Palladium-Catalyzed Coupling of Propargylic Alcohols with Boronic Acids under Ambient Conditions

Article abstract of DOI:10.1002/cjoc.201900442

A highly efficient palladium-catalyzed direct coupling of propargylic alcohols with organoboronic acids to synthesize tri- and tetra-substituted allenes has been developed under mild reaction conditions. Many useful functional groups are tolerated in this process with high to excellent yields. Preliminary biological studies showed that several tri- and tetra-substituted allenes exhibited potent anti-diabetic activities.

Full text of DOI:10.1002/cjoc.201900442

Chinese Journal
of Chemistry
CJC
中 国 化 学 - An International Journal
Accepted Article
Title: Palladium-Catalyzed Suzuki Coupling of Propargylic Alcohols with Boronic
Acids under Ambient Conditions
Authors: Anni Qin, Hui Qian, Qin Chen,* and Shengming Ma*
This manuscript has been accepted and appears as an Accepted Article online.
This work may now be cited as: Chin. J. Chem. 2020, 38, 10.1002/cjoc.201900442.
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published online in Early View: http://dx.doi.org/10.1002/cjoc.201900442.
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Palladium-Catalyzed Suzuki Coupling of Propargylic Alcohols with
Boronic Acids under Ambient Conditions
Anni Qin,a Hui Qian,a Qin Chen,*a and Shengming Ma*a,b
a Research Center for Molecular Recognition and Synthesis, Department of Chemistry, Fudan University, 220 Handan Lu, Shanghai 200433, P. R. China.
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai
200032, P. R. China.
Cite this paper: Chin. J. Chem. 2019, 37, XXX—XXX. DOI: 10.1002/cjoc.201900XXX
Summary of main observation and conclusion A highly efficient palladium-catalyzed direct Suzuki coupling of propargylic alcohols with organoboronic
acids to synthesize tri- and tetra-substituted allenes has been developed under mild reaction conditions. Many useful functional groups are tolerated in
this process with high to excellent yields. Preliminary biological studies showed that several tri- and tetra-substituted allenes exhibited potent
anti-diabetic activities.
Scheme 1 Transition metal-catalyzed cross-coupling to synthesize allenes
Background and Originality Content
cross-coupling
Conventional
of
derivatives with boronic acids to allenes
propargylic
a)
Allenes are important synthetic building blocks in organic
synthesis and many natural products and pharmaceutical drugs
contain allene motifs.1,2 Consequently, many studies have been
focused on the synthesis of different types of allenes.3 Transition
metal-catalyzed cross-coupling reactions are powerful tools for
C-C bond formation.4 The Suzuki coupling reaction has been
widely exploited in last few decades.5 Pd-catalyzed Suzuki coupling
of propargylic compounds with organoboronic acids is one of the
most straightforward approaches for allene synthesis.6 However,
reactive substrates bearing a good leaving group such as
propargylic halides, esters or carbonates were required in these
protocols (Scheme 1a).6
Suzuki coupling of propargylic alcohols has less been reported
due to the difficulty encountered in the step of oxidative addition
with a transition metal catalyst.7-9 Dou and co-workers reported
Rh-catalyzed cross-coupling of propargylic alcohols with
arylboroxines affording allenes via SN2’-type mechanism (Scheme
1b).7a Yoshida and Ihara found the Pd-catalyzed direct coupling of
propargylic alcohols with arylboronic acids affording allenes
and/or alkynes could be achieved at 100 °C (Scheme 1c, up).6j
Sherburn and co-workers developed Pd-catalyzed direct coupling
of 2-butynyl 1,4-diols with boronic acids generating allenes and/or
dienes at 80 °C (Scheme 1c, down).6k Recently, our group put
forward a new concept of utilizing a catalytic amount of Brønsted
acid to form a transient leaving group from the hydroxy group,
and successfully achieved the atom-economic synthesis of
2,3-allenoates and 2,3-allenoic acids via the carboxylation with
CO.8 With our goal of developing more efficient methods in the
synthesis of allenes with simple starting substrates, we propose a
direct Suzuki coupling of organoboronic acids with propargylic
alcohols under mild conditions under the co-catalysis of Pd(0) and
an organic acid (Scheme 1d).
R2
R3
R1
R4
R2
R3
cat.
[Pd]
X
•
+
R4
[B]
R1
=
X
halides
O(CO)OR, O(CO)R,
Rh-catalyzed reaction of
alcohols with
affording allenes
propargylic
b)
c)
arylboroxines
R2
R3
OH
2.5 mol%
Ar
R2
R3
[Rh(OH)(cod)]2
•
+
(ArBO)3
THF, 65 o
C
R1
R1
cross-coupling
Pd-catalyzed
of
alcohols with boronic acids
propargylic
R2
R2
R3
OH
R3
R4
cat.
R1
R4
R2
R3
Pd(PPh3)4
dioxane, 100 ο
+
•
R4
and/or
B(OH)2
C
R1
R1
R2
R2
OH
R3
R2
R2
R1
R1
R3
R1
cat.
Pd(PPh3)4
dioxane, 80 ο
•
HO
+
R3
and/or
B(OH)2
R2
R2
R1
R1
C
R3
R1
HO
Pd/H+ co-catalyzed
of
alcohols with boronic acids this
propargylic
(
cross-coupling
work
)
d)
R2
R3
OH
R1
R4
R3
R2
Pd/H+
,
rt
•
+
R4
B(OH)2
R1
♠
♠
♠
Mild reaction conditions
Broad substrate
scope
Excellent
regioselectivity
Results and Discussion
We began our investigation with the propargylic alcohol 1a
which bears one phenyl and one methyl group on the α-carbon
and phenylboronic acid 2a to identify the ligands for the reaction
at room temperature (Scheme 2). We initially used
o-(diphenylphosphino) benzaldehyde (L1), which performed
efficiently in the system of propargylic carbonates.6g Unfortunately,
94% of propargylic alcohol 1a was recovered and the desired
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Report
product 3aa was not formed. Triphenylphosphine (L2) was then
employed as the ligand and the desired allene product 3aa was
formed in only 10% yield. Tri(o-tolyl)phosphine (L3) provided 5%
yield of 3aa with 69% recovery of 1a.6h,6i Zheda-phos (L4) also
failed to give the allene product.9 We next investigated the effect
of bidentated phosphine ligand. However, both BINAP (L5) and
DPEPhos (L6) could not afford allene product 3aa. To our surprise,
using of Pd(PPh3)4 instead of Pd2(dba)3·CHCl3 could give 91% yield
allene product 3aa without any recovery of 1a.
and methoxy also afforded allene products in good yields (3ae,
3ah, and 3ai). The halo-substituted (F, Cl) aryl boronic acid also
worked (3af and 3ag). The electron-withdrawing groups such as
nitro, cyano, acetyl, formyl in aryl were all tolerated under
ambient conditions (3aj-3am). The useful functional groups such
as trifluoromethyl and ester afforded the corresponding allenes
successfully (3an and 3ao). 4-Biphenylboronic acid and 2-naphthyl
boronic acid were also suitable (3ap and 3aq). Heterocycles such
as furan and thiophene may also be tolerated with 80% and 75%
yields, respectively (3ar and 3as).
Scheme 2 Ligand Screeninga
Table 1 Optimization of the reaction conditionsa
2.5 mol% Pd
•CHCl3
2(dba)3
Ligand
POOH
5 mol%
Me Ph
OH
Ph
Ph
5 mol%
5 mol%
5 mol% additive
(PhO)2
Me Ph
OH
Pd(PPh3)4
+
Ph
Ph
PhB(OH)2
+
dioxane, rt, N2 18 h
,
n
Ph[B]
-Bu
Me
n
-Bu
n
solvent, rt, N2 15 h
,
1a
2a
3aa
-Bu
Me
equiv)
(2
n
-Bu
1a
2
3aa
equiv)
(2
Me
P
PCy2
P
P
MeO
N
Ph
Me
NMR yield recovery of
Me
Me
entry
Solvent
additive
none
Ph[B]
O
of 3aa (%)
10
1a (%)
90
L1
,
L2
,10%
L3
, 5%
L4
1b
2b
3b
4
dioxane
dioxane
dioxane
THF
PhB(OH)2
trace
trace
(87%)
,
(94%)
(84%)
PPh2
(69%)
(PhO)2POOH PhB(OH)2
4 equiv H2O PhB(OH)2
(PhO)2 POOH PhB(OH)2
(PhO)2 POOH PhB(OH)2
(PhO)2 POOH PhB(OH)2
(PhO)2 POOH PhB(OH)2
(PhO)2 POOH PhB(OH)2
91
trace
100
38
PPh2
Pd
Pd
and
instead of
(PPh3)4
trace
44
PPh2
PPh2
O
•CHCl3
2(dba)3
without
ligand
5
DME
38
38
L5
,
L6
trace
,
trace
91%b
(74%)
(97%)
6
Toluene
MeCN
44
24
a
,
,
2a
reaction was
mmol of
mmol of
mol% of
2.5
1a
The
conducted with 0.2
0.4
7
trace
60
85
and
Pd
•CHCl3 5 mol%
5 mol% of
POOH in 1.0 mL of
anhydrous
,
2(dba)3
ligand,
(PhO)2
and recovery were
at rt
dioxane
by 1H NMR
for 18 h under N
The
determined
2 atmosphere.
recovery of
yield
is shown in the
8c
9d
10d
11d
dioxane
dioxane
dioxane
dioxane
16
b
and
the
mol%
5
1a
parentheses.
analysis,
was used and
reaction time is 13 h.
(PhO)2 POOH
(PhO)2 POOH (PhBO)3
(PhO)2 POOH PhBF3K
PhBpin
trace
trace
trace
98
Pd(PPh3)4
91
After identifying Pd(PPh3)4 as the best catalyst, other reaction
parameters were then studied (Table 1). Only 10% of desired
allene product was observed without adding (PhO)2POOH as
additive (entry 1). And no reaction occurred when 4 equiv of
water were added as the additive (entry 3). Next, solvent was
found to be crucial for this Suzuki coupling process. Moderate
efficiency was observed in THF, DME, and Toluene (entries 4-6),
while no reaction occurred in CH3CN (entry 7). The yield dropped
to 60% when reducing the amount of PhB(OH)2 to 1.5 equiv (entry
8). We also investigated the reactivity of other boron reagents
(entries 9–11): PhBpin, (PhBO)3, and PhBF3K failed to afford the
desired product. Thus, optimal conditions have been defined as 5
mol% of Pd(PPh3)4 and 5 mol% of (PhO)2POOH in dioxane at room
temperature under N2 atmosphere.
86
a The reaction was conducted with 0.2 mmol of 1a, 0.4 mmol of 2, 5 mol%
of Pd(PPh3)4, and 5 mol% of additive in 1.0 mL of anhydrous solvent at rt
for 15 h under N2 atmosphere. The yield and recovery were determined by
b
1H NMR analysis. Reaction time is 13 h. c 1.5 equiv PhB(OH)2 was used. d
Reaction time is 18.5 h.
With the optimized condition in hand, we examined the scope
of boronic acids with propargylic alcohol 1a. As shown in Scheme
3, a wide range of aryl boronic acids with different substituents at
different positions all reacted smoothly with 1a to form the
corresponding tetrasubstituted allene products 3 with good to
excellent efficiency. The reaction is amenable to both
electron-withdrawing and electron-donating groups. Aryl boronic
acid bearing ortho-, meta-, or para-methyl substitutions gave the
products in high yields under optimal reaction conditions
(3ab-3ad). Other electron-donating substituents such as tert-butyl
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Chin. J. Chem. 2019, 37, XXX－XXX
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Running title
Chin. J. Chem.
