Diboron-Assisted Copper-Catalyzed Z-Selective Semihydrogenation of Alkynes Using Ethanol as a Hydrogen Donor

Article abstract of DOI:10.1021/acs.joc.9b00321

We herein describe a B₂Pin₂-assisted copper-catalyzed semihydrogenation of alkynes. A variety of alkenes were obtained in good to excellent yields with Z-selectivity under mild reaction conditions. Mechanistic studies indicated that a transfer hydrogenation process was involved and ethanol acted as both a solvent and a hydrogen donor in this reaction. The present protocol enabled convenient synthesis of deuterium-substituted Z-alkenes such as Z-Combretastain A4-d₂ in a high deuteration ratio by using readily available ethanol-d₁ as the deuterium source.

Full text of DOI:10.1021/acs.joc.9b00321

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Article
Diboron-Assisted Copper-Catalyzed Z-Selective
Semihydrogenation of Alkynes Using Ethanol as a Hydrogen Donor
Hanyang Bao, Bingwei Zhou, Hongwei Jin, and Yunkui Liu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00321 • Publication Date (Web): 25 Feb 2019
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Diboron-Assisted Copper-Catalyzed Z-Selective Semihydrogenation of Alkynes
Using Ethanol as a Hydrogen Donor
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Hanyang Bao, Bingwei Zhou, Hongwei Jin,* and Yunkui Liu*
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, College of Chemical
Engineering, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China
E-mail: ykuiliu@zjut.edu.cn; jhwei828@zjut.edu.cn
TOC graphic
H
H
R2
R1
R2
Yield: up to 95%;
Z/E: up to 99 : 1
L-Cu-H
EtOH
EtOH
R1
B2Pin2
L-Cu-BPin
generated in situ
L-Cu-OR
D
D
EtOD
MeO
MeO
MeO
EtOD
L-Cu-D
MeO
MeO
OH
OMe
hydrolysis
OMe
OMe
(Z)-Combretastatin A4-d2
64% (94% D, Z/E = 20 : 1)
OAc
ABSTRACT
We herein describe a B2Pin2-assisted copper-catalyzed semihydrogenation of alkynes. A variety of
alkenes were obtained in good to excellent yields with Z-selectivity under mild reaction conditions.
Mechanistic studies indicated that a transfer hydrogenation process was involved and ethanol acted as
both a solvent and a hydrogen donor in this reaction. The present protocol enabled convenient synthesis
of deuterium-substituted Z-alkenes such as Z-Combretastain A4-d2 in high deuteration ratio by using
readily available ethanol-d1 as the deuterium source.
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Introduction
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Z-Alkene moieties are among the most important structural units in organic molecules due to
their practical utilities in some advanced materials as well as their potential bioactivities in various
drugs and natural products.1 As such, a wide range of synthetically useful methods have been
established, among which the transition metal-catalyzed (especially palladium) semihydrogenation
of alkynes with hydrogen dominates this field for decades.1d,2 However, the inevitable use of
flammable hydrogen gas in those reactions2d,3 prompts chemists to explore more safe and facile
hydrogenation processes.4-10 In this regard, catalytic transfer hydrogenation (TH) emerges as an
alternative way to access Z-alkenes, which necessitates the development of various transfer
hydrogenating reagents such as ammonia borane,4 silane,5 formic acid-triethylamine,2f,6
isopropanol,7 ethanol,8 and even water.9 Among them, ethanol and water have received
considerable attention due to their intrinsic advantages of easy availability and non-toxicity. Thus,
the exploration of TH reactions with water or ethanol as the economical hydrogen sources is still
highly desirable.
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Typically, diboron reagents served as efficient boron precursors in traditional cross-coupling
reactions, C-H activations, and functionalizations of alkenes, etc.11 In addition, diboron reagents
could also serve as reductants for generating hydride from water as exemplified in the reduction of
various unsaturated C-C bonds.12-14 In 2016, Stokes group first described a palladium-catalyzed
transfer hydrogenation of alkenes and alkynes with water under the assistance of B2(OH)4 (Scheme
1a).12 Soon later, Song group independently reported a palladium-catalyzed transfer hydrogenation
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of N-heteroaromatics using a combined H2O/B2Pin2 system as the hydrogen source (Scheme 1b).13
Similarly, Prabhu group conducted a palladium-catalyzed reduction of alkenes or alkynes by using
the combined H2O/B2Pin2 system to produce hydrogen (Scheme 1c).14 Note that these
diboron-assisted transfer hydrogenation reactions inevitably produce alkanes, while the selective
reduction of alkynes to (Z)-alkenes remains challenging.12-14 As part of our continued efforts to
develop copper-catalyzed efficient transformations,15 we herein disclose an efficient
copper-catalyzed semihydrogenation of alkynes5b-e,16 to access Z-alkenes with excellent
stereoselectivity by using a combined ethanol/B2pin2 system as the hydrogen source.
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Scheme 1. Diboron-assisted transfer hydrogenation reactions
a) Stokes' work:
Pd/C, B2(OH)2
H2O
R2
R2
or R1
R2
R1
R1
solvent, rt.
b) Song's work:
Pd(OAc)2
B2Pin2
N
N
Ar
Ar
N
N
H2O, w/o base, rt.
c) Prabhu's work:
[Pd(OAc)2]3
PCy3
H2O
[Pd(OAc)2]3
R2
H2
R1
+
R2
B2Pin2
R1
d) this work:
CuCl/Ligand
H
H
B2Pin2/t-BuOK
R1
R2
EtOH, r.t.
R1
R2
CuCl/Ligand
D
D
B2Pin2/t-BuOK
EtOD, r.t.
R1
R2
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Results and Discussion
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Initially, diphenylacetylene 1a was selected as the model substrate to investigate the optimal
reaction conditions (Table 1). Screening of various ligands revealed that the NHC L5 gave a high
conversion of alkyne in the presence of CuCl (10 mol %), B2Pin2 (1.2 equiv) and t-BuOK (1.0 equiv) in
THF, but a considerable amount of hydroboronated product 3a was detected (entries 1-5, Table 1).
Unfortunately, no hydrogenation occurred when the reaction was carried out in water (entry 6).12-14 We
then chose ethanol as a hydrogen donor as well as a solvent. Gratifyingly, in this case 2a was obtained
in 94% yield with an excellent Z-selectivity (Z/E > 99/1, entry 7, Table 1). Several other alcohols were
also surveyed and ethanol was proved to be the most suitable one (entries 8-10 vs 7, Table 1). The use
of other NHC ligands in ethanol or in the absence of a ligand only resulted in lower yields of 2a
together with poor Z/E stereoselectivities (entries 11-14 vs 7, Table 1). Several other diboron reagents
were also investigated for the reaction, it was found that B2(OH)4 and B2(nep)2 (bis(neopentyl
glycolato)diboron) could also give good conversion as well as high stereoselectivity, while B2(cat)2
(biscatecholato)diboron) gave poor results (entries 15-17 vs 7, Table 1). Controlled experiments
indicated that B2Pin2 and CuCl were indispensable for this semihydrogenation reaction (entries 18, 19,
Table 1). Reducing the amount of copper salt, ligand, t-BuOK, and B2Pin2, respectively, would lower
the yield of 2a (entries 20-23 vs 7, Table 1). When t-BuONa was used as a base instead of t-BuOK, a
comparable yield of 2a was obtained in 94%, but in slightly lower conversion (entry 24, Table 1). The
reaction failed to give 2a when HBPin was used instead of B2Pin2 (entry 25, Table 1).
