Cu/Ni-Catalyzed Cyanomethylation of Alkenes with Acetonitrile for the Synthesis of β,γ-Unsaturated Nitriles

Article abstract of DOI:10.1021/acs.joc.0c00141

We have developed a protocol for the Cu/Ni-catalyzed cyanomethylation of alkenes with acetonitrile for the synthesis of β,γ-unsaturated nitriles. This is the first example of a direct coupling of the alkene sp² C - H bond and the acetonitrile sp³ C - H bond for the preparation of β,γ-unsaturated nitriles. Acetonitrile, an inexpensive and stable solvent, is demonstrated to be a useful cyanomethyl source. The combination of copper and nickel catalysts resulted in a high reaction efficiency.

Full text of DOI:10.1021/acs.joc.0c00141

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Note
Cu/Ni-Catalyzed Cyanomethylation of Alkenes with
Acetonitrile for the Synthesis of #,#-Unsaturated Nitriles
Saisai Zhang, Zengming Shen, and Hong Jian
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00141 • Publication Date (Web): 31 Mar 2020
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Cu/Ni-Catalyzed Cyanomethylation of Alkenes with Acetonitrile for the
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Synthesis of β,γ-Unsaturated Nitriles
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Saisai Zhang, † Zengming Shen, †,* and Hong Jian‡,*
†Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and
Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240,
China
‡Sixth People's Hospital South Campus, Shanghai Jiao Tong University, No.6600 Nanfeng Road，
Shanghai 201499, China；
Email: shenzengming@sjtu.edu.cn; 15990136088@139.com
C(sp3)-H activation of acetonitrile
Cross-dehygogen coupling
R1
R2
R1
R2
Cu/Ni
CN
+
H
H
CN
R1 = aryl
R2 = aryl, alkyl, Br
49-80% yields
Abstract
We developed a protocol for Cu/Ni-catalyzed cyanomethylation of alkenes with
acetonitrile for the synthesis of β,γ-unsaturated nitriles. This is the first example of the
direct coupling of alkene sp2 C–H bond and acetonitrile sp3 C–H bond for preparing
β,γ-unsaturated nitriles. Acetonitrile, an inexpensive and stable solvent, is
demonstrated to be a useful cyanomethyl source. The combination of copper and
nickel catalysts results in high reaction efficiency.
The nitrile group not only plays key roles in the fields of materials and medicines
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but also serves as a versatile synthetic intermediate in organic transformations.1 β,γ-
Unsaturated nitriles are an especially useful class of nitriles in synthetic chemistry
because they are common skeletons in natural compounds and exhibit various
biological activities.2 Consequently, the development of new methods for preparing
β,γ-unsaturated nitriles is of great interest in organic chemistry.
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Scheme 1. Methods for the synthesis of β,γ-unsaturated nitriles
Previous work:
KCN, NaCN, BrCN, TMSCN
R1
X
R1
CN
(1)
(2)
X = Cl, Br, OH, OAc etc
R'
R'
Ni(PPh3)4, dppp, K3PO4
toluene, 100 o
CN
+
R
Br
Br
CN
CN
C
or mesitylene,160 o
C
CuI, Phen
+
R
(3)
R
CN
DBU, CH3CN
110 oC, N2
This work:
R1
R1
R2
Cu/Ni
R2
H
CN
+
H
(4)
CN
R1 = aryl
R2 = aryl, alkyl, Br
C(sp3)-H activation of acetonitrile
Cross-dehygogen coupling
During the past decade, cross-dehydrogenative coupling (CDC) has received
considerable attention for its ability to construct C–C bonds.3 This methodology
provides an efficient means of forming C–C bonds directly through activation of two
C–H bonds without special leaving groups. Inspired by the seminal works reported by
Murahashi4 and Li,5,6 we predicted that the straightforward cyanomethylation of
alkenes could construct β,γ-unsaturated nitriles. This would be a relatively simple and
efficient method compared with the traditional methods of cyanation of allylic
substituted substrates (halides, alcohols, carbonates, and esters) with HCN, BrCN,
NaCN, and trimethylsilyl cyanide as cyanide sources (Scheme 1, eq 1).7 Recently,
metal-catalyzed cyanomethylation of alkenes with -bromoalkylnitriles for the
synthesis of β,γ-unsaturated nitriles has been described by Lei group and Lv group,
respectively (Scheme 1, eqs 2 and 3).8 Remarkably, the ideal approach was employing
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acetonitrile, the simplest alkylnitrile, to generate cyanomethyl group in situ by
directly activating the acetonitrile sp3 C–H bond. However, acetonitrile is generally
considered as an inert chemical reagent and is frequently used as a solvent.9
Accordingly, related reports are still few and limited.10 Recently, Zhu11 and Li12
research groups respectively reported the coupling reactions of alkyl nitriles with
different kinds of unsaturated compounds. To the best of our knowledge, however,
only one example was reported by Dong group in the synthesis of γ,δ-unsaturated
nitriles catalyzed by Cu salt13, which provided β,γ-unsaturated nitriles in low yield
(10% yield) with 20:1 configuration. Therefore, the direct coupling of alkene sp2 C–H
bond with acetonitrile sp3 C–H bond through the CDC reaction to form β,γ-
unsaturated nitriles remains a considerable challenge. Herein, we document an
efficient and direct CDC process to provide β,γ-unsaturated nitriles by the use of
simple alkenes and acetonitrile as starting materials catalyzed by copper and nickel
complexes (Scheme 1, eq 4).
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Initially, we selected 1,1-diphenylethylene 1a as a model substrate to test the
cyanomethylation of alkenes with acetonitrile in the presence of Cu(OTf)2/1,10-
phenanthroline and tert-butyl peroxybenzoate (TBPB). To our delight, Cu-catalyzed
oxidative CDC reaction of 1a and CH3CN produced the desired 4,4-diphenylbut-3-
enenitrile 2a in 32% yield (Table 1, entry 1). By varying the loading amounts of
ligand, we found that the use of 30 mol% 1,10-phenanthroline increased the yield to
50% (Table 1, entries 2 to 4). Although the examination of other catalyst-ligand ratios
was carried out, the reaction efficiency was not improved (see the Supporting
information, Table S1). Therefore, 50 mol% catalyst combined with 30 mol% 1,10-
Phen was
Table 1. Optimization of reaction conditions a,b,c
Ph
CN
Ph
Ph
catalyst, 1,10-Phen
TBPB, N2
+
H
CN
Ph
3a
Ph
2a
Ph
1a
by-product
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temp. (oC) yieldc (%)
entry
catalyst (mol%)
1,10-phen (mol%)
5
6
1
2
Cu(OTf)2(50)
Cu(OTf)2(50)
20
30
150
150
32
50
7
8
9
Cu(OTf)2(50)
Cu(OTf)2(50)
3
4
5
6
50
100
30
150
150
150
150
23
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Cu(OTf)2(30)/NiCl2(20)
Cu(OTf)2(30)/Ni(acac)2(20)
37
43
30
Cu(OTf)2(30)/Ni(PPh3)2Cl2(20)
Cu(OTf)2(30)/Ni(dppp)Cl2(20)
Cu(OTf)2(30)/ NiCl2(DME)(20)
Cu(OTf)2(30)/ NiCl2(DME)(20)
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8
30
30
30
30
150
150
150
80
64
68
71
30
9
10
Cu(OTf)2(30)/ NiCl2(DME)(20)
Cu(OTf)2(30)/ NiCl2(DME)(20)
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12
30
30
100
120
57
68
Cu(OTf)2(20)/ NiCl2(DME)(20)
Cu(OTf)2(20)/ NiCl2(DME)(20)
13
20
20
120
120
71
14b
trace
aConditions: 1a (0.2 mmol), TBPB (3 equiv.), CH3CN (2 mL), under nitrogen, 120 °C in a sealed
tube. bDTBP (3 equiv.) instead of TBPB. cIsolated yields. Phen = phenanthroline; TBPB = tert-
butyl peroxybenzoate; DTBP = di-tert-butyl peroxide.