Scheme 3 Scope of boronic acids with 1aa
Scheme 4 Substrate scopea
5 mol%
Pd(PPh3)4
POOH
5 mol%
Me Ph
5 mol%
Pd(PPh
)
3
4
R1
R2
R3
OH
R2
R4
R1
Me
Ph
(PhO)2
5 mol%
POOH
(PhO)2
R1
+
+
•
•
R4
OH
B(OH)2
dioxane, 25 o
N 17 h
,
2
B(OH)2
dioxane, 25 o
N 17 h
,
2
C,
n
-Bu
R3
C,
n
-Bu
1a
2
3a
R1
equiv)
(2
1
2
3
equiv)
(2
Me
Me
Ph
Me
Ph
Cl
Ph
Me
Ph
Me
Ph
Me
Ph
•
•
•
•
TBSO
Me
•
n
-Hex
Ph
3da
76%
,
Ph
,
Me
Ph
Me
Me
Ph
Me
Ph
c
3ba
3ca
84%
88%
,
,
•
3ea 69%b
,
•
•
n
-Bu
n
n
n
-Bu
3ab
Ph
92%
-Bu
3ac
-Bu
3ad
-
t Bu
3aa
,
81%
79%
86%
,
,
,
t-Bu
F
Cl
MeO
-
n
Bn
H
Ph
Ph
Pr
Et
Ph
Ph
•
•
•
•
n
n
n
-Bu
Ph
-Bu
Ph
-Bu
Me
Ph
Me
Ph
Me
Ph
Me
Ph
TBSO
•
•
•
•
O
3fa 67%d
66%e
3ha 76%
3ia 57%c,d
n
n
n
n
-Bu
3ae
-Bu
3af
-Bu
3ag
-Bu
3ah
,
,
,
3ge
,
O
,
85%
79%
80%
88%b
,
,
,
OHC
MeO2C
OMe
•
NO2
NC
Ac
H
H
•
•
Me
Ph
Me
Ph
Me
Ph
Me
Ph
•
•
•
nBu
3im
Ph
63%d
nBu
3io 74%d
Ph
n
n
-Bu
n
n
-Bu
-Bu
-Bu
3al
,
,
3ai 77%b
3aj 72%b
3ak 74%c
78%d,e
,
,
,
,
a
,
,
2
5
,
reaction was
mmol of
mmol of
mol% of
and mol%
5
1a
OHC
F3C
MeO2C
Ph
The
conducted with 1.0
mL of
2.0
Pd(PPh3)4
dioxane 25 oC for 17 h under N
10
b
of
at
mol
%
POOH in 5.0
(PhO)2
anhydrous
2 atmosphere.
of
was used. c
POOH
Reaction time is 36 h. d The reaction conducted at 40 oC. e Reaction
was
(PhO)2
time is 39.5 h.
Me
Ph
81%f
Me
Ph
Me
Ph
Me
•
•
•
•
,
n
n
n
n
-Bu
-Bu
-Bu
-Bu
3ao
Ph
82%
3am
3an 77%
3ap
76%
,
,
,
To demonstrate the practicality of the efficient Suzuki coupling
process, we carried out the reaction for gram scale synthesis of
3ao: 1.4572 g 3ao was afforded with 91% yield under standard
conditions (eq 1). We studied the reaction of optically active
propargylic alcohols10 with boronic acid 2a under the standard
reaction conditions leading to the formation of (R)-3aa in 2% ee
(eq 2). The Pd(0) would undergo SN2’-type oxidative addition with
propargylic alcohol (R)-1a in the presence of H+ in
anti-stereospecific manner to give intermediate (Sa)-II, which
would racemize via the η3-propargylic/allenylpalladium (II’)
resulting in the formation of 3aa with low enantioselectivity
(Scheme 5b).11
O
S
Me
Ph
Me
•
Me
Ph
•
•
n
n
n
-Bu
-Bu
-Bu
Ph
80%d
3aq
3ar
3as 75%
,
88%
,
,
a
,
,
2
5
,
reaction was
mmol of
mmol of
at
mol% of
and
5
1a
The
conducted with 1.0
mL of
2.0
Pd(PPh3)4
dioxane 25 oC for 17 h under N
mol% of
POOH in 5.0
2 atmosphere.
(PhO)2
anhydrous
was
c
o
b Reaction time is 36 h. The reaction
conducted at 40 C. d 10
POOH
mol of
%
was
(PhO)2
used. e
Reaction time is 24 h. f Reaction time is 19 h.
As shown in Scheme 4, a wide range of propargylic alcohols
may participate in the efficient process to form the desired
allenes. Propargylic alcohols with different chain lengths of alkyl
groups did not affect the yield under standard conditions (3ba).
Alkyl chain with different functional groups, such as
silyl-protected alcohol (3ca and 3fa), halide (3da) and vinyl (3ea)
were well tolerated in this transformation. Ethyl, propyl and
benzyl substitutions on the α-carbon of propargylic alcohol
performed well to afford corresponding allenes (3fa, 3ge, and
3ha). It is worth noting that secondary propargylic alcohol 1i also
worked with different arylboronic acids to afford trisubstituted
allenes with moderate to good yields (3ia, 3im and 3io).
MeO2C
Me
Ph
OH
5 mol%
5 mol%
dioxane, 25 o Ar, 17 h
Pd(PPh3)4
POOH
B(OH)2
+
(PhO)2
(1)
Me
Ph
MeO2C
2o
•
n
C,
-Bu
1a
equiv)
n
-Bu
(2
3ao
mmol,
5.0
1.0065 g
1.4572 91%
g,
Me
Ph
OH
5 mol%
Pd(PPh3)4
POOH
Ph
Me
5 mol%
(PhO)2
dioxane,25 o
+
•
PhB(OH)2
2a
(2)
N
17 h
,
n
-Bu
n
-Bu
C,
Ph
Ra
-3aa
)
2
-1a
ee
R
)
equiv)
(
(2
(
ee
55%, 2%
96%
A possible catalytic cycle is proposed in Scheme 5a. The
reaction of propargylic alcohol with Brønsted acid (HB) would
yield the oxonium ion I, which would easily undergo oxidative
addition reaction with Pd(0) to produce the allenylpalladium
intermediate II. Here the racemization would occur. Subsequently,
intermediate II would undergo transmetalation with the boronic
acid to form the allenyl aryl palladium intermediate III, which
would result in the formation of allenes and regenerate of Pd(0)
species to complete the catalytic cycle via reductive elimination.
Chin. J. Chem. 2019, 37, XXX－XXX
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First author et al.
Report
Scheme 5 The proposed mechanism
4
(R)-BINAP
/
/
61
catalytic
a The reaction was conducted with 0.1 mmol of 1a, 0.2 mmol of 2a, 5
mol% of Pd2(dba)3•CHCl3, 12 mol% of Ligand, and 10 mol% of (PhO)2POOH
in 1.0 mL of anhydrous dioxane at 60 oC for 16 h under N2 atmosphere.
The NMR yield and recovery were determined by 1H NMR analysis.
cycle
a) Proposed
R1
R4
R3
R2
Pd0Ln
OH
R2
R3
3
R1
reductive
elimination
HB
Finally, the potential biological activities of the newly
synthesized compounds were evaluated. We first examined the
effect of the compounds on the secretion of glucagon-like
peptide-1 (GLP-1), which is an attractive therapeutic target for
type II diabetes. As shown in Table 3, 3aj, 3da and 3ha markedly
stimulated GLP-1 release in mouse intestinal cell line STC-1 at 100
μM, which were more effective than the positive control
phorbol-12-myristate-13-acetate (PMA, 1 μM). Then the three
compounds were further tested and the half maximal effective
concentration (EC50) was measured. Notably, 3da possessed the
most potent stimulatory activity with an EC50 of 1.6 μM,
suggesting that it might be a promising anti-diabetic agent for
further study.
H
H
R1
R3
R2
O
B
R3
R2
R4
PdII
III
R1
oxidative
addition
I
transmetalation
R1
PdII
R3
R2
R4
B-
B(OH)2
H2O
II
Rationale for racemization
b)
Ph
PdII
Pd0/H+
Me
n
Ph
Me
n
-Bu
-Bu
Ph
Ph
Me
OH
PdII
-
PdII
Me
n
-Bu
n
-Bu
Sa
)-
η3
1a
)-
R
II
II
Ra
( )-
(
II'
(
Table 3 Stimulation of GLP-1 release in STC-1 cells
PhB(OH)2
Ph
PhB(OH)2
Ph
Compound
3aa
Relative activity (%)a
EC50 (μM)b
n
-Bu
Ph
46.1
66.5
51.2
44.5
103.5
5.9
n
Me
Me
Ph
-Bu
(
3ab
3ad
3ae
3aj
3aa
)-
Ra 3aa
)-
Sa
(
We tried to realize the catalytic asymmetric synthesis of chiral
tetrasubstituted allenes. So we screened some chiral ligands at 60
oC (Table 2). 86% of propargylic alcohol 1a was recovered when
we use (R)-Ph-Segphos as ligand (Entry 1). Other ligands, such as
(R)-MeO-BIPHEP, (R)-Ph-Garphos and (R)-BINAP, also failed to
afford the desired allene product 3aa (Entries 2-4). We are still
working on it.
24.5±7.4
3al
3an
3ao
3aq
3ar
51.5
5.0
80.1
74.9
60.0
37.9
1.3
Table 2 Chiral ligand screeninga
5 mol% Pd
•CHCl3
Ligand
POOH
2(dba)3
12 mol%
3as
Me Ph
OH
Ph
Ph
10 mol%
(PhO)2
dioxane, 60 o
3ba
3ca
+
PhB(OH)2
N
16 h
,
2
C,
n
-Bu
Me
n
-Bu
1a
2a
3aa
equiv)
(2.0
3da
3ea
3ha
107.4
76.8
127.8
1.6±0.0
> 50
OMe
O
O
O
MeO
MeO
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
PPh2
MeO
MeO
a The concentration of the tested compounds was 100 μM. The level of
GLP-1 was normalized to that in the presence of the positive control PMA
(1μM). b EC50s are presented as mean ± SD.
O
R
(
R
(
R
( )-BINAP
)-Ph-Segphos
)-MeO-BIPHEP
OMe
)-Ph-Garphos
R
(
The anti-diabetic effect of the compounds was also evaluated
by using another cell model. Since diabetic patients often have
defect in glucose consumption by the peripheral tissues such as
skeletal muscle, we used rat L6 myotube cells to investigate the
effect of the compounds on the utilization of glucose. Intriguingly,
3ab, 3ad, 3ae, 3aj, 3an, 3ao, 3da and 3ea effectively stimulated
glucose consumption at 100 μM, leading to more than 1.5-fold
improvement over the vehicle control DMSO. While lowering the
concentration to 30 μM, 3ad, 3an and 3ao still exhibited good
NMR yield
ee of
recovery of
entry
Ligand
of 3aa (%)
3aa (%)
1a (%)
1
2
3
(R)-Ph-Segphos
(R)-MeO-BIPHEP
(R)-Ph-Garphos
/
/
/
/
/
/
86
83
89
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Running title
Chin. J. Chem.
activity (> 1.2-fold). Further investigations of their anti-diabetic
activities and mechanisms are under way.
benzophenone as the indicator and distilled freshly before use. All
the temperatures are referred to the Reaction Block used. NMR
yield of allenes were determined by 1H NMR analysis using
dibromomethane as the internal standard. The starting
propargylic alcohols were synthesized according to the reported
procedures.12
Table 4 Stimulation of glucose consumption in rat L6 myotube cells
Relative activity (%)a
Compound
30 μM
100.7±2.2
119.8±3.3
123.2±1.3
108.1±2.3
104.3±6.6
113.6±3.7
120.9±2.5
120.4±1.1
109.8±4.0
101.5±6.2
105.6±1.5
105.7±4.7
97.0±4.0
100 μM
127.2±7.6
161.5±8.0
168.4±6.1
157.9±4.0
157.6±4.4
131.5±5.0
170.5±3.2
151.7±5.1
139.6±2.0
103.0±1.2
147.7±1.5
137.8±6.3
101.7±6.2
153.1±1.9
155.0±3.0
96.1±4.3
1. Synthesis of allenes
(1) Preparation of 2.4-diphenyl-2,3-octadiene (3aa, QAN-2-149)
3aa
3ab
5
mol%
Pd(PPh3)4
POOH
Ph
Me
OH
Me
Ph
5 mol%
•
(PhO)2
n
-Bu
+
3ad
PhB(OH)2
2a
dioxane, 25 o
N
2
n
-Bu
Ph
C,17 h,
3ae
1a
3aa
81%
,
equiv)
(2.0
3aj
3al
Typical Procedure: To an oven-dried 20 mL vial equipped with a
3an
stirring bar were added phenylboronic acid (243.9 mg, 2.0 mmol)
and (PhO)2POOH (12.7 mg, 0.05 mmol). Then the vial was
transferred to a glovebox with nitrogen atmosphere. After adding
Pd(PPh3)4 (57.7 mg, 0.05 mmol), 1a (202.6 mg, 1.0 mmol), and
anhydrous dioxane (5 mL), the vial was capped with a Teflon lined
lid, sealed with electrical tape, and transferred out of the
glovebox. After stirring for 17 h in the reaction block at 25 oC, the
reaction mixture were filtered through a short column silica gel (3
cm) eluted with ethyl acetate (20 mL). After removal of the
solvent under vacuum, the crude product was analyzed by H
NMR with CH2Br2 (35 µL) as the internal standard: 77% NMR yield
of 3aa was formed based on H NMR analysis. The residue was
purified by column chromatography on silica gel to afford 3aa
3ao
3aq
3ar
3as
3ba
3ca
1
3da
102.7±5.9
108.1±5.1
105.3±2.9
100.0±5.5
148.3±3.2
3ea
1
3ha
DMSOb
Metforminc
(216.8 mg, 81%, 99% purity) as an oil [eluent: petroleum ether
1
(200 mL)]; H NMR (400 MHz, CDCl3): δ = 7.43 (t, J = 7.4 Hz, 4 H,
Ar-H), 7.34-7.25 (m, 4 H, Ar-H), 7.23-7.16 (m, 2 H, Ar-H), 2.55 (t, J
= 7.6 Hz, 2 H, CH2), 2.20 (s, 3 H, CH3), 1.57 (quintet, J = 7.6 Hz, 2 H,
CH2), 1.48-1.34 (m, 2 H, CH2), 0.91 (t, J = 7.2 Hz, 3 H, CH3); 13C
NMR (100 MHz, CDCl3): δ = 205.6, 137.3, 137.1, 128.41, 128.38,
126.7, 126.6, 126.1, 125.6, 107.8, 103.6, 30.1, 30.0, 22.6, 16.8,
14.0; MS (70 eV, EI) m/z (%): 263 (M++1, 1.60), 262 (M+, 7.01), 205
(100); IR (neat): v = 3026, 2955, 2925, 2859 1934, 1596, 1490,
1443, 1372, 1065, 1025 cm-1; HRMS calcd for C20H22 [M+]:
262.1722; found 262.1724.
a Data were normalized to that of the DMSO group and presented as mean
± SD. The concentration of DMSO was 1%. The concentration of
metformin was 10 mM.
b
c
Conclusions
In conclusion, we have developed a general and highly
efficient catalytic system for the Suzuki coupling of propargylic
alcohols with boronic acids. Many functional groups are
compatible under the very mild reaction conditions to afford
trisubstituted and tetrasubstituted allenes facilely. Several newly
synthesized compounds in this study displayed potent
anti-diabetic activities. Further studies on the details of the
reaction mechanism as well as the asymmetric protocol are in
progress in our laboratory.
