrated. The residue was diluted with water
(10 mL) and the mixture was extracted with CH2Cl2 (3 ꢁ 20 mL).
The combined organic layers were washed with brine, dried,
filtered and evaporated to afford crude product under reduced
pressure. Purification on silica gel (hexanes/EtOAc ¼ 4/1e2/1)
afforded skeleton 5q and 5r. For 5q, Yield ¼ 46% (207 mg); Colorless
solid; mp ¼ 147e149 ꢀC (recrystallized from hexanes and EtOAc);
HRMS (ESI, Mþþ1) calcd for C27H31O4S 451.1943, found 451.1944;
(100 MHz, CDCl3):
d 157.64, 151.93, 151.55, 142.20, 140.67, 137.01,
131.04, 129.09 (2x), 128.95 (2x), 127.96 (2x), 125.74, 122.04, 113.45
(2x), 106.94, 60.56, 60.48, 55.86, 55.14, 44.59, 41.92.
4.5.17. Compound (1q)
Yield ¼ 68% (277 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
d
25H29O5 409.2015, found 409.2018; 1H NMR (400 MHz, CDCl3):
7.12 (d, J ¼ 8.8 Hz, 2H), 7.01 (d, J ¼ 8.4 Hz, 1H), 6.95 (d, J ¼ 8.4 Hz,
2H), 6.79 (d, J ¼ 8.8 Hz, 2H), 6.73 (d, J ¼ 8.4 Hz, 2H), 6.65 (d,
J ¼ 8.8 Hz, 1H), 4.51 (t, J ¼ 7.6 Hz, 1H), 3.84 (s, 3H), 3.83 (s, 3H), 3.76
(s, 3H), 3.74 (s, 3H), 3.50 (s, 3H), 3.26e3.16 (m, 2H); 13C NMR
(100 MHz, CDCl3):
d 157.63, 157.60, 151.88, 151.54, 142.19, 137.05,
1H NMR (400 MHz, CDCl3):
d
7.51 (d, J ¼ 8.0 Hz, 2H), 7.21e7.10 (m,
132.72, 131.11, 129.93 (2x), 128.94 (2x), 121.99, 113.42 (2x), 113.34
(2x), 106.94, 60.51, 60.48, 55.81, 55.09, 55.07, 44.76, 40.99; Anal.
Calcd for C25H28O5: C, 73.51; H, 6.91. Found: C, 73.72; H, 6.80.
7H), 6.65 (d, J ¼ 8.8 Hz, 1H), 6.61 (d, J ¼ 2.0 Hz, 1H), 6.60 (dd, J ¼ 2.0,
8.8 Hz, 1H), 4.63e4.61 (m, 1H), 4.53 (t, J ¼ 7.2 Hz, 1H), 3.85 (d,
J ¼ 7.2 Hz, 2H), 3.76 (s, 3H), 2.36 (s, 3H), 1.88e1.78 (m, 4H),
1.63e1.56 (m, 4H) 13C NMR (100 MHz, CDCl3):
d 148.91, 147.63,
4.5.18. Compound (1r)
144.10, 141.74, 136.67, 133.82, 129.40 (2x), 128.63 (2x), 127.97 (2x),
127.47 (2x), 126.73, 119.51, 114.71, 111.96, 80.30, 61.89, 56.03, 45.71,
32.74, 32.72, 24.02, 24.00, 21.50. Single-crystal X-Ray diagram:
crystal of compound 5q was grown by slow diffusion of EtOAc into a
solution of compound 5q in CH2Cl2 to yield colorless prisms. The
compound crystallizes in the monoclinic crystal system, space
group P 21/c, a ¼ 9.2777(10) Å, b ¼ 12.0117(13) Å, c ¼ 21.164(2) Å,
Yield ¼ 60% (238 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
d
24H26FO4 397.1815, found 397.1820; 1H NMR (400 MHz, CDCl3):
7.08 (d, J ¼ 8.8 Hz, 2H), 6.98 (d, J ¼ 8.4 Hz, 1H), 6.96e6.94 (m, 2H),
6.88e6.82 (m, 2H), 6.79e6.75 (m, 2H), 6.64 (d, J ¼ 8.8 Hz, 1H), 4.46
(t, J ¼ 7.6 Hz, 1H), 3.83 (s, 3H), 3.81 (s, 3H), 3.76 (s, 3H), 3.48 (s, 3H),
3.27e3.17 (m, 2H); 13C NMR (100 MHz, CDCl3):
d 161.18 (d,
J ¼ 241.8 Hz), 157.70, 152.02, 151.54, 142.23, 136.67, 136.24 (d,
J ¼ 2.3 Hz), 130.77, 130.40 (d, J ¼ 7.5 Hz, 2x), 128.94 (2x), 121.93,
114.69 (d, J ¼ 21.2 Hz, 2x), 113.49 (2x), 106.94, 60.56, 60.51, 55.85,
55.14, 44.84, 41.05.