selected for further optimization. In the Cu/Phen system, synthesis of the desired
product was accompanied by the formation of impurities from 1,1-diphenylethylene
1a, and these impurities could not be determined. We predicted that the use of
additives would inhibit the formation of impurities. Therefore, various nickel salts (20
mol%) were screened to improve the chemoselectivity of the reaction (Table 1, entries
5 to 9). Surprisingly, NiCl2(DME) serving as a cocatalyst demonstrated favorable
reactivity. We discovered that NiCl2(DME) combined with Cu(OTf)2
(30
mol%)/1,10-Phen (30 mol%) increased the yield to 71% (Table 1, entry 9). Another
byproduct, prop-1-ene-1,1-diyldibenzene 3a, was obtained because of the addition of
a nickel catalyst. The effect of temperature was investigated, and the most satisfactory
outcome was obtained at 120 °C (68% yield of 2a; Table 1, entry 12). By varying the
loading amounts of the catalyst and ligand again (see the Supporting Information,
Table S2), we found that Cu(OTf)2 (20 mol%)/1,10-Phen (20 mol%) and NiCl2(DME)
(20 mol%) successfully provided the target product 2a in 71% yield (Table 1, entry
13). Di-tert-butyl peroxide (DTBP), a common oxidant,14 failed to yield the desired
product 2a (Table 1, entry 14). Overall, heating a solution of 1a in MeCN in the
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presence of Cu(OTf)2 (20 mol%), 1,10-Phen (20 mol%), NiCl2(DME) (20 mol%), and
5
6
TBPB (3 equiv.) in an inert atmosphere at 120 °C afforded 2a in 71% yield.
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Scheme 2. Scope of the cyanomethylation of alkenesa,b
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CN
Cu(OTf)2 (20 mol%) / 1,10-Phen (20 mol%)
NiCl2(DME) (20 mol%), TBPB (3 equiv)
R2
R1
H
CN
R2
+
R1
N2 , 120 oC,
2
1
F
Cl
CN
CN
CN
CN
F
Cl
2a, 71%
2b, 71%
2c, 64%
2d, 71%
Cl
Br
F
CN
CN
CN
CN
2e, 78% (E:Z = 6:1)
2f, 72% (E:Z = 7:1)
2g, 80% (E:Z = 4:1)
2h, 73% (E:Z = 3:1)
CN
CN
CN
CN
F
Cl
Br
2i, 72% (E:Z = 1:1)
2j, 67% (E:Z = 1:1)
2k, 65% (E:Z= 1:1)
2l, 75% (E:Z= 2:1)
CN
CN
CN
CN
N
S
CN
Br
Br
2m, 69% (E:Z = 1:1)
2n, trace
2o, trace
2p, 52% (E:Z = 1:1) 2q, 57% (E:Z = 1:1)
aConditions: substrate 1 (0.2 mmol), Cu(OTf)2 (20 mol%), 1,10-Phen (20 mol%), NiCl2(DME) (20
mol%), TBPB (3 equiv), CH3CN (2.0 mL), under a nitrogen atmosphere at 120 °C in a sealed
tube. bIsolated yield.
With the optimal conditions in hand, the generality and limitations of the synthesis
of β,γ-unsaturated nitriles through oxidative CDC reaction of acetonitrile and alkenes
were explored, as illustrated in Scheme 2. When symmetric 1,1-diarylethylenes were
used as the substrates, diaryl-substituted β,γ-unsaturated nitriles were exclusively
produced with high yields and regioselectivity. We discovered that both electron-
donating (Me) and electron-withdrawing (F and Cl) groups on the aromatic rings of
1,1-diarylethylenes were tolerated, and the corresponding products were obtained in
59%–80% yields (2a–2d). When asymmetric 1,1-diarylethylenes (1e-1m) were
subjected to the standard conditions, β,γ-unsaturated nitriles could be provided in high
yields regardless of the ortho, meta and para-substituted aromatic groups, in which
the formation of E-type configuration products would be accompanied by the
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generation of Z-configuration products. However, other heterocycle substituents such
as pyridine and thiophene at the α-position of styrene (2n,2o) were unsuccessful in
providing the desired product under the standard conditions. Surprisingly, (1-
bromovinyl)benzene readily provided the compound 2p in a 52% yield with a clear
1H NMR spectrum. To determine the configuration of compound 2p, we allowed it to
react with p-tolylboronic acid through the Suzuki–Miyaura coupling reaction to obtain
4-phenyl-4-(p-tolyl)but-3-enenitrile 2l (See the Supporting Information), the
configuration of which was determined as a 1:1 ratio of the E and Z configurations.
Consequently, we speculated that compound 2p was a 1:1 mixture of the E and Z
configurations. The same phenomenon was observed in 2q compound.