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Table 1. Optimization of reaction conditionsa
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CuCl, ligand
B2pin2, t-BuOK
H
H
H
Bpin
Ph
+
Ph
Ph
Ph
+
Ph
solvent, rt, 5 h
Ph
Ph
Ph
4a
1a
2a
3a
entry ligand solvent H2O (equiv) diboron (equiv) conversion (%) yield of 2a/3a/4a (%)b Z/E for 2ac
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1
2
L1
L2
L3
L4
L5
L5
L5
L5
L5
L5
L6
L7
L8
--
THF
THF
7.5
7.5
7.5
7.5
7.5
--
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2(OH)4
94
84
95
92
90
23
99
89
90
89
73
92
74
43
99
25/67/2
4/80/0
>99/1
--
3
THF
40/54/1
45/46/1
28/61/1
0/23/0
>99/1
>99/1
>99/1
--
4
THF
5
THF
6
H2O
7
EtOH
MeOH
i-PrOH
t-BuOH
EtOH
EtOH
EtOH
EtOH
EtOH
--
94d/4/0
32/13/0
20/68/0
0/86/0
>99/1
>99/1
>99/1
--
8
--
9
--
10
11
12
13
14
15
--
--
32/37/0
70/22/0
36/33/0
15/15/0
90/0/1
46/1
56/1
15/1
11/2
>99/1
--
--
--
L5
--
(1.2)
16
17
L5
L5
EtOH
EtOH
--
--
B2(cat)2 (1.2)
B2(nep)2
4
3/0/0
--
97
92/0/0
>99/1
(1.2)
18
19e
20f
21g
22h
23
L5
L5
L5
L5
L5
L5
L5
L5
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
--
--
--
--
--
--
--
--
--
0
0/0/0
6/4/0
--
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.2)
B2Pin2 (1.0)
B2Pin2 (1.2)
--
10
81
99
0
1/1
78/3/0
89/9/0
0/0/0
>99/1
>99/1
--
91
95
0
86/4/0
94/1/0
0/0/0
>99/1
>99/1
--
24i
25j
aReaction conditions: 1a (0.2 mmol), CuCl (10 mol %), ligand (15 mol %), B2Pin2 (0.24 mmol),
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t-BuOK (0.2 mmol), solvent (3.0 mL), 25 ºC for 5 h under N2 atmosphere unless otherwise noted.
5
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7
c
bYield was determined by GC analysis using diphenyl as an internal standard. Z/E ratio was
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d
e
f
determined by GC analysis. Isolated yield: 92%. Without CuCl. CuCl (5 mol%) and L5 (7.5
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g
h
i
mol%). t-BuOK (50 mol%). t-BuOK (15 mol%). t-BuONa (1.0 equiv.) was used instead of
t-BuOK. jHBPin (1.2 equiv.) was used instead of B2Pin2.
PPh2
P(Cy)2
Ph2P
O
PPh2
PPh2
L2
L1
dppe (
)
L4
)
Xantphos (
)
CyJohnPhos (
N
N
N
N
Ar
Ar
Ar
Ar
Cl
Cl
IMes•HCl ( ): Ar = 2,4,6-trimethylphenyl
L6
L7
SIMes•HCl ( ): Ar = 2,4,6-trimethylphenyl
L8
SIPr•HCl ( ): Ar = 2,6-diisopropylphenyl
L5
IPr•HCl ( ): Ar = 2,6-diisopropylphenyl
With the optimized reaction conditions in hand, the substrate scope of alkynes 1 was first
examined as shown in Table 2. Both electron-donating and electron-withdrawing substituents on the
benzene ring of alkynes 1 were compatible with the reaction conditions and the desired Z-alkenes 2
were obtained in good yields (except 1h) with excellent stereoselectivities (2a-g, 2k-o). Alkynes
bearing a heteroarene such as 4-pyridinyl or 2-thienyl ring were also tolerable under the current
reaction conditions to give Z-alkenes in good yields with high stereoselectivity (2p, 2q). Notably, this
transfer semihydrogenation process could be applied to ynamines leading to the formation of
Z-enamines which could be used as versatile building blocks in organic synthesis (2r-t). Aryl alkyl
acetylenes such as hex-1-yn-1-ylbenzene 1u and 2-(3,3-dimethylbut-1-yn-1-yl)naphthalene 1v were
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also workable for the semihydrogenation to give highly selective Z-alkene albeit in moderate yields (2u,
2v). An aliphatic internal alkyne 1w could also be semihydrogenated to give the corresponding
Z-alkene 2w in excellent stereoselectivity (2w). As expected, the semihydrogenation of terminal
alkynes also proceeded smoothly to give the corresponding alkenes in moderate to excellent yields
(2x-2z, 2zb) except in the case of 1za as a substrate.
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Table 2. Substrate scope of alkynes.a,b
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CuCl (10 mol %)

IMes HCl (15 mol %)
B2Pin2 (1.2 equiv)
t-BuOK (1.0 equiv)
H
H
R1
R2
EtOH, rt, 5 h
R1
R2
1
2
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H
H
H
2a
2b
2c
2d
2e
: R = H, 92% (>99:1);
: R = Me, 82% (>99:1);
: R = OMe, 90% (>99:1);
: R = NH2, 62% (16:1);
: R = F, 91% (>99:1);
2i
2j
:R= Me, 92% (>99:1);
: R = Cl, 89% (40:1);
H
H
R
H
2k
: R= Me, 85% (>99:1);
R
2f
: R = Cl, 82% (>99:1);
2l
: R = Br, 93% (>99:1);
c
R
2g
2h
: R = CF3, 86% (21:1)
: R = NO2, 0%
c
2m
: R = CN, 95% (>99:1);
c
2n
: R = CO2Et, 88% (>99:1);
H
H
H
H
H
H
H
H
N R
S
N
2r
:R= Ms, 92% (33:1);
c
2p
: 79% ( >99:1)
2o
2q
: 93% ( >99:1)
: 85% ( 11:1)
2s
: R = Ts, 69% (>99:1);
H
H
H
H
H
H
H
H
H
H
N Ms
H
n-pentyl
n-pentyl
Ph
Ph
c
d
g
e
h
2x
: 95%
2t
2v
: 41% (>99:1)
: 62% (>99:1)
2u
2w
: 49% (>99:1)
: 85% (>99:1)
78%f (>99:1)
70%i (>99:1)
H
H
H
H
H
MeO
H
H
H
( )8
Ph
O
H
H
H
H
MeO
OHC
OMe
c
e
c
2y
2zb
: 53%
: 79%
76%f
2za
: 0%
2z
: 80%
88%f
aReaction conditions: 1 (0.2 mmol), CuCl (10 mol %), IMes·HCl (15 mol %), B2Pin2 (0.24 mmol),
t-BuOK (0.2 mmol), ethanol (3.0 mL), 25 ºC for 5 h under N2 atmosphere unless otherwise noted. bThe
c.