V ¼ 2311.6(4) Å3, Z ¼ 4, dcalcd ¼ 1.295 mg/cm3, F(000) ¼ 960, 2
q
range 1.959e26.457ꢀ,
R
indices (all data) R1
¼
0.1260,
wR2 ¼ 0.2145. For 5r, Yield ¼ 34% (153 mg); Colorless gum; HRMS
(ESI, Mþþ1) calcd for C27H31O4S 451.1943, found 451.1944; 1H NMR
(400 MHz, CDCl3):
d
7.50 (d, J ¼ 8.4 Hz, 2H), 7.21e7.10 (m, 7H),
4.5.19. Compound (1s)
6.65e6.56 (m, 3H), 4.67e4.63 (m, 1H), 4.54 (t, J ¼ 7.2 Hz, 1H), 3.86
(d, J ¼ 7.2 Hz, 2H), 3.72 (s, 3H), 2.36 (s, 3H), 1.89e1.78 (m, 4H),
Yield ¼ 78% (284 mg); Colorless oil; HRMS (ESI, Mþþ1) calcd for
C
27H25O 365.1905, found 365.1911; 1H NMR (400 MHz, CDCl3):
1.63e1.56 (m, 4H); 13C NMR (100 MHz, CDCl3):
d 149.80, 146.68,
d
7.58e7.55 (m, 2H), 7.49 (d, J ¼ 8.4 Hz, 2H), 7.44e7.40 (m, 2H),
144.08, 141.71, 136.67, 133.53, 129.37 (2x), 128.62 (2x), 127.96 (2x),
127.50 (2x), 126.74, 119.63, 114.51, 111.86, 80.22, 61.89, 55.98, 45.81,
32.79 (2x), 24.02 (2x), 21.49. t-BuOK (67 mg, 0.6 mmol) was added
to a stirred solution of 5q (180 mg, 0.4 mmol) in DMF (5 mL) at rt.
The reaction mixture was stirred at 80 ꢀC for 4 h 6d (200 mg,
1.0 mmol) in DMF (1 mL) was added to the reaction mixture at rt.
After 10 min, Pd(OAc)2 (11 mg, 0.05 mmol) in DMF (1 mL) was
7.34e7.27 (m, 3H), 7.21e7.12 (m, 5H), 7.05e7.03 (m, 2H), 6.82 (d,
J ¼ 8.8 Hz, 2H), 4.24 (d, J ¼ 7.6 Hz, 1H), 3.77 (s, 3H), 3.37 (d,
J ¼ 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3):
d 157.92, 144.02, 140.89,
140.30, 138.89, 136.48, 129.09 (2x), 128.96 (2x), 128.68 (2x), 128.28
(2x), 128.06 (2x), 127.02 (3x), 126.94 (2x), 125.86, 113.73 (2x), 55.18,
51.89, 42.26.
Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.01.030

8
Y.-S. Lin et al. / Tetrahedron xxx (2017) 1e8
(b) Houpis IN, Molina A, Dorziotis I, Reamer RA, Volante RP, Reider PJ. Tetra-
hedron Lett. 1997;38:7131e7134.
4. For Mn-mediated synthesis of CDP-840, see: Lynch JE, Choi W-B,
added to the reaction mixture at rt. The reaction mixture was
refluxed for 25 h, cooled to rt, and the solvent was concentrated.
The residue was diluted with water (10 mL) and the mixture was
extracted with CH2Cl2 (3 ꢁ 20 mL). The combined organic layers
were washed with brine, dried, filtered and evaporated to afford
crude product. Purification on silica gel (hexanes/EtOAc ¼ 4/1e1/3)
afforded 1v. Yield ¼ 66% (98 mg); Colorless gum; HRMS (ESI,
Mþþ1) calcd for C25H28NO2 374.2120, found 374.2125; 1H NMR
Churchill HRO, Volante RP, Reamer RA, Ball RG
J Org Chem. 1997;62:
9223e9228.