(2) Preparation of 2-phenyl-4-(4-methylphenyl)-2,3-octadiene
(3ab, QAN-5-120)
Me
5 mol%
5 mol%
Pd(PPh3)4
OH
Me
Ph
Me
Ph
POOH
(PhO)2
•
n
-Bu
+
Me
B(OH)2
equiv)
dioxane, 25 o
N
n
-Bu
C,17 h,
2
1a
2b
(2.0
3ab
92%
,
Experimental
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.6 mg,
General Information. NMR spectra were taken with an
0.05 mmol), p-tolylboronic acid (271.6 mg, 2.0 mmol),
(PhO)2POOH (12.5 mg, 0.05 mmol), 1a (202.3 mg, 1.0 mmol), and
Agilent-400 spectrometer (400 MHz for H NMR, 100 MHz for 13C
1
NMR, and 376 MHz for 19F NMR) in CDCl3. Chemical shifts were
recorded in ppm in relative to the TMS in CDCl3 and coupling
constants were reported in Hz. All reactions were carried out in
vial. Pd(PPh3)4 was purchased from J&K Chemicals and chembee;
PhB(OH)2 was purchased from bokachem Reagent Co; Petroleum
ether (b.p. 60-90 oC) was purchased from Shanghai Titan Scientific
Co., Ltd. 1,4-dioxane was dried over sodium wire with
o
anhydrous dioxane (5 mL) at 25 C afforded 3ab (255.0 mg, 92%)
1
as an oil [eluent: petroleum ether (200 mL)]; H NMR (400 MHz,
CDCl3): δ = 7.44 (d, J = 8.0 Hz, 2 H, Ar-H), 7.34-7.24 (m, 4 H, Ar-H),
7.23-7.16 (m, 1 H, Ar-H), 7.11 (d, J = 7.6 Hz, 2 H, Ar-H), 2.52 (t, J =
7.4 Hz, 2 H, CH2), 2.32 (s, 3 H, CH3), 2.19 (s, 3 H, CH3), 1.55 (quintet,
J = 7.4 Hz, 2 H, CH2), 1.45-1.33 (m, 2 H, CH2), 0.90 (t, J = 7.4 Hz, 3 H,
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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This article is protected by copyright. All rights reserved.

First author et al.
Report
CH3); 13C NMR (100 MHz, CDCl3): δ = 205.3, 137.4, 136.4, 134.0,
129.1, 128.3, 126.5, 126.0, 125.6, 107.6, 103.4, 30.1, 30.0, 22.6,
21.0, 16.9, 14.0; MS (70 eV, EI) m/z (%): 277 (M++1, 3.31), 276 (M+,
13.79), 219 (100); IR (neat): v = 3023, 2924, 2858, 1931, 1597,
1510, 1443, 1377, 1183, 1109, 1065, 1026 cm-1; HRMS calcd for
C21H24 [M+]: 276.1878; found 276.1877.
t-Bu
5 mol%
Pd(PPh3)4
Me
OH
Me
Ph
5 mol%
POOH
(PhO)2
•
+
n
-Bu
t-Bu
B(OH)2
dioxane, 25 o
N
h,
n
C,17
2
-Bu
Ph
85%
3ae
,
1a
2e
(2.0
equiv)
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), (4-(tert-butyl)phenyl)boronic acid (356.3 mg, 2.0
mmol), (PhO)2POOH (12.6 mg, 0.05 mmol), 1a (202.0 mg, 1.0
mmol), and anhydrous dioxane (5 mL) at 25 oC afforded 3ae (270.6
mg, 85%) as a white solid [eluent: petroleum ether (200 mL)]; M.p.
(3) Preparation of 2-phenyl-4-(3-methylphenyl)-2,3-octadiene
(3ac, QAN-2-160)
Me
Me
5 mol%
5 mol%
Pd(PPh3)4
POOH
1
OH
Me
Ph
64.3-68.4 °C (petroleum ether); H NMR (400 MHz, CDCl3): δ =
Me
Ph
(PhO)2
+
n
-Bu
•
dioxane, 25 o
N
2
B(OH)2
equiv)
7.48-7.42 (m, 2 H, Ar-H), 7.40-7.27 (m, 6 H, Ar-H), 7.24-7.15 (m, 1
H, Ar-H), 2.53 (t, J = 7.6 Hz, 2 H, CH2), 2.19 (s, 3 H, CH3), 1.65-1.54
(m, 2 H, CH2), 1.50-1.38 (m, 2 H, CH2), 1.31 (s, 9 H, 3 x CH3), 0.90 (t,
C,17 h,
n
-Bu
1a
2c
3ac
,
79%
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.9 mg, J = 7.2 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 205.4, 149.7,
0.05 mmol), m-tolylboronic acid (272.3 mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (202.3 mg, 1.0 mmol), and
137.4, 134.0, 128.3, 126.5, 125.7, 125.6, 125.3, 107.5, 103.5, 34.4,
31.3, 30.1, 29.9, 22.7, 16.9, 14.0; MS (70 eV, EI) m/z (%): 318 (M+,
2.39), 261 (100); IR (neat): v = 3033, 2954, 2923, 2860, 1928, 1713,
1602, 1494, 1437, 1271, 1180, 1106 cm-1; Anal. Calcd. for C24H30: C:
90.51, H: 9.49; Found: C: 90.53, H: 9.67.
o
anhydrous dioxane (5 mL) at 25 C afforded 3ac (232.5 mg, 79%,
1
94.5% purity) as an oil [eluent: petroleum ether (200 mL)]; H
NMR (400 MHz, CDCl3): δ = 7.44 (d, J = 8.0 Hz, 2 H, Ar-H), 7.31 (t, J
= 7.6 Hz, 2 H, Ar-H), 7.26-7.12 (m, 4 H, Ar-H), 7.01 (d, J = 7.2 Hz, 1
H, Ar-H), 2.62-2.48 (m, 2 H, CH2), 2.32 (s, 3 H, CH3), 2.20 (s, 3 H,
CH3), 1.62-1.50 (m, 2 H, CH2), 1.47-1.33 (m, 2 H, CH2), 0.90 (t, J =
7.2 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 205.5, 137.9,
137.3, 137.0, 128.4, 128.3, 127.5, 126.7, 126.6, 125.6, 123.2,
107.8, 103.4, 30.11, 30.05, 22.6, 21.5, 16.8, 14.0; MS (70 eV, EI)
m/z (%): 277 (M++1, 2.50), 276 (M+, 10.75), 219 (100); IR (neat): v
= 3024, 2924, 2859, 1933, 1599, 1489, 1444, 1372, 1176, 1094,
1064 cm-1; HRMS calcd for C21H24 [M+]: 276.1878; found 276.1876.
(6) Preparation of 2-phenyl-4-(4-fluorophenyl)-2,3-octadiene
(3af, QAN-5-070)
F
5 mol%
Pd(PPh3)4
Me
Ph
OH
Me
Ph
5 mol%
POOH
(PhO)2
•
n
-Bu
+
F
B(OH)2
equiv)
dioxane, 25 o
N
n
-Bu
C,17 h,
2
1a
2f
3af,
79%
(2.0
Following Typical Procedure , the reaction of Pd(PPh3)4 (57.7
mg, 0.05 mmol), (4-fluorophenyl)boronic acid (280.2 mg, 2.0
mmol), (PhO)2POOH (12.5 mg, 0.05 mmol), 1a (201.7 mg, 1.0
mmol), and anhydrous dioxane (5 mL) at 25 oC afforded 3af (220.8
(4) Preparation of 2-phenyl-4-(2-methylphenyl)-2,3-octadiene
(3ad, QAN-3-078)
Me
5 mol%
Pd(PPh3)4
1
Me
mg, 79%) as an oil [eluent: petroleum ether (400 mL)]; H NMR
OH
Me
Ph
5 mol%
POOH
•
(PhO)2
dioxane, 25 o 17
Me
n
-Bu
+
B(OH)2
equiv)
(400 MHz, CDCl3): δ = 7.43 (d, J = 7.6 Hz, 2 H, Ar-H), 7.39-7.26 (m,
4 H, Ar-H), 7.20 (t, J = 7.2 Hz, 1 H, Ar-H), 6.98 (t, J = 8.6 Hz, 2 H,
Ar-H), 2.58-2.42 (m, 2 H, CH2), 2.20 (s, 3 H, CH3), 1.58-1.50 (m, 2 H,
CH2), 1.46-1.35 (m, 2 H, CH2), 0.91 (t, J = 7.2 Hz, 3 H, CH3); 13C
NMR (100 MHz, CDCl3): δ = 205.2 (d, J = 1.5 Hz), 161.8 (d, J =
244.9 Hz), 137.1, 133.0 (d, J = 3.2 Hz), 128.4, 127.5 (d, J = 7.9 Hz),
126.7, 125.6, 115.2 (J = 21.4 Hz), 107.0, 103.8, 30.2, 30.0, 22.6,
16.8, 13.9; 19F NMR (376 MHz, CDCl3): δ = -116.7; MS (70 eV, EI)
m/z (%): 280 (M+, 4.63), 190 (100); IR (neat): v = 3046, 2956, 2928,
2859, 1934, 1600, 1506, 1464, 1227, 1158, 1065 cm-1; HRMS calcd
m/z for C20H21F [M+]: 280.1622; found 280.1620.
n
-Bu
Ph
86%
N
h,
C,
2
1a
2d
(2.0
3ad
,
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), o-tolylboronic acid (271.9 mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (201.9 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 25 C afforded 3ad (236.5 mg, 86%)
1
as an oil [eluent: petroleum ether (200 mL)]; H NMR (400 MHz,
CDCl3): δ = 7.45-7.38 (m, 2 H, Ar-H), 7.34-7.26 (m, 3 H, Ar-H),
7.20-7.09 (m, 4 H, Ar-H), 2.54-2.33 (m, 5 H, CH2 and CH3), 2.15 (s,
3 H, CH3), 1.55-1.44 (m, 2 H, CH2), 1.43-1.33 (m, 2 H, CH2), 0.89 (t,
J = 7.2 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 203.3, 138.1,
137.8, 135.8, 130.4, 128.2, 128.1, 126.7, 126.3, 125.74, 125.71,
106.7, 100.7, 34.0, 30.1, 22.5, 20.7, 17.1, 14.0; MS (70 eV, EI) m/z
(%): 277 (M++1, 1.60), 276 (M+, 6.31), 219 (100); IR (neat): v =
3059, 2924, 2860, 1941, 1799, 1596, 1488, 1449, 1373, 1102,
1064, 1027 cm-1; HRMS calcd for C21H24 [M+]: 276.1878; found
276.1879.