d
Z/E ratios were determined by GC-MS. The reaction time was prolonged to 12 h. 39% of 1s was
recovered. eThe reaction temperature was increased to 80 ºC and the reaction time was prolonged to 12
h. fB2(OH)4 (0.24 mmol) was used instead of B2Pin2 at 25 ºC and the reaction time was prolonged to 12
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g
h
h. 26% of 1t was recovered. Reaction condition: 1w (0.2 mmol), CuCl (15 mol%), IMes·HCl (22.5
mol %), B2Pin2 (0.3 mol), t-BuOK (0.2 mmol), ethanol (3.0 mL), 80 ºC for 36 h under N2 atmosphere.
iReaction condition: 1w (0.2 mmol), CuCl (15 mol %), IMes·HCl (22.5 mol%), B2OH4 (0.3 mol),
t-BuOK (0.2 mmol), ethanol (3.0 mL), 25 ºC for 12 h under N2 atmosphere.
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In addition, a gram-scale (8.0 mmol of 1a used) synthesis of 2a was also tried, and the target
Z-alkene 2a was obtained in 85% yield (eq. 1).
CuCl (10 mol %)

IMes HCl (15 mol %)
B2Pin2 (1.2 equiv)
t-BuOK (1.0 equiv)
H
H
(1)
Ph
1a
Ph
EtOH, rt, 8 h
Ph
Ph
: 8.0 mmol
2a
: 1.2 g, 85%
To gain insight into the mechanism of the reaction, a deuterium-labeled experiments was first carried
out (Scheme 2a). When EtOD (99% D-enrichment of the hydroxyl proton) was used as the solvent, the
deuterium was incorporated into both the 1,2-olefinic positions of 2m-d2 (both 94% D-enrichment)
(Scheme 2a). This result suggested that ethanol acted as a hydrogen donor in this reaction. To probe the
possible intermediate,17 the byproduct 3a was subjected to the standard conditions without the extra
addition of B2Pin2 (Scheme 2b). As a result, a low yield of 2a (19%) was obtained which indicated that
3a might not be the most likely intermediate in the catalytic cycle.
Scheme 2. Mechanistic experiments
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CuCl (10 mol%)
94% D
94% D

IMes HCl (15 mol%)
D
D
B2Pin2 (1.2 equiv.)
t-BuOK (1 equiv.)
CN
NC
a)
EtOD (99% D), r.t., 12 h
9
2m-d :
93 %,
1m
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2
deuterium incorporation was measured by 1H NMR
CuCl (10 mol%)
IMes HCl (15 mol%)
t-BuOK (1 equiv.)
BPin

b)
EtOH, r.t., 5 h
3a
2a:
19 %
On the basis of the above experiments and previous literature,12-14,18 a plausible mechanism was
described in Scheme 3. The alkoxocopper species Cu-A was first formed and it further reacted with
B2Pin2 to produce the Cu-boron complex Cu-C. Ethanol could then coordinate to boron atom, followed
by a hydrogen transfer to generate copper hydride species Cu-E. The syn-addition of Cu-E to the
alkyne 1a afforded the vinylcuprate intermediate Cu-F. The protonation of Cu-F by ethanol released
the Z-alkene and regenerated the active catalyst.
Scheme 3. Proposed mechanism
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CuCl + IMes•HCl
KCl
t-BuOK
Ph
Ph
6
L Cu OBut
7
8
9
2a
Cu-A
Cu-B
or
L Cu OEt
B2Pin2
EtOH
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PinB OBut
or
LCu
Ph
H
Ph
PinB OEt
Cu-F
LCu
Ph
BPin
Ph
L Cu BPin
1a
Cu-C
L Cu H
Cu-G
Ph
Ph
Cu-E
ethanol
protodecupration
1a
L Cu BPin
H OEt
EtOH
3a
PinB OEt
Cu-D
Recent researches indicated that the incorporation of deuterium into drugs or nature products would
significantly improve their pharmacological and biological activities.19 From the above mechanism
illustration, we can expect that the present protocol enables an expedient way to access olefinic
deuterium-incorporated Z-alkenes by using commercially available ethanol-d1 as the deuterium source.
To fully demonstrate the synthetic potential of the present protocol, the synthesis of deuterated
Z-Combretastation A-4-d2 5b from alkyne 1zc was carried out under our catalytic system (Scheme
4).4b,5d Gratifyingly, a total 64% yield of 5b with a 94% D-enrichment at both the 1,2-olefinic positions
was obtained through a two-step process. Furthermore, the resulting intermediate 5a from 1zc could be
easily converted to the corresponding phenanthrenes-d2 6a and 6b almost without a deuterium loss.20
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Note that these deuterium-labeled compounds might exhibit unique bioactivities compared to the
unlabeled ones.1c,21,22
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8
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Scheme 4. Synthesis of Z-Combretastation A-4-d2 and Phenanthrenes-d2
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94 % D
94 % D
94 % D
94 % D
D
D
D
D
MeO
MeO
MeO
OAc
OMe
a
b
MeO
MeO
OH
OMe
MeO
MeO
5a:
OAc
OMe
OMe
OMe
e
f
5b:
1zc
Z-Combretastation A-4-d2
92%e, Z/E ratio = 20: 1f
70% , Z/E ratio = 49:1
c
92 % D
92 % D
92 % D
92 % D
D
D
D
D
d
MeO
MeO
OAc
OMe
MeO
MeO
OH
OMe
OMe
OMe
e
e
6b:
89%
6a:
52%
Reaction condition: (a) 1zc (0.2 mmol), CuCl (10 mol %), IMes·HCl (15 mol %), B2Pin2 (0.24 mmol),
t-BuOK (0.2 mmol), EtOD (3.0 mL, 99% D-enrichment), 25 ºC for 10 h under N2 atmosphere. (b) 5a
(0.2 mmol), K2CO3 (0.6 mmol), MeOH (6 mL), 25 ºC for 5 h. (c) 5a (0.2 mmol), I2 (0.2 mmol),
cyclohexane (100 mL), irradiated at a distance of 5 cm from 500 W high pressure mercury lamp for 5 h
at room temperature. (d) 6a (0.2 mmol), K2CO3 (0.6 mmol), MeOH (6 mL), 25 ºC for 5 h. (e) Isolated
yields. (f) Z/E ratios were determined by GC analysis and deuterium incorporations were measured by
1H NMR analysis.
