Copper(I)-Catalyzed Intramolecular N-N Coupling of Cyclopropyl O-Acyl Ketoximes: Synthesis of Spiro-fused Pyrazolin-5-ones

Article abstract of DOI:10.1002/cjoc.201600479

A convenient copper-catalyzed approach has been developed for the synthesis of substituted spiro-fused pyrazolin-5-ones from readily available cyclopropyl O-acyl ketoximes via an intramolecular N N bond formation reaction. These catalytic reactions proceed in excellent yields with a broad scope.

Full text of DOI:10.1002/cjoc.201600479

FULL PAPER
DOI: 10.1002/cjoc.201600479
Copper(I)-Catalyzed Intramolecular N-N Coupling of
Cyclopropyl O-Acyl Ketoximes: Synthesis
of Spiro-fused Pyrazolin-5-ones
Zhiguo Zhang,*,a,b Junlong Li,a Guoqing Huang,c Kai Sun,a,d Guisheng Zhang,*,a
Nana Ma,a Qingfeng Liu,a and Tongxin Liua
a Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory
of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering,
Henan Normal University, Xinxiang, Henan 453007, China
b Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis, Northeast Normal
University, Changchun, Jilin 130024, China
c Handan Purification Equipment Research Institute, Handan, Hebei 056027, China
d College of Chemistry and Chemical Engineering, Anyang Normal University, Anyang, Henan 455000, China
A convenient copper-catalyzed approach has been developed for the synthesis of substituted spiro-fused
pyrazolin-5-ones from readily available cyclopropyl O-acyl ketoximes via an intramolecular N－N bond formation
reaction. These catalytic reactions proceed in excellent yields with a broad scope.
Keywords copper-catalyzed, N-N bond formation, O-acyl ketoximes, pyrazolin-5-ones, cyclopropyl oximes
Introduction
Dong’s group[6] developed a tandem ketoxime tosyla-
tion and intramolecular cyclization for the synthesis of
fully substituted spiro-fused pyrazolin-5-ones by treat-
ment of cyclopropyl O-acetyl oximes with p-toluene-
sulfonyl chloride in the presence of potassium hydrox-
ide (Figure 1). The development of new methods for the
synthesis of spiro-fused pyrazolin-5-one derivatives is
of considerable interest, although several useful meth-
ods have been established.
Very recently, we have achieved a convenient
iron(III)-catalyzed intramolecular cyclization of
1-(N-arylpyrrol-2-yl)ethanone O-acyl oximes (1) for the
synthesis of substituted pyrrolo[1,2-a]quinoxalines (2)
through N－O bond cleavage and directed C－H aryla-
tion reactions in acetic acid (Eq. 1).[7] Combined with
other recent researches on the copper-catalyzed oxime
acetates participated reactions,[8] we speculated that the
dinitrogen-containing seven-membered ring benzo[b]-
[1,4]diazepin-2-one derivatives (4) should be synthe-
sized via an intramolecular cyclization reaction using
1-carbamoyl-1-O-acyl ketoximylcycloalkanes (3) (Eq.
2).
Pyrazolones are very important nitrogen-containing
intermediates and products. They have been widely used
in analytical, dye, biological and pharmaceutical chem-
istry owing to the broad biological activities and struc-
tural complexity.[1] To date, numerous effective meth-
ods have been built for the synthesis of pyrazo-
lones.[1a,1b,2] However, a systematic review of the litera-
ture showed that it remains lack of alternative methods
for the synthesis of spiro-fused pyrazolin-5-ones, alt-
hough their potential applications are included in or-
ganic synthesis and pharmaceutical chemistry. A mul-
ti-step strategy for the synthesis of spiro-fused pyra-
zolin-5-ones was first reported by Wamhoff and Korte[3]
in 1966. Subsequently, in order to test the pharmaco-
logical activity of several 3-pyrazolone analogues, as
the key intermediates, Krogsgaard-Larsen and
co-works[4] prepared the spiro-fused pyrazolin-5-ones
via multi-step (Figure 1). In 2010, Rao and Reddy[5]
reported a multicomponent cascade approach (involves
simultaneous cyclization, leading to the formation of
thiazole, pyrazolone, and cyclopropane rings) for the
synthesis of spiro-fused pyrazolin-5-ones in a single
step from aryl bromomethylketones, heteroarylbromo-
methylketones with thiosemicarbazide and α-bromoace-
tyl-γ-butyrolactone in POCl3 under heating (Figure 1).
In this paper, we present our efforts toward the cop-
per-catalyzed intramolecular directed N－N bond for-
mation of cyclopropyl O-acetyl oximes for the synthesis
of spiro-fused pyrazolin-5-ones (Figure 1).
*
E-mail: zhangzg@htu.edu.cn and zgs6668@yahoo.com; Tel.: 0086-0373-3325250
Received July 29, 2016; accepted September 18, 2016; published online XXXX, 2016.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201600479 or from the author.
Chin. J. Chem. 2016, XX, 1—12
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Zhang et al.
FULL PAPER
R1
N
ref. 3: H+ or SOCl2
A
Krogsgaard-Larsen's
and Wamhoff's works:
ref. 4: (EtO2C)2CNaNHAc
X
O
A = OH, Br, Cl; X = NH, NPh; R1 = Me, Ph.
Ac
S
POCl3
ref. 5
O
Rao's work:
H2N
+
+
Br
N
NH2
Ar
O
O
H
R1
N
R2
O
N
HO
O
TsCl/KOH
ref. 6
N
R2
Dong's works:
R1
N
H
R1 = Me or Ph; R2 = Ar.
CuBr (10 mol%)
Toluene, 100 oC
AcO
R1
N
O
R2
This work:
N
H
R1, R2 = Alkyl, Aryl. Up to 96% yield
Figure 1 General synthetic routes to the spiro-fused pyrazolin-5-one derivatives.
was carried out on SiO2 (silica gel 200－300 mesh).
General procedure for the synthesis of 6 and 3
To a round-bottom flask (25 mL) was added 5 (2.0
mmol) in EtOH (6.0 mL)/H2O (0.24 mL), hyoxylamine
hydrochloride (4.0 mmol, 2.0 equiv.) and NaOAc (4.0
mmol, 2.0 equiv.). The mixture was heated at 100 ℃
for 12－24 h. After cooling to room temperature, the
reaction was quenched by water, the mixture was ex-
tracted with dichloromethane (DCM) (4.0 mL×3), the
organic layer was dried over anhydrous Na2SO4 and
concentrated under reduced pressure, and the residue
was purified by column chromatography on silica gel to
provide the desired product 6.
Then to a 25 mL flask was added 6 (0.5 mmol), tri-
ethylamine (TEA, 1.0 mmol, 2.0 equiv.) and DCM (5
mL) at 0 ℃, a solution of acetyl chloride (0.75 mmol,
1.5 equiv.) in DCM (1.0 mL) was added dropwise to
this stirred cooled solution. The reaction mixture was
stirred at 0 ℃ for 5 min. After the reaction was
quenched by water, the mixture was extracted with
DCM (5.0 mL×3), and the combined extracts were
washed with NaHCO3 (aq.) (5.0 mL) and brine (5.0 mL).
The organic layer was dried over anhydrous Na2SO4 and
concentrated in vacuo. The residue was purified by
column chromatography on silica gel to provide the de-
sired product 3.
Experimental
General
All reactions were carried out under an air atmos-
phere, unless otherwise indicated. All the reagents were
commercially available, and toluene was distilled from
1
sodium. H NMR and 13C NMR spectra were recorded
on a Bruker Avance/400 (1H: 400 MHz, 13C: 100 MHz
at 25 ℃) with TMS as internal standard. Data are rep-
resented as follows: chemical shift, integration, multi-
plicity (br＝broad, s＝singlet, d＝doublet, dd＝double
doublet, t＝triplet, q＝quartet, m＝multiplet), coupling
constants in Hertz (Hz). All high-resolution mass spec-
tra (HRMS) were measured on a mass spectrometer by
using electrospray ionization (ESI-oa-TOF), and the
purity of all samples used for HRMS (＞95%) were
General procedure for the synthesis of 7
A solution of O-acyl oxime 3 (0.3 mmol) and CuBr
(4.3 mg, 10 mol%) in toluene (3.0 mL, 0.1 mol/L) was
heated at 100 ℃ until 3 was completely consumed
(monitored by TLC). After cooling to room temperature,
the mixture was quenched with water (10 mL), and then
it was extracted with dichloromethane (DCM) (5 mL×
3). The organic extracts were dried over anhydrous
1
confirmed by H NMR and 13C NMR spectroscopic
analysis. Melting points were measured on a melting
point apparatus equipped with a thermometer and were
uncorrected. All reactions were monitored by TLC with
GF254 silica gel coated plates. Flash chromatography
2
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Chin. J. Chem. 2016, XX, 1—12

Copper(I)-Catalyzed Intramolecular N-N Coupling of Cyclopropyl O-Acyl Ketoximes
Na2SO4 and concentrated in vacuo. The crude product
was purified by column chromatography (silica gel,
PE/EtOAc).
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (153.9
1
mg, 83%): m.p. 106－108 ℃; H NMR (400 MHz,
CDCl3) δ: 10.41 (s, 1H), 7.65 (d, J＝8.8 Hz, 2H), 7.26
－7.20 (m, 6H), 2.37 (s, 3H), 2.04 (s, 3H), 1.75 (q, J＝
4.0 Hz, 2H), 1.11 (q, J＝4.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 168.7, 168.2, 167.8, 140.5, 137.1,
129.0, 128.6, 128.5, 127.8, 127.4, 120.9, 29.7, 21.3,
19.2, 16.6. HRMS (ESI) calcd for C20H19ClN2O3 ([M＋
Na]＋) 393.0976, found 393.0975.
General procedure for the radical trapping experi-
ments
A solution of O-acyl oxime 3g (97 mg, 0.3 mmol),
CuBr (4.3 mg, 10 mol%) and radical scavenger (47 mg,
100 mol% and 470 mg, 1000 mol% TEMPO) in toluene
(3.0 mL) was heated at 100 ℃ until 3g was completely
consumed (monitored by TLC). After cooling to room
temperature, the mixture was quenched with water (10
mL), and then it was extracted with dichloromethane
(DCM) (5 mL×3). The organic extracts were dried
over anhydrous Na2SO4 and concentrated in vacuo. The
crude product was purified by column chromatography
(silica gel, PE/EtOAc)
(E)-1-((Acetoxyimino)(m-tolyl)methyl)-N-(4-
chlorophenyl)cyclopropane-1-carboxamide
(3e)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (150.2
mg, 81%), m.p. 61－63 ℃; 1H NMR (400 MHz, CDCl3)
δ: 10.64 (s, 1H), 7.66 (d, J＝8.8 Hz, 2H), 7.28 (t, J＝7.8
Hz, 1H), 7.24－7.18 (m, 3H), 7.07－7.01 (m, 2H), 2.35
(s, 3H), 2.00 (s, 3H), 1.74 (q, J＝4.2 Hz, 2H), 1.09 (q,
J＝4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 168.7,
168.0, 167.6, 138.1, 137.2, 130.7, 130.3, 128.6, 128.5,
128.2, 127.7, 124.5, 120.9, 29.4, 21.3, 19.1, 16.8.
HRMS (ESI) calcd for C20H19ClN2O3 ([M＋Na]＋ )
393.0976, found 393.0981.
(E)-1-((Acetoxyimino)(4-methoxyphenyl)methyl)-
N-phenylcyclopropane-1-carboxamide (3a)
The
product was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (146.2 mg,
1
83%), m.p. 49－51 ℃; H NMR (400 MHz, CDCl3) δ:
9.71 (s, 1H), 7.63 (d, J＝7.6 Hz, 2H), 7.47 (d, J＝8.8
Hz, 2H), 7.28 (t, J＝8.0 Hz, 2H), 7.06 (t, J＝7.4 Hz,
1H), 6.92 (d, J＝8.8 Hz, 2H), 3.82 (s, 3H), 2.10 (s, 3H),
1.77 (q, J＝4.4 Hz, 2H), 1.16 (q, J＝4.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 168.4, 167.9, 167.8, 161.0,
138.4, 130.4, 128.7, 123.9, 122.7, 119.7, 113.7, 55.2,
30.4, 19.4, 16.3. HRMS (ESI) calcd for C20H20N2O4 ([M
＋Na]＋) 375.1315, found 375.1302.
(E)-1-((Acetoxyimino)(4-chlorophenyl)methyl)-N-
(4-chlorophenyl)cyclopropane-1-carboxamide
(3f)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (170.2
1
mg, 87%), m.p. 98－100 ℃; H NMR (400 MHz,
CDCl3) δ: 10.43 (s, 1H), 7.69－7.63 (m, 2H), 7.45－
7.41 (m, 2H), 7.29－7.25 (m, 4H), 2.07 (s, 3H), 1.80 (q,
J＝4.4 Hz, 2H), 1.09 (q, J＝4.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 167.9, 167.5, 167.3, 137.1, 136.4,
129.1, 129.0, 128.9, 128.8, 128.7, 121.0, 29.6, 19.2,
16.7. HRMS (ESI) calcd for C19H16Cl2N2O3 ([M＋Na]＋)
413.0430, found 413.0437.
(E)-1-((Acetoxyimino)(4-methoxyphenyl)methyl)-
N-(p-tolyl)cyclopropane-1-carboxamide (3b)
The
product was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (152.1 mg,
1
83%), m.p. 112－114 ℃; H NMR (400 MHz, CDCl3)
δ: 9.55 (s, 1H), 7.49 (t, J＝7.4 Hz, 4H), 7.08 (d, J＝8.4
Hz, 2H), 6.92 (d, J＝8.8 Hz, 2H), 3.82 (s, 3H), 2.28 (s,
3H), 2.10 (s, 3H), 1.76 (q, J＝4.2 Hz, 2H), 1.16 (q, J＝
4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 168.4,
167.7, 167.7, 161.0, 135.8, 133.4, 130.4, 129.2, 122.8,
119.8, 113.7, 55.2, 30.4, 20.7, 19.4, 16.1. HRMS (ESI)
calcd for C21H22N2O4 ([M＋Na]＋ ) 389.1472, found
389.1472.
(E)-1-((Acetoxyimino)(4-methoxyphenyl)methyl)-
N-(4-chlorophenyl)cyclopropane-1-carboxamide (3c)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (164.4
mg, 85%), m.p. 65－67 ℃; 1H NMR (400 MHz, CDCl3)
δ: 10.06 (s, 1H), 7.65－7.60 (m, 2H), 7.43－7.38 (m,
2H), 7.25－7.20 (m, 2H), 6.93－6.89 (m, 2H), 3.81 (s,
3H), 2.08 (s, 3H), 1.75 (q, J＝4.4 Hz, 2H), 1.12 (q, J＝
4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 168.5,
168.3, 168.0, 161.0, 137.1, 130.3, 128.6, 128.6, 122.4,
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-phenyl-
cyclopropane-1-carboxamide (3g) The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶7] as a white solid (153.1 mg, 95%), m.p.
1
144－146 ℃; H NMR (400 MHz, CDCl3) δ: 10.25 (s,
1H), 7.69 (d, J＝8.4 Hz, 2H), 7.45－7.38 (m, 3H), 7.36
－7.26 (m, 4H), 7.06 (t, J＝7.4 Hz, 1H), 2.02 (s, 3H),
1.78 (q, J＝4.2 Hz, 2H), 1.13 (q, J＝4.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 168.29, 167.95, 167.46,
138.39, 130.58, 129.99, 128.68, 128.29, 127.54, 123.82,
119.69, 29.68, 19.07, 16.42. HRMS (ESI) calcd for
C19H18N2O3 ([M＋Na]＋) 345.1210, found 345.1201.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(p-
tolyl)cyclopropane-1-carboxamide (3h) The product
was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (143.0 mg,
1
85%), m.p. 115－117 ℃; H NMR (400 MHz, CDCl3)
δ: 10.07 (s, 1H), 7.55 (d, J＝8.4 Hz, 2H), 7.45－7.39 (m,
3H), 7.36－7.33 (m, 2H), 7.10 (d, J＝8.4 Hz, 2H), 2.29
(s, 3H), 2.03 (s, 3H), 1.77 (q, J＝4.2 Hz, 2H), 1.14 (q,
J＝4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 168.30,
168.00, 167.29, 135.87, 133.36, 130.71, 130.03, 129.20,
128.32, 127.62, 119.70, 29.73, 20.74, 19.14, 16.33.
120.9, 113.7, 55.2, 30.2, 19.3, 16.5. HRMS (ESI) calcd
＋
for C20H19ClN2O4 ([M ＋ Na] ) 409.0926, found
409.0932.
(E)-1-((Acetoxyimino)(p-tolyl)methyl)-N-(4-
chlorophenyl)cyclopropane-1-carboxamide
(3d)
Chin. J. Chem. 2016, XX, 1—12
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3

Zhang et al.
FULL PAPER
HRMS (ESI) calcd for C20H20N2O3 ([M ＋ Na] ＋
)
CDCl3) δ: 10.30 (s, 1H), 7.46 (s, 1H), 7.42－7.39 (m,
3H), 7.34－7.29 (m, 2H), 7.20－7.16 (m, 2H), 6.65－
6.60 (m, 1H), 3.77 (s, 3H), 2.01 (s, 3H), 1.76 (q, J＝4.2
Hz, 2H), 1.13 (q, J＝4.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 168.1, 167.9, 167.5, 159.8, 139.6, 130.5,
123.0, 129.4, 128.3, 127.5, 111.9, 110.1, 105.0, 55.0,
29.7, 19.1, 16.4. HRMS (ESI) calcd for C20H20N2O4 ([M
＋Na]＋) 375.1315, found 375.1310.
359.1366, found 359.1368.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(m-
tolyl)cyclopropane-1-carboxamide (3i) The product
was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (144.7 mg,
1
86%), m.p. 69－71 ℃; H NMR (400 MHz, CDCl3) δ:
10.16 (s, 1H), 7.58 (s, 1H), 7.44 (d, J＝8.4 Hz, 1H),
7.42－7.37 (m, 3H), 7.35－7.31 (m, 2H), 7.16 (t, J＝7.8
Hz, 1H), 6.88 (d, J＝7.6 Hz, 1H), 2.31 (s, 3H), 2.00 (s,
3H), 1.77 (q, J＝4.4 Hz, 2H), 1.14 (q, J＝4.2 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ: 168.0, 167.8, 167.3,
138.3, 138.2, 130.5, 129.9, 128.4, 128.2, 127.4, 124.5,
120.2, 116.7, 29.6, 21.3, 18.9, 16.2. HRMS (ESI) calcd
for C20H20N2O3 ([M＋Na]＋) 359.1366, found 359.1362.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(o-
tolyl)cyclopropane-1-carboxamide (3j) The product
was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶6] as a white solid (146.3 mg,
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(2-
methoxyphenyl)cyclopropane-1-carboxamide
(3n)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (144.5
mg, 82%), m.p. 77－79 ℃; 1H NMR (400 MHz, CDCl3)
δ: 9.02 (s, 1H), 8.23 (q, J＝1.2 Hz, 1H), 7.52－7.47 (m,
2H), 7.42－7.38 (m, 3H), 6.99－6.94 (m, 1H), 6.88－
6.84 (m, 1H), 6.79 (q, J＝1.2 Hz, 1H), 3.77 (s, 3H),
2.08 (s, 3H), 1.74 (q, J＝4.2 Hz, 2H), 1.34 (q, J＝4.2
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 167.7, 167.3,
164.7, 148.0, 131.2, 130.1, 128.2, 127.9, 127.4, 123.6,
120.4, 119.6, 109.7, 55.3, 30.7, 19.3, 16.1. HRMS (ESI)
calcd for C20H20N2O4 ([M＋Na]＋ ) 375.1315, found
375.1312.
1
87%), m.p. 84－86 ℃; H NMR (400 MHz, CDCl3) δ:
9.18 (s, 1H), 7.68 (d, J＝8.0 Hz, 1H), 7.45 (s, 5H), 7.16
(t, J＝8.0 Hz, 2H), 7.07－7.01 (m, 1H), 2.17 (s, 3H),
2.02 (s, 3H), 1.80 (q, J＝4.4 Hz, 2H), 1.28 (q, J＝4.2
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 167.7, 167.6,
166.9, 135.7, 130.9, 130.2, 130.1, 130.0, 128.3, 127.7,
126.1, 125.0, 123.4, 29.7, 19.1, 17.6, 16.4. HRMS (ESI)
calcd for C20H20N2O3 ([M＋Na]＋ ) 359.1366, found
359.1377.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(4-
chlorophenyl)cyclopropane-1-carboxamide
(3o)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (153.4
mg, 86%), m.p. 119－121 ℃; H NMR (400 