Nickel-Catalyzed Transformation of Alkene-Tethered Oxime Ethers to Nitriles by a Traceless Directing Group Strategy

Article abstract of DOI:10.1021/acs.joc.9b02705

Nickel-catalyzed transformation of alkene-tethered oxime ethers to nitriles using a traceless directing group strategy has been developed. A series of alkene-tethered oxime ethers derived from benzaldehyde and cinnamyl aldehyde derivatives were converted into the corresponding benzonitriles and cinnamonitriles in 46-98% yields using the nickel catalyst system. Control experiments showed that the alkene group tethered to an oxygen atom on the oximes via one methylene unit plays a key role as a traceless directing group during the catalysis.

Full text of DOI:10.1021/acs.joc.9b02705

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Note
Nickel-Catalyzed Transformation of Alkene-Tethered Oxime
Ethers to Nitriles by a Traceless Directing Group Strategy
Yoshiyuki Takahashi, Hiroaki Tsuji, and Motoi Kawatsura
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02705 • Publication Date (Web): 26 Dec 2019
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Nickel-Catalyzed Transformation of Alkene-Tethered Oxime
Ethers to Nitriles by a Traceless Directing Group Strategy
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Yoshiyuki Takahashi, Hiroaki Tsuji*, and Motoi Kawatsura*
Department of Chemistry, College of Humanities & Sciences, Nihon University,
Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan
*E-mail: tsuji@chs.nihon-u.ac.jp
*E-mail: kawatsur@chs.nihon-u.ac.jp
Abstract: Nickel-catalyzed transformation of alkene-tethered oxime ethers to nitriles
using a traceless directing group strategy has been developed.
A series of
alkene-tethered oxime ethers derived from benzaldehyde and cinnamyl aldehyde
derivatives were converted into the corresponding benzonitriles and cinnamonitriles in
46–98% yields using the nickel catalyst system. Control experiments showed that the
alkene group tethered to an oxygen atom on the oximes via one methylene unit plays a
key role as a traceless directing group during the catalysis.
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The transition-metal-catalyzed substrate-directed reaction provides an
efficient tool accessing to complex organic molecules in chemo-, regio-, and
enantioselective fashions.1 Although the method has made a great contribution to the
progress of organic synthesis, the use of existing functional groups on the substrates is
necessary for achieving the directed reaction, and the installation of the directing group
and its removal are required via additional chemical steps. As one of the strategies
that overcomes these drawbacks, the traceless directing group strategy has recently
received much attention, because the directing group is tracelessly cleavable during the
catalysis.2 While this strategy has been utilized for the development of the
transition-metal-catalyzed C-H and B-H functionalization reactions,3,4 only scattered
attention has been paid for its application to the other organic transformations.5 Herein,
we report the nickel-catalyzed transformation of alkene-tethered oxime ethers to nitriles
using a traceless directing group strategy.
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Nitrile is one of the most important and fundamental constituents in
biologically active compounds,6 natural products,7 functional materials8 as well as
synthetic intermediates.9 Due to the prominent importance of the nitrile in organic
synthesis, various synthetic methods have already been developed.10 The catalytic
transformation of oxime derivatives into nitriles is one of the useful approaches for the
synthesis of nitriles.11,12 Although various catalyst systems have been established,
developing a novel method that utilizes oximes as an accessible starting material
continues to be an active area of research in the synthetic organic chemistry. In this
context, we envisioned that alkene-tethered oxime ethers would be converted into
nitriles in the presence of a transition metal catalyst, proving a novel method for the
catalytic synthesis of nitriles from oxime derivatives as shown in Scheme 1. Initially,
the oxidative addition of a N-O bond13 or an oxime C-H bond14 of the alkene-tethered
oxime ethers to a low valent metal center would occur via intermediate I to generate
intermediate II or III. As shown in intermediate I, we speculate that the oxidative
addition step might be accelerated by the directing effect of the alkene group to the
metal center.15 Subsequent -hydride elimination from intermediate II or -oxygen
elimination from intermediate III16 would produce intermediate IV that undergoes
reductive elimination to give the desired nitriles along with the formation of allyl
alcohol and regeneration of the low valent metal catalyst.
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Scheme 1. Our Working Hypothesis
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Based on this hypothesis, we initially examined the trans-formation of
alkene-tethered oxime ether 1a into benzonitrile (2a) in the presence of several
transition metals as the catalyst in THF at 60 ˚C for 17 h (Table 1). The
alkene-tethered oxime ether 1a can be easily prepared by the reaction of benzaldehyde
with O-allylhydroxylamine hydrochloride (Details for the preparation of alkene-tethered
oxime ethers, see experimental section). [Cp*Ru(CH3CN)3]PF6 showed the catalytic
activity in the transformation, producing benzonitrile (2a) in 79% GC yield (entry 1).
The use of [RhCl(cod)]2 and [IrCl(cod)]2 as the metal catalysts led to unsatisfactory
yields (Entries 2 and 3). We were pleased to find that Ni(cod)2 exhibited the high
catalytic activity, providing 2a in 95% GC yield (Entry 4). In contrast, the reaction did
not take place in the presence of Pd2(dba)3•CHCl3, Pd(PPh3)4, Pt(C2H4)(PPh3)2, and
CuCl as the catalysts (Entries 5–8). We next tested the other phosphine ligands using
Ni(cod)2 as the metal catalyst. The nickel catalyst systems consisting of DPPE and
DPPP as the bidentate ligands showed the poor catalytic activity (Entries 9 and 10).
The transformation of 1a in the presence of the Ni(cod)2/DPPB catalyst system afforded
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2a in 70% yield (Entry 11). When DPPPent, DPEphos, and Xantphos were used as the
ligands, the desired product 2a was formed in high yields (Entries 12–14).
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Table 1. Screening of Transition-metal Catalysts and Ligandsa
entry
1
conv.b (%)
88
yieldb (%)
79
M
L
[Cp*Ru(CH3CN)3]PF6
[RhCl(cod)]2
[IrCl(cod)]2
Ni(cod)2
DPPF
DPPF
DPPF
DPPF
DPPF
–
2c
3c
4
28
24
36
29
>99
7
95
5c
6
Pd2(dba)3•CHCl3
Pd(PPh3)4
Pt(C2H4)(PPh3)2
CuCl
<1
<1
<1
7
–
10
<1
8
DPPF
DPPE
DPPP
DPPB
DPPPent
DPEphos
Xantphos
PPh3
2
<1
9
Ni(cod)2
36
25
10
11
12
13
14
15d
16
Ni(cod)2
17
15
Ni(cod)2
80
70
Ni(cod)2
>99
>99
>99
>99
47
91
Ni(cod)2
98
Ni(cod)2
97
Ni(cod)2
87
Ni(cod)2
–
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aReaction conditions: 1a (0.3 mmol, as a 94:6 mixture of stereoisomers), M (0.03
mmol), L (0.03 mmol) in THF (1.2 mL) at 60 ˚C for 17 h. bDetermined by GC
analysis using n-octane as an internal standard. cWith 5 mol% metal catalysts. dWith
20 mol% of PPh3.
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In particular, a combination of Ni(cod)2 and DPEphos was the most effective for this
transformation, and the catalyst system furnished 2a in 98% GC yield (Entry 13).
Replacing the bidentate phosphine ligand to monodenate one led to a slight decrease of
the catalytic performance (Entry 15). The reaction also took place in the absence of
phosphine ligands to give 2a albeit with moderate yield (Entry 16).
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With a suitable metal catalyst in hand, we next investigated several control
experiments to elucidate the effect of the traceless directing group in this transformation
(Scheme 2). Initially, we evaluated the effect of the tether length between the terminal
alkene and oxygen atom on the oxime (Scheme 2, eq 1). When oxime ether 3
including two methylene units was subjected to the optimized reaction conditions, the
desired benzonitrile 2a was formed in only 7% GC yield. The use of oxime ether 4
bearing three methylene units also led to the diminished yield of 2a.
Scheme 2. Control Experiments
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We next examined the reaction of oxime 5 and oxime methyl ether 6 containing no
alkene groups. As a result, the reaction of these substrates yielded 2a in low yield
(Scheme 2, eq 2). These results indicated that the alkene group tethered to an oxygen
atom on the oxime via the one methylene unit is essential to proceed the directed
transformation.17,18 Additionally, we also carried out the transformation of secondary
oxime ether 7 under the same reaction conditions (Scheme 2, eq. 3). GC analysis of
the reaction mixture showed that 2a, 1-phenyl-2-propen-1-ol, and propiophenone19 were
formed in 98%, 82%, and 1% GC yield, respectively. This result indicated that the
present catalysis would be involved in the oxidative addition of a N-O bond or an oxime
C-H bond to Ni(0) and subsequent -hydride elimination or -oxygen
elimination/reductive elimination sequence as shown in Scheme 1.
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We next examined the transformation of alkene-tethered oxime ethers 1
bearing various substituents to nitriles under the optimized reaction conditions (Scheme
3). The reaction of oxime ether 1b bearing a 4-methoxyphenyl group proceeded
smoothly to give the desired benzonitrile derivative 2b in 85% yield. In addition, the
reaction could be carried out on a 3 mmol scale without any loss of the catalytic
performance, giving 2b in 89% yield. Electron-rich (1c, 1d) and -poor (1e, 1f)
substrates were well tolerated to give nitriles 2c–f in 71–90% yields.
4-Biphenylcarbonitrile (2g) was obtained in 77% yield by the reaction of oxime ether 1g
using triphenylphosphine as the ligand because nitrile 2g and DPEphos were
inseparable by silica-gel column chromatography. Oxime ethers 1h–j having methoxy
and cyano substituents at the meta-position on their phenyl ring also underwent the
reaction to afford the corresponding nitriles 2h–j in 57–82% yields. The reaction of
oxime ether 1k took place at 100 ˚C in 1,4-dioxane probably due to the steric effect of
the ortho methoxy group on the phenyl ring to give nitrile 2k in 57% yield.
Naphthonitriles (2l, 2n) and their derivatives (2m, 2o) were obtained in 64–94% yields
from the corresponding alkene-tethered oxime ethers 1l–o using the nickel catalyst
system. Although slightly harsh conditions were required, the present nickel catalysis
was also applicable to the transformation of oxime ethers derived from pyridine (1p)
and indole (1q), providing nitriles 2p and 2q in satisfactory yields. We also examined
the reaction of alkene-tethered oxime ethers bearing chlorine, bromine, amide, and nitro
groups on the phenyl rings. However, the reaction of these substrates did not work
well under the nickel catalysis. In addition, we also carried out the reaction of
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Scheme 3. Scope of Alkene-Tethered Oxime Ethers 1a
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aReaction conditions: 1 (0.6 mmol, as a mixture of stereoisomers), Ni(cod)2 (0.06
mmol), DPEphos (0.06 mmol) in THF (2.4 mL) at 60 ˚C for 17 h. Isolated yields were
shown. b3 mmol scale. cThe reaction was performed in 1,4-dioxane at 80 ˚C. dPPh3
(20 mol%) was used instead of DPEPhos. eThe reaction was performed in 1,4-dioxane
at 100 ˚C. fThe reaction was carried out for 48 h.
the aliphatic oxime ether having a phenethyl group, but the desired aliphatic nitrile was
not obtained.
We next turned our attention to the transformation of alkene-tethered oxime
ethers derived from cinnamyl aldehyde derivatives into alkenylnitriles using the
traceless directing group strategy (Scheme 4). The reaction of alkene-tethered oxime
ether 8a proceeded in the presence of 20 mol% of Ni(cod)2 and DPEphos at 100 ˚C to
give the desired cinnamonitrile (9a) in 57% yield. We assumed that the requirement of
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the slightly higher loading amount of the catalyst and elevated reaction temperature
would be attributed to the coordination of the alkene group of the substrate and the
product to the nickel center. p-Dimethylamino (8b), p-methoxy (8c), and p-fluoro (8d)
substituents on the phenyl rings did not affect the reaction efficiency, providing the
desired nitriles 9b–d in 62–67% yields. 4-Acetoxy-3-methoxyphenyl (8e) and furanyl
(8f) rings were compatible with the reaction conditions to give the desired nitriles 9e
and 9f in 64% and 51% yield, respectively. Oxime ether 8g bearing a methyl
substituent at the  position also be applicable to the nickel catalysis, affording
-methyl cinnamonitrile 9g in 77% yield. In addition, the reaction of 8h having a
phenyl group at the  position took place to give nitrile 9h in 57% yield.
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In conclusion, we have developed the nickel-catalyzed transformation of
alkene-tethered oxime ethers to nitriles in which the alkene group tethered to an oxygen
atom on the oxime via one methylene unit plays a critical role as a traceless directing
group. A wide variety of functionalized benzonitrile and cinnamyl nitrile derivatives
Scheme 4. Transformation of Alkene-Tethered Oxime Ethers 8 into Alkenylnitriles
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aReaction conditions: 8 (0.6 mmol, as a mixture of stereoisomers), Ni(cod)2 (0.12
mmol), DPEphos (0.12 mmol) in 1,4-dioxane (2.4 mL) at 100 ˚C for 17 h. Isolated
yields were shown.
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could be prepared in good yields by the nickel-catalyzed traceless directing group
strategy. The development of other organic transformations using the novel traceless
directing group is currently underway in our laboratory.
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Experimental Section
General Information
Commercially available chemicals were purchased from Aldrich, TCI, Kanto, and Wako
and used without further purification unless otherwise noted.
But-3-en-1-yl
4-methylbenzenesulfonate and pent-4-en-1-yl 4-methylbenzenesulfonate were prepared
by the reaction of the corresponding alcohols with TsCl. NMR spectra were recorded
at 25 ˚C on a JEOL EX-270 spectrometer (270 MHz for 1H, 67.8 MHz for 13C{1H}) or a
JEOL JNM ECP-500 spectrometer (126 MHz for 13C{1H}, 471 MHz for 19F).
Chemical shifts are reported in 
ppm) for 1H NMR. Chemical shifts of 13C NMR are given relative to the solvent peak
as an internal standard.
19F NMR data are reported relative to external
-trifluorotoluene (–63.7 ppm). Multiplicities are indicated as br (broad), s
(singlet), d (doublet), t (triplet), q (quartet), or m (multiplet). Coupling constants (J)
are reported in Hertz (Hz). Melting points were measured on a Yanako MP-500P.
Infrared (IR) spectra were recorded on JASCO FT/IR-460. GC analyses were carried
out using a SHIMADZU GC-2014AFsc. HRMS analyses were carried out using a
JEOL AccuTOF LCplus for ESI-MS and APCI-MS and JEOL GCmate for EI-MS.
Column chromatography and preparative thin-layer chromatography were conducted
with silica gel 60N (KANTO CHEMICAL, spherical, neutral, 40-50 or 63-210 m) and
Wakogel® B-5F (45 m), respectively. For thin-layer chromatography (TLC) analyses
throughout this work, Merck precoated TLC plates (silica gel 60 F254 0.25 mm) were
used. Visualization was accomplished by UV light (254 nm), phosphomolybdic acid.
Oil bath was used as the heat source for the reactions that require heating.
General procedure for the preparation of starting materials
Preparation of benzaldehyde O-allyl oxime (1a)20
Sodium acetate (615 mg, 7.5 mmol, 1.5 equiv) and O-allylhydroxylamine hydrochloride
(657 mg, 6.0 mmol 1.2 equiv) were charged into a round flask. After the addition of
MeOH (14 mL) and H2O (1.3 mL) into the flask, benzaldehyde (0.51 mL, 5.0 mmol)
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was added dropwise to the mixture at room temperature. The reaction mixture was
stirred at room temperature overnight. The resulting mixture was concentrated by
evaporation and then H2O was added. The resulting aqueous phase was extracted with
EtOAc (20 mL×3). The combined organic phase was washed with water (30 mL×3),
brine, dried over MgSO4. After removal of the solvent, the resulting crude mixture
was purified by silica gel column chromatography (Hexane/EtOAc = 99/1) to give
benzaldehyde O-allyl oxime (1a) as a yellow oil (541 mg, 3.35 mmol, 67% yield as a
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1
94:6 mixture of stereoisomers). H NMR (270 MHz, CDCl3): (major isomer)4.68
(ddd, J = 5.9 1.4, 1.4 Hz, 2H), 5.25 (ddt, J = 10.4, 1.6, 1.4 Hz, 1H), 5.36 (ddt, J = 17.3,
1.6, 1.4 Hz, 1H), 6.06 (ddt, J = 17.3, 10.4, 5.9 Hz, 1H), 7.33–7.42 (m, 3H), 7.55–7.64
(m, 2H), 8.12 (s, 1H); (minor isomer)4.73 (ddd, J = 5.7, 1.4, 1.4 Hz, 2H), 7.87–7.92
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(m, 2H), the other peaks were not found probably due to overlapping.; C{1H} NMR
(67.8 MHz, CDCl3): (major isomer) 75.0, 117.7, 126.9, 128.5, 129.6, 132.1, 134.0,
148.6;(minor isomer)  75.6, 117.4, 128.3, 129.8, 130.8, 134.1, 145.9, one peak was
not found probably due to overlapping; GC-MS (EI): m/z 160 [M-H]+.
4-Methoxybenzaldehyde O-allyl oxime (1b)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99/1). Pale yellow oil (155 mg, 0.812 mmol, 81% yield as a 93:7
mixture of stereoisomers); IR (neat) 3079, 2933, 2838, 1607, 1513, 1252, 1109, 1031,
1
831 cm–1; H NMR (270 MHz, CDCl3): (major isomer) 3.82 (s, 3H), 4.65 (ddd, J =
5.9, 1.4, 1.4 Hz, 2H), 5.24 (ddt, J = 10.4, 1.8, 1.4 Hz, 1H), 5.35 (ddt, J = 17.5, 1.8, 1.4
Hz, 1H), 6.05 (ddt, J = 17.5, 10.4, 5.9 Hz, 1H), 6.86–6.91 (m, 2H), 7.49–7.54 (m, 2H),
8.07 (s, 1H); (minor isomer)3.83 (s, 3H),4.71 (ddd, J = 5.7, 1.5, 1.5 Hz, 2H), 7.87–
13
7.90 (m, 2H), the other peaks were not found probably due to overlapping.; C{1H}
NMR (67.8 MHz, CDCl3): (major isomer) 55.3, 75.0, 114.1, 117.8, 128.5, 134.1,
148.5, 160.9, one peak for aromatic carbon was not found probably due to
overlapping(minor isomer)  75.6, 113.7, 124.8, 132.9, 145.7, the other peaks were
not found probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for
C11H14NO2 192.1025; Found 192.1022.
Benzo[d][1,3]dioxole-5-carbaldehyde O-allyl oxime (1c)
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This compound was prepared according to the similar method to 1a and the desired
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product was obtained after purification by silica gel column chromatography
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(Hexane/EtOAc = 99/1).
Yellow oil (563 mg, 2.74 mmol, 91% yield as a 99:1
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mixture of stereoisomers); IR (neat) 3081, 2989, 2904, 2782, 1595, 1504, 1449, 1250,
1038, 931, 809 cm–1; 1H NMR (270 MHz, CDCl3): (major isomer) 4.64 (ddd, J = 5.7,
1.4, 1.4 Hz, 2H), 5.24 (ddt, J = 10.1, 1.5, 1.4 Hz, 1H), 5.34 (ddt, J = 17.2, 1.5, 1.4 Hz,
1H), 5.97–6.12 (m, 3H), 6.79 (d, J = 8.1 Hz, 1H), 6.94 (dd, J = 8.1, 1.6 Hz, 1H), 7.20 (d,
J = 1.6 Hz, 1H), 8.02 (s, 1H); (minor isomer)4.70 (ddd, J = 5.9, 1.5, 1.5 Hz, 2H), the
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other peaks were not found probably due to overlapping.; C{1H} NMR (67.8 MHz,
CDCl3): (major isomer) 75.0, 101.3, 105.6, 108.2, 117.8, 122.8, 126.5, 134.0, 148.1,
148.4, 149.1; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C11H12NO3 206.0817; Found
206.0807.
3,4-Dimethoxybenzaldehyde O-allyl oxime (1d)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 9/1, 4/1, 7/3). Yellow oil (662 mg, 2.99 mmol, >99% yield as a
93:7 mixture of stereoisomers); IR (neat) 3081, 2935, 2837, 1602, 1514, 1264, 1027,
1
809 cm–1; H NMR (270 MHz, CDCl3): (major isomer) 3.90 (s, 3H), 3.92 (s, 3H),
4.67 (ddd, J = 5.9, 1.5, 1.5 Hz, 2H), 5.22–5.28 (m, 1H), 5.35 (ddt, J = 17.2, 1.8, 1.5 Hz,
1H), 6.06 (ddt, J = 17.2, 10.5, 5.9 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 7.01 (dd, J = 8.3,
1.8 Hz, 1H), 7.24 (d, J = 1.8 Hz 1H), 8.05 (s, 1H); (minor isomer)4.72 (ddd, J = 5.4,
1.3, 1.3 Hz 2H), 6.89 (d, J = 8.3 Hz 1H), 7.42 (dd, J = 8.3, 2.0 Hz, 1H), 7.64 (d, J = 2.0
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Hz, 1H), the other peaks were not found probably due to overlapping.; C{1H} NMR
(67.8 MHz, CDCl3): (major isomer) 55.7, 74.8, 107.8, 110.5, 117.7, 121.5, 124.9,
134.0, 148.5, 149.1, 150.5, one peak for methoxy carbon was not found probably due to
overlapping;(minor isomer)  75.5, 110.3, 113.6, 117.3, 124.8, 145.7, the other peaks
were not found probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd
for C12H16NO3 222.1130; Found 222.1133.
4-(((Allyloxy)imino)methyl)benzonitrile (1e)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
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(Hexane/EtOAc = 9/1, 4/1). White solid (529 mg, 2.84 mmol, 94% yield as a 84:16
mixture of stereoisomers); M.p. 48.5–50.4 ˚C; IR (KBr) 3087, 2921, 2866, 2227, 1604,
1109, 929, 835, cm–1; 1H NMR (270 MHz, CDCl3): (major isomer) 4.70 (ddd, J = 5.9,
1.4, 1.4 Hz, 2H), 5.26 (ddt, J = 10.5, 1.4, 1.4 Hz, 1H), 5.36 (ddt, J = 17.1, 1.4, 1.4 Hz,
1H), 6.04 (ddt, J = 17.1, 10.5, 5.9 Hz, 1H), 7.62–7.70 (m, 4H), 8.10 (s, 1H); (minor
isomer)4.75 (ddd, J = 5.7, 1.4, 1.4 Hz, 2H), 7.37 (s, 1H), 7.97–8.00 (m, 2H), the other
peaks were not found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3):
(major isomer) 75.9, 113.2, 118.6, 118.7, 127.6, 132.7, 133.9, 136.8, 147.2;(minor
isomer)  76.5, 113.4, 118.5, 131.3, 132.4, 134.3, 144.4, the other peaks were not found
probably due to overlapping; HRMS (EI) m/z: [M]+ Calcd for C11H10N2O 186.0793;
Found 186.0797.
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Methyl 4-(((allyloxy)imino)methyl)benzoate (1f)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 92/8, 9/1). White solid (632 mg, 2.88 mmol, 95% yield as a
92:8 mixture of stereoisomers); M.p. 36.1–38.3 ˚C; IR (KBr) 3086, 2958, 2873, 1719,
1
1609, 1285, 1038, 818 cm–1; H NMR (270 MHz, CDCl3): (major isomer) 
3H), 4.71 (ddd, J = 5.9, 1.5, 1.5 Hz, 2H), 5.27 (ddt, J = 10.5, 1.6, 1.5 Hz, 1H), 5.36 (ddt,
J = 17.2, 1.6, 1.5 Hz, 1H), 6.05 (ddt, J = 17.2, 10.5, 5.9 Hz, 1H), 7.63–7.67 (m, 2H),
8.01–8.06 (m, 2H), 8.14 (s, 1H); (minor

J = 5.7,
1.4, 1.4 Hz, 2H), 7.39 (s, 1H), 7.94–7.97 (m, 2H), 8.09 (m, 1H), the other peaks were
not found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major
isomer) 
minor
isomer)  52.2, 76.0, 117.8, 129.5, 130.6, 133.8, 145.0, the other peaks were not found
probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C12H14NO3
220.0974; Found 220.0976.
[1,1'-Biphenyl]-4-carbaldehyde O-allyl oxime (1g)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99/1). Pale yellow solid (677 mg, 2.85 mmol, 94% yield as a 97:3
mixture of stereoisomers); M.p. 42.0–44.1 ˚C; IR (KBr) 3085, 2925, 2871, 1607, 1035,
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832, 763 cm–1; H NMR (270 MHz, CDCl3): (major isomer) 4.69 (ddd, J = 5.9, 1.5,
1.5 Hz, 2H), 5.25 (ddt, J = 10.3, 1.6, 1.5 Hz, 1H), 5.34 (ddt, J = 17.4, 1.6, 1.5 Hz, 1H),
6.06 (ddt, J = 17.4, 10.3, 5.9 Hz, 1H), 7.31–7.37 (m, 1H), 7.39–7.46 (m, 2H), 7.56–7.66
(m, 6H), 8.14 (s, 1H); (minor isomer) 4.74 (ddd, J = 5.4, 1.5, 1.5 Hz, 2H), 7.95–7.98
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(m, 4H), the other peaks were not found probably due to overlapping.; C{1H} NMR
(67.8 MHz, CDCl3): (major isomer) 75.2, 118.0, 127.0, 127.3, 127.5, 127.7, 128.8,
131.1, 134.0, 140.3, 142.5, 148.5; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for
C16H16NO 238.1232; Found 238.1223.
3-Methoxybenzaldehyde O-allyl oxime (1h)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99/1). Yellow oil (495 mg, 2.59 mmol, 86% yield as a 96:4 mixture
of stereoisomers); IR (neat) 3078, 2920, 2836, 1599, 1577, 1264, 1041, 783 cm–1; H
1
NMR (270 MHz, CDCl3): (major isomer) 3.83 (s, 3H), 4.68 (ddd, J = 5.8, 1.5, 1.5 Hz,
2H), 5.22–5.28 (m, 1H), 5.35 (ddt, J = 17.1, 1.8, 1.5 Hz, 1H), 6.05 (ddt, J = 17.1, 10.3,
5.8 Hz, 1H), 6.92 (ddd, J = 8.1, 2.7, 0.95 Hz, 1H), 7.11–7.17 (m, 2H), 7.28 (dd, J = 8.1,
8.1 Hz, 1H), 8.08 (s, 1H); (minor isomer) 4.72 (ddd, J = 5.7, 1.5, 1.5 Hz, 2H), the
other peaks were not found probably due to overlapping.; C{1H} NMR (67.8 MHz,
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CDCl3): (major isomer) 55.3, 75.2, 111.1, 116.1, 118.0, 120.1, 129.6, 133.5, 133.9,
148.7, 159.7; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C11H14NO2 192.1025; Found
192.1023.
3,5-Dimethoxybenzaldehyde O-allyl oxime (1i)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 85/15, 4/1). Pale yellow oil (631 mg, 2.85 mmol, 94% yield as a 98:2
mixture of stereoisomers); IR (neat) 3082, 2938, 2840, 1615, 1586, 1206, 1156, 1037,
837 cm–1; H NMR (270 MHz, CDCl3): (major isomer) 3.80 (s, 6H), 4.68 (ddd, J =
1
5.9, 1.4, 1.4 Hz, 2H), 5.25 (ddt, J = 10.4, 1.6, 1.4 Hz, 1H), 5.35 (ddt, J = 17.0, 1.6, 1.4
Hz, 1H), 6.05 (ddt, J = 17.0, 10.4, 5.9 Hz, 1H), 6.47 (t, J = 2.3 Hz, 1H), 6.73 (d, J = 2.4
Hz, 2H), 8.03 (s, 1H); (minor isomer)4.72 (ddd, J = 5.7, 1.5, 1.5 Hz, 2H), 6.52 (t, J =
2.3 Hz, 1H), 7.07 (d, J = 2.2 Hz, 2H), the other peaks were not found probably due to
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overlapping.; C{1H} NMR (67.8 MHz, CDCl3): (major isomer) 55.3, 75.1, 102.3,
104.8, 117.9, 133.9, 134.0, 148.7, 160.8;(minor isomer)  75.7, 102.4, 108.8, 117.5,
145.9, 160.4, the other peaks were not found probably due to overlapping; HRMS
(APCI/TOF) m/z: [M+H]+ Calcd for C12H16NO3 222.1130; Found 222.1134.
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3-(((Allyloxy)imino)methyl)benzonitrile (1j)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 9/1). Yellow oil (483 mg, 2.59 mmol, 85% yield as a 9:1
mixture of stereoisomers); IR (neat) 3081, 2925, 2871, 2232, 1612, 1156, 1033, 927 cm–
1
1; H NMR (270 MHz, CDCl3): (major isomer) 4.70 (ddd, J = 5.8, 1.5, 1.5 Hz, 2H),
5.25–5.30 (m, 1H), 5.36 (ddt, J = 17.2, 1.6, 1.5 Hz, 1H), 6.04 (ddt, J = 17.2, 10.4, 5.8
Hz, 1H), 7.49 (dd, J = 7.8, 7.8 Hz, 1H), 7.64 (ddd, J = 7.8, 1.6, 1.6 Hz, 1H), 7.79 (ddd, J
= 7.8, 1.6, 1.6 Hz, 1H), 7.89 (dd, J = 1.6, 1.6 Hz, 1H), 8.10 (s, 1H); (minor
isomer)4.76 (ddd, J = 5.4, 1.3, 1.3 Hz, 2H), 7.34 (s, 1H), 7.54–7.57 (m, 1H), 8.01
(ddd, J = 7.8, 1.5, 1.5 Hz, 1H), 8.32 (dd, J = 1.5, 1.5 Hz 1H), the other peaks were not
found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)
75.9, 113.3, 118.5, 118.6, 129.8, 130.5, 131.3, 133.1, 133.9, 134.0, 146.8; (minor
isomer)  76.5, 113.1, 129.7, 131.7, 133.3, 134.5, 135.0, 143.9, the other peaks were not
found probably due to overlapping; HRMS (EI) m/z: [M]+ Calcd for C11H10N2O
186.0793; Found 186.0794.
2-Methoxybenzaldehyde O-allyl oxime (1k)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99/1). Pale yellow oil (522 mg, 2.73 mmol, 91% yield as a 96:4
mixture of stereoisomers); IR (neat) 3078, 2936, 2839, 1607, 1253, 1028, 754 cm–1; 1H
NMR (270 MHz, CDCl3): (major isomer) 3.83 (s, 3H), 4.67 (ddd, J = 5.4, 1.4, 1.4 Hz,
2H), 5.24 (ddt, J = 10.7, 1.6, 1.4 Hz, 1H), 5.35 (ddt, J = 17.3, 1.6, 1.4 Hz, 1H), 5.98–
6.13 (m, 1H), 6.87–6.97 (m, 2H), 7.30–7.36 (m, 1H), 7.78 (dd, J = 7.7, 1.8 Hz, 1H),
8.51 (s, 1H); (minor isomer)3.85 (s, 3H), 4.70–4.71 (m, 2H), the other peaks were not
found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)
55.5, 75.0, 111.0, 117.7, 120.7, 120.8, 126.4, 131.0, 134.2, 145.0, 157.5;(minor
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isomer)  75.5, 110.6, 117.3, 120.1, 132.0, 141.2, the other peaks were not found
probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C11H14NO2
192.1025; Found 192.1022.
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2-Naphthaldehyde O-allyl oxime (1l)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5). White semi-solid (610 mg, 2.89 mmol, 96% yield as a 94:6
mixture of stereoisomers); IR (neat) 3059, 2919, 2866, 1609, 1125, 1037, 933, 820, 746
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cm–1; H NMR (270 MHz, CDCl3): (major isomer) 
J = 5.6, 1.3, 1.3 Hz,
2H), 5.28 (ddt, J = 10.2, 1.7, 1.3 Hz, 1H), 5.39 (ddt, J = 17.4, 1.7, 1.3 Hz, 1H), 6.09 (ddt,
J = 17.4, 10.2, 5.6 Hz, 1H), 7.46–7.56 (m, 2H), 7.79–7.90 (m, 5H), 8.26 (s, 1H); (minor

J = 5.7, 1.4, 1.4 Hz, 2H), 7.97–8.00 (m, 1H), 8.42 (s, 1H), the
other peaks were not found probably due to overlapping.; C{1H} NMR (67.8 MHz,
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CDCl3): (major isomer) 
129.9, 133.1, 134.0, 148.9, one peak was not found probably due to
overlapping. minor isomer)  75.8, 117.5, 126.3, 127.3, 127.4, 127.5, 127.9, 128.9,
131.5, 132.9, 133.6, 134.2, 146.1, one peak was not found probably due to overlapping;
HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C14H14NO 212.1075; Found 212.1070.
6-Methoxy-2-naphthaldehyde O-allyl oxime (1m)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5). White solid (650 mg, 2.69 mmol, 89% yield as a 97:3 mixture
of stereoisomers); M.p. 79.2–80.6 ˚C; IR (KBr) 3064, 2942, 2867, 1625, 1270, 1119,
1047, 857, 817 cm–1; 1H NMR (270 MHz, CDCl3): (major isomer) 
(ddd, J = 5.9, 1.4, 1.4 Hz, 2H), 5.27 (ddt, J = 10.3, 1.6, 1.4 Hz, 1H), 5.38 (ddt, J = 17.4,
1.6, 1.4 Hz, 1H), 6.09 (ddt, J = 17.4, 10.3, 5.9 Hz, 1H), 7.11–7.17 (m, 2H), 7.70 (d, J =
7.8 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.79–7.83 (m, 2H), 8.23 (s, 1H); C{1H} NMR
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(67.8 MHz, CDCl3): (major isomer) 
127.7, 128.1, 128.5, 129.8, 134.1, 135.4, 149.1, 158.4; HRMS (APCI/TOF) m/z:
[M+H]+ Calcd for C15H16NO2 242.1181; Found 242.1179.
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1-Naphthaldehyde O-allyl oxime (1n)
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This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 97/3, 95/5). Colorless oil (598 mg, 2.83 mmol, 94% yield as a 95:5
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mixture of stereoisomers); IR (neat) 3056, 2919, 2866, 1583, 1042, 799, 774 cm–1; H
NMR (270 MHz, CDCl3): (major isomer) 4.76–4.79 (m, 2H), 5.27–5.32 (m, 1H),
5.37–5.45 (m, 1H), 6.05–6.20 (m, 1H), 7.44–7.60 (m, 3H), 7.76 (d, J = 6.8 Hz, 1H),
7.85–7.89 (m, 2H), 8.55 (dd, J = 8.1, 0.81 Hz, 1H), 8.77 (s, 1H); (minor isomer)4.68–
4.71 (m, 2H), 7.98–8.05 (m, 2H), the other peaks were not found probably due to
overlapping.; C{1H} NMR (67.8 MHz, CDCl3): (major isomer) 75.2, 118.1, 124.5,
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125.2, 126.1, 127.0, 127.4, 128.0, 128.7, 130.4, 130.6, 133.8, 134.1, 148.7(minor
isomer)  75.5, 117.6, 124.0, 125.0, 125.9, 126.6, 129.9, 134.2, 144.6, the other peaks
were not found probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd
for C14H14NO 212.1075; Found 212.1070.
4-Methoxy-1-naphthaldehyde O-allyl oxime (1o)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 97/3, 95/5). Yellow oil (649 mg, 2.69 mmol, 90% yield as a 97:3
mixture of stereoisomers); IR (neat) 3078, 2938, 2845, 1625, 1514, 1247, 1096, 1034
cm–1; H NMR (270 MHz, CDCl3): (major isomer)3.99 (s, 3H), 4.75 (ddd, J = 5.7,
1
1.5, 1.5 Hz, 2H), 5.25–5.31 (m, 1H), 5.41 (ddt, J = 17.2, 1.6, 1.5 Hz, 1H), 6.12 (ddt, J =
17.2, 10.4, 5.7 Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 7.47–7.61 (m, 2H), 7.63 (d, J = 8.0 Hz,
1H), 8.29–8.33 (m, 1H), 8.62 (dd, J = 8.1, 1.1 Hz, 1H), 8.65 (s, 1H); (minor
isomer)4.70 (ddd, J = 5.4, 1.5, 1.5 Hz, 2H), 7.96–8.02 (m, 2H), 8.19 (d, J = 8.1, Hz,
1H), the other peaks were not found probably due to overlapping.; C{1H} NMR (67.8
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MHz, CDCl3): (major isomer) 55.6, 75.0, 103.3, 117.9, 120.6, 122.4, 124.7, 125.5,
minor isomer) 75.4, 103.0, 117.4,
123.3, 125.2, 127.2, 143.9, the other peaks were not found probably due to overlapping;
HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C15H16NO2 242.1181; Found 242.1181.
6-Methoxynicotinaldehyde O-allyl oxime (1p)
This compound was prepared according to the similar method to 1a and the desired
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product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 9/1). Yellow oil (545 mg, 2.84 mmol, 95% yield as a 89:11
mixture of stereoisomers); IR (neat) 3081, 2949, 2850, 1615, 1497, 1289, 1022, 834
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cm–1; H NMR (270 MHz, CDCl3): (major isomer) 3.95 (s, 3H), 4.65 (ddd, J = 5.9,
1.5, 1.5 Hz, 2H), 5.22–5.27 (m, 1H), 5.34 (ddt, J = 17.2, 1.6, 1.5 Hz, 1H), 6.04 (ddt, J =
17.2, 10.4, 5.9 Hz, 1H), 6.73–6.77 (m, 1H), 7.93 (dd, J = 8.4, 2.2 Hz, 1H), 8.07 (s, 1H),
8.19 (d, J = 2.2 Hz, 1H); (minor isomer)3.97 (s, 3H),4.71 (ddd, J = 5.7, 1.4, 1.4 Hz,
2H), 7.24 (s, 1H), 8.24 (dd, J = 8.9, 2.2 Hz, 1H), 8.62 (d, J = 2.2 Hz, 1H), the other
peaks were not found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3):
(major isomer) 53.4, 75.0, 111.3, 117.7, 121.7, 133.9, 135.5, 145.5, 146.7, 164.8;
(minor isomer)  75.6, 110.4, 117.6, 120.7, 140.5, 142.9, 150.0, 164.1, the other peaks
were not found probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd
for C10H13N2O2 193.0977; Found 193.0977.
1H-Indole-3-carbaldehyde O-allyl oxime (1q)
This compound was prepared according to the similar method to 1a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 85/15, 4/1, 75/25). White solid (579 mg, 2.89 mmol, 96% yield as a
4:1 mixture of stereoisomers); M.p. 50.0–51.4 ˚C; IR (KBr) 3266, 2984, 2871, 1658,
1610, 1444, 1029, 750 cm–1; H NMR (270 MHz, CDCl3): (major isomer)4.70–4.72
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(m, 2H), 5.24–5.28 (m, 1H), 5.34–5.43 (m, 1H), 6.04–6.19 (m, 1H), 7.19–7.40 (m, 4H),
8.15–8.21 (m, 1H), 8.34 (brs, 1H), 8.34 (s, 1H); (minor isomer)4.79 (ddd, J = 5.7, 1.3,
1.3 Hz, 2H), 7.75–7.79 (m, 2H), 8.53 (brs, 1H), the other peaks were not found
probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)74.8,
110.0, 111.3, 117.9, 121.2, 122.1, 123.3, 124.4, 127.2, 134.3, 136.5, 144.8; (minor
isomer)75.2, 106.8, 111.4, 117.5, 118.0, 121.0, 122.8, 126.3, 130.7, 134.3, 134.7,
HRMS (ESI/TOF) m/z: [M+H]+ Calcd for C12H13N2O 201.1028; Found
201.1028.
Preparation of benzaldehyde oxime (5)21
This compound was prepared according to the similar method to 1a using
hydroxylamine hydrochloride and the desired benzaldehyde oxime (5) was obtained
after purification by silica gel column chromatography (Hexane/EtOAc = 9/1) as a pale
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yellow oil (421 mg, 3.47 mmol, 69% yield as a 94:6 mixture of stereoisomers). 1H
NMR (270 MHz, CDCl3): (major isomer) 7.33–7.42 (m, 3H), 7.54–7.59 (m, 2H), 8.18
(s, 1H), 9.35 (brs, 1H); (minor isomer) 7.95–7.97 (m, 2H), the other peaks were not
found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)
127.0, 128.7, 130.0, 131.8, 150.4; (minor isomer) 128.4, 130.2, 130.9, 146.7, one
peak was not found probably due to overlapping; GC-MS (EI): m/z 121 [M]+.
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Preparation of benzaldehyde O-methyl oxime (6)22
This compound was prepared according to the similar method to 1a using
O-methylhydroxylamine hydrochloride and the desired benzaldehyde O-methyl oxime
(6) was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99.5/0.5) as a pale yellow oil (483 mg, 3.57 mmol, 36% yield as 96:4
mixture of stereoisomers). 1H NMR (270 MHz, CDCl3): (major isomer) 3.98 (s, 3H),
7.34–7.39 (m, 3H), 7.55–7.62 (m, 2H), 8.06 (s, 1H); (minor isomer) 4.03 (s, 3H),
7.85–7.89 (m, 2H), the other peaks were not found probably due to overlapping.;
13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)  62.0, 127.0, 128.7, 129.8, 132.1,
148.6; GC-MS (EI): m/z 135 [M]+.
Preparation of benzaldehyde O-but-3-en-1-yl oxime (3)
Benzaldehyde oxime (5) (848 mg, 7.0 mmol) was charged into a two-necked round
flask and the flask was refilled with N2. THF (25 mL) and potassium tert-butoxide
1.73 g, 15.4 mmol, 2.2 equiv) were added to the flask. A solution of but-3-en-1-yl
4-methylbenzenesulfonate (2.37 g, 10.5 mmol, 1.5 equiv) in THF (20 mL) was added
dropwise to the mixture at room temperature. The reaction mixture was stirred
overnight at 60 ˚C and then allowed to cool to room temperature. The reaction was
quenched with H2O (20 mL) and the resulting aqueous phase was extracted with Et2O
(40 mL×3). The combined organic phase was washed with brine, dried over MgSO4.
After removal of the solvent, the resulting crude mixture was purified by silica gel
column chromatography (Hexane/EtOAc = 99.5/0.5) to give benzaldehyde
O-but-3-en-1-yl oxime (3) as a pale yellow oil (425 mg, 2.43 mmol, 35% yield as a 95:5
mixture of stereoisomers). IR (neat) 3079, 2931, 2876, 1642, 1447, 1211, 1051, 756,
692 cm–1; 1H NMR (270 MHz, CDCl3): (major isomer) 2.49 (dtdd, J = 6.8, 6.6, 1.4,
1.4 Hz, 2H), 4.22 (t, J = 6.8 Hz, 2H), 5.05–5.18 (m, 2H), 5.87 (ddt, J = 17.3, 10.5, 6.6
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Hz, 1H), 7.34–7.38 (m, 3H), 7.56–7.61 (m, 2H), 8.09 (s, 1H); (minor isomer) 4.27 (t,
J = 6.8 Hz, 2H), 7.30 (s, 1H), 7.87–7.89 (m, 2H), the other peaks were not found
probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)
33.673.3, 116.6, 126.9, 128.6, 129.6, 132.3, 134.7, 148.4; HRMS (APCI/TOF) m/z:
[M+H]+ Calcd for C11H14NO 176.1075; Found 176.1084.
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Preparation of benzaldehyde O-pent-4-en-1-yl oxime (4)
This compound was prepared according to the similar method to 3 using pent-4-en-1-yl
4-methylbenzenesulfonate and the desired benzaldehyde O-pent-4-en-1-yl oxime (4)
was obtained after purification by silica gel column chromatography (Hexane/EtOAc =
99.5/0.5) as a yellow oil (188 mg, 0.992 mmol, 15% yield as a 95:5 mixture of
stereoisomers). IR (neat) 3079, 2934, 2872, 1640, 1447, 1211, 1055, 755, 692 cm–1;
1H NMR (270 MHz, CDCl3): (major isomer) 1.77–1.87 (m, 2H), 2.14–2.22 (m, 2H),
4.19 (t, J = 6.6 Hz, 2H), 4.96–5.10 (m, 2H), 5.85 (ddt, J = 17.0, 10.3, 6.7 Hz, 1H), 7.34–
7.42 (m, 3H), 7.55–7.60 (m, 2H), 8.08 (s, 1H)(minor isomer) 4.24 (t, J = 7.3 Hz, 2H),
7.30 (s, 1H), 7.88–7.91 (m, 2H), the other peaks were not found probably due to
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overlapping.; C{1H} NMR (67.8 MHz, CDCl3): (major isomer) 28.3, 30.0, 73.6,
114.9, 126.9, 128.6, 129.7, 132.4, 138.1, 148.3; HRMS (APCI/TOF) m/z: [M+H]+ Calcd
for C12H16NO 190.1232; Found 190.1227.
Preparation of benzaldehyde O-(1-phenylallyl) oxime (7)23
1-Phenylallyl acetate (881 mg, 5.0 mmol), benzaldehyde oxime 5 (727 mg, 6.0 mmol,
1.2 equiv), and [IrCl(cod)]2 (16.8 mg, 0.025 mmol 0.005 equiv) were charged into a
two-necked round flask and the flask was refilled with N2. THF (20 mL) was added to
the flask. Et2Zn (1.09 M in hexane, 2.8 mL, 3.0 mmol 0.6 equiv) was added dropwise
to the mixture at 0 ˚C. The reaction mixture was stirred at room temperature overnight.
The reaction was quenched with H2O (10 mL) and the resulting aqueous phase was
extracted with EtOAc (20 mL×3). The combined organic phase was washed with
brine, dried over MgSO4. After removal of the solvent, the resulting crude mixture was
purified by silica gel column chromatography (Hexane/EtOAc = 99/1, 99/3) to give
O-(1-phenylallyl) oxime (7) as a pale yellow oil (549 mg, 2.31 mmol, 50% yield as a
99:1 mixture of branch and linear regioisomers. The branch regioisomer was obtained
as a 95:5 mixture of stereoisomers). 1H NMR (270 MHz, CDCl3): (major isomer)
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5.27–5.36 (m, 2H), 5.71 (d, J = 6.5, 1H), 6.16 (ddd, J = 17.1, 10.5, 6.5 Hz, 1H), 7.26–
7.43 (m, 8H), 7.52–7.57 (m, 2H), 8.18 (s, 1H); (minor isomer) 7.92–7.96 (m, 2H), the
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other peaks were not found probably due to overlapping.; C{1H} NMR (67.8 MHz,
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CDCl3): (major isomer) 86.1, 117.3, 127.1, 127.3, 127.8, 128.4, 128.6, 129.8, 132.2,
137.6, 140.1, 149.1; LRMS (APCI/TOF) m/z: [M+H]+ 238.
Preparation of (E)-cinnamaldehyde O-allyl oxime (8a)
Sodium acetate (369 mg, 4.5 mmol, 1.5 equiv) and O-allylhydroxylamine hydrochloride
(394 mg, 3.6 mmol 1.2 equiv) were charged into a round flask. After the addition of
MeOH (8.3 mL) and H2O (0.75 mL) into the flask, cinnamaldehyde (0.38 mL, 3.0
mmol) was added dropwise to the mixture at room temperature. The reaction mixture
was stirred at room temperature overnight. The resulting mixture was concentrated by
evaporation and then H2O was added. The resulting aqueous phase was extracted with
EtOAc (12 mL×3). The combined organic phase was washed with brine, dried over
MgSO4. After removal of the solvent, the resulting crude mixture was purified by
silica gel column chromatography (Hexane/EtOAc = 98/2, 95/5) to give
(E)-cinnamaldehyde O-allyl oxime (8a) as a pale yellow oil (537 mg, 2.87 mmol, 96%
yield as a 74:26 mixture of stereoisomers). IR (neat) 3081, 2920, 2867, 1626, 1027,
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974, 750 cm–1; H NMR (270 MHz, CDCl3): (major isomer) 4.62 (ddd, J = 5.9 1.4,
1.4 Hz, 2H), 5.26 (ddt, J = 10.3, 1.5, 1.4 Hz, 1H), 5.34 (ddt, J = 17.2, 1.5, 1.4 Hz, 1H),
6.03 (ddt, J = 17.2, 10.3, 5.9 Hz, 1H), 6.75–6.90 (m, 1H), 7.19–7.52 (m, 6H), 7.92 (dd,
J = 8.1, 1.1 Hz, 1H); (minor isomer)4.66 (ddd, J = 5.9, 1.4, 1.4 Hz, 2H), the other
peaks were not found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3):
(major isomer) 75.0, 116.3, 117.9, 121.9, 126.8, 128.7, 133.9, 135.9, 138.5, 150.8;
(minor isomer) 75.2, 117.6, 127.4, 129.2, 134.3, 135.8, 139.8, 148.2, the other peaks
were not found probably due to overlapping HRMS (APCI/TOF) m/z: [M+H]+ Calcd
for C12H14NO 188.1075; Found 188.1070.
(E)-3-(4-(Dimethylamino)phenyl)acrylaldehyde O-allyl oxime (8b)
This compound was prepared according to the similar method to 8a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 9/1, 85/15). Yellow solid (602 mg, 2.61 mmol, 87% yield as a
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71:29 mixture of stereoisomers); M.p. 47.8–50.9 ˚C; IR (KBr) 3077, 2911, 1606, 1032,
981, 840 cm–1; 1H NMR (270 MHz, CDCl3): (major isomer) 2.99 (s, 6H), 4.59 (ddd, J
= 5.9, 1.5, 1.5 Hz, 2H), 5.24 (ddt, J = 10.3, 1.7, 1.5 Hz, 1H), 5.34 (ddt, J = 17.2, 1.7, 1.5
Hz, 1H), 5.95–6.11 (m, 1H), 6.59–6.79 (m, 4H), 7.08–7.41 (m, 2H), 7.89 (dd, J = 8.5,
0.68 Hz, 1H); (minor isomer) 3.00 (s, 6H), 4.64 (ddd, J = 5.7, 1.4, 1.4 Hz, 2H), the
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other peaks were not found probably due to overlapping.; C{1H} NMR (67.8 MHz,
CDCl3): (major isomer) 40.2, 74.7, 112.0, 117.0, 117.7, 124.1, 128.1, 134.1, 139.1,
150.7, 151.7(minor isomer) 40.1, 74.9, 111.8, 111.9, 117.3, 123.7, 128.9, 134.5,
140.6, 149.2, 151.0; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C14H19N2O 231.1497;
Found 231.1497.
(E)-3-(4-Methoxyphenyl)acrylaldehyde O-allyl oxime (8c)
This compound was prepared according to the similar method to 8a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 93/7, 9/1). White semi-solid (637 mg, 2.93 mmol, 95% yield as
a 75:25 mixture of stereoisomers); IR (KBr) 2938, 2839, 1605, 1509, 1030, 973, 812
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cm–1; H NMR (270 MHz, CDCl3): (major isomer) 3.80 (s, 3H), 4.60 (ddd, J = 5.7,
1.4, 1.4 Hz, 2H), 5.22–5.26 (m, 1H), 5.33 (ddt, J = 17.4, 1.8, 1.4 Hz, 1H), 5.95–6.09 (m,
1H), 6.64–6.80 (m, 1H), 6.85–6.88 (m, 2H), 7.15–7.45 (m, 3H), 7.89 (dd, J = 5.9, 3.2
Hz, 1H); (minor isomer) 4.65 (ddd, J = 5.9, 1.4, 1.4 Hz, 2H), the other peaks were not
found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)
55.2, 74.9, 114.2, 117.8, 119.6, 128.2, 128.9, 134.0, 138.2, 151.1, 160.1(minor
isomer) 75.0, 114.2, 117.5, 128.5, 128.7, 134.4, 139.6, 148.5, 160.5, the other peaks
were not found probably due to overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd
for C13H16NO2 218.1181; Found 218.1184.
(E)-3-(4-Fluorophenyl)acrylaldehyde O-allyl oxime (8d)
This compound was prepared according to the similar method to 8a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5). Yellow oil (543 mg, 2.65 mmol, 88% yield as a 75:25 mixture
of stereoisomers); IR (neat) 3080, 2922, 2868, 1626, 1601, 1508, 1232, 1028, 819 cm–1;
1H NMR (270 MHz, CDCl3): (major isomer) 4.62 (ddd, J = 5.8, 1.4, 1.4 Hz, 2H), 5.26
(ddt, J = 10.5, 1.6, 1.4 Hz, 1H), 5.34 (ddt, J = 17.3, 1.6, 1.4 Hz, 1H), 6.02 (ddt, J = 17.3,
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10.5, 5.8 Hz, 1H), 6.75–6.83 (m, 1H), 7.00–7.11 (m, 2H), 7.17–7.51 (m, 3H), 7.89–7.92
(m, 1H); (minor isomer) 4.66 (ddd, J = 5.7, 1.4, 1.4 Hz, 2H), the other peaks were not
found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3): (major isomer)
75.0, 115.7 (d, JCF = 21.7 Hz), 117.8, 121.6 (d, JCF = 2.2 Hz), 128.4 (d, JCF = 8.3 Hz),
132.1 (d, JCF = 3.3 Hz), 133.9, 137.0, 150.5, 162.8 (d, JCF = 249 Hz); (minor isomer) 
75.1, 116.0 (d, JCF = 2.2 Hz), 117.6, 129.1 (d, JCF = 8.3 Hz), 132.0 (d, JCF = 3.3 Hz),
134.0 (d, JCF = 21.2 Hz), 138.4, 147.9, 163.1 (d, JCF = 249 Hz), one peak was not found
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probably due to overlapping; F NMR (471 MHz, CDCl3): (major isomer) -113.0 –
-113.1 (m); (minor isomer) -112.17 – -112.23 (m); HRMS (APCI/TOF) m/z: [M+H]+
Calcd for C12H13FNO 206.0981; Found 206.0973.
4-((E)-3-((Allyloxy)imino)prop-1-en-1-yl)-2-methoxyphenyl acetate (8e)
This compound was prepared according to the similar method to 8a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 9/1, 85/15, 4/1). Pale yellow oil (315 mg, 1.14 mmol, 38%
yield as a 72:28 mixture of stereoisomers); M.p. 96.7–99.3 ˚C; IR (KBr) 3010, 2925,
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2874, 1762, 1629, 1599, 1013, 828 cm–1; H NMR (270 MHz, CDCl3): (major isomer)
2.32 (s, 3H), 3.85 (s, 3H), 4.62 (ddd, J = 5.7, 1.3, 1.3 Hz, 2H), 5.26 (ddt, J = 10.5, 1.6,
1.3 Hz, 1H), 5.35 (ddt, J = 17.2, 1.6, 1.3 Hz, 1H), 5.95–6.11 (m, 1H), 6.72–6.86 (m, 2H),
7.01–7.33 (m, 3H), 7.91 (dd, J = 7.2, 2.0 Hz, 1H); (minor isomer) 3.87 (s, 3H), 4.67
(ddd, J = 5.4, 1.4, 1.4 Hz, 2H), the other peaks were not found probably due to
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overlapping.; C{1H} NMR (67.8 MHz, CDCl3): (major isomer) 20.6, 55.7, 75.0,
109.9, 117.9, 119.9, 122.1, 123.0, 133.9, 134.9, 137.6, 140.1, 150.5, 151.2,
168.8(minor isomer) 55.8, 75.2, 110.5, 116.3, 117.7, 120.6, 134.2, 134.7, 139.2,
140.6, 147.9, 151.2, 168.8, the other peaks were not found probably due to
overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C15H18NO4 276.1236; Found
276.1232.
(E)-3-(Furan-2-yl)acrylaldehyde O-allyl oxime (8f)
This compound was prepared according to the similar method to 8a using and the
desired product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 95/5, 9/1). Reddish brown oil (483 mg, 2.72 mmol, 90% yield as a
72:28 mixture of stereoisomers); IR (neat) 3082, 2921, 2867, 1630, 1015, 740 cm–1; 1H
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NMR (270 MHz, CDCl3): (major isomer)  4.61 (ddd, J = 5.8, 1.4, 1.4 Hz, 2H), 5.25
(ddt, J = 10.3, 1.4, 1.4 Hz, 1H), 5.33 (ddt, J = 17.1, 1.4, 1.4 Hz, 1H), 6.02 (ddt, J = 17.1,
10.3, 5.8 Hz, 1H), 6.40–6.78 (m, 4H), 7.42–7.45 (m, 1H), 7.85 (d, J = 9.7 Hz, 1H);
(minor isomer)4.66 (ddd, J = 5.4, 1.3, 1.3 Hz, 2H), 7.13–7.25 (m, 2H), the other
peaks were not found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3):
(major isomer) 75.0, 110.8, 111.8, 117.9, 120.2, 125.4, 133.9, 143.3, 150.4,
152.1(minor isomer) 75.2, 112.0, 112.3, 114.5, 117.5, 126.3, 134.3, 143.8, 147.8,
152.0; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C10H12NO2 178.0868; Found
178.0866.
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(E)-2-Methyl-3-phenylacrylaldehyde O-allyl oxime (8g)
This compound was prepared according to the similar method to 8a using and the
desired product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 98/2, 95/5). Yellow oil (579 mg, 2.88 mmol, 96% yield); IR (neat)
3082, 2921, 2865, 1646, 1601, 1050, 752 cm–1; 1H NMR (270 MHz, CDCl3): 2.11 (d,
J = 1.4 Hz, 3H), 4.63 (ddd, J = 5.9, 1.5, 1.5 Hz, 2H), 5.22–5.27 (m, 1H), 5.34 (ddt, J =
17.0, 1.6, 1.5 Hz, 1H), 5.97–6.11 (m, 1H), 6.63 (s, 1H), 7.25–7.32 (m, 1H), 7.34–7.40
13
(m, 4H), 7.89 (s, 1H); C{1H} NMR (67.8 MHz, CDCl3): 13.1, 75.0, 117.8, 127.4,
128.3, 129.3, 132.2, 134.1, 136.1, 136.5, 153.9; HRMS (APCI/TOF) m/z: [M+H]+
Calcd for C13H16NO 202.1232; Found 202.1236.
3,3-Diphenylacrylaldehyde O-allyl oxime (8h)
This compound was prepared according to the similar method to 8a and the desired
product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 98/2, 95/5). Colorless oil (758 mg, 2.88 mmol, 95% yield as a
76:24 mixture of stereoisomers); IR (neat) 3058, 2920, 2866, 1646, 1606, 1076, 768
1
cm–1; H NMR (270 MHz, CDCl3): (major isomer) 4.59 (ddd, J = 5.9, 1.5, 1.5 Hz,
2H), 5.21–5.27 (m, 1H), 5.31 (ddt, J = 17.2, 1.8, 1.5 Hz, 1H), 5.92–6.12 (m, 1H), 6.79
(d, J = 10.4 Hz, 1H), 7.19–7.43 (m, 10H), 7.79 (d, J = 10.4 Hz, 1H); (minor
isomer)4.66 (ddd, J = 5.7, 1.4, 1.4 Hz, 2H), 7.11 (d, J = 9.5 Hz, 1H), the other peaks
were not found probably due to overlapping.; 13C{1H} NMR (67.8 MHz, CDCl3):
(major isomer) 75.0, 118.0, 120.3, 127.7, 128.1, 128.3 (2C), 128.4, 130.1, 133.8,
138.3, 140.9, 149.2, 149.7(minor isomer) 75.2, 114.7, 117.6, 128.2, 128.3, 128.4,
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128.8, 130.4, 134.3, 138.0, 141.0, 146.3, 150.7, one peak was not found probably due to
overlapping; HRMS (APCI/TOF) m/z: [M+H]+ Calcd for C18H18NO 264.1388; Found
264.1381.
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Procedure for the nickel-catalyzed transformation of alkene-tethered
oxime ether 1a to benzonitrile (2a) by a traceless directing group
strategy
Benzaldehyde O-allyl oxime (1a) (48.4 mg, 0.30 mmol) and DPEphos (16.2 mg, 0.03
mmol, 0.1 equiv) were charged into a screw cap vial and the vial was taken into a glove
box. In the glove box, Ni(cod)2 (8.3 mg, 0.03 mmol, 0.1 equiv) and THF (1.2 mL)
were added to the vial and the reaction vial was taken from the glove box. The resulting
mixture was stirred at 60 ˚C for 17 h. The reaction mixture was allowed to cool to room
temperature and octane (34.3 mg, 0.30 mmol) was added to the mixture as an internal
standard. After filtration of the mixture with a pad of celite, the yield of benzonitrile
(2a) was determined to be 98% by GC analyses.
Procedure for the nickel-catalyzed transformation of alkene-tethered
oxime ethers 1 to benzonitriles 2 by a traceless directing group strategy
4-Methoxybenzaldehyde O-allyl oxime (1b) (115 mg, 0.60 mmol) and DPEphos (32.3
mg, 0.06 mmol, 0.1 equiv) were charged into a screw vial and the vial was taken into a
glove box. In the glove box, Ni(cod)2 (16.5 mg, 0.06 mmol, 0.1 equiv) and THF (2.4
mL) were added to the vial and the reaction vial was taken from the glove box. The
resulting mixture was stirred at 60 ˚C for 17 h. The reaction was allowed to cool to
room temperature and then quenched with water (1 mL). The reaction mixture was
filtrated with a pad of celite and additional water was added. The resulting aqueous
phase was extracted with EtOAc. The organic phase was washed with brine and dried
over MgSO4. After removal of the solvent, the resulting crude mixture was purified by
silica gel column chromatography (Hexane/EtOAc
=
95/5) to give
4-methoxybenzonitrile (2b)24 as a white solid (67.8 mg, 0.509 mmol, 85% yield).
When the reaction was conducted on a 3.0 mmol scale the desired product 2b was
obtained in 89% yield (354 mg, 2.66 mmol). 1H NMR (270 MHz, CDCl3): 3.86 (s,
3H), 6.93–6.98 (m, 2H), 7.57–7.62 (m, 2H); 13C{1H} NMR (67.8 MHz, CDCl3):
55.5,103.9, 114.7, 119.2, 134.0, 162.8; GC-MS (EI): m/z 133 [M]+.
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Benzo[d][1,3]dioxole-5-carbonitrile (2c)25
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This compound was prepared according to the procedure to 2b and the desired product
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was obtained after purification by silica gel column chromatography (Hexane/EtOAc =
1
99/1, 98/2, 96/4). White solid (78.8 mg, 0.536 mmol, 90% yield); H NMR (270 MHz,
CDCl3): 6.08 (s, 2H), 6.87 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 1.5 Hz, 1H), 7.22 (dd, J =
8.0, 1.5 Hz, 1H); 13C{1H} NMR (67.8 MHz, CDCl3): 102.2,104.8, 109.1, 111.3,
118.8, 128.2, 148.0, 151.5; GC-MS (EI): m/z 146 [M-H]+.
3,4-Dimethoxybenzonitrile (2d)24
3,4-Dimethoxybenzaldehyde O-allyl oxime (1d) (133 mg, 0.60 mmol) and DPEphos
(32.3 mg, 0.06 mmol, 0.1 equiv) were charged into a screw vial and the vial was taken
into a glove box. In the glove box, Ni(cod)2 (16.5 mg, 0.06 mmol, 0.1 equiv) and
1,4-dioxane (2.4 mL) were added to the vial and the reaction vial was taken from the
glove box. The resulting mixture was stirred at 80 ˚C for 17 h. The reaction was
allowed to cool to room temperature and then quenched with water (1 mL). The
reaction mixture was filtrated with a pad of celite and additional water was added. The
resulting aqueous phase was extracted with EtOAc. The organic phase was washed
with brine and dried over MgSO4. After removal of the solvent, the resulting crude
mixture was dissolved in MeOH (1 mL) and NaBH3CN (18.9 mg, 0.30 mmol) was
added to the mixture for removing the trace amount of 3,4-dimethoxybenzaldehyde
generated during the catalysis. The reaction mixture was stirred at room temperature
for 1 h and then concentrated by evaporation. Water (1 mL) was added to the resulting
mixture and the aqueous phase was extracted with EtOAc (2 mL×1). The organic
phase was washed with brine and dried over MgSO4. After removal of the solvent, the
resulting crude mixture was purified by silica gel column chromatography
(Hexane/EtOAc = 9/1, 85/15, 4/1) to give 3,4-dimethoxy benzonitrile (2d) as a pale
yellow solid (75.9 mg, 0.465 mmol, 77% yield). 1H NMR (270 MHz, CDCl3): 3.91
(s, 3H), 3.94 (s, 3H), 6.91 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 1.9 Hz, 1H), 7.29 (dd, J = 8.4,
1.9 Hz, 1H); 13C{1H} NMR (67.8 MHz, CDCl3): 56.0,56.1, 103.8, 111.2, 113.8, 119.2,
126.4, 149.1, 152.8; GC-MS (EI): m/z 163 [M]+.
Terephthalonitrile (2e)26
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This compound was prepared according to the procedure to 2d (THF was used instead
of 1,4-dioxane at 60 ˚C) and the desired product was obtained after purification by silica
gel column chromatography (Hexane/EtOAc = 95/5, 9/1, 4/1). White solid (54.7 mg,
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0.427 mmol, 71% yield); H NMR (270 MHz, CDCl3): 7.80 (s, 4H); C{1H} NMR
(67.8 MHz, CDCl3):  116.7, 117.0, 132.8; GC-MS (EI): m/z 128 [M]+.
1
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Methyl 4-cyanobenzoate (2f)24
This compound was prepared according to the procedure to 2d (THF was used instead
of 1,4-dioxane at 60 ˚C) and the desired product was obtained after purification by silica
gel column chromatography (Hexane/EtOAc = 98/2, 96/4, 9/1). White solid (71.0 mg,
1
0.441 mmol, 74% yield); H NMR (270 MHz, CDCl3): 3.97 (s, 3H), 7.73–7.77 (m,
2H), 8.13–8.17 (m, 2H); 13C{1H} NMR (67.8 MHz, CDCl3): 52.6,116.2, 117.9, 130.0,
132.1, 133.8, 165.3; GC-MS (EI): m/z 161 [M]+.
[1,1'-Biphenyl]-4-carbonitrile (2g)24
This compound was prepared according to the procedure to 2d (PPh3 (20 mol%) and
THF were used instead of DPEphos and 1,4-dioxane, respectively, at 60 ˚C) and the
desired product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99/1, 98/2, 9/1) and preparative thin-layer chromatography
1
(Hexane/EtOAc = 9/1). White solid (83.1 mg, 0.464 mmol, 77% yield); H NMR (270
MHz, CDCl3): 7.38–7.51 (m, 3H), 7.55–7.60 (m, 2H), 7.64–7.72 (m, 4H); C{1H}
13
NMR (67.8 MHz, CDCl3): 110.8,118.9, 127.1, 127.6, 128.6, 129.0, 132.5, 139.1,
145.6; GC-MS (EI): m/z 179 [M]+.
3-Methoxybenzonitrile (2h)24
This compound was prepared according to the procedure to 2d (THF was used instead
of 1,4-dioxane at 60 ˚C) and the desired product was obtained after purification by
preparative thin-layer chromatography (Hexane/EtOAc = 9/1). Pale yellow oil (45.4
mg, 0.341 mmol, 57% yield); 1H NMR (270 MHz, CDCl3): 3.83 (s, 3H), 7.11–7.16 (m,
2H), 7.22–7.25 (m, 1H), 7.35–7.41 (m, 1H); 13C{1H} NMR (67.8 MHz, CDCl3):
55.4,113.0, 116.7, 118.6, 119.2, 124.3, 130.2, 159.5; GC-MS (EI): m/z 133 [M]+.
3,5-Dimethoxybenzonitrile (2i)26
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This compound was prepared according to the procedure to 2d (THF was used instead
of 1,4-dioxane at 60 ˚C) and the desired product was obtained after purification by silica
gel column chromatography (Hexane/EtOAc = 98/2, 95/5, 9/1). White solid (79.8 mg,
0.489 mmol, 82% yield); 1H NMR (270 MHz, CDCl3): 3.81 (s, 6H), 6.66 (t, J = 2.3
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Hz, 1H), 6.76 (d, J = 2.4 Hz, 2H); C{1H} NMR (67.8 MHz, CDCl3): 55.5,105.5,
109.8, 113.3, 118.7, 160.9; GC-MS (EI): m/z 163 [M]+.
Isophthalonitrile (2j)27
This compound was prepared according to the procedure to 2d (THF was used instead
of 1,4-dioxane at 60 ˚C) and the desired product was obtained after purification by silica
gel column chromatography (Hexane/EtOAc = 9/1, 85/15, 4/1). White solid (45.5 mg,
1
0.355 mmol, 59% yield); H NMR (270 MHz, CDCl3): 7.64–7.70 (m, 1H), 7.90–7.98
(m, 3H); 13C{1H} NMR (67.8 MHz, CDCl3): 114.1,116.5, 130.3, 135.3, 135.9;
GC-MS (EI): m/z 128 [M]+.
2-Methoxybenzonitrile (2k)24
This compound was prepared according to the procedure to 2b (1,4-dioxane was used
instead of THF at 100 ˚C) and the desired product was obtained after purification by
preparative thin-layer chromatography (Hexane/EtOAc = 4/1). Yellow oil (45.6 mg,
1
0.342 mmol, 57% yield); H NMR (270 MHz, CDCl3): 3.94 (s, 3H), 6.96–7.04 (m,
2H), 7.51–7.58 (m, 2H); 13C{1H} NMR (67.8 MHz, CDCl3): 55.9,101.6, 111.2, 116.4,
120.7, 133.6, 134.3, 161.1; GC-MS (EI): m/z 133 [M]+.
2-Naphthonitrile (2l)24
This compound was prepared according to the procedure to 2d (PPh3 (20 mol%) and
THF were used instead of DPEphos and 1,4-dioxane, respectively, at 60 ˚C) and the
desired product was obtained after purification by silica gel column chromatography
(Hexane/EtOAc = 99/1, 98/2, 9/1) and preparative thin-layer chromatography
1
(Hexane/EtOAc = 9/1). White solid (58.4 mg, 0.381 mmol, 64% yield); H NMR (270
MHz, CDCl3): 7.54–7.66 (m, 3H), 7.83–7.89 (m, 3H), 8.17 (s, 1H); C{1H} NMR
13
(67.8 MHz, CDCl3): 109.2,119.1, 126.2, 127.5, 127.9, 128.3, 128.9, 129.1, 132.1,
134.0, 134.5; GC-MS (EI): m/z 153 [M]+.
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6-Methoxy-2-naphthonitrile (2m)25
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8
This compound was prepared according to the procedure to 2b and the desired product
9
was obtained after purification by silica gel column chromatography (Hexane/EtOAc =
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98/2, 96/4, 94/6, 9/1). White solid (104 mg, 0.566 mmol, 94% yield); H NMR (270
MHz, CDCl3): 3.95 (s, 3H), 7.14 (d, J = 2.3 Hz, 1H), 7.24 (dd, J = 8.9, 2.3 Hz, 1H),
7.55 (dd, J = 8.2, 1.8 Hz, 1H)7.76 (d, J = 1.9 Hz, 1H), 7.79 (s, 1H), 8.12 (s, 1H);
13C{1H} NMR (67.8 MHz, CDCl3): 55.4,105.8, 106.6, 119.5, 120.6, 127.0, 127.6,
127.7, 129.9, 133.7, 136.3, 159.9; GC-MS (EI): m/z 183 [M]+.
1-Naphthonitrile (2n)24
This compound was prepared according to the procedure to 2d (PPh3 (20 mol%) and
THF were used instead of DPEphos and 1,4-dioxane, respectively, at 60 ˚C) and the
desired product was obtained after purification by preparative thin-layer
chromatography (Hexane/EtOAc = 9/1). Pale yellow oil (75.2 mg, 0.491 mmol, 82%
1
yield); H NMR (270 MHz, CDCl3): 7.47–7.55 (m, 1H), 7.57–7.72 (m, 2H), 7.87–
7.92 (m, 2H), 8.04–8.09 (m, 1H), 8.20–8.25 (m, 1H); 13C{1H} NMR (67.8 MHz,
CDCl3): 110.0,117.7, 124.8, 125.0, 127.4, 128.5(2C), 132.2, 132.5, 132.8, 133.2;
GC-MS (EI): m/z 153 [M]+.
4-Methoxy-1-naphthonitrile (2o)24
This compound was prepared according to the procedure to 2b and the desired product
was obtained after purification by silica gel column chromatography (Hexane/EtOAc =
1
98/2, 96/4, 94/6, 9/1). White solid (103 mg, 0.562 mmol, 94% yield); H NMR (270
MHz, CDCl3): 4.06 (s, 3H), 6.82 (d, J = 8.0 Hz, 1H), 7.55–7.61 (m, 1H), 7.66–7.72
(m, 1H), 7.85 (d, J = 8.0 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 8.31 (dd, J = 8.0, 0.95 Hz,
1H); 13C{1H} NMR (67.8 MHz, CDCl3): 55.9,101.7, 103.2, 118.4, 122.7, 124.8,
125.1, 126.6, 128.8, 133.3, 134.0, 159.3; GC-MS (EI): m/z 183 [M]+.
6-Methoxynicotinonitrile (2p)28
This compound was prepared according to the procedure to 2d and the desired product
was obtained after purification by silica gel column chromatography (Hexane/EtOAc =
1
98/2, 96/4, 92/8). White solid (53.4 mg, 0.398 mmol, 66% yield); H NMR (270 MHz,
CDCl3): 4.00 (s, 3H), 6.83 (dd, J = 8.6, 0.81 Hz, 1H), 7.79 (dd, J = 8.6, 2.3 Hz, 1H),
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8.495–8.503 (m, 1H); C{1H} NMR (67.8 MHz, CDCl3): 54.2,102.3, 111.7, 117.2,
140.8, 151.9, 165.9; GC-MS (EI): m/z 133 [M-H]+.
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1H-Indole-3-carbonitrile (2q)29
This compound was prepared according to the procedure to 2b (1,4-dioxane was used
instead of THF at 100 ˚C for 48 h) and the desired product was obtained after
purification by silica gel column chromatography (Hexane/EtOAc = 9/1, 85/15, 4/1)
and preparative thin-layer chromatography (Toluene/EtOAc = 9/1). Pale yellow solid
1
(39.2 mg, 0.276 mmol, 46% yield); H NMR (270 MHz, Acetone-d6): 7.25–7.35 (m,
2H), 7.59–7.62 (m, 1H), 7.69–7.72 (m, 1H), 8.11 (d, J = 3.0 Hz, 1H), 11.2 (brs, 1H);
13C{1H} NMR (67.8 MHz, Acetone-d6):  86.7, 113.5, 116.4, 119.5, 122.6, 124.4, 128.0,
134.2, 136.4; GC-MS (EI): m/z 142 [M]+.
Procedure for the nickel-catalyzed transformation of alkene-tethered oxime ethers
8 to cinnamonitriles 9 by a traceless directing group strategy
(E)-Cinnamaldehyde O-allyl oxime (8a) (112 mg, 0.60 mmol) and DPEphos (64.6 mg,
0.12 mmol, 0.2 equiv) were charged into a screw vial and the vial was taken into a
glove box. In the glove box, Ni(cod)2 (33.0 mg, 0.12 mmol, 0.2 equiv) and
1,4-dioxane (2.4 mL) were added to the vial and the reaction vial was taken from the
glove box. The resulting mixture was stirred at 100 ˚C for 17 h. The reaction was
allowed to cool to room temperature and then quenched with water (1 mL). The
reaction mixture was filtrated with a pad of celite and additional water was added. The
resulting aqueous phase was extracted with EtOAc. The organic phase was washed
with brine and dried over MgSO4. After removal of the solvent, the resulting crude
mixture was purified by silica gel column chromatography (Hexane/EtOAc = 98/2, 96/4,
94/6) to give cinnamonitrile (9a)30 as a yellow oil (43.9 mg, 0.340 mmol, 57% yield).
1H NMR (270 MHz, CDCl3): 5.88 (d, J = 16.5 Hz, 1H), 7.38–7.48 (m, 6H); C{1H}
13
NMR (67.8 MHz, CDCl3): 96.3, 118.1, 127.3, 129.1, 131.2, 133.5, 150.6 GC-MS
(EI): m/z 129 [M]+.
(E)-3-(4-(Dimethylamino)phenyl)acrylonitrile (9b)
This compound was prepared according to the procedure to 9a and the desired product
was obtained after purification by silica gel column chromatography (Hexane/EtOAc =
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