(7) Preparation of 2-phenyl-4-(4-chlorophenyl)-2,3-octadiene
(3ag, QAN-2-159, cfsy-3-181)
Cl
5 mol%
Pd(PPh3)4
Me
Ph
OH
Me
Ph
5 mol%
POOH
(PhO)2
•
+
n
-Bu
Cl
B(OH)2
dioxane, 25 o
N
n
-Bu
C,17 h,
2
1a
3ag,
80%
(5) Preparation of 2-phenyl-4-(4-tert-butylphenyl)-2,3-octadiene
equiv)
2g
(2.0
(3ae, QAN-2-164)
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.9 mg,
0.05 mmol), (4-chlorophenyl)boronic acid (312.7 mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (201.3 mg, 1.0 mmol), and
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© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
o
anhydrous dioxane (5 mL) at 25 C afforded 3ag (259.5 mg, 80%,
91% purity) as an oil [eluent: petroleum ether (200 mL)]; 1H NMR
(400 MHz, CDCl3): δ = 7.42 (d, J = 7.2 Hz, 2 H, Ar-H), 7.37-7.26 (m,
4 H, Ar-H), 7.25-7.13 (m, 3 H, Ar-H), 2.59-2.42 (m, 2 H, CH2), 2.20
(s, 3 H, CH3), 1.59-1.48 (m, 2 H, CH2), 1.47-1.33 (m, 2 H, CH2), 0.90
(t, J = 7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 205.5,
136.9, 135.5, 132.3, 128.5, 128.4, 127.3, 126.8, 125.6, 107.0,
104.0, 30.0, 29.9, 22.6, 16.8, 14.0; MS (70 eV, EI) m/z (%): 298
(M+(37Cl), 3.15), 296 (M+(35Cl), 9.08), 239 (100); IR (neat): v = 3056,
3025, 2959, 2924, 2857, 1929, 1594, 1489, 1462, 1405, 1181,
1090, 1067 cm-1; HRMS calcd for C20H2235Cl [M+H+]: 297.1405;
found 297.1403.
137.2, 129.3, 128.4, 126.6, 125.6, 118.7, 112.1, 111.7, 107.7,
103.6, 55.2, 30.1, 30.0, 22.6, 16.8, 14.0; MS (70 eV, EI) m/z (%):
293 (M++1, 5.98), 292 (M+, 25.45), 235 (100); IR (neat): v = 3059,
2957, 2929, 2836, 1925, 1604, 1580, 1440, 1374, 1240, 1176,
1114, 1040 cm-1; HRMS calcd m/z for C21H24O [M+]: 292.1822;
found 292.1827.
(10) Preparation of 2-phenyl-4-(3-nitrophenyl)-2,3-octadiene
(3aj, QAN-2-150)
NO2
O2N
5 mol%
5 mol%
Pd(PPh3)4
POOH
Me
Ph
OH
Me
Ph
•
(PhO)2
+
n
-Bu
B(OH)2
dioxane, 25 o 36
C,
N
n
-Bu
h,
2
(8) Preparation of 2-phenyl-4-(4-methoxylphenyl)-2,3-octadiene
(3ah, QAN-2-152)
1a
3aj,
72%
equiv)
2j
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.9 mg,
MeO
0.05 mmol), (3-nitrophenyl)boronic acid (334.0 mg, 2.0 mmol),
5 mol%
5 mol%
Pd(PPh3)4
POOH
(PhO)2POOH (12.7 mg, 0.05 mmol), 1a (202.5 mg, 1.0 mmol), and
OH
Me
Ph
Me
Ph
(PhO)2
+
MeO
•
n
-Bu
B(OH)2
o
dioxane, 25 o 36
C,
N
2
anhydrous dioxane (5 mL) at 25 C afforded 3aj (242.2 mg, 72%,
h,
n
-Bu
91% purity) as an oil [eluent: petroleum ether (150 mL) to
1a
2h
(2.0
3ah,
88%
equiv)
1
petroleum ether/DCM/Et2O = 100/1/1 (~400 mL)]; H NMR (400
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.9 mg, MHz, CDCl3): δ = 8.23 (s, 1 H, Ar-H), 8.02 (d, J = 8.0 Hz, 1 H, Ar-H),
0.05 mmol), (4-methoxyphenyl)boronic acid (304.1 mg, 2.0 mmol), 7.73 (d, J = 8.0 Hz, 1 H, Ar-H), 7.42 (t, J = 7.4 Hz, 3 H, Ar-H), 7.33 (t,
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (201.8 mg, 1.0 mmol), and
anhydrous dioxane (5 mL) at 25 C afforded 3ah (269.4 mg, 88%,
J = 7.4 Hz, 2 H, Ar-H), 7.23 (t, J = 6.4 Hz, 2 H, Ar-H), 2.70-2.47 (m, 2
H, CH2), 2.25 (s, 3 H, CH3), 1.58 (quintet, J = 7.2 Hz, 2 H, CH2),
1.50-1.33 (m, 2 H, CH2), 0.93 (t, J = 7.4 Hz, 3 H, CH3); 13C NMR (100
MHz, CDCl3): δ = 205.9, 148.6, 139.3, 136.2, 132.2, 129.1, 128.5,
127.1, 125.7, 121.4, 120.3, 106.5, 105.1, 29.83, 29.80, 22.5, 16.7,
13.9; MS (70 eV, EI) m/z (%): 308 (M++1, 2.72), 307 (M+, 11.84),
250 (100); IR (neat): v = 3084, 2956, 2926, 2861, 1933, 1598, 1493,
1443, 1344, 1067, 1025 cm-1; HRMS calcd for C20H21NO2 [M+]:
307.1572; found 307.1574.
o
95% purity) as an oil [eluent: petroleum ether (150 mL) to
1
petroleum ether/DCM/Et2O = 200/1/1 (400 mL)]; H NMR (400
MHz, CDCl3): δ = 7.50-7.41 (m, 2 H, Ar-H), 7.38-7.25 (m, 4 H, Ar-H),
7.24-7.16 (m, 1 H, Ar-H), 6.85 (d, J = 8.4 Hz, 2 H, Ar-H), 3.79 (s, 3 H,
CH3), 2.65-2.42 (m, 2 H, CH2), 2.19 (s, 3 H, CH3), 1.60-1.50 (m, 2 H,
CH2), 1.48-1.33 (m, 2 H, CH2), 0.90 (t, J = 7.2 Hz, 3 H, CH3); 13C
NMR (100 MHz, CDCl3): δ = 205.0, 158.5, 137.5, 129.2, 128.3,
127.1, 126.5, 125.6, 113.9, 107.3, 103.4, 55.3, 30.12, 30.08, 22.6,
16.9, 14.0; MS (70 eV, EI) m/z (%): 293 (M++1, 4.92), 292 (M+,
21.34), 235 (100); IR (neat): v = 3082, 3059, 2929, 2836, 1926,
1604, 1508, 1441, 1374, 1176, 1114, 1064 cm-1; HRMS calcd for
C21H25O [M+H+]: 293.1900; found 293.1897.
(11) Preparation of 2-phenyl-4-(4-cyanophenyl)-2,3-octadiene
(3ak, QAN-3-031)
NC
5 mol%
Pd(PPh3)4
POOH
Me
Ph
OH
Me
Ph
5 mol%
(PhO)2
dioxane, 40 o 17
•
n
-Bu
+
NC
2k
B(OH)2
equiv)
(9) Preparation of 2-phenyl-4-(3-methoxylphenyl)-2,3-octadiene
n
-Bu
N
h,
C,
2
(3ai, QAN-2-161)
1a
3ak,
74%
(2.0
OMe
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.6 mg,
0.05 mmol), (4-cyanophenyl)boronic acid (294.0, 2.0 mmol),
MeO
5 mol%
Pd(PPh3)4
POOH
Me
Ph
OH
Me
Ph
5 mol%
(PhO)2
dioxane, 25 o 36
•
n
-Bu
+
(PhO)2POOH (12.8 mg, 0.05 mmol), 1a (202.0 mg, 1.0 mmol), and
B(OH)2
equiv)
n
-Bu
N
h,
C,
2
o
anhydrous dioxane (5 mL) at 40 C afforded 3ak (212.7 mg, 74%)
1a
2i
3ai, 77%
(2.0
as an oil eluent: petroleum ether (200 mL) to petroleum
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.7 mg, ether/DCM/Et2O
0.05 mmol), (3-methoxyphenyl)boronic acid (304.1, 2.0 mmol),
=
100/1/1 (400 mL) to petroleum
ether/DCM/Et2O = 50/1/1 (300 mL)]; 1H NMR (400 MHz, CDCl3): δ
= 7.57 (d, J = 8.8 Hz, 2 H, Ar-H), 7.49 (d, J = 8.8 Hz, 2 H, Ar-H),
7.44-7.37 (m, 2 H, Ar-H), 7.34 (t, J = 7.6 Hz, 2 H, Ar-H), 727-7.21 (m,
1 H, Ar-H), 2.60-2.45 (m, 2 H, CH2), 2.22 (s, 3 H, CH3), 1.63-1.50 (m,
(PhO)2POOH (12.7 mg, 0.05 mmol), 1a (201.8 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 25 C afforded 3ai (231.8 mg, 77%,
1
97% purity) as an oil [eluent: petroleum ether (400 mL); H NMR
(400 MHz, CDCl3): δ = 7.44 (d, J = 8.0 Hz, 2 H, Ar-H), 7.31 (t, J = 7.8
Hz, 2 H, Ar-H), 7.27-7.12 (m, 2 H, Ar-H), 7.03 (d, J = 7.6 Hz, 1 H,
Ar-H), 7.00-6.96 (m, 1 H, Ar-H), 6.75 (dd, J1= 8.2 Hz, J2= 2.2 Hz, 1 H,
Ar-H), 3.78 (s, 3 H, CH3), 2.62-2.42 (m, 2 H, CH2), 2.20 (s, 3 H, CH3),
1.64-1.50 (m, 2 H, CH2), 1.46-1.33 (m, 2 H, CH2), 0.90 (t, J = 7.4 Hz,
3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 205.6, 159.7, 138.7,
2 H, CH2), 1.48-1.36 (m, 2 H, CH2), 0.92 (t, J = 7.4 Hz, 3 H, CH3); 13
C
NMR (100 MHz, CDCl3): δ = 206.8, 142.2, 136.1, 132.2, 128.5,
127.1, 126.5, 125.6, 119.1, 109.8, 107.1, 104.8, 29.9, 29.6, 22.5,
16.6, 13.9; MS (70 eV, EI) m/z (%): 288 (M++1, 1.12), 287 (M+,
4.60), 230 (100); IR (neat): v = 3058, 2924, 2851, 2226, 1926, 1598,
1496, 1308, 1182, 1064, 1024 cm-1; HRMS calcd m/z for C21H21N
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

First author et al.
Report
[M+]: 287.1669; found 287.1661.
F3C
5 mol%
5 mol%
Pd(PPh3)4
(PhO)2
(12) Preparation of 2-phenyl-4-(4-acetylphenyl)-2,3-octadiene
(3al, QAN-3-039)
Me
OH
Me
Ph
POOH
•
n
-Bu
+
F3C
2n
B(OH)2
dioxane, 25 o
N
n
-Bu
Ph
3an, 77%
C,17 h,
2
Ac
1a
equiv)
(2.0
5 mol%
Pd(PPh3)4
POOH
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
Me
Ph
OH
Me
Ph
10 mol%
(PhO)2
•
+
n
-Bu
Ac
B(OH)2
0.05 mmol), (4-(trifluoromethyl)phenyl)boronic acid (378.0 mg,
2.0 mmol), (PhO)2POOH (12.6 mg, 0.05 mmol), 1a (202.5 mg, 1.0
mmol), and anhydrous dioxane (5 mL) at 25 oC afforded 3an
dioxane, 25 o 24
C,
N
2
n
-Bu
h,
1a
2l
3al,
78%
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg, (282.0 mg, 77%, 91% purity) as an oil [eluent: petroleum ether
0.05 mmol), (4-acetylphenyl)boronic acid (327.8 mg, 2.0 mmol),
(PhO)2POOH (25.2 mg, 0.10 mmol), 1a (202.1 mg, 1.0 mmol), and
anhydrous dioxane (5 mL) at 25 oC afforded 3al (237.0 mg, 78%) as
an oil [eluent: petroleum ether/DCM/Et2O = 100/1/1 (200 mL) to
(200 mL)]; 1H NMR (400 MHz, CDCl3): δ = 7.59-7.45 (m, 4 H, Ar-H),
7.43 (d, J = 7.6 Hz, 2 H, Ar-H), 7.33 (t, J = 7.6 Hz, 2 H, Ar-H), 7.23 (t,
J = 7.2 Hz, 1 H, Ar-H), 2.63-2.44 (m, 2 H, CH2), 2.22 (s, 3 H, CH3),
1.63-1.51 (m, 2 H, CH2), 1.49-1.33 (m, 2 H, CH2), 0.92 (t, J = 7.2 Hz,
3 H, CH3); 19F NMR (376 MHz, CDCl3): δ = -62.9; 13C NMR (100 MHz,
CDCl3): δ = 206.3, 140.9, 136.6, 128.54 (q, J = 32.1 Hz), 128.51,
127.0, 126.2, 125.7, 125.3 (q, J = 3.8 Hz), 124.3 (q, J = 270.2 Hz),
107.1, 104.4, 30.0, 29.8, 22.6, 16.7, 13.9; MS (70 eV, EI) m/z (%):
331 (M++1, 2.52), 330 (M+, 10.68), 273 (100); IR (neat): v = 3082,
2957, 2933, 2866, 1927, 1613, 1463, 1375, 1323, 1156, 1113,
1
petroleum ether/DCM/Et2O = 40/1/1 (~400 mL)]; H NMR (400
MHz, CDCl3): δ = 7.89 (d, J = 8.4 Hz, 2 H, Ar-H), 7.50 (d, J = 8.0 Hz,
2 H, Ar-H), 7.43 (d, J = 7.6 Hz, 2 H, Ar-H), 7.33 (t, J = 7.6 Hz, 2 H,
Ar-H), 7.27-7.18 (m, 1 H, Ar-H), 2.62-2.46 (m, 5 H, CH2 and CH3),
2.23 (s, 3 H, CH3), 1.57 (quintet, J = 7.3 Hz, 2 H, CH2), 1.49-1.35 (m,
2 H, CH2), 0.92 (t, J = 7.2 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3):
δ = 206.8, 197.5, 142.2, 136.5, 135.3, 128.55, 128.46, 126.9, 126.0, 1066 cm-1; HRMS calcd for C21H21F3 [M+]: 330.1595; found
125.7, 107.5, 104.3, 30.0, 29.8, 26.5, 22.5, 16.7, 13.9; MS (70 eV,
EI) m/z (%): 305 (M++1, 6.24), 304 (M+, 26.17), 43 (100); IR (neat):
v = 3346, 3081, 2958, 2924, 2858, 1926, 1680, 1596, 1492, 1410,
1358, 1260, 1183, 1021 cm-1; HRMS calcd for C22H24O [M+]:
304.1827; found 304.1831.