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Conclusion
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In summary, we have developed an efficient copper-catalyzed transfer semihydrogenation of
various alkynes to stereoselectively afford Z-alkenes in high yields with a combined ethanol/B2Pin2
system as the hydrogen source. The present protocol has advantages of mild reaction conditions,
inexpensive catalyst, excellent stereoselectivity, and good functional group tolerance. Moreover, the
present strategy enabled a convenient way to access deuterium-labeled molecules such as
Z-Combretastation A-4-d2 and Phenanthrenes-d2 in highly selective manner using readily available
ethanol-d1 as the deuterium source which demonstrates the practically useful application of our protocol
in organic synthesis.
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Experimental Section
Unless otherwise stated, all reagents were purchased from commercial suppliers and used as received.
1
13
Melting points are uncorrected. H and C NMR spectra were recorded on a spectrometer at 25 C in
CDCl3 at 500 MHz, 125 MHz, respectively, with TMS as internal standard. Chemical shifts () are
expressed in ppm and coupling constants J are given in Hz. GC-MS experiments were performed with
EI source; high resolution mass spectra (HRMS) were obtained on a TOF-MS instrument with EI or
ESI source.
Preparation of the starting material 1 and 3a. Alkynes (1a-1q, 1v) were synthesized via a
Sonogashira cross-coupling reaction according to the literature procedure.4c The ynamines (1r-1t) were
synthesized according to the known literature procedure.23 Alkynes (1y-1za) were synthesized via a
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Sonogashira cross-coupling reaction of corresponding aryl iodide with trimethylsilylacetylene
according to the literature procedure, subsequently hydrolysis of trimethysilylethynyl-substrates.24 The
3a was synthesized from 1a under the standard reaction conditions by using t-BuOH as the solvent
instead of EtOH.
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Preparation of the starting material 1zc.4b,5d 5-ethynyl-1,2,3-trimethoxybenzene (1.77 g, 3 mmol),
5-iodo-2-methoxyphenol (0.75 g, 3 mmol), Pd(PPh3)4 (158 mg, 0.14 mmol) and CuI (23 mg, 0.12
mmol) were added to a 50 mL Schlenk flash with a stir bar under an atmosphere of nitrogen. Then
pyrrolidine (20 mL) were added sequentially. The reaction mixture was stirred at 80 ºC overnight. Then
a saturated NH4Cl solution (20 mL) was added into it. The mixture was extracted with Et2O (20 mL ×
3), the combined organic fractions were washed with brine and dried with MgSO4. After filtration, the
solvent was removed under vacuum and the residue was purified by column chromatography on silica
gel (100-200 mesh), eluting with the mixture of ethyl acetate (EA)/petroleum ether (PE) = 3/1 to give
1
2-methoxy-5-((3,4,5-trimethoxyphenyl)ethynyl)phenol (yellow solid, 740.0 mg, 77%). H NMR
(CDCl3, 500 MHz): δ 7.10 (d, J = 2.0 Hz, 1H), 7.07 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz, 1H), 6.83 (d, J = 8.5
Hz, 1H), 6.79 (s, 2H), 5.70 (s, 1H), 3.92 (s, 3H), 3.88 (s, 6H), 3.87 (s, 3H).5d Then acetyl chloride (197
mg,
2.61
mmol)
was
added
slowly
to
a
solution
of
2-methoxy-5-((3,4,5-trimethoxyphenyl)ethynyl)phenol (740 mg, 2.4 mmol), Et3N (0.75 mL, 5.2 mmoL)
and dry CH2Cl2 (3 mL) at 0 ºC under an atmosphere of nitrogen, the mixture was allowed to warm to
room temperature and stirred for 6 h. Upon completion, quenching the reaction with water (5 mL). The
mixture was extracted with CH2Cl2, the organic fractions were combined. Afterwards the solvent was
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removed under vacuum and the residue was purified by column chromatography on silica gel (100-200
mesh), eluting with the mixture of ethyl acetate (EA)/ petroleum ether (PE) = 3/1 to give pure 1zc
(white solid, 752.0 mg, 89%). 1H NMR (CDCl3, 500 MHz): δ 7.34 (dd, J1 = 8.5 Hz, J2 = 2.5 Hz, 1H),
7.23 (d, J = 2.5 Hz, 1H), 6.94 (d, J = 8.5 Hz, 1H), 6.75 (s, 2H), 3.88 (s, 6H), 3.87 (s, 3H), 3.86 (s, 3H),
2.33 (s, 3H).
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General procedure for the synthesis of Z-alkenes 2. CuCl (2.0 mg, 0.02 mmol, 10 mol %),
IMes·HCl (10.2 mg, 0.03 mmol, 15 mol %) and t-BuOK (22.4 mg, 0.2 mmol, 1 equiv) were placed in a
dried 25 mL Schlenk tube. The tube was evacuated and refilled with N2 three times. Ethanol (1.0 mL)
was added and the resulting mixture was stirred at room temperature for 15 min. A solution of 1 (0.2
mmol), B2Pin2 (61.0 mg, 0.24 mmol, 1.2 equiv) and ethanol (2 mL) was then added and the mixture
was stirred at room temperature for 5 h. Upon completion, the reaction mixture was concentrated under
vacuum and the residue was purified by column chromatography on silica gel (100-200 mesh), eluting
with the indicated mixture of ethyl acetate (EA)/petroleum ether (PE) to give pure Z-alkene 2.
Gram-scale synthesis of 2a. CuCl (79.0 mg, 0.8 mmol, 10 mol %), IMes·HCl (409.0 mg, 1.2 mmol,
15 mol %) and t-BuOK (898.0 mg, 8.0 mmol, 1 equiv.) were placed in a dried 250 mL Schlenk flash.
The flash was evacuated and refilled with N2 three times. Ethanol (40 mL) was added and the resulting
mixture was stirred at room temperature for 15 min. A solution of 1a (1.4 g, 8.0 mmol), B2Pin2 (2.4 g,
9.6 mmol, 1.2 equiv) and ethanol (80 mL) was then added and the mixture was stirred at room
temperature for 8 h. Upon completion, the reaction mixture was concentrated under vacuum and the
residue was purified by column chromatography on silica gel (100-200 mesh), eluting with petroleum
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ether (PE) to give pure Z-alkene 2a as colorless liquid (1.2 g, 85%).
5
6
7
8
9
(Z)-1,2-diphenylethene (2a)4c
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1
Product was isolated via column chromatography (PE) as colorless liquid (33.0 mg, 92%). H NMR
(CDCl3, 500 MHz): δ 7.25-7.15 (m, 10H), 6.59 (s, 2H); C{1H} NMR (CDCl3, 125 MHz): δ 137.3,
13
130.3, 128.9, 128.2, 127.1.
(Z)-1-methyl-4-styrylbenzene (2b)4c
Product was isolated via column chromatography (PE) as colorless liquid (31.8 mg, 82%). 1H NMR
(CDCl3, 500 MHz): δ 7.27-7.13 (m, 7H), 7.01 (d, J = 8.0 Hz, 2H), 6.55 (s, 2H), 2.30 (s, 3H); 13C{1H}
NMR (CDCl3, 125 MHz): δ 137.6, 136.9, 134.3, 130.3, 129.6, 128.9, 128.9, 128.8, 128.2, 127.0, 21.3.
(Z)-1-methoxy-4-styrylbenzene (2c)4c
OCH3
Product was isolated via column chromatography (PE/EA 100:1) as yellow liquid (37.9 mg, 90%). 1H
NMR (CDCl3, 500 MHz): δ 7.34-7.22 (m, 7H), 6.62-6.79 (m, 2H), 6.59 (d, J = 12.0 Hz, 1H), 6.56 (d, J
= 12.0 Hz, 1H), 3.82 (s, 3H); C{1H} NMR (CDCl3, 125 MHz): δ 158.7, 137.6, 130.2, 129.8, 129.7,
13
128.82, 128.78, 128.2, 126.9, 113.6, 55.2.
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(Z)-2-styrylaniline (2d)4c
4
5
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8
9
NH2
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Product was isolated via column chromatography (PE/EA 20:1-5:1) as yellow liquid (24.3 mg, 62%).
1H NMR (CDCl3, 500 MHz): δ 7.35-7.20 (m, 5H), 7.11 (d, J = 8.0 Hz, 2H), 6.57-6.55 (m, 2H), 6.52 (d,
J = 12.0 Hz, 1H), 6.47 (d, J = 12.0 Hz, 1H), 3.68 (s, 2H); 13C{1H} NMR (CDCl3, 125 MHz): δ 145.5,
138.0, 130.2, 130.1, 128.8, 128.2, 127.6, 127.5, 126.7, 114.7.
(Z)-1-fluoro-4-styrylbenzene (2e)4c
F
1
Product was isolated via column chromatography (PE) as colorless liquid (36 mg, 91%). H NMR
(CDCl3, 500 MHz): δ 7.29-7.22 (m, 7H), 6.94 (t, J = 8.8 Hz, 2H), 6.63 (d, J = 12.2 Hz, 1H), 6.58 (d, J =
12.2 Hz, 1H); 13C{1H} NMR (CDCl3, 125 MHz): δ 161.8 (d, J =246.7 Hz), 137.1, 133.2 (d, J = 3.5 Hz),
130.5 (d, J = 7.9 Hz), 130.3 (d, J = 1.0 Hz), 129.1, 128.8, 128.3, 127.2, 115.2 (d, J = 21.4 Hz).
(Z)-1-chloro-4-styrylbenzene (2f)4c
Cl
1
Product was isolated via column chromatography (PE) as colorless liquid (35 mg, 82%). H NMR
(CDCl3, 500 MHz): δ 7.29-7.21 (m, 9H), 6.68 (d, J = 12.2 Hz, 1H), 6.58 (d, J = 12.2 Hz, 1H). 13C{1H}
NMR (CDCl3, 125 MHz): δ 136.9, 135.7, 132.8, 131.0, 130.2, 128.9, 128.8, 128.4, 128.3, 127.3.
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(Z)-1-styryl-4-(trifluoromethyl)benzene (2g)4c
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9
CF3
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Product was isolated via column chromatography (PE) as colorless liquid (42.8 mg, 86%). 1H NMR
(CDCl3, 500 MHz): δ 7.50 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.30-7.24 (m, 5H), 6.75 (d, J =
13
12.2 Hz, 1H), 6.62 (d, J = 12.2 Hz, 1H); C{1H} NMR (CDCl3, 125 MHz): δ 141.0, 136.6, 132.3,
129.1, 129.0 (q, J = 32.5 Hz ), 128.8, 128.7, 128.4, 127.6, 125.1 (q, J = 3.8 Hz), 124.2 (q, J = 270.1
Hz).
(Z)-1-methyl-3-styrylbenzene (2i)4c
1
Product was isolated via column chromatography (PE) as colorless liquid (35.8 mg, 92%). H NMR
(CDCl3, 500 MHz): δ 7.32-7.21 (m, 5H), 7.17-7.05 (m, 4H), 6.62 (s, 2H), 2.31 (s, 3H); 13C{1H} NMR
(CDCl3, 125 MHz): δ 137.8, 137.4, 137.2, 130.4, 130.1, 129.6, 128.9, 128.2, 128.1, 127.9, 127.1, 125.9,
21.3.
(Z)-1-chloro-3-styrylbenzene (2j)4c
Cl
Product was isolated via column chromatography (PE) as colorless liquid (38.3 mg, 89%). 1H NMR
(CDCl3, 500 MHz): δ 7.30-7.14 (m, 9H), 6.69 (d, J = 12.2 Hz, 1H), 6.56 (d, J = 12.2 Hz, 1H); 13C{1H}
NMR (CDCl3, 125 MHz): δ 139.1, 136.6, 134.1, 131.6, 129.4, 128.9, 128.8, 128.7, 128.3, 127.5, 127.1,
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127.0.
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(Z)-1-methyl-2-styrylbenzene (2k)4c
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1
Product was isolated via column chromatography (PE) as colorless liquid (33 mg, 85%). H NMR
(CDCl3, 500 MHz): δ 7.25-7.08 (m, 9H), 6.70 (d, J = 12.2 Hz, 1H), 6.66 (d, J = 12.2 Hz, 1H), 2.32 (s,
3H); C{1H} NMR (CDCl3, 125 MHz): δ 137.13, 137.05, 136.1, 130.5, 130.1, 129.6, 128.93, 128.89,
13
128.1, 127.2, 127.0, 125.7, 19.9.
(Z)-1-bromo-2-styrylbenzene (2l)25
Br
Product was isolated via column chromatography (PE) as colorless liquid (48.3 mg, 93%). 1H NMR
(CDCl3, 500 MHz): δ 7.67-7.62 (m, 1H), 7.24-7.17 (m, 6H), 7.14-7.10 (m, 2H), 6.73 (d, J = 12.1 Hz,
1H), 6.66 (d, J = 12.1 Hz, 1H); 13C{1H} NMR (CDCl3, 125 MHz): δ 138.0, 136.4, 132.7, 131.4, 130.9,
129.5, 129.0, 128.7, 128.2, 127.3, 127.0, 123.9.
(Z)-2-styrylbenzonitrile (2m)
CN
1
Product was isolated via column chromatography (PE/EA 100:1) as yellow liquid (39.0 mg, 95%). H
NMR (CDCl3, 500 MHz): δ 7.67 (d, J = 8.3 Hz, 1H), 7.40-7.30 (m, 3H), 7.25-7.23 (m, 3H), 7.18-7.16
(m, 2H), 6.88 (d, J = 12.2 Hz, 1H), 6.80 (d, J = 12.2 Hz, 1H); C{1H} NMR (CDCl3, 125 MHz): δ
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141.2, 135.9, 134.4, 132.9, 132.2, 129.7, 128.9, 128.4, 127.8, 127.5, 125.9, 117.9, 112.3; HRMS (ESI)
for C15H11NNa [M + Na]+: calcd. 228.0784, found 228.0786.
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8
9
ethyl (Z)-2-styrylbenzoate (2n)
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COOEt
1
Product was isolated via column chromatography (PE/EA 100:1) as yellow liquid (44.4 mg, 88%). H
NMR (CDCl3, 500 MHz): δ 8.05-8.01 (m, 1H), 7.34-7.29 (m, 2H), 7.25-7.22 (m, 1H), 7.18-7.12 (m,
3H), 7.10-7.07 (m, 3H), 6.67 (d, J = 12.0 Hz, 1H), 4.38 (q, J = 7.0 Hz, 2H), 1.40 (t, J = 7.0 Hz, 3H);
13C{1H} NMR (CDCl3, 125 MHz): δ 167.1, 139.6, 136.8, 131.8 131.0, 130.5, 129.6, 129.5, 129.2,
128.0 (2C), 127.0, 126.9, 61.0, 14.3; HRMS (ESI) for C17H17O2 [M + H]+: calcd. 253.1223, found
253.1224.
(Z)-1-styrylnaphthalene (2o)26
1
Product was isolated via column chromatography (PE) as colorless liquid (42.7 mg, 93%). H NMR
(CDCl3, 500 MHz): δ 7.84-7.75 (m, 3H), 7.70 (d, J = 8.5 Hz, 1H), 7.50-7.47 (m, 2H), 7.41 (dd, J1 = 8.5
Hz, J2 = 1.5 Hz, 1H), 7.36-7.34 (m, 2H), 7.30-7.24 (m, 3H), 6.82 (d, J = 12.0 Hz, 1H), 6.74 (d, J = 12.0
Hz, 1H); C{1H} NMR (CDCl3, 125 MHz): δ 137.3, 134.9, 133.5, 132.6, 130.6, 130.2, 129.0, 128.3,
13
128.0, 128.0, 127.6, 127.5, 127.2, 127.0, 126.0, 125.9.
(Z)-4-styrylpyridine (2p)4c
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N
Product was isolated via column chromatography (PE/EA = 10:1-3:1) as colorless liquid (28.6 mg,
79%). 1H NMR (CDCl3, 500 MHz): δ 8.46 (d, J = 1.0 Hz, 2H), 7.28-7.21 (m, 5H), 7.12 (d, J = 5.5 Hz,
2H), 6.81 (d, J = 12.0 Hz, 1H), 6.51 (d, J = 12.0 Hz, 1H); 13C{1H} NMR (CDCl3, 125 MHz): δ 149.8,
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145.0, 136.2, 134.1, 128.8, 128.5, 127.9, 127.6, 123.5.
(Z)-2-styrylthiophene (2q)26
S
Product was isolated via column chromatography (PE) as colorless liquid (31.3 mg, 85%). 1H NMR
(CDCl3, 500 MHz): δ 7.43-7.33 (m, 5H), 7.13 (d, J = 5.0 Hz, 1H), 7.02 (d, J = 3.5 Hz, 1H), 6.93 (dd, J1
= 5.1 Hz, J2 = 3.6 Hz, 1H), 6.75 (d, J = 12.0 Hz, 1H), 6.63 (d, J = 12.0 Hz, 1H); 13C{1H} NMR (CDCl3,
125 MHz): δ 139.8, 137.4, 128.9, 128.8, 128.5, 128.1, 127.5, 126.4, 125.5, 123.4.
(Z)-N-methyl-N-styrylmethanesulfonamide (2r)
O
N S
O
Product was isolated via column chromatography (PE/EA = 10:1) as colorless liquid (38.9 mg, 92%).
1H NMR (CDCl3, 500 MHz): δ 7.42-7.41 (m, 2H), 7.36-7.33 (m, 2H), 7.28-7.26 (m, 1H), 6.35 (d, J =
9.0 Hz, 1H), 6.07 (d, J = 9.0 Hz, 1H), 2.94 (s, 3H), 2.90 (s, 3H); 13C{1H} NMR (CDCl3, 125 MHz): δ
134.6, 128.9, 128.2, 127.6, 126.9, 120.5, 36.4, 36.1; HRMS (ESI) for C10H13NNaO2S [M + Na]+: calcd.
234.0559, found 234.0569.
(Z)-N,4-dimethyl-N-styrylbenzenesulfonamide (2s)8
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Product was isolated via column chromatography (PE/EA = 10:1) as colorless liquid (39.5 mg, 69%).
1H NMR (CDCl3, 500 MHz): δ 7.78-7.76 (m, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.29-7.21 (m, 5H), 6.27 (d,
J = 9.0 Hz, 1H), 6.03 (d, J = 9.0 Hz, 1H), 2.77 (s, 3H), 2.47 (s, 3H); 13C{1H} NMR (CDCl3, 125 MHz):
δ 144.0, 134.9, 134.2, 129.8, 129.0, 128.2, 127.6, 127.5, 127.3, 121.0, 36.6, 21.6.
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(Z)-4-methyl-N-phenyl-N-styrylbenzenesulfonamide (2t)
O
N S
Ph
O
Product was isolated via column chromatography (PE/EA = 10:1) as yellow solid (22.4 mg, 41%). m.p.
93.5-94.6 ºC; 1H NMR (CDCl3, 500 MHz): δ 7.32-7.31 (m, 2H), 7.20-7.16 (m, 4H), 7.11-7.04 (m, 4H),
13
6.71 (d, J = 9.1 Hz, 1H), 6.15 (d, J = 9.1 Hz, 1H), 2.94 (s, 3H); C{1H} NMR (CDCl3, 125 MHz): δ
139.1, 133.8, 128.92, 128.90, 127.7, 127.3, 127.2, 126.9, 126.2, 121.8, 37.1; HRMS (ESI) for
C15H15NNaO2S [M + Na]+: calcd. 296.0716, found 296.0724.
(Z)-hex-1-en-1-ylbenzene (2u)26
1
Product was isolated via column chromatography (PE) as colorless liquid (27.2 mg, 85%). H NMR
(CDCl3, 500 MHz): δ 7.38-7.31 (m, 4H), 7.27-7.23 (m, 1H), 6.44 (d, J = 11.7 Hz, 1H), 5.71 (dt, J1 =
11.7 Hz, J2 = 7.3 Hz, 1H), 2.40-2.35 (m, 2H), 1.51-1.45 (m, 2H), 1.43-1.36 (m, 2H), 0.94 (t, J = 7.2 Hz,
13
3H); C{1H} NMR (CDCl3, 125 MHz): δ 137.8, 133.2, 128.7, 128.7, 128.1, 126.4, 32.2, 28.3, 22.4,
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(Z)-1-(3,3-dimethylbut-1-en-1-yl)naphthalene (2v)
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Product was isolated via column chromatography (PE/EA = 50:1) as colorless liquid (26.0 mg, 62%).
1H NMR (CDCl3, 500 MHz): δ 7.85-7.82 (m, 2H), 7.79 (d, J = 8.5 Hz, 1H), 7.51-7.45 (m, 2H), 7.67 (s,
1H), 7.37 (dd, J1 = 8.5 Hz, J2 = 1.5 Hz, 1H), 6.58 (d, J = 12.5 Hz, 1H), 5.73 (d, J = 12.5 Hz, 1H), 1.04
13
(s, 9H); C{1H} NMR (CDCl3, 125 MHz): δ 143.1, 140.0, 133.0, 132.0, 127.8, 127.7, 127.6, 127.3,
127.1, 127.0, 126.0, 125.5, 34.3, 31.3. HRMS (EI) for C16H18 [M+]: calcd. 210.1409, found 210.1415.
(Z)-dodec-6-ene (2w)4c
Product was isolated via column chromatography (PE) as colorless liquid (23.6 mg, 70%, conversion:
82%). 1H NMR (CDCl3, 500 MHz): δ 5.40-5.34 (m, 2H), 2.05-2.01 (m, 4H), 1.39-1.27 (m, 12H), 0.91
(t, J = 7.0 Hz, 6H); 13C{1H} NMR (CDCl3, 125 MHz): δ 129.9, 31.6, 29.5, 27.2, 22.6, 14.1.
4-vinyl-1,1'-biphenyl (2x)27
Product was isolated via column chromatography (PE) as white solid (34.1 mg, 95%). m.p.
1
122.5-123.8 °C (lit.27 m.p. 118-120 °C); H NMR (CDCl3, 500 MHz): δ 7.60-7.55 (m, 4H), 7.49-7.41
(m, 4H), 7.35-7.31 (m, 1H), 6.75 (dd, J1 = 18.0 Hz, J2 = 11.0 Hz, 1H), 5.79 (dd, J1 = 17.5 Hz, J2 = 1.0
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Hz, 1H), 5.27 (dd, J1 = 11.0 Hz, J2 = 1.0 Hz, 1H); C{1H} NMR (CDCl3, 125 MHz) δ 140.8, 140.6,
5
6
7
136.7, 136.5, 128.8, 127.3, 127.3, 127.0, 126.7, 113.9.
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phenyl(4-vinylphenyl)methanone (2y)28
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O
Product was isolated via column chromatography (PE/EA = 20:1) as colorless liquid (36.7 mg, 88%).
1H NMR (CDCl3, 500 MHz): δ 7.82-7.80 (m, 4H), 7.60 (t, J = 7.4 Hz, 1H), 7.53-7.49 (m, 4H), 6.80 (dd,
J1 = 17.6 Hz, J2 = 10.9 Hz, 1H), 5.91 (d, J = 17.6 Hz, 1H), 5.43 (d, J = 10.9 Hz, 1H); C{1H} NMR
13
(CDCl3, 125 MHz) δ 196.2, 141.6, 137.8, 136.7, 136.0, 132.3, 130.6, 130.0, 128.3, 126.1, 116.6.
1,2,3-trimethoxy-5-vinylbenzene (2z)29
MeO
MeO
OMe
Product was isolated via column chromatography (PE/EA = 50:1) as colorless liquid (31.0 mg, 80%).
1H NMR (CDCl3, 500 MHz): δ 6.68-6.62 (m, 3H), 5.67 (d, J = 17.5 Hz, 1H), 5.23 (d, J = 10.8 Hz, 1H),
3.90 (s, 6H), 3.86 (s, 3H); 13C{1H} NMR (CDCl3, 125 MHz) δ 153.3, 138.1, 136.8, 133.3, 113.2, 103.3,
60.9, 56.1.
dodec-1-ene (2zb)30
1
Product was isolated via column chromatography (PE) as colorless liquid (26.7 mg, 79%). H NMR
(CDCl3, 500 MHz): δ 5.88-5.79 (m, 1H), 5.03-4.99 (m, 1H), 5.96-5.93 (m, 1H), 2.08-2.04 (m, 2H),
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1.41-1.28 (m, 16H), 0.90 (t, J = 7.0 Hz, 3H); C{1H} NMR (CDCl3, 125 MHz) δ 139.3, 114.1, 33.9,
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31.9, 29.7 (2C), 29.5, 29.4, 29.2, 29.0, 22.7, 14.1.
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Mechanistic Studies.
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Reaction of 1m in EtOD. CuCl (2.0 mg, 0.02 mmol, 10 mol %), IMes·HCl (10.2 mg, 0.03 mmol, 15
mol %) and t-BuOK (22.4 mg, 0.2 mmol, 1 equiv.) were placed in a dried 25 mL Schlenk flash. The
tube was evacuated and refilled with N2 three times. EtOD (1.0 mL) was added and the result mixture
was stirred at room temperature for 15 min. Subsequently, a solution of 1l (40.6 mg, 0.2 mmol), B2Pin2
(61 mg, 0.24 mmol, 1.2 equiv.) and EtOD (2.0 mL) was added, and the resulting mixture was stirred at
room temperature for 12 h. Upon completion, the solvent was removed under vacuum and the residue
was purified by column chromatography on silica gel (100-200 mesh), eluting with the mixture of
1
PE/EA = 50/1 to give pure products in 93% yield. The resulting product 2m-d2 was sampled for H
NMR analysis (see Figure S1 in Supporting Information).
Reaction of 3a under the standard reaction conditions in the absence of B2Pin2. CuCl (2.0 mg, 0.02
mmol, 10 mol%), IMes·HCl (10.2 mg, 0.03 mmol, 15 mol%) and t-BuOK (22.4 mg, 0.2 mmol, 1
equiv.) were placed in a dried 25 mL Schlenk flash. The tube was evacuated and refilled with N2 three
times. Then, ethanol (1.0 mL) was added, and the result mixture was stirred at room temperature for 15
min. Subsequently, a solvent of 3a (61.2 mg, 0.2 mmol) and ethanol (2.0 mL) was added, and the
resulting mixture was stirred at room temperature for 5 h. Upon completion, after evaporation of the
solvent under vacuum, the residue was purified by column chromatography on silica gel (100-200
mesh), eluting with PE to give 2a in 19% yield.
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Synthesis of (Z)-2-methoxy-5-(2-(3,4,5-trimethoxyphenyl)vinyl-1,2-d2)phenyl acetate (5a) CuCl
(2.0 mg, 0.02 mmol, 10 mol%), IMes·HCl (10.2 mg, 0.03 mmol, 15 mol%) and t-BuOK (22.4 mg, 0.2
mmol, 1 equiv.) were placed in a dried 25 mL Schlenk tube. The tube was evacuated and refilled with
N2 three times. EtOD (1.0 mL) was added and the resulting mixture was stirred at room temperature for
15 min. 2-methoxy-5-((3,4,5-trimethoxyphenyl)ethynyl)phenyl acetate 1zc (0.2 mmol) and B2Pin2
(61.0 mg, 0.24 mmol, 1.2 equiv) was added under N2 atmosphere. Then EtOD (2.0 mL) was added to
wash 1zc and B2Pin2 which might remain on the Schlenk tube wall. The reaction was stirred at room
temperature for 10 h. Upon completion, the reaction mixture was concentrated under vacuum and the
residue was purified by column chromatography on silica gel (200-300 mesh), eluting with the mixture
of ethyl acetate (EA)/petroleum ether (PE) = 6/1-3/1 to give pure 5a (colorless liquid, 50.4 mg, 70 %).
1H NMR (CDCl3, 500 MHz): δ 7.14 (dd, J1 = 8.5 Hz, J2 = 2.0 Hz, 1H), 7.03 (d, J = 2.0 Hz, 1H), 6.87 (d,
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J = 8.5 Hz, 1H), 6.52 (s, 2H), 3.85 (s, 3H), 3.82 (s, 3H), 3.72 (s, 6H), 2.28 (s, 3H); C{1H} NMR
(CDCl3, 125 MHz): δ 168.8, 152.9, 150.2, 139.3, 137.1, 132.3, 129.9, 129.0 (t, J = 23.4 Hz), 128.1 (t, J
= 23.4 Hz), 127.7, 123.1, 111.9, 105.7, 60.8, 55.8, 20.6.
Synthesis of Z-Combretastation A-4-d2 (5b). 5a (72.0 mg, 0.2 mmol), K2CO3 (83 mg, 0.6 mmol) and
MeOH (6 mL) was added to a 15 mL reaction tube with a stir bar. The reaction mixture was stirred at
room temperature for 5 h. Upon completion, extra water (15 mL) was added and the mixture was
extract with CH2Cl2 (20 mL × 3). The organic phase was combined. Afterwards the solvent was
removed under vacuum and the residue was purified by column chromatography on silica gel (200-300
mesh), eluting with the mixture of ethyl acetate (EA)/ petroleum ether (PE) = 6/1-3/1 to give 5b21e
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( colorless liquid, 58.5 mg, 92%); 1H NMR (CDCl3, 500 MHz): δ 6.94 (d, J = 2.0 Hz, 1H), 6.82 (dd, J1
= 8.0 Hz, J2 = 2.0 Hz, 1H), 6.74 (d, J = 8.0 Hz, 1H), 6.55 (s, 2H), 5.58 (s, 1H), 3.87 (s, 3H), 3.85 (s,
3H), 3.71 (s, 6H); 13C{1H} NMR (CDCl3, 125 MHz): δ 152.7, 145.8, 145.2, 137.0, 132.5, 130.4, 128.9
(t, J = 23.4 Hz), 128.4 (t, J = 23.3 Hz), 121.0, 114.9, 110.3, 106.0, 60.8, 55.81, 55.79.
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Synthesis of 3,5,6,7-tetramethoxyphenanthren-2-yl-9,10-d2 acetate (6a).20 Iodine (50.8 mg, 0.2
mmol) was added to a solution of 5a (72 mg, 0.2 mmol) and cyclohexane (100 mL) with a stir bar. The
reaction mixture was irradiated at a distance of 5 cm from 500 W high pressure mercury lamp and
stirred for 5 h at room temperature. Then extra sat. Na2S2O8 was added until the solution turn to
colorless and the mixture was extract with CH2Cl2. The organic phase was combined. Afterwards the
solvent was removed under vacuum and the residue was purified by column chromatography on silica
gel (200-300 mesh), eluting with the mixture of ethyl acetate (EA)/ petroleum ether (PE) = 10/1-3/1 to
give 6a (colorless liquid, 37 mg, 52%). 1H NMR (CDCl3, 500 MHz): δ 9.21 (s, 1H), 7.52 (s, 1H), 7.10
13
(s, 1H), 4.06 (s, 6H), 4.05 (s, 3H), 4.03 (s, 3H), 2.42 (s, 3H); C{1H} NMR (CDCl3, 125 MHz): δ
169.2, 152.5, 152.1, 150.2, 142.7, 138.9, 130.2, 128.9, 126.6, 125.8 (t, J = 24.6 Hz), 124.6 (t, J = 24.5
Hz), 120.9, 118.4, 108.9, 105.3, 61.3, 60.5, 55.86, 55.84, 20.7.
Synthesis of 3,5,6,7-tetramethoxyphenanthren-9,10-d2-2-ol (6b). 6a (71.7 mg, 0.2 mmol), K2CO3
(83 mg, 0.6 mmol) and MeOH (6 mL) was added to a 15 mL reaction tube with a stir bar. The reaction
mixture was stirred at room temperature for 5 h. Upon completion, extra water (15 mL) was added and
the mixture was extract with CH2Cl2 (20 mL × 3). The organic phase was combined. Afterwards the
solvent was removed under vacuum and the residue was purified by column chromatography on silica
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7
1
give 6b31 (white solid, 56.3 mg, 89%). m.p. 162.9-163.7 ºC. H NMR (CDCl3, 500 MHz): δ 9.09 (s,
8
9
1H), 7.34 (s, 1H), 7.09 (s, 1H), 5.95 (s, 1H), 4.11 (s, 3H), 4.06 (s, 3H), 4.05 (s, 3H), 4.02 (s, 3H);
13C{1H} NMR (CDCl3, 100 MHz): δ 151.7, 151.5, 146.7, 144.7, 142.5, 129.3, 127.6, 125.8 (t, J = 24.0
Hz), 124.4 (t, J = 24.0 Hz), 124.0, 118.7, 111.1, 107.1, 105.2, 61.4, 60.4, 55.9 (2C).
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Acknowledgement
We are grateful to the Natural Science Foundation of China (No. 21772176 and 21372201) for
financial support.
Supporting Information
1
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Charts for mechanistic studies as well as copies of H and C NMR spectra of the products. This
material is available free of charge via the Internet at http://pubs.acs.org.
References
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Alkyne Reductions Chemo-, Regio-, and Stereoselective Enough To Provide Pure (Z)-Olefins in
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(4Z,7Z,10Z,12E,16Z,18E)-14,20-Dihydroxy-4,7,10,12,16,18-docosahexaenoic
Acid
and
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Modular and Stereodivergent Approach to Unbranched 1,5,9,n-Polyenes: Total Synthesis of
Chatenaytrienin-4. J. Org. Chem. 2016, 81, 8175-8186.
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Kalyani, A. Advances in chemoselective and/or stereoselective semihydrogenation of alkynes.
Tetrahedron Lett. 2018, 59, 419-472. Selected examples of Pd-catalyzed semihydrogenation of alkynes,
see: (d) Lindlar, H. Ein neuer Katalysator für selektive Hydrierungen. Helv. Chim. Acta. 1952, 35,
446-450. (e) Trost, B. M.; Braslau, R. A convenient chemoselective semihydrogenation of acetylenes
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