5. For sulfur ylide-mediated synthesis of CDP-840, see: Aggarwal V,K, Bae I, Lee H-
Y, Richardson J, Williams DT Angew Chem Int Ed. 2003;42:3274e3278.
6. (a) Chang M-Y, Chen Y-C, Chan C-K. Tetrahedron. 2014;70:8908e8913;
(b) Chang M-Y, Chen Y-C, Chan C-K. Synlett. 2014;25:1739e1744;
(c) Chang M-Y, Cheng Y-C, Lu Y-J. Org Lett. 2014;16:6252e6255;
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(e) Chang M-Y, Cheng Y-C, Lu Y-J. Org Lett. 2015;17:3142e3145;
(f) Chang M-Y, Cheng Y-C. Org Lett. 2015;17:5702e5705;
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7. For BF3$OEt2-mediated Friedel-Crafts reactions, see: (a) Huang JW, Shi M.
Tetrahedron Lett. 2003;44:9343e9346;
(400 MHz, DMSO-d6):
d
8.74 (d, J ¼ 6.4 Hz, 2H), 7.87 (d, J ¼ 6.0 Hz,
2H), 7.38e7.36 (m, 2H), 7.29e7.25 (m, 2H), 7.17e7.14 (m, 1H), 6.89
(s, 1H), 6.80 (s, 2H), 4.75e4.73 (m, 1H), 4.48 (t, J ¼ 8.0 Hz, 1H), 3.71
(dd, J ¼ 8.0, 14.0 Hz, 1H), 3.65 (dd, J ¼ 8.0 Hz, 14.0 Hz, 1H), 3.65 (s,
3H), 1.85e1.78 (m, 2H), 1.70e1.52 (m, 6H); 13C NMR (100 MHz,
DMSO-d6):
d 161.22, 148.20, 146.70, 143.88, 141.01 (2x), 135.50,
128.43 (2x), 127.56 (2x), 127.39 (2x), 126.37, 119.84, 114.78, 112.21,
79.36, 55.46, 49.72, 40.21, 32.19, 32.09, 23.56 (2x).
(b) Xie L-H, Hou X-Y, Hua Y-R, Tang C, Liu F, Fan QL. Org Lett. 2006;8:
3701e3704;
(c) Caturvedi D, Chaturvedi AK, Mishra N, Mishra V. Synlett. 2012;23:
2627e2630;
Acknowledgments
(d) Naganaboina RT, Peddinti RK. J Org Chem. 2013;78:12819e12824;
(e) Reddy BVS, Chaya DN, Yadav JS, Chatterjee D, Kunwar AC. Tetrahedron Lett.
2011;52:2961e2964;
(f) Li Y, Xiong Y, Li XM, Ling XG, Huang RF, Yang JC. Green Chem. 2014;16:
2976e2981;
The authors would like to thank the Ministry of Science and
Technology of the Republic of China for its financial support (MOST
105-2113-M-037-001).
(g) Zhang ST, Zhang XH, Ling XG, et al. RSC Adv. 2014;4:30768e30774;
(h) Huang R, Zhang X, Pan J, et al. Tetrahedron. 2015;71:1540e1546;
(i) Kumar A, Singh TV, Thomas SP, Venugopalan P. Eur J Org Chem. 2015:
1226e1234.
8. For the synthetic application of b-arylsulfones, see: (a) Mauleon P, Carretero JC.
Org Lett. 2004;6:3195e3198;
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2017.01.030.
(b) Ranu BC, Guchait SK, Ghosh K. J Org Chem. 1998;63:5250e5251.
9. For the synthesis on the useful skeletons with a -diarylethyl groups, for am-
b
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10. CCDC 1044469 (1g) and 1400683 (5q) contain the supplementary crystallo-
graphic data for this paper. This data can be obtained free of charge via www.
ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: 44-1223-336033; e-mail: deposit@ccdc.cam.ac.
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Please cite this article in press as: Lin Y-S, et al., Palladium-mediated synthesis of 1,1,2-triarylethanes. Application to the synthesis of CDP-840,
Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.01.030