330.1597.
(15) Preparation of 2-phenyl-4-(4-methoxylcarbonylphenyl)-2,3-
octadiene (3ao, QAN-2-145)
MeO2C
5 mol%
5 mol%
Pd(PPh3)4
POOH
OH
Me
Ph
(13) Preparation of 2-phenyl-4-(4-formylphenyl)-2,3-octadiene
(3am, QAN-3-122)
Me
Ph
(PhO)2
+
n
-Bu
•
MeO2C
B(OH)2
dioxane, 25 o
N
2
C,17 h,
n
-Bu
1a
2o
3ao,
OHC
76%
equiv)
(2.0
5 mol%
5 mol%
Pd(PPh3)4
POOH
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
OH
Me
Ph
Me
Ph
(PhO)2
+
n
-Bu
•
OHC
B(OH)2
equiv)
dioxane, 25 o
N
2
0.05 mmol), (4-(methoxycarbonyl)phenyl)boronic acid (360.1 mg,
2.0 mmol), (PhO)2POOH (12.6 mg, 0.05 mmol), 1a (202.1 mg, 1.0
mmol), and anhydrous dioxane (5 mL) at 25 oC afforded 3ao
C,19 h,
n
-Bu
3am,
1a
2m
(2.0
81%
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.7 mg, (246.1 mg, 76%, 99% purity) as a white solid [eluent: petroleum
0.05 mmol), (4-formylphenyl)boronic acid (300.1 mg, 2.0 mmol),
ether (200 mL) to petroleum ether/DCM/Et2O = 100/1/1 (200
mL)]; M.p. 65.7-70.8 °C (petroleum ether/dichloromethane); H
NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 2 H, Ar-H),
7.52-7.38 (m, 4 H, Ar-H), 7.33 (t, J = 7.6 Hz, 2 H, Ar-H), 7.22-7.16
(m, 1 H, Ar-H), 3.90 (s, 3 H, CH3), 2.63-2.50 (m, 2 H, CH2), 2.22 (s, 3
H, CH3), 1.62-1.43 (m, 2 H, CH2), 1.50-1.32 (m, 2 H, CH2), 0.91 (t, J
= 7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 206.6, 166.9,
1
(PhO)2POOH (12.7 mg, 0.05 mmol), 1a (202.3 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 25 C afforded 3am (236.4 mg, 81%)
as a white solid [eluent: petroleum ether (200 mL) to petroleum
1
ether/DCM/Et2O = 50/1/1 (~410 mL)]; M.p. 56.3-59.4 °C; H NMR
(400 MHz, CDCl3): δ = 9.96 (s, 1 H, CHO), 7.81 (d, J = 8.0 Hz, 2 H,
Ar-H), 7.57 (d, J = 8.4 Hz, 2 H, Ar-H), 7.45-7.39 (m, 2 H, Ar-H), 7.34
(t, J = 7.6 Hz, 2 H, Ar-H), 7.26-7.20 (m, 1 H, Ar-H), 2.60-2.54 (m, 2 H, 142.0, 136.6, 129.7, 128.4, 128.1, 126.9, 125.8, 125.6, 107.5,
CH2), 2.24 (s, 3 H, CH3), 1.63-1.50 (m, 2 H, CH2), 1.49-1.39 (m, 2 H,
CH2), 0.92 (t, J = 7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ =
207.2, 191.7, 143.8, 136.4, 134.7, 129.9, 128.5, 127.0, 126.4,
125.7, 107.6, 104.5, 30.0, 29.8, 22.5, 16.7, 13.9; MS (70 eV, EI) m/z
(%): 291 (M++1, 3.75), 290 (M+, 15.17), 205 (100); IR (neat): v =
3356, 3083, 2925, 2854, 1924, 1694, 1596, 1491, 1459, 1304,
1208, 1110, 1064 cm-1; Anal. Calcd. for C21H22O(%): C: 86.85, H:
7.64; Found: C: 86.66, H: 7.69.
104.2, 52.0, 30.0, 29.8, 22.5, 16.7, 13.9; MS (70 eV, EI) m/z
(%):321 (M++1, 3.04), 320 (M+, 12.24), 263 (100); IR (neat): v =
3033, 2954, 2923, 2860, 1928, 1712, 1602, 1494, 1372, 1271,
1180, 1106, 1019 cm-1; Anal. Calcd. for C22H24O2(%): C: 82.46, H:
7.55; Found: C: 82.37, H: 7.62.
(16) Preparation of 2-phenyl-4-biphenyl-2,3-octadiene (3ap,
QAN-2-169)
(14) Preparation of 2-phenyl-4-(4-trifluoromethylphenyl)-2,3-
octadiene (3an, QAN-2-157)
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
o
Ph
anhydrous dioxane (5 mL) at 25 C afforded 3ar (201.8 mg, 80%)
1
as an oil [eluent: petroleum ether (300 mL)]; H NMR (400 MHz,
5 mol%
Pd(PPh3)4
POOH
Me
Ph
CDCl3): δ = 7.48-7.37 (m, 3 H, Ar-H), 7.36-7.26 (m, 3 H, Ar-H), 7.20
(t, J = 7.4 Hz, 1 H, Ar-H), 6.35 (d, J = 0.8 Hz, 1 H, Ar-H), 2.48-2.25
(m, 2 H, CH2), 2.17 (s, 3 H, CH3), 1.62-1.50 (m, 2 H, CH2), 1.48-1.31
(m, 2 H, CH2), 0.90 (t, J = 7.2 Hz, 3 H, CH3); 13C NMR (100 MHz,
CDCl3): δ = 204.1, 143.1, 138.2, 137.4, 128.3, 126.6, 125.8, 123.5,
109.4, 103.2, 100.6, 30.7, 29.9, 22.6, 17.0, 14.0; MS (70 eV, EI)
m/z (%): 253 (M++1, 4.92), 252 (M+, 15.16), 105 (100); IR (neat): v
= 3059, 2956, 2927, 2863, 1935, 1762, 1598, 1446, 1265, 1157,
1066 cm-1; HRMS calcd for C18H20O [M+]: 252.1514; found
252.1510.
OH
Me
Ph
5 mol%
(PhO)2
dioxane, 25 o 17
•
+
n
Ph
-Bu
B(OH)2
n
-Bu
3ap,
N
h,
C,
2
1a
82%
equiv)
2p
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.7 mg,
0.05 mmol), [1,1'-biphenyl]-4-ylboronic acid (396.3, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (202.3 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 25 C afforded 3ap (302.6 mg, 82%,
purity: 92%) as an oil [eluent: petroleum ether (200 mL); 1H NMR
(400 MHz, CDCl3): δ = 7.63-7.38 (m, 10 H, Ar-H), 7.36-7.27 (m, 3 H,
Ar-H), 7.25-7.16 (m, 1 H, Ar-H), 2.58 (t, J = 7.4 Hz, 2 H, CH2), 2.23 (s,
3 H, CH3), 1.59 (quintet, J = 7.5 Hz, 2 H, CH2), 1.50-1.35 (m, 2 H,
CH2), 0.92 (t, J = 7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ =
205.8, 140.9, 139.5, 137.2, 136.0, 128.7, 128.4, 127.1, 126.9,
126.7, 126.5, 125.7, 107.5, 103.8, 30.1, 30.0, 22.6, 16.9, 14.0; MS
(70 eV, EI) m/z (%): 339 (M++1, 6.58), 338 (M+, 22.32), 281 (100);
IR (neat): v = 3055, 3027, 2923, 2857, 1931, 1596, 1486, 1370,
1230, 1111, 1067 cm-1; HRMS calcd m/z for C26H26 [M+]: 338.2029;
found 338.2027.
(19) Preparation of 2-phenyl-4-(3-thienyl)-2,3-octadiene (3as,
QAN-2-196)
S
5 mol%
5 mol%
Pd(PPh3)4
POOH
Me
Ph
OH
Me
Ph
•
(PhO)2
S
+
n
-Bu
B(OH)2
equiv)
dioxane, 25 o
C,17 h,
N
n
-Bu
2
1a
2s
3as,
75%
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), thiophen-3-ylboronic acid (256.1mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (201.9 mg, 1.0 mmol), and
(17) Preparation of 2-phenyl-4-(2-napthyl)-2,3-octadiene (3aq,
QAN-2-174)
o
anhydrous dioxane (5 mL) at 25 C afforded 3as (217.1 mg, 75%,
93% purity) as an oil [eluent: petroleum ether (300 mL)]; 1H NMR
(400 MHz, CDCl3): δ = 7.48-7.38 (m, 2 H, Ar-H), 7.34-7.25 (m, 2 H,
Ar-H), 7.23-7.15 (m, 2 H, Ar-H), 7.14-7.03 (m, 2 H, Ar-H), 2.32 (dt,
J1 = 7.2 Hz, J2 = 2.3 Hz, 2 H, CH2), 2.18 (s, 3 H, CH3), 1.57 (quintet, J
= 7.4 Hz, 2 H, CH2), 1.48-1.33 (m, 2 H, CH2), 0.90 (t, J = 7.2 Hz, 3 H,
CH3); 13C NMR (100 MHz, CDCl3): δ = 205.3, 139.0, 137.3, 128.3,
127.0, 126.6, 125.7, 125.2, 118.8, 104.1, 103.2, 30.7, 30.0, 22.6,
17.0, 14.0; MS (70 eV, EI) m/z (%): 269 (M++1, 5.23), 268 (M+,
24.95), 211 (100); IR (neat): v = 3026, 2954, 2924, 2858, 1934,
1597, 1491, 1373, 1233, 1178, 1065 cm-1; HRMS calcd for C18H20S
[M+]: 268.1286; found 268.1289.
5 mol%
5 mol%
Pd(PPh3)4
POOH
Me
Ph
OH
Me
Ph
•
(PhO)2
+
n
-Bu
B(OH)2
dioxane, 25 o
N
2
n
-Bu
C,17 h,
1a
3aq,
88%
equiv)
2q
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), naphthalen-2-ylboronic acid (344.2 mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1a (202.6 mg, 1.0 mmol), and
anhydrous dioxane (5 mL) at 25 C afforded 3aq (276.0 mg, 88%)
as a white solid [eluent: petroleum ether (200 mL)]; M.p.