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In response to these results, we turned our attention to more challenging 1-aryl-
1-alkylethylenes (Scheme 3). First, we selected α-methylstyrene 1r as a model
substrate for performing an oxidative CDC reaction under the optimal conditions. A
mixture of the products 2r and 2r’ were obtained in a 1:1 ratio. A variety of
substituents on the aromatic rings of α-methylstyrene, such as F (1s), Br (1t), Me (1u)
and t-Bu (1v), were proven to be compatible to give mixtured products due to the
regioselectivity in the process of β-H elimination. Next, but-1-en-2-ylbenzene (1w)
and (3-methylbut-1-en-2-
Scheme 3. Scope of the cyanomethylation of alkenesa,b
CN
Cu(OTf)2 (20 mol%) / 1,10-Phen (20 mol%)
NiCl2(DME) (20 mol%), TBPB (3 equiv)
R2
R1
H
CN
CN
+
R1
N2 , 120 oC,
2
1
CN
CN
CN
CN
CN
F
F
Br
Br
2r
2r'
2s
49% (
2s'
2t
57% (
2t'
' = 2:1)
2r 2r
:
2s 2s
:
2t 2t
:
67% (
' = 1:1)
' = 1:1)
CN
CN
CN
CN
CN
CN
2u
2u'
2v
2v'
2u 2u
:
2v 2v
:
2w
2x
, trace
53% (
' = 3:1)
68% (
' = 1:1)
, trace
aConditions: substrate 1 (0.2 mmol), Cu(OTf)2 (20 mol%), 1,10-Phen (20 mol%), NiCl2(DME) (20
mol%), TBPB (3 equiv), CH3CN (2.0 mL), under a nitrogen atmosphere at 120 °C in a sealed
tube. bIsolated yield.
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yl)benzene 1x were tested under the standard conditions, but the desired product was
not obtained.
9
Diaryl-substituted β,γ-unsaturated nitriles are fundamental moieties found in
numerous bioactive compounds.15 Amitriptyline, a well-known drug used to treat
mental disorders, was efficiently synthesized using our procedure. As illustrated in
Scheme 4, the employment of compound 1y as a substrate provided the critical
intermediate 2y in a 66% yield under the standard conditions. Notably, 2y underwent
reduction followed by simple substitution to access amitriptyline. The traditional
procedure for preparing intermediate 2y of amitriptyline requires several steps.16
Accordingly, our method clearly demonstrated its potential applications (Scheme 3).
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Scheme 4. Synthetic application of the proposed method
reduction
substitution
standard condition
66%
ref.14
ref.14
N
CN
NH2
1y
2y
amitriptyline
Scheme 5. Control experiments
NiCl2(DME) (20 mol%)
Ph
Ph
CN
(5)
(6)
+
+
CH3CN
CH3CN
TBPB, N2,120 o
C
Ph
1a
Ph
Ph
2a
Ph
CN
Ph
standard conditions
TEMPO (2 equiv)
or BHT (2 equiv)
Ph
1a
2a
no product
CN
standard conditions
57% yield
+
(7)
CH3CN
Ph
4
5
To gain insight into the reaction mechanism, a series of mechanistic studies were
conducted, as illustrated in Scheme 5. First, no reaction occurred in the absence of a
copper catalyst (eq 5), suggesting that copper is essential to the reaction. Second, the
formation of -unsaturated nitrile 2a was inhibited in the presence of TEMPO
(2,2,6,6-tetramethylpiperidine N-oxide) or BHT (2,6-di-tert-butyl-4-methylphenol),
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which are known radical inhibitors and trappers (eq 6). These experiments indicated
that a radical mechanism could be involved in the reaction process. Third, we
executed a radical-clock experiment to obtain evidence supporting the proposed
radical mechanism. Compound 5 was obtained in a 57% yield through the treatment
of (1-cyclopropylvinyl)benzene 4 and acetonitrile under the standard conditions (eq
7). This study revealed sequential ring opening of the cyclopropylmethyl radical
intermediate and cyclization. In addition, during optimization of the reaction
conditions, the formation of byproduct 3a also indicated the existence of methyl
radicals in our reaction system.
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Scheme 6. Proposed mechanism
CH3CN
HX
X = PhCOO-
LX2CuII
LXCuII
CN
or OTf-
PhCOO-
TBPB
+
LXCuI
1a
t-BuO
Ph
Ph
3a
LXCuI
Me
CN
Acetone
Ph
CN
Ph
MeCN
Ph
Ph
Ph
1a
2a
CuIIILX2
Ph
CN
Ph
CN
Ph
LX2CuII
A
B
NiII
NiIIX
Ph
CN
TBPB
C
Ph

elimination
Ni(0)
2a
HX
H-Ni-X
On the basis of these experiments and previous reports,13,17 a tentative reaction
mechanism was proposed and outlined in Scheme 6. We considered cyanomethyl
radicals to be generated along two pathways. First, acetonitrile undergoes a process of
deprotonation with Cu(II) complex to obtain the cyanoalkylcopper (II) species, which
provides a cyanomethyl radical through homolytic cleavage11a-d,11g. Subsequently, the
addition of the cyanomethyl radical to the alkene generates the radical intermediate A,
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which can form the Cu(III) intermediate B with the Cu(II) complex. The intermediate
B undergoes reductive elimination to yield the β,γ-unsaturated nitrile 2a and Cu (I)
species. The Cu (I) species decomposes TBPB to generate the Cu(II) complex and a
methyl radical, as proven by the verification of byproduct 3a (Table 1, entry 9). The
methyl radical could abstracts hydrogen from acetonitrile to produce a cyanomethyl
radical13, which is followed by treatment with alkene to form the intermediate B.
However, we also thought the possibility that t-BuO radical is capable of abstracting
a hydrogen atom from acetonitrile to produce a cyanomethyl radical.12b-c Cu-catalyzed
β-H elimination of the intermediate B yields the desired product 2a. However, the
addition of NiCl2 dramatically increases the yield of 2a. We considered the nickel
catalyst plays an essential role in this reaction through transmetalation to produce the
intermediate C, which shows the superior ability of nickel catalyst in the process of β-
H elimination,18 giving the β,γ-unsaturated nitrile 2a. Subsequently, through the
release of one molecule of HX, the H-Ni-X complex affords Ni(0) species, which are
oxidized into a Ni(II) complex by TBPB again.
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In conclusion, we report an efficient and direct CDC process that provides β,γ-
unsaturated nitriles through the use of simple alkenes and acetonitrile as starting
materials catalyzed by copper and nickel complexes. The Cu/Ni-catalyzed direct
coupling of alkene sp2 C–H bond and acetonitrile sp3 C–H bond is the first example of
the synthesis of β,γ-unsaturated nitriles. Notably, acetonitrile, a cheap and stable
solvent, is discovered to be a useful cyanomethyl source. The combination of copper
and nickel catalysts results in a highly efficient reaction. Formal synthesis of
amitriptyline implies that our method may be applicable in the development of
medicines.
■ EXPERIMENTAL SECTION
General Considerations
All solvents were dried and distilled before using according to the standard methods.
Analytical thin layer chromatography (TLC) was performed on percolated silica gel
60 F254 plates. Visualization on TLC was achieved with UV light (254 nm) and
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potassium permanganate as visualization methods. H and 13C NMR spectra were
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recorded on Bruker-400 (400 MHz) and Bruker-500 (500 MHz). Data for H NMR
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spectra are reported as follows: chemical shift (δ shift), multiplicity (s = singlet, d =
doublet, t = triplet, q = quartet, m = multiplet, dd = double of doublet, ddd = double of
dd, dt = double of triplet, td = triple of doublet), integration, coupling constant (Hz),
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and assignment. Data for C NMR spectra are reported as follows: Chemical shifts
were reported in ppm referenced to the center line of a triplet at 77.0 ppm of
chloroform-d. High resolution mass spectra were obtained with ACQUITYTM UPLC
& Q-TOF MS Premier Spectrometer. Note: the operator should check whether
peroxides is left before evaporating the solvent, otherwise explosions can occur.
General procedure for the preparation of substrates
Methyltriphenylphosphonium bromide (3 equiv, 4.29 g) was added into dry THF (20
mL) and cooled to 0 °C. Tert-BuOK (3 equiv, 1.35 g) was added in one portion and
the reaction was stirred at 0 °C for 30 min. Ketone (1 equiv, 4 mmol) was added and
the reaction was let to warm to R.T. and stirred until completion observed by TLC (2
to 16 h). The reaction was quenched with H2O and extracted 3x with EtOAc. The
combined organic layers were washed with water and dried over Na2SO4, filtered and
concentrated under reduced pressure. The crude product was purified by flash column
chromatography on silica gel using EA/PE to give the pure alkene.
4,4'-(Ethene-1,1-diyl)bis(fluorobenzene) (1b)11d: White solid, 80% yield (691mg);
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The eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.32–7.24 (m, 4H), 7.02 (t, J = 8.6 Hz, 4H), 5.39 (s, 2H).
4,4'-(Ethene-1,1-diyl)bis(chlorobenzene)(1c) 11d:White solid, 61% yield (608mg);
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The eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.31 (d, J = 8.6 Hz, 4H), 7.24 (d, J = 8.6 Hz, 4H), 5.45 (s, 2H).
4,4'-(Ethene-1,1-diyl)bis(methylbenzene)(1d)11d: colorless oil, 56% yield (466mg);
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The eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.25–7.22 (m, 4H), 7.13 (d, J = 8.0 Hz, 4H), 5.38 (s, 2H), 2.36 (s,
6H).
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1-Chloro-2-(1-phenylvinyl)benzene(1e)19: colorless oil, 64% yield (550 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
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Chloroform-d) δ 7.40–7.36 (m, 1H), 7.32– 7.24 (m, 8H), 5.82 (s, 1H), 5.27 (s, 1H).
1-Bromo-2-(1-phenylvinyl)benzene(1f)20: colorless oil, 53% yield (549 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.58 (d, J = 7.7 Hz, 1H), 7.28 (qd, J = 7.3, 2.6 Hz, 7H), 7.22–7.16
(m, 1H), 5.83 (d, J = 0.9 Hz, 1H), 5.26 (d, J = 0.9 Hz, 1H).
1-Fluoro-2-(1-phenylvinyl)benzene(1g)21: colorless oil, 77% yield (609 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.43–7.31 (m, 7H), 7.25–7.11 (m, 2H), 5.83 (s, 1H), 5.50 (s, 1H).
1-Methyl-2-(1-phenylvinyl)benzene(1h)11d:colorless oil, 79% yield (613 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.29–7.16 (m, 9H), 5.76 (s, 1H), 5.19 (s, 1H), 2.05 (s, 3H).
1-Fluoro-4-(1-phenylvinyl)benzene(1i)11d: colorless oil, 68% yield (538 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.33–7.27 (m, 7H), 7.00 (t, J = 8.7 Hz, 2H), 5.42 (d, J = 9.0 Hz, 2H).
1-Chloro-4-(1-phenylvinyl)benzene(1j)19: colorless oil, 73% yield (628 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.33–7.30 (m, 4H), 7.28 (d, J = 6.1 Hz, 3H), 7.25 (d, J = 1.9 Hz,
1H), 7.23–7.14 (m, 1H), 5.45 (dd, J = 7.4, 0.9 Hz, 2H).
1-Bromo-4-(1-phenylvinyl)benzene(1k)11d: colorless oil, 65% yield (673 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.47–7.43 (m, 2H), 7.32 (q, J = 4.1, 3.2 Hz, 5H), 7.22–7.19 (m, 2H),
5.45 (d, J = 6.9 Hz, 2H).
1-Methyl-4-(1-phenylvinyl)benzene(1l)11d: colorless oil, 69% yield (535 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.32 (dd, J = 5.7, 3.1 Hz, 5H), 7.25–7.21 (m, 2H), 7.14 (d, J = 8.0
Hz, 2H), 5.42 (dd, J = 11.2, 1.1 Hz, 2H), 2.36 (s, 3H).
1-Methyl-3-(1-phenylvinyl)benzene)(1m)11d: colorless oil, 51% yield (395 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
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Chloroform-d) δ 7.34 (d, J = 6.5 Hz, 5H), 7.21 (d, J = 7.1 Hz, 1H), 7.16 – 7.11 (m,
3H), 5.44 (s, 2H), 2.34 (s, 3H).
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1-Bromo-4-(prop-1-en-2-yl)benzene(1t)22: colorless oil, 64% yield (504 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
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Chloroform-d) δ 7.44 (dd, J = 8.6, 2.3 Hz, 2H), 7.32 (dd, J = 8.7, 2.1 Hz, 2H), 5.36 (s,
1H), 5.10 (s, 1H), 2.12 (s, 3H).
1-Methyl-4-(prop-1-en-2-yl)benzene(1u)22: colorless oil, 69% yield (364 mg); The
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eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.36 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 8.0 Hz, 2H), 5.33 (s, 1H), 5.03
(s, 1H), 2.34 (s, 3H), 2.13 (s, 3H).
1-(Tert-butyl)-4-(prop-1-en-2-yl)benzene(1v)22: colorless oil, 76% yield (529 mg);
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The eluent used was ethyl acetate/petroleum ether (1:100): H NMR (400 MHz,
Chloroform-d) δ 7.42 (dd, J = 8.3, 1.6 Hz, 2H), 7.35 (dd, J = 8.5, 1.5 Hz, 2H), 5.35 (s,
1H), 5.04 (s, 1H), 2.14 (s, 3H), 1.32 (s, 9H).
Procedure for the synthesis of compound 1q23: P(OPh)3 (9.16 mL, 35 mmol) was
o
added into CH2Cl2 (200 mL) and cooled to -40 C . Br2 (1.95 mL, 38 mmol) was
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added and the reaction was stirred at -40 C for 10 min. NEt3 (5.56 mL) and ketone
o
(30 mmol) were added consecutively. The mixture was stirred at -40 C for 20 h and
was then allowed to warm to room temperature. Saturated Na2S2O3 solution (50 mL)
was added to quench the remaining bromine. The solution was extracted with CH2Cl2
(20 mL x 3), dried over Na2SO4, filtered and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography to give.1-(1-
Bromovinyl)-4-methylbenzene (1q) (colorless oil, 42 % yield (2.5g)). The eluent
used was ethyl acetate/petroleum ether (1:100): 1H NMR (400 MHz, Chloroform-d) δ
7.48 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.2 Hz, 2H), 6.07 (d, J = 1.9 Hz, 1H), 5.71 (d, J
= 1.9 Hz, 1H), 2.35 (s, 3H).
General procedure for Cu/Ni-catalyzed cyanomethylation of alkenes with
acetonitrile for the synthesis of β,γ-Unsaturated nitriles
Cu(OTf)2 (20 mol%, 14.5 mg) and 1,10-Phen (20 mol%, 7.2 mg) were dissolved in
dry and degassed acetonitrile (2.0 mL) in a sealed tube and stirred at room
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temperature under a nitrogen atmosphere for 20 minutes. After that, NiCl2(DME) (20
mol%, 8.8 mg), corresponding alkenes (1 equiv, 0.2 mmol), TBPB (3 equiv, 117 mg)
were added and the mixture solution was heated at 120 oC in oil bath for the indicated
time. The reaction mixture was filtered and concentrated under reduced pressure
(please first check for the presence of peroxides), the crude product was purified by
column chromatography using EA/PE to give the corresponding products.
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4,4-Diphenylbut-3-enenitrile (2a)24: Yellow oil, 71% yield (31 mg), 3h; The eluent
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used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz, Chloroform-d) δ
7.45–7.38 (m, 3H), 7.31–7.29 (m, 3H), 7.22 (dd, J = 6.8, 3.0 Hz, 2H), 7.19–7.16 (m,
2H), 6.04 (t, J = 7.4 Hz, 1H), 3.15 (d, J = 7.4 Hz, 2H). HRMS (ESI) m/z: [M+ H]+
calcd for C16H14N 220.1121; found 220.1121.
4,4-Bis(4-fluorophenyl)but-3-enenitrile (2b)24: Yellow oil, 71% yield (36 mg), 6 h;
1
The eluent used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz,
Chloroform-d) δ 7.19–7.13 (m, 6H), 7.00 (t, J = 8.6 Hz, 2H), 5.99 (t, J = 7.4 Hz, 1H),
3.13 (d, J = 7.4 Hz, 2H). HRMS (ESI) m/z: [M+H]+ calcd for C16H12F2N 256.0932;
found 256.0934.
4,4-Bis(4-chlorophenyl)but-3-enenitrile (2c): Yellow oil, 64% yield( 37 mg), 6h;
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The eluent used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz,
Chloroform-d) δ 7.42 (d, J = 8.5 Hz, 2H), 7.32–7.28 (m, 2H), 7.12 (t, J = 8.8 Hz, 4H),
6.04 (t, J = 7.4 Hz, 1H), 3.13 (d, J = 7.4 Hz, 2H). 13C{1H} NMR (126 MHz,
Chloroform-d) δ 145.4 , 138.7 , 135.8 , 134.5 , 130.7 , 129.2 , 128.6 , 117.6 , 116.4 ,
18.3. HRMS (ESI) m/z: [M+Na]+ calcd for C16H11Cl2NNa 310.0161; found 310.0163.
4,4-Di-p-tolylbut-3-enenitrile (2d): Yellow oil, 71% yield (35 mg), 6h; The eluent
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used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz, Chloroform-d) δ
7.22 (d, J = 7.9 Hz, 2H), 7.14– 7.03 (m, 6H), 5.96 (t, J = 7.4 Hz, 1H), 3.14 (d, J = 7.4
Hz, 2H), 2.36 (d, J = 23.7 Hz, 6H). 13C{1H} NMR (126 MHz, Chloroform-d) δ 138.2 ,
138.0 , 135.3 , 130.0 , 129.4 , 129.1 , 127.5 , 118.5 , 114.4 , 21.4, 18.5. HRMS (ESI)
m/z: [M+Na]+ calcd for C18H17NNa 270.1253; found 270.1253.
4-(2-Chlorophenyl)-4-phenylbut-3-enenitrile(2e): Mixture of isomers (6:1,
major/minor calculated via 1H NMR integration). Yellow oil, 78%yield (39 mg), 16 h;
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The eluent used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz,
Chloroform-d,E/Z mixture) δ major isomer—7.49 (dd, J = 6.0, 3.3 Hz, 1H), 7.36 (dd,
J = 5.9, 3.4 Hz, 2H), 7.30 (dd, J = 5.3, 1.9 Hz, 3H), 7.22 (dt, J = 6.5, 3.2 Hz, 3H),
6.19 (t, J = 7.2 Hz, 1H), 3.12–2.93 (m, 2H); minor isomer—7.49 (dd, J = 6.0, 3.3 Hz,
1H), 7.36 (dd, J = 5.9, 3.4 Hz, 2H), 7.30 (dd, J = 5.3, 1.9 Hz, 3H), 7.22 (dt, J = 6.5,
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3.2 Hz, 3H), 5.78 (d, J = 7.4 Hz, 1H), 3.32 (d, J = 7.4 Hz, 2H). C {1H}NMR (126
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MHz, Chloroform-d, E/Z mixture) δ 145.6 , 144.4 , 140.8 , 138.9 , 137.5 , 136.6 ,
133.6 , 131.3 , 131.2 , 130.2 , 129.9 , 129.7 , 129.3 , 129.1 , 128.7 , 128.6 , 128.5 ,
128.3 , 127.5 , 126.8 , 126.7 , 119.7 , 118.0 , 117.8 , 117.4 , 117.3 , 18.3 , 18.2. HRMS
(ESI) m/z: [M+Na]+ calcd for C16H12ClNNa 276.0550; found 276.0552.
4-(2-Bromophenyl)-4-phenylbut-3-enenitrile(2f): Mixture of isomers (7:1,
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major/minor calculated via H NMR integration). Yellow oil, 72% yield (43 mg), 16
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h; The eluent used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz,
Chloroform-d,E/Z mixture) δ major isomer—7.68 (dd, J = 8.0, 1.0 Hz, 1H), 7.41 (td,
J = 7.5, 1.1 Hz, 2H), 7.30 (dt, J = 3.9, 2.0 Hz, 3H), 7.24–7.20 (m, 3H), 6.21–6.16 (m,
1H), 3.11–2.91 (m, 2H); minor isomer—7.68 (dd, J = 8.0, 1.0 Hz, 1H), 7.41 (td, J =
7.5, 1.1 Hz, 2H), 7.30 (dt, J = 3.9, 2.0 Hz, 3H), 7.24–7.20 (m, 3H), 5.76 (t, J = 7.4 Hz,
1H), 3.33 (d, J = 7.4 Hz, 2H). 13C{1H} NMR (126 MHz, CDCl3, E/Z mixture) δ 145.8,
138.5, 133.3, 131.0, 129.8, 128.5, 128.3, 127.9, 126.6, 123.5, 117.6, 116.9, 18.2.
HRMS (ESI) m/z: [M+Na]+ calcd for C16H12BrNNa 320.0045; found 320.0050.
4-(2-Fluorophenyl)-4-phenylbut-3-enenitrile (2g): Mixture of isomers (4:1,
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major/minor calculated via H NMR integration). Yellow oil, 80% yield (38 mg), 16
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h; The eluent used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz,
Chloroform-d, E/Z mixture) δ major isomer—7.42–7.35 (overlapped, 1H), 7.31
(overlapped, 3H), 7.23 (overlapped, 3H), 7.20–7.13 (overlapped, 2H), 6.16 (t, J = 7.2
Hz, 1H), 3.10 (d, J = 7.2 Hz, 2H); minor isomer—7.42–7.35 (overlapped, 1H), 7.31
(overlapped, 3H), 7.23 (overlapped, 3H), 7.20–7.13 (overlapped, 2H), 6.03 (t, J = 7.4
Hz, 1H), 3.22 (d, J = 7.4 Hz, 2H). C{1H} NMR (126 MHz, CDCl3, E/Z mixture) δ
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142.2, 140.9, 139.6, 137.8, 131.5, 131.4, 131.0, 131.0, 130.4, 130.4, 129.7, 129.6,
128.8, 128.7, 128.5, 128.3, 128.1, 126.8, 124.6, 124.6, 124.0, 124.0, 119.6, 119.5,
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117.9, 116.2, 116.1, 116.1, 116.0, 18.3. HRMS (ESI) m/z: [M+H]+ calcd for
C16H13FN 238.1027; found 238.1028.
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4-Phenyl-4-(o-tolyl)but-3-enenitrile(2h)24: Mixture of isomers (3:1, major/minor
calculated via 1H NMR integration). Yellow oil, 73% yield (34 mg), 16 h; The eluent
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used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz, Chloroform-d,
E/Z mixture) δ major isomer—7.31–7.26 (m, 6H), 7.22 (m, 2H), 7.18–7.08 (m, 1H),
6.16 (t, J = 7.2 Hz, 1H), 2.99 (dd, J = 7.2, 4.2 Hz, 2H), 2.06 (s, 3H); minor isomer—
7.31–7.26 (m, 6H), 7.22 (m, 2H), 7.18–7.08 (m, 1H), 5.70 (t, J = 7.5 Hz, 1H), 3.32
(dd, J = 7.5 Hz, 2H), 2.04 (s, 3H). HRMS (ESI) m/z: [M+H]+ calcd for C17H16N
234.1277; found 234.1277.
4-(4-Fluorophenyl)-4-phenylbut-3-enenitrile (2i)24: Equal E/Z mixture( calculated
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via H NMR integration). Yellow oil, 72%yield (34 mg), 16 h; The eluent used was
ethyl acetate/petroleum ether (1:30): 1H NMR (400 MHz, Chloroform-d, E/Z mixture)
δ first isomer—7.41 (overlapped, 2H), 7.32–7.29 (overlapped, 1H), 7.22–7.10
(overlapped, 5H), 7.01–6.96 (overlapped, 1H), 6.04 (t, J = 7.4 Hz, 1H), 3.13 (s, 2H);
second isomer—7.41 (overlapped, 2H), 7.32–7.29 (overlapped, 1H), 7.22–7.10
(overlapped, 5H), 7.01–6.96 (overlapped, 1H), 5.98 (t, J = 7.4 Hz, 1H), 3.14 (s, 2H).
HRMS (ESI) m/z: [M+Na]+ calcd for C16H12FNNa 260.0846; found 260.0853.
4-(4-Chlorophenyl)-4-phenylbut-3-enenitrile (2j)24: Equal E/Z mixture( calculated
1
via H NMR integration). Yellow oil, 67% yield (34 mg), 16 h; The eluent used was
ethyl acetate/petroleum ether (1:30): 1H NMR (500 MHz, Chloroform-d, E/Z mixture)
δ first isomer—7.43–7.40 (overlapped, 2H), 7.34 (overlapped, 2H), 7.3–7.30
(overlapped, 3H), 7.16–7.14 (overlapped, 2H), 6.06–6.04 (m, 1H), 3.13 (d, J = 2.6 Hz,
2H); second isomer—7.43–7.40 (overlapped, 2H), 7.34 (overlapped, 2H), 7.3–7.30
(overlapped, 3H), 7.16–7.14 (overlapped, 2H), 6.04–6.01 (m, 1H), 3.15 (d, J = 2.5 Hz,
2H). HRMS (ESI+) m/z: [M+Na]+ calcd for C16H12ClNNa 276.0550; found 276.0552.
4-(4-Bromophenyl)-4-phenylbut-3-enenitrile (2k)24: Equal E/Z mixture( calculated
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via H NMR integration). Yellow oil, 65% yield (39 mg), 16 h; The eluent used was
ethyl acetate/petroleum ether (1:30): 1H NMR (400 MHz, Chloroform-d, E/Z mixture)
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δ first isomer—7.56 (overlapped, 1H), 7.44–7.38 (overlapped, 3H), 7.31–7.29
(overlapped, 1H), 7.21–7.18 (overlapped, 1H), 7.16–7.13 (overlapped, 1H), 7.07
(overlapped, 2H), 6.06 (d, J = 7.5 Hz, 1H), 3.12 (s, 2H); second isomer—7.56
(overlapped, 1H), 7.44–7.38 (overlapped, 3H), 7.31–7.29 (overlapped, 1H), 7.21–7.18
(overlapped, 1H), 7.16–7.13 (overlapped, 1H), 7.07 (overlapped, 2H), 6.02 (d, J = 7.4
Hz, 1H), 3.14 (s, 2H). HRMS (ESI) m/z: [M+Na]+ calcd for C16H12BrNNa 320.0045;
found 320.0047.
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4-Phenyl-4-(p-tolyl)but-3-enenitrile (2l)24: Mixture of isomers (2:1, major/minor
calculated via 1H NMR integration). Yellow oil, 75% yield (35 mg), 16 h; The eluent
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used was ethyl acetate/petroleum ether (1:30): H NMR (400 MHz, Chloroform-d,
E/Z mixture) δ major isomer—7.45–7.37 (m, 3H), 7.29 (overlapped, 1H), 7.23
(overlapped, 1H), 7.17 (overlapped, 1H), 7.11 (overlapped, 2H), 7.06 (d, J = 8.0 Hz,
1H), 6.00 (t, J = 7.4 Hz, 1H), 3.13 (d, J = 7.4 Hz, 2H), 2.34 (s, 3H); minor isomer—
7.45–7.37 (m, 3H), 7.29 (overlapped, 1H), 7.23 (overlapped, 1H), 7.17 (overlapped,
1H), 7.11 (overlapped, 2H), 7.06 (d, J = 8.0 Hz, 1H), 6.00 (t, J = 7.4 Hz, 1H), 3.16 (d,
J = 7.4 Hz, 2H), 2.40 (s, 3H). HRMS (ESI+) m/z: [M+Na]+ calcd for C17H15NNa
256.1097; found 256.1102.
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4-Phenyl-4-(m-tolyl)but-3-enenitrile(2m): Equal E/Z mixture (calculated via H
NMR integration). Yellow oil, 69% yield (32 mg), 16 h; The eluent used was ethyl
1
acetate/petroleum ether (1:30): H NMR (400 MHz, Chloroform-d, E/Z mixture) δ
first isomer—7.40 (overlapped, 2H), 7.30 (overlapped, 2H), 7.23( overlapped, 1H),
7.17 (overlapped, 2H), 7.11–6.96 (overlapped, 2H), 6.02 (overlapped, 1H), 3.13 (d, J
= 4.1 Hz, 2H), 2.31 (s, 3H); second isomer—7.40 (overlapped, 2H), 7.30 (overlapped,
2H), 7.23( overlapped, 1H), 7.17 (overlapped, 2H), 7.11–6.96 (overlapped, 2H), 6.02
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(overlapped, 1H), 3.15 (d, J = 4.1 Hz, 2H), 2.37 (s, 3H). C{1H} NMR (126 MHz,
Chloroform-d) δ 147.8 , 140.9 , 140.8 , 138.7 , 138.2 , 138.1 , 138.1 , 130.0 , 129.5 ,
129.1 , 129.0 , 128.9 , 128.8 , 128.5 , 128.4 , 128.3 , 128.2 , 128.2 , 127.5 , 126.5 ,
118.3 , 118.3 , 115.4 , 21.6 , 21.5 , 18.5 , 18.5. HRMS (ESI) m/z: [M+Na]+ calcd for
C17H15NNa 256.1097; found 256.1109.
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4-Bromo-4-phenylbut-3-enenitrile(2p): Equal E/Z mixture. Yellow oil, 52% yield
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(23 mg) ,16 h; The eluent used was ethyl acetate/petroleum ether (1:30): H NMR
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(400 MHz, Chloroform-d, E/Z mixture) δ first isomer—7.53 (d, J = 9.6 Hz, 2H), 7.38
(d, J = 4.1 Hz, 3H), 6.23 (t, J = 6.6 Hz, 1H), 3.45 (d, J = 6.6 Hz, 2H); second
isomer—7.53 (d, J = 9.6 Hz, 2H), 7.38 (d, J = 4.1 Hz, 3H), 6.23 (t, J = 6.6 Hz, 1H),
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3.45 (d, J = 6.6 Hz, 2H). C{1H} NMR (126 MHz, Chloroform-d, E/Z mixture) δ
138.4 , 131.6 , 129.7 , 128.7 , 127.7 , 118.7 , 116.9 , 21.2. HRMS (ESI) m/z: [M+Na]+
calcd for C10H8BrNNa 243.9732; found 243.9735.
4-Bromo-4-(p-tolyl)but-3-enenitrile (2q): Equal E/Z mixture. Yellow oil, 57% yield
1
(27 mg), 16 h; The eluent used was ethyl acetate/petroleum ether (1:30): H NMR
(400 MHz, Chloroform-d, E/Z mixture) δ first isomer—7.42 (d, J = 8.3 Hz, 2H), 7.17
(d, J = 7.9 Hz, 2H), 6.18 (t, J = 6.6 Hz, 1H), 3.43 (d, J = 6.6 Hz, 2H), 2.37 (s, 3H);
second isomer—7.42 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 7.9 Hz, 2H), 6.18 (t, J = 6.6 Hz,
1H), 3.43 (d, J = 6.6 Hz, 2H), 2.37 (s, 3H). 13C{1H} NMR (126 MHz, Chloroform-d,
E/Z mixture) δ 139.8 , 135.4, 131.6, 129.2 , 127.5 ,117.6 , 116.8 , 21.0. HRMS (ESI)
m/z: [M+Na]+ calcd for C11H10BrNNa 257.1129; found 257.1131.
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(E)-4-Phenylpent-3-enenitrile (2r)25: H NMR (500 MHz, Chloroform-d) δ 7.35
(overlapped, 5H), 5.71 (t, J = 7.0 Hz, 1H), 3.26 (d, J = 7.8 Hz, 2H), 2.10 (s, 3H). 4-
1
phenylpent-4-enenitrile (2r’)13: H NMR (500 MHz, Chloroform-d) δ 7.35
(overlapped, 5H), 5.42 (s, 1H), 5.21 (s, 1H), 2.87 (t, J = 7.9 Hz, 2H), 2.47 (t, J = 7.4
Hz, 2H). Mixture, 2r:2r’ = 1:1. Yellow oil, 67% yield (21 mg), 16 h. The eluent used
was ethyl acetate/petroleum ether (1:30): HRMS (ESI) m/z: [M+Na]+ calcd for
C11H11NNa 180.0784; found 180.0786.
(E)-4-(4-Fluorophenyl)pent-3-enenitrile (2s): 1H NMR (400 MHz, Chloroform-d) δ
7.37–7.30 (overlapped, 2H), 7.07–7.00 (overlapped, 2H), 5.66 (t, J = 7.7 Hz, 1H),
3.24 (d, J = 7.0 Hz, 2H), 2.08 (s, 3H). 4-(4-fluorophenyl)pent-4-enenitrile (2s’): 1H
NMR (400 MHz, Chloroform-d) δ 7.37–7.30 (overlapped, 2H), 7.07–7.00
(overlapped, 2H), 5.36 (s, 1H), 5.19 (s, 1H), 2.83 (t, J = 7.3 Hz, 2H), 2.47 (t, J = 7.3
Hz, 2H). Mixture, 2s:2s’ = 1:1.Yellow oil, 49% yield (17 mg),16h; The eluent used
13
was ethyl acetate/petroleum ether (1:30): C{1H} NMR (126 MHz, Chloroform-d,
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mixture) δ 163.7 , 161.6 , 143.9 , 140.5 , 138.1 , 135.5 , 127.9 , 127.9 , 127.6 , 127.6 ,
119.1 , 118.1 , 115.8 , 115.6 , 115.5 , 115.3 , 115.0 , 114.7 , 31.5 , 17.1 , 16.6. HRMS
(ESI) m/z: [M+Na]+ calcd for C11H10FNNa 198.0689; found 198.0690.
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(E)-4-(4-Bromophenyl)pent-3-enenitrile (2t): 1H NMR (400 MHz, Chloroform-d) δ
7.47 (overlapped, 2H), 7.26–7.21 (overlapped, 2H), 5.70 (t, J = 7.6 Hz, 1H), 3.24 (d, J
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= 7.0 Hz, 2H), 2.07 (s, 3H). 4-(4-bromophenyl)pent-4-enenitrile (2t’): H NMR
(400 MHz, Chloroform-d) δ 7.47 (overlapped, 2H), 7.26–7.21 (overlapped, 2H), 5.41
(s, 1H), 5.23 (s, 1H), 2.82 (t, J = 7.3 Hz, 2H),2.46 (t, J = 7.3 Hz, 2H). Mixture,
2t:2t’=2:1. Yellow oil, 57% yield (27 mg), 16h; The eluent used was ethyl
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acetate/petroleum ether (1:30): C{1H} NMR (126 MHz, Chloroform-d, mixture) δ
140.9 , 140.4 , 138.3 , 131.9 , 131.6 , 127.8 , 127.6 , 122.2 , 121.9 , 119.0 , 117.9 ,
115.6 , 115.3 , 31.1 , 17.1 , 16.5 , 16.3. HRMS (ESI) m/z: [M+Na]+ calcd for
C11H10BrNNa 257.9889; found 257.9890.
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(E)-4-(p-Tolyl)pent-3-enenitrile (2u)25: H NMR (400 MHz, Chloroform-d) δ 7.25
(d, J = 2.2 Hz, 2H), 7.15 (overlapped, 2H), 5.67 (t, J = 7.6 Hz, 1H), 3.23 (d, J = 7.0
1
Hz, 2H), 2.35 (overlapped, 3H), 2.07 (s, 3H). 4-(p-tolyl)pent-4-enenitrile(2u’)13: H
NMR (400 MHz, Chloroform-d) δ 7.25 (d, J = 2.2 Hz, 2H), 7.15 (overlapped, 2H),
5.38 (s, 1H), 5.15 (s, 1H), 2.83 (t, J = 7.4 Hz, 2H), 2.45 (t, J = 7.4 Hz, 2H), 2.35
(overlapped, 3H). Mixture, 2u:2u’ = 3:1. Yellow oil, 53% yield (18 mg), 16 h; The
eluent used was ethyl acetate/petroleum ether (1:30): HRMS (ESI) m/z: [M+Na]+
calcd for C12H13NNa 194.0940; found 194.0942.
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(E)-4-(4-(Tert-butyl)phenyl)pent-3-enenitrile (2v): H NMR (500 MHz, Chloro-
form-d) δ 7.39–7.35 (overlapped, 2H), 7.33–7.30 (overlapped, 2H), 5.72–5.68 (m,
1H), 3.25( d, J=7.0 Hz, 2H), 2.09 (s, 3H), 1.32 (overlapped, 9H).
4-(4-(Tert-butyl)phenyl)pent-4-enenitrile (2v’): 1H NMR (500 MHz, Chloroform-d)
δ 7.39–7.35 (overlapped, 2H), 7.33–7.30 (overlapped, 2H), 5.40 (s, 1H), 5.16 (s, 1H),
2.85 (t, J = 7.8 Hz, 2H), 2.48 (t, J = 7.4 Hz, 2H), 1.32 (overlapped, 9H). Mixture,
2v:2v’ = 1:1. Yellow oil, 68% yield (29 mg), 52 h; The eluent used was ethyl
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acetate/petroleum ether (1:30): C{1H} NMR (126 MHz, Chloroform-d, mixture) δ
134.3 , 132.9 , 126.2 , 125.6 , 117.4 , 115.8 , 34.6 , 31.2 , 20.7. HRMS (ESI) m/z:
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[M+Na]+ calcd for C15H19NNa 236.1410; found 236.1412.
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3-(10,11-Dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propanenitrile(2y)24:
Yellow oil, 66 % yield (32 mg), 59 h; The eluent used was ethyl acetate/petroleum
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ether (1:30): H NMR (400 MHz, Chloroform-d) δ 7.29 (dd, J = 7.2, 1.8 Hz, 1H),
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7.26 – 7.16 (m, 5H), 7.12 (s, 1H), 7.08–7.05 (m, 1H), 5.86 (t, J = 7.4 Hz, 1H), 3.33 (t,
J = 17.5 Hz, 2H), 3.15 (dd, J = 18.6, 7.3 Hz, 2H), 2.96 (t, J = 13.9 Hz, 1H), 2.84–2.76
(m, 1H). HRMS (ESI) m/z: [M+Na]+ calcd for C18H15NNa 268.1097; found 268.1095.
Prop-1-ene-1,1-diyldibenzene (3a)26: Colorless oil. 21% yield (8 mg), 3h. The eluent
1
used was ethyl acetate/petroleum ether (1:50): H NMR (400 MHz, Chloroform-d) δ
7.40–7.35 (m, 2H), 7.33–7.26 (m, 2H), 7.24 –7.17 (m, 6H), 6.18 (q, J = 7.0 Hz, 1H),
1.76 (d, J = 7.0 Hz, 3H). HRMS (ESI) m/z: [M+H]+ calcd for C15H15 195.1195; found
195.1193.
The synthesis of 3-(3,4-Dihydronaphthalen-1-yl)propanenitrile (5)13: Cu(OTf)2
(20 mol%, 14.5 mg) and 1,10-Phen (20 mol%, 7.2 mg) were dissolved in dry and
degassed acetonitrile (2.0 mL) in the sealed tube and stirred at room temperature
under nitrogen for 20 minutes. After that, NiCl2(DME) (20 mol%, 8.8 mg), (1-
cyclopropylvinyl)benzene(0.2 mmol, 28.8 mg), TBPB (3 equiv, 117 mg) were added
o
and the mixture solution was heated at 120 C in oil bath for 16 h. The reaction
mixture was filtered and concentrated under reduced pressure, the crude product was
purified by column chromatography to give the corresponding product 511 (colorless
oil, yield: 57% (21 mg)). The eluent used was ethyl acetate/petroleum ether (1:30): 1H
NMR (400 MHz, Chloroform-d) δ 7.20–7.11 (m, 4H), 6.00 (t, J = 4.6 Hz, 1H), 2.84–
2.74 (m, 4H), 2.57 (t, J = 7.4 Hz, 2H), 2.33–2.26 (m, 2H). HRMS (ESI) m/z: [M+H]+
calcd for C13H14N 184.1097; found 184.1099.
Supporting Information Available. Copies of 1H NMR and 13C NMR spectra for all
new products. These materials are available free of charge via the Internet at
http://pubs.acs.org.
Acknowledgments
This work was supported by the National Natural Sciences Foundation of China (No.
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21672144) and the Shanghai Key Laboratory for Molecular Engineering of Chiral
Drugs (No. 17DZ2260400). We are grateful to the Instrumental Analysis Center of
Shanghai Jiao Tong University for compound analysis.
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