72.7-79.8 °C; H NMR (400 MHz, CDCl3): δ = 7.87-7.43 (m, 3 H,
Ar-H), 7.71 (d, J = 8.8 Hz, 1 H, Ar-H), 7.63-7.52(m, 1 H, Ar-H),
7.50-7.36 (m, 4 H, Ar-H), 7.33 (t, J = 7.6 Hz, 2 H, Ar-H), 7.28-7.15
(m, 1 H, Ar-H), 2.68 (t, J = 7.6 Hz, 2 H, CH2), 2.25 (s, 3 H, CH3), 1.63
(quintet, J = 7.5 Hz, 2 H, CH2), 1.53-1.37 (m, 2 H, CH2), 0.93 (t, J =
7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 206.3, 137.2,
134.5, 133.7, 132.5, 128.4, 128.0, 127.8, 127.5, 126.7, 126.0,
125.7, 125.6, 125.5, 123.6, 108.1, 103.9, 30.1, 30.0, 22.7, 16.9,
14.0; MS (70 eV, EI) m/z (%): 313 (M++1, 5.92), 312 (M+, 22.68),
255 (100); IR (neat): v = 3055, 2955, 2923, 2866, 1922, 1628, 1595,
1491, 1463, 1261, 1187, 1127, 1064 cm-1; HRMS calcd m/z for
C24H24 [M+]: 312.1873; found 312.1870.
o
1
(20)
Preparation
of
2,4-diphenyl-2,3-decadiene
(3ba,
QAN-3-090)
5 mol%
5 mol%
Pd(PPh3)4
POOH
Ph
Me
OH
Me
Ph
-
•
(PhO)2
n
+
Hex
PhB(OH)2
-
dioxane, 25 o
C,17 h,
N
n
Hex
Ph
2
1b
2a
3ba
84%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), phenylboronic acid (243.9, 2.0 mmol), (PhO)2POOH
(12.6 mg, 0.05 mmol), 1b (229.8 mg, 1.0 mmol), and anhydrous
dioxane (5 mL) at 25 oC afforded 3ba (251.1 mg, 84%, 96% purity)
1
as an oil [eluent: petroleum ether (200 mL)]; H NMR (400 MHz,
CDCl3): δ = 7.43 (t, J = 7.4 Hz, 4 H, Ar-H), 7.34-7.26 (m, 4 H, Ar-H),
7.22-7.15 (m, 2 H, Ar-H), 2.60-2.45 (m, 2 H, CH2), 2.20 (s, 3 H, CH3),
1.58 (quintet, J = 7.4 Hz, 2 H, CH2), 1.45-1.32 (m, 2 H, CH2),
1.29-1.20 (m, 4 H, 2 x CH2), 0.85 (t, J = 6.6 Hz, 3 H, CH3); 13C NMR
(100 MHz, CDCl3): δ = 205.6, 137.3, 137.1 128.40, 128.37, 126.7,
126.6, 126.1, 125.6, 107.8, 103.6, 31.7, 30.2, 29.3, 27.9, 22.7, 16.8,
14.0; MS (70 eV, EI) m/z (%): 291 (M++1, 1.68), 290 (M+, 6.86), 205
(100); IR (neat): v = 3027, 2923, 2855, 1935, 1595, 1490, 1447,
1372, 1181, 1067, 1024 cm-1; HRMS calcd for C22H26 [M+]:
290.2035; found 290.2037.
(18) Preparation of 2-phenyl-4-(3-furyl)-2,3-octadiene (3ar,
QAN-3-003)
O
5 mol%
Pd(PPh3)4
POOH
Me
Ph
OH
Me
Ph
10 mol%
O
•
(PhO)2
+
B(OH)2
equiv)
n
-Bu
dioxane, 25 o
C,17 h,
N
n
-Bu
2
1a
2r
3ar,
80%
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), furan-3-ylboronic acid (223.9 mg, 2.0 mmol),
(PhO)2POOH (25.2 mg, 0.10 mmol), 1a (202.4 mg, 1.0 mmol), and
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

First author et al.
Report
7.22-7.17 (m, 2 H, Ar-H), 6.05-5.90 (m, 1 H, =CH), 5.22-5.14 (m, 1
H, =CH), 5.08-5.01 (m, 1 H, =CH), 3.28-3.34 (m, 2 H, CH2), 2.20 (s, 3
H, CH3); 13C NMR (100 MHz, CDCl3): δ = 206.0, 137.0, 136.4, 135.8,
128.42, 128.39, 126.8, 126.1, 125.7, 116.2, 106.1, 104.0, 34.9,
16.8; MS (70 eV, EI) m/z (%): 247 (M++1, 12.63), 246 (M+, 59.29),
154 (100); IR (neat): v = 3063, 2913, 1941, 1590, 1472, 1438, 1379,
1174, 1079 cm-1; HRMS calcd for C19H18 [M+]: 246.1409; found
246.1406.
(21) Preparation of 2,4-diphenyl-2,3-heptadiene-7-(tert-butyldi-
methylsilyloxy) ether (3ca, QAN-3-102)
TBSO
5 mol%
5 mol%
Pd(PPh3)4
POOH
Ph
Me
Ph
OH
Me
Ph
•
(PhO)2
+
PhB(OH)2
2a
dioxane, 25 o
N
2
C,17 h,
TBSO
1c
3ca
88%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), phenylboronic acid (244.2 mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1c (318.3 mg, 1.0 mmol), and
(24) Preparation of 3,5-diphenyl-3,4-heptadiene-7-(tert-butyldi-
methylsilyloxy) ether (3fa, QAN-3-058)
o
anhydrous dioxane (5 mL) at 25 C afforded 3ca (332.9 mg, 88%)
5 mol%
Pd(PPh3)4
as an oil [eluent: petroleum ether (200 mL) to petroleum
Ph
Et
TBSO
OH
Et
Ph
5 mol%
POOH
(PhO)2
•
+
1
PhB(OH)2
2a
ether/DCM/Et2O = 100/1/1 (400 mL)]; H NMR (400 MHz, CDCl3):
dioxane, 40 o
N
Ph
C,17 h,
2
δ = 7.49-7.43 (m, 4 H, Ar-H), 7.35-7.28 (m, 4 H, Ar-H), 7.24-7.17 (m,
2 H, Ar-H), 3.72 (t, J = 6.2 Hz, 2 H, CH2), 2.65 (t, J = 7.4 Hz, 2 H, CH2),
2.22 (s, 3 H, CH3), 1.90-1.79 (m, 2 H, CH2), 0.91 (s, 9 H, 3 x CH3),
0.05 (s, 6 H, 2 x CH3); 13C NMR (100 MHz, CDCl3): δ = 205.4, 137.1,
136.9, 128.42, 128.39, 126.73, 126.69, 126.0, 125.6, 107.5, 104.0,
62.8, 31.2, 26.5, 26.0, 18.3, 16.9, -5.3; MS (ESI) m/z (%): 247
(M-OTBS)+, 379 (M+H)+; IR (neat): v = 3056, 3028, 2930, 2856,
1933, 1935, 1596, 1491, 1460, 1384, 1251, 1184, 1098 cm-1;
HRMS calcd for C25H35OSi [M+H] +: 379.2452; found 379.2448.
TBSO
1f
3fa
67%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), phenylboronic acid (243.7 mg, 2.0 mmol),
(PhO)2POOH (12.7 mg, 0.05 mmol), 1f (318.2 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 40 C afforded 3fa (257.4 mg, 67%,
98% purity) as an oil [eluent: petroleum ether (200 mL) to
1
petroleum ether/DCM/Et2O = 100/1/1 (200 mL)]; H NMR (400
MHz, CDCl3): δ = 7.64-7.51 (m, 4 H, Ar-H), 7.44 (t, J = 7.6 Hz, 4 H,
Ar-H), 7.37-7.27 (m, 2 H, Ar-H), 4.10-3.90 (m, 2 H, CH2), 2.96 (t, J =
7.4 Hz, 2 H, CH2), 2.78-2.58 (m, 2 H, CH2), 1.31 (t, J = 7.2 Hz, 3 H,
CH3), 1.03-0.90 (m, 9 H, 3 x CH3), 0.16 (d, J = 3.6 Hz, 6 H, 2 x CH3);
13C NMR (100 MHz, CDCl3): δ = 205.0, 136.7, 128.44, 128.42,
128.2, 126.8, 125.9, 125.8, 110.8, 106.5, 62.3, 33.8, 25.94, 25.88,
23.3, 18.3, 12.6, -5.3; MS (70 eV, EI) m/z (%): 378 (M+, 1.25), 349
(100); IR (neat): v = 3029, 2955, 2930, 2857, 1934, 1595, 1491,
1460, 1387, 1252, 1096 cm-1; HRMS calcd for C25H34OSi [M+]:
378.2379; found 378.2385.
(22) Preparation of 2,4-diphenyl-8-chloro-2,3- octadien (3da,
QAN-3-103)
Cl
5 mol%
5 mol%
Pd(PPh3)4
POOH
Ph
Me
OH
Me
Ph
•
(PhO)2
+
PhB(OH)2
dioxane, 25 o
C,17 h,
N
2
Ph
Cl
3da
1d
2a
(2.0
equiv)
76%
,
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), phenylboronic acid (244.2 mg, 2.0 mmol),
(PhO)2POOH (12.6 mg, 0.05 mmol), 1d (236.5 mg, 1.0 mmol), and
(25) Preparation of 4-(3,4-methylenedioxyphenyl)-6-(4-t-butyl-
phenyl)-4,5-decadiene (3ge, QAN-3-046)
o
anhydrous dioxane (5 mL) at 25 C afforded 3da (234.8 mg, 76%,
96% purity) as an oil [eluent: petroleum ether (500 mL)]; 1H NMR
(400 MHz, CDCl3): δ = 7.49-7.38 (m, 4 H, Ar-H), 7.36-7.21 (m, 4 H,
Ar-H), 7.25-7.15 (m, 2 H, Ar-H), 3.50 (t, J = 6.8 Hz, 2 H, CH2), 2.58 (t,
J = 7.6 Hz, 2 H, CH2), 2.21 (s, 3 H, CH3), 1.92-1.81 (m, 2 H, CH2),
1.78-1.62 (m, 2 H, CH2); 13C NMR (100 MHz, CDCl3): δ = 205.4,
136.9, 136.6, 128.5, 128.4, 126.81, 126.77, 126.0, 125.6, 107.1,
104.1, 44.7, 32.3, 29.4, 25.1, 16.9; MS (70 eV, EI) m/z (%): 298
(M+(37Cl), 3.17), 296 (M+(35Cl), 8.77), 205 (100); IR (neat): v = 3078,
2988, 2941, 2853, 1927, 1591, 1444, 1331, 1283, 1209, 1069 cm-1;
HRMS calcd for C20H2235Cl [M+H +]: 297.1405; found 297.1403.
t-Bu
5 mol%
Pd(PPh3)4
POOH
n
-Pr
OH
-Pr
5 mol%
(PhO)2
dioxane, 25 o 39.5
•
+
n
-Bu
n
t-Bu
B(OH)2
n
-Bu
N
h,
C,
2
O
O
O
O
1g
2e
(2.0
66%
,
equiv)
3ge
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), (4-(tert-butyl)phenyl)boronic acid (356.3 mg, 2.0
mmol), (PhO)2POOH (12.8 mg, 0.05 mmol), 1g (274.0 mg, 1.0
mmol), and anhydrous dioxane (5 mL) at 25 oC afforded 3ge (257.4
mg, 66%) as a white solid [eluent: petroleum ether (200 mL) to
(23) Preparation of 2,4-diphenyl-2,3,6-heptatriene (3ea,
QAN-3-107)
petroleum ether/DCM/Et2O
=
100/1/1 (400 mL)]; M.p.
5 mol%
Pd(PPh3)4
POOH
Ph
Me
OH
Me
Ph
1
10 mol%
•
(PhO)2
67.2-71.2 °C (petroleum ether/ethyl acetate); H NMR (400 MHz,
CDCl3): δ = 7.45-7.28 (m, 4 H, Ar-H), 7.01-6.83 (m, 2 H, Ar-H), 6.75
(d, J = 8.0 Hz, 1 H, Ar-H), 5.98-5.82 (m, 2 H, CH2), 2.59-2.37 (m, 4 H,
2 x CH2), 1.62-1.52 (m, 4 H, 2 x CH2), 1.46-1.35 (m, 2 H, CH2), 1.31
(s, 9 H, 3 x CH3), 0.99 (t, J = 7.2 Hz, 3 H, CH3), 0.91 (t, J = 7.4 Hz, 3 H,
CH3); 13C NMR (100 MHz, CDCl3): δ = 204.7, 149.6, 147.8, 146.4,
134.1, 131.4, 125.5, 125.3, 118.9, 108.8, 108.7, 108.1, 106.7,
100.9, 34.4, 32.9, 31.3, 30.3, 30.1, 22.8, 21.4, 14.3, 14.0; MS (ESI)
m/z: 391 ([M+H+]); IR (neat): v = 3080, 2956, 2927, 2871, 1926,
+
PhB(OH)2
2a
dioxane, 25 o 36
C,
N
2
Ph
h,
1e
3ea
69%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.9 mg,
0.05 mmol), phenylboronic acid (244.0 mg, 2.0 mmol),
(PhO)2POOH (25.0 mg, 0.10 mmol), 1e (185.9 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 25 C afforded 3ae (170.0 mg, 69%)
1
as an oil [eluent: petroleum ether (400 mL)]; H NMR (400 MHz,
CDCl3): δ = 7.46-7.40 (m, 4 H, Ar-H), 7.34-7.28 (m, 4 H, Ar-H),
www.cjc.wiley-vch.de
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.

Running title
Chin. J. Chem.
1602, 1503, 1464, 1362, 1111, 1086, 1042 cm-1; Anal. Calcd. for
C27H34O2 (%): C: 83.03, H: 8.77; Found: C: 82.60, H: 8.78
as an oil [eluent: petroleum ether/DCM/Et2O = 100/1/1 (200 mL)
1
to petroleum ether/DCM/Et2O = 50/1/1 (400 mL)]; H NMR (400
MHz, CDCl3): δ = 9.98 (s, 1 H, CHO), 7.82 (d, J = 8.4 Hz, 2 H, Ar-H),
7.60 (d, J = 8.4 Hz, 2 H, Ar-H), 7.36-7.28 (m, 4 H, Ar-H), 7.23-7.16
(m, 1 H, Ar-H), 6.60 (t, J = 3.0 Hz, 1 H, =CH), 2.62-2.52 (m, 2 H, CH2),
1.68-1.56 (m, 2 H, CH2), 1.48-1.40 (m, 2 H, CH2), 0.93 (t, J = 7.4 Hz,
3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 208.0, 191.7, 142.9,
135.0, 133.8, 129.9, 128.8, 127.4, 126.9, 126.6, 109.7, 98.5, 30.0,
29.7, 22.6, 13.9; MS (70 eV, EI) m/z (%): 276 (M+, 1.33), 133 (100);
IR (neat): v = 3030, 2957, 2930, 2869, 1930, 1697, 1600, 1454,
1383, 1169, 1013 cm-1; HRMS calcd for m/z C20H20O [M+]:
276.1509; found 276.1513.
(26) Preparation of 1,3-diphenyl-1-benzyl-2,3-heptadiene (3ha,
QAN-3-106)
5 mol%
5 mol%
Pd(PPh3)4
POOH
Ph
Bn
OH
Bn
Ph
•
(PhO)2
+
n
-Bu
PhB(OH)2
2a
dioxane, 25 o
N
2
n
-Bu
Ph
C,17 h,
1h
3ha
76%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), phenylboronic acid (244.1 mg, 2.0 mmol),
(PhO)2POOH (12.7 mg, 0.05 mmol), 1h (278.9 mg, 1.0 mmol), and
o
anhydrous dioxane (5 mL) at 25 C afforded 3ha (257.1 mg, 76%)
(29) Preparation of 1-phenyl-3-(4-methoxylcarbonylphenyl)-1,2-
heptadiene (3io, QAN-3-148)
1
as an oil [eluent: petroleum ether (600 mL)]; H NMR (400 MHz,
CDCl3): δ = 7.47-7.41 (m, 2 H, Ar-H), 7.35-7.24 (m, 2 H, Ar-H),
7.30-7.23 (m, 6 H, Ar-H), 7.22-7.10 (m, 5 H, Ar-H), 3.90 (s, 2 H,
CH2), 2.58-2.38 (m, 2 H, CH2), 1.51-1.41 (m, 2 H, CH3), 1.40-1.30
(m, 2 H, CH2), 0.87 (t, J = 7.2 Hz, 3 H, CH3); 13C NMR (100 MHz,
CDCl3): δ = 206.8, 139.4, 136.7, 136.5, 128.9, 128.4, 128.3, 128.2,
126.73, 126.69, 126.11, 126.06, 126.04, 109.4, 107.9, 37.2, 30.21,
30.18, 22.7, 14.0; MS (70 eV, EI) m/z (%): 339 (M++1, 4.70), 338
(M+, 17.22), 91 (100); IR (neat): v = 3039, 2935, 2859, 1941, 1591,
1468, 1444, 1375, 1173, 1018 cm-1; HRMS calcd for C26H26 [M+]:
338.2035; found 338.2038.
MeO2C
5 mol%
5 mol%
Pd(PPh3)4
POOH
OH
Ph
H
(PhO)2
+
•
n
-Bu
MeO2C
2o
B(OH)2
dioxane, 40 o
C,17 h,
N
2
n
-Bu
Ph
1i
3io
74%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.8 mg,
0.05 mmol), (4-(methoxycarbonyl)phenyl)boronic acid (360.1 mg,
2.0 mmol), (PhO)2POOH (12.5 mg, 0.05 mmol), 1i (188.3 mg, 1.0
o
mmol), and anhydrous dioxane (5 mL) at 40 C afforded 3io6h
(226.7 mg, 74%) as an oil [eluent: petroleum ether/ethyl acetate =
(27) Preparation of 1,3-diphenyl-1,2-heptadiene (3ia,
QAN-3-151)
60/1 (240 mL) to petroleum ether/ethyl acetate = 30/1 (300 mL)
1
to petroleum ether/ethyl acetate = 20/1 (200 mL)]; H NMR (400
5 mol%
Pd(PPh3)4
Ph
H
OH
MHz, CDCl3): δ = 7.97 (d, J = 8.4 Hz, 2 H, Ar-H), 7.50 (d, J = 8.4 Hz, 2
H, Ar-H), 7.35-7.27 (m, 4 H, Ar-H), 7.24-7.18 (m, 1 H, Ar-H), 6.58 (t,
J = 2.8 Hz, 1 H, =CH), 3.90 (s, 3 H, OCH3), 2.62-2.47 (m, 2 H, CH2),
1.64-1.53 (m, 2 H, CH2), 1.48-1.39 (m, 2 H, CH2), 0.92 (t, J = 7.2 Hz,
3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 207.5, 166.9, 141.2,
134.0, 129.8, 128.8, 128.5, 127.2, 126.8, 126.0, 109.6, 98.3, 52.0,
30.0. 29.7, 22.6, 13.9; MS (70 eV, EI) m/z (%): 306 (M+, 1.5), 163
(100); IR (neat): v = 3029, 2954, 2930, 2867, 1931, 1719, 1604,
1435, 1409, 1185, 1016 cm-1.
5 mol%
POOH
(PhO)2
dioxane, 40 o 36
•
n
+
-Bu
PhB(OH)2
2a
n
N
h,
Ph
-Bu
Ph
C,
2
1i
3ia
57%
,
equiv)
(2.0
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.9 mg,
0.05 mmol), phenylboronic acid (243.8 mg, 2.0 mmol),
(PhO)2POOH (12.5 mg, 0.05 mmol), 1i (188.1mg, 1.0 mmol), and
anhydrous dioxane (5 mL) at 40 oC afforded 3ia6h (142.1 mg, 57%)
1
as an oil [eluent: petroleum ether (200 mL)]; H NMR (400 MHz,
CDCl3): δ = 7.45 (d, J = 7.6 Hz, 2 H, Ar-H), 7.36-7.27 (m, 6 H, Ar-H),
7.23-7.16 (m, 2 H, Ar-H), 6.52 (t, J = 2.8 Hz, 1 H, =CH), 2.63-2.47 (m,
2 H, CH2), 1.66-1.54 (m, 2 H, CH2), 1.48-1.38 (m, 2 H, CH2), 0.92 (t,
J = 7.4 Hz, 3 H, CH3); 13C NMR (100 MHz, CDCl3): δ = 206.5, 136.3,
134.7, 128.7, 128.5, 127.0, 126.9, 126.7, 126.1, 110.0, 97.8, 30.1,
29.9, 22.6, 13.9`; MS (70 eV, EI) m/z (%): 248 (M+, 4.04), 105 (100);
IR (neat): v = 3028, 2928, 2870, 1932, 1724, 1597, 1493, 1447,
1378, 1264, 1204, 1071 cm-1.
2. Gram scale synthesis of 2-phenyl-4-(4-methoxylcarbonylphen-
yl)-2,3-octadiene (3ao, QAN-3-119)
MeO2C
5 mol%
5 mol%
Pd(PPh3)4
POOH
OH
Me
Ph
Me
Ph
(PhO)2
+
n
-Bu
•
MeO2C
B(OH)2
dioxane, 25 o 17 Ar
C,
h,
n
-Bu
1a
2o
(2.0
3ao
91%
,
equiv)
To an oven-dried 100 mL Schlenk tube were added
(4-(methoxycarbonyl)phenyl)boronic acid (1.7962 g, 10.0 mmol),
(PhO)2POOH (62.6 mg, 0.25 mmol), and Pd(PPh3)4 (288.9 mg, 0.25
mmol). After replacing air with argon for three times at rt by
vacuum, 1a (1.0065 g, 5.0 mmol), and anhydrous dioxane (25 mL)
were added sequentially. The reulting mixture was stirred for 17 h
in oil bath at 25 oC and filtered through a short column of silica gel
(3 cm) eluted with ethyl acetate (50 mL). After removal of the
(28) Preparation of 1-phenyl-3-(4-formylphenyl)-1,2-heptadiene
(3im, QAN-3-155)
OHC
5 mol%
Pd(PPh3)4
H
OH
Ph
5 mol%
POOH
(PhO)2
•
,
+
n
-Bu
OHC
2m
B(OH)2
equiv)
dioxane, 40 o
N
n
-Bu
Ph
C,17 h,
2
1i
3im
63%
(2.0
1
Following Typical Procedure, the reaction of Pd(PPh3)4 (57.7 mg,
0.05 mmol), (4-formylphenyl)boronic acid (299.7 mg, 2.0 mmol),
solvent under vacuum, the crude product was analyzed by H
NMR with CH2Br2 (70 μL) as the internal standard: 96% NMR yield
1
(PhO)2POOH (12.6 mg, 0.05 mmol), 1i (188.0 mg, 1.0 mmol), and
of 3ao was formed based on H NMR analysis. The residue was
o
anhydrous dioxane (5 mL) of 40 C afforded 3im (173.6 mg, 63%)
Chin. J. Chem. 2019, 37, XXX－XXX
© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
This article is protected by copyright. All rights reserved.

First author et al.
Report
purified by column chromatography on silica gel to afford 3ao
(1.4572 g, 91%) as
a
white solid eluent: petroleum
ether/DCM/Et2O 100/1/1 (~200 mL) to petroleum
=
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.2018xxxxx.
ether/DCM/Et2O = 50/1/1 (~200 mL) to petroleum ether/
DCM/Et2O = 40/1/1 (420 mL)]; 1H NMR (400 MHz, CDCl3): δ = 7.96
(d, J = 8.4 Hz, 2 H, Ar-H), 7.50-7.40 (m, 4 H, Ar-H), 7.32 (t, J = 7.6
Hz, 2 H, Ar-H), 7.25-7.18 (m, 1 H, Ar-H), 3.89 (s, 3 H, CH3),
2.58-2.51 (m, 2 H, CH2), 2.22 (s, 3 H, CH3), 1.63-1.51 (m, 2 H, CH2),
1.48-1.35 (m, 2 H, CH2), 0.91 (t, J = 7.2 Hz, 3 H, CH3); 13C NMR (100
MHz, CDCl3): δ = 206.6, 167.0, 142.0, 136.6, 129.7, 128.4, 128.1,
126.9, 125.8, 125.7, 107.5, 104.2, 51.9, 30.0, 29.8, 22.5, 16.7,
13.9.
Acknowledgement
Financial support from National Natural Science Foundation
of China (Grant No. 21690063 for S. Ma and Grant No. 21801041
for H. Qian), and Shanghai Sailing Program (18YF1402000 for H.
Qian) are greatly appreciated. We thank Mr. Junjie Fan in this
group for reproducing the results of 3ag, 3aj and 3ba presented in
this study.
3. Preparation of (R)- 2,4-diphenyl-2,3-octadiene ((R)-3aa,
QAN-3-125)
Me
Ph
5 mol%
Pd(PPh3)4
POOH
Ph
Me
Ph
5 mol%
(PhO)2
dioxane,25 o
+
•
References
[1] Modern Allene Chemistry, ed. Krause, N.; Hashmi, A. S. K. Wiley-VCH,
Weinheim, 2004.
[2] Hoffmann-Röder, A.; Krause, N. Synthesis and Properties of Allenic
Natural Products and Pharmaceuticals. Angew. Chem. Int. Ed. 2004,
43, 1196-1216; Angew. Chem. 2004, 116, 1216–1236.
OH
PhB(OH)2
2a
N
17 h
,
n
-Bu
n
C,
-Bu
2
R
R
)-3aa
equiv)
(
)-1a
ee
(
(2
ee
96%
55%, 2%
Following Typical Procedure I, The reaction of Pd(PPh3)4 (11.6
mg, 0.01 mmol), phenylboronic acid (49.0 mg, 0.4 mmol),
(PhO)2POOH (2.5 mg, 0.01 mmol), (R)-1a (40.3 mg, 0.2 mmol),
and anhydrous dioxane (1 mL) of 25 ℃ afforded (R)-3aa (28.7
mg, 55%, 2% ee) as an oil [eluent: petroleum ether (200 mL)];
HPLC conditions: OJ-H column, hexane/i-PrOH = 200/1, 0.7
mL/min, λ= 214 nm, tR (minor) = 6.2 min, tR (major) = 7.5 min.
[3] For reviews on the synthesis of allenes, see: (a) Chapters 1–8 in ref. 1.
(b) Neff, R. K.; Frantz, D. E. Recent Advances in the Catalytic
Syntheses of Allenes: A Critical. ACS Catal. 2014, 4, 519-528. (c) Yu, S.;
Ma, S. How Easy Are the Syntheses of Allenes? Chem. Commun. 2011,
47, 5384-5418. (d) Ogasawara, M. Catalytic Enantioselective
Synthesis of Axially Chiral Allenes. Tetrahedron: Asymmetry. 2009, 20,
259-271. (e) Brummond, K. M.; DeForrest, J. E. Synthesizing Allenes
Today (1982–2006). Synthesis. 2007, 795-818. (f) Hammond, G. B.
Functionalized Fluorinated Allenes. ACS Symp. Ser. 2005, 911,
204-215. (g) Krause, N.; Hoffmann-Röder, A. Synthesis of Allenes
with Organometallic Reagents. Tetrahedron. 2004, 60, 11671-11694.
(h) Huang, X.; Ma, S. Allenation of Terminal Alkynes with Aldehydes
and Ketones. Acc. Chem. Res. 2019, 52, 1301−1312.
[4] For selected reviews on C-C bond formation via cross-coupling
reactions, see: (a) Stille, J. K. The Palladium-Catalyzed Cross-Coupling
Reactions of Organotin Reagents with Organic Electrophiles. Angew.
Chem. Int. Ed. 1986, 25, 508–524; Angew. Chem. 1986, 98, 504-519.
(b) Littke, A. F.; Fu, G. C. Palladium-Catalyzed Coupling Reactions of
Aryl Chlorides. Angew. Chem. Int. Ed. 2002, 41, 4176-4211; Angew.
Chem. 2002, 114, 4350-4386. (c) Yin, L.; Liebscher, J. Carbon-Carbon
Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts.
Chem. Rev. 2007, 107, 133-173. (d) Martin R.; Buchwald, S. L.
Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions
Employing Dialkylbiaryl Phosphine Ligands. Acc. Chem. Res. 2008, 41.
1461-1473. (e) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu, J.-Q.
Palladium(II)-Catalyzed C-H Activation / C-C Cross-Coupling Reactions:
Versatility and Practicality. Angew. Chem. Int. Ed. 2009, 48,
5094–5115; Angew. Chem. 2009, 121, 5196-5217. (f) Yeung, C. S.;
Dong, V. M. Catalytic Dehydrogenative Cross-Coupling: Forming
Carbon-Carbon Bonds by Oxidizing Two Carbon-Hydrogen Bonds.
Chem. Rev. 2011, 111, 1215–1292. (g) Milligan J. A.; Phelan, J. P.;
Badir, S. O.; Molander, G. A. Alkyl Carbon–Carbon Bond Formation by
Nickel/Photoredox Cross-Coupling. Angew. Chem. Int. Ed. 2019, 58,
6152–6163; Angew. Chem. 2019, 131, 6212-6224.
4. Biological Activity Study
(1) GLP-1 measurement
Mouse intestinal cell line STC-1 was kindly provided by Dr. Jia Li
(Shanghai Institute of Materia Medica, Chinese Academy of
Sciences) and cultured in DMEM medium, containing 15% FBS,
100 U/mL penicillin and 100 μg/mL streptomycin at 37 °C in a
humidified atmosphere of 5% CO2. The cells were seeded in
96-well plates at a density of 40000 cells/well. After cultured
overnight, the cells were treated 0.1% DPP-IV inhibitor PK44 in
KRB buffer containing 0.2% fatty acid-free BSA for 2 hr. Cells were
then treated with vehicle control (DMSO), positive control (1.0 μM
PMA) or tested compounds for another 2 hr. The supernatants of
the culture medium were collected and the concentration of
GLP-1 in the supernatants was measured by using active GLP-1 kit
according to the manufacturer’s instructions (Cisbio, Bedford,
MA).
(2) Glucose consumption
Rat L6 myotube cells were kindly provided by Dr. Jia Li (Shanghai
Institute of Materia Medica, Chinese Academy of Sciences) and
cultured in high-glucose (4.5 g/L) DMEM medium supplemented
with 10% FBS, 100 U/mL penicillin and 100 μg/mL streptomycin.
For differentiation, the cells were maintained in high-glucose (4.5
g/L) DMEM containing 2% FBS for 6 days and the medium was
changed every two days. After differentiation, the myotube cells
were incubated in serum-free, low-glucose (1.0 g/L) DMEM
medium for 6 hr and treated with vehicle control (DMSO), positive
control (10 mM metformin) or tested compounds for 24 hr. The
concentration of glucose in medium was measured with glucose
assay reagent (Mingdian, Shanghai, China) according to the
glucose oxidase method.
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Running title
Chin. J. Chem.
[5] For selected reviews on Suzuki coupling reactions, see: (a) Miyaura,
N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of
Organoboron Compounds. Chem. Rev. 1995, 95, 2457-2483. (b)
Polshettiwar, V.; Decottignies, A.; Len, C.; Fihri, A. Suzuki–Miyaura
Cross-Coupling Reactions in Aqueous Media: Green and Sustainable
Syntheses of Biaryls. ChemSusChem. 2010, 3, 502-522. (c) Fihri, A.;
Bouhrara, M.; Nekoueishahraki, B.; Basset, J.-M.; Polshettiwar, V.
Nanocatalysts for Suzuki Cross-Coupling Reactions. Chem. Soc. Rev.
2011, 40, 5181-5203. (d) Han, F.-S. Transition-Metal-Catalyzed
Suzuki–Miyaura Cross-Coupling Reactions: a Remarkable Advance
from Palladium to Nickel Catalyst. Chem. Soc. Rev. 2013, 42,
5270-5298. (e) Hooshmand, S. E.; Heidari, B.; Sedghi, R.; Varma, R. S.
Recent Advances in the Suzuki–Miyaura Cross-Coupling Reaction
Using Efficient Catalysts in Eco-Friendly Media. Green Chem. 2019, 21,
381-405.
[6] (a) Moriya, T.; Miyaura, N.; Suzuki, A. Synthesis of Allenes by
Palladium-Catalyzed Cross-Coupling Reaction of Organoboron
Compounds with Propargylic Carbonates: Transmetallation of
Organoboron Compounds with (Alkoxo)palladium Complexes Under
Neutral Conditions. Synlett. 1994, 149-151. (b) Ishikura, M.; Agata, I.
The Palladium Catalysed Cross-Coupling Reaction of Triethyl
(1-Methylindol-2-yl)borate with Propargyl Carbonate. Heterocycles.
1996, 43, 1591-1595. (c) Ishikura, M.; Matsuzaki, Y.; Agata, I.; Katagiri,
N. Palladium Catalyzed Cross-Coupling Reaction of Indolylborates.
Tetrahedron. 1998, 54, 13929-13942. (d) Yoshida, M.; Ueda, H.; Ihara,
M. Palladium-Catalyzed Coupling Reaction of Propargylic Oxiranes
with Arylboronic Acids in Aqueous Media. Tetrahedron Lett. 2005, 46,
6705-6708. (e) Molander, G. A.; Sommers, E. M.; Baker, S. R.
Palladium(0)-Catalyzed Synthesis of Chiral Ene-allenes Using Alkenyl
Trifluoroborates. J. Org. Chem. 2006, 71, 1563-1568. (f) Yoshida, M.;
Okada, T.; Shishido, K. Enantiospecific Synthesis of 1,3-Disubstituted
Allenes by Palladium-Catalyzed Coupling of Propargylic Compounds
Propargylic Alcohols with Arylboronic Acids. Tetrahedron Lett. 2004,
45, 5573-5575. (k) Green, N. J.; Willis, A. C.; Sherburn, M. S. Direct
Cross-Couplings of Propargylic Diol. Angew. Chem. Int. Ed. 2016, 55,
9244-9248; Angew. Chem. 2016, 128, 9390-9394.
[7] (a) Liu, N.; Zhi, Y.; Yao, J.; Xing, J.; Lu, T.; Dou, X.
Rhodium(I)-Catalyzed Arylation/Dehydroxylation of tert-Propargylic
Alcohols Leading to Tetrasubstituted Allenes. Adv. Synth. Catal. 2018,
360, 642-646. For Rh-catalyzed arylation of propargylic alcohols, see:
(b) Wu, S.; Fu, C.; Ma, S. Asymmetric SN2’-type C–H Functionalization
of Arenes with Propargylic Alcohols. Org. Chem. Front. 2017, 4,
2002-2007.
[8] (a) Zhang, W.; Huang, C.; Yuan, Y.; Ma, S. Catalytic Transient Leaving
Group for Atom-Economic Synthesis of Allenes from 2-alkynols.
Chem. Commun. 2017, 53, 12430-12433. (b) Zheng, W.-F.; Zhang, W.;
Huang, J.; Qian, H.; Ma, S. 2,3-Allenoic Acids via Palladium-Catalyzed
Carboxylation of Propargylic Alcohols. Org. Chem. Front. 2018, 5,
1900-1904. (c) Zheng, W.-F.; Zhang, W.; Huang, C.; Wu P.; Qian, H.;
Wang, L.; Guo, Y.; Ma, S. Tetrasubstituted Allenes via the
Palladium-Catalysed Kinetic Resolution of Propargylic Alcohols Using
a Supporting Ligand. Nat. Catal. 2019, 2, 997-1005.
[9] Li, P.; Lü, B.; Fu, C.; Ma, S. Zheda-Phos for General α-Monoarylation
of Acetone with Aryl Chlorides. Adv. Synth. Catal. 2013, 355,
1255-1259.
[10] Zhang, W.; Ma, S. Palladium/H+ Cocatalyzed Kinetic Resolution of
Tertiary Propargylic Alcohols. Chem. Commun. 2018, 54, 6064-6067.
[11] (a) Ogoshi, S.; Nishida, T.; Shinagawa, T.; Kurosawa, H. Key Process in
Palladium-Catalyzed Asymmetric Transformation of Propargyl
Electrophiles. Racemization of Optically Active η1-Allenylpalladium(II).
J. Am. Chem. Soc. 2001, 123, 7164-7165. (b) Wang, Y.; Zhang, W.; Ma,
S. Identifying a Non-chiral Ligand for the Efficient Chirality Transfer in
Carbonylation of Propargylic Mesylates. Org. Chem. Front. 2014, 1,
807-811.
with Arylboronic Acids. Tetrahedron, 2007, 63, 6996-7002. (g) Luo, H.; [12] Pennell, M. N.; Foster, R. W.; Turner, P. G.; Hailes, H. C.; Tame, C. J.;
Yu, Y.; Ma, S. Suzuki Coupling for Preparation of Allenes-Ligand
Effects and Chirality Transfer. Org. Chem. Front. 2016, 3, 1705-1710.
(h) Xiao, J.; Luo, H.; Huang, S.; Qian, H.; Ma, S. Tri(o-tolyl)phosphine
for Highly Efficient Suzuki Coupling of Propargylic Carbonates with
Boronic Acids. Chem. Commun. 2018, 54, 10451-10454. (i) Yao, Y.;
Zhu, G.; Qin, C.; Qian, H.; Ma, S. Efficient Synthesis of
Tetrasubstituted 2,3-allenoates and Preliminary Studies on
Bioactivities. Org. Chem. Front. 2019, 6, 304-308. (j) Yoshida, M.;
Gotou, T.; Ihara, M. Palladium-Catalyzed Direct Coupling Reaction of
Sheppard, T. D. Chem. Commun. 2014, 50, 1302-1304.
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Manuscript received: XXXX, 2019
Manuscript revised: XXXX, 2019
Manuscript accepted: XXXX, 2019
Accepted manuscript online: XXXX, 2019
Version of record online: XXXX, 2019
Chin. J. Chem. 2019, 37, XXX－XXX
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Palladium-Catalyzed Suzuki Coupling of
Propargylic Alcohols with Boronic Acids under
Ambient Conditions
R2
R3
OH
R1
R4
R3
R2
Pd/H+
,
rt
•
+
R4
B(OH)2
R1
♠
♠
♠
Mild reaction conditions
Broad substrate
scope
Excellent
regioselectivity
Pd/H+ co-catalyzed cross-coupling of propargylic alcohols with boronic acids has been established
for the synthesis of tri- and tetra-substituted allenes with various useful functional groups.
Anni Qin, Hui Qian, Qin Chen,* and Shengming
Ma*
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© 2019 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2019, 37, XXX－XXX
This article is protected by copyright. All rights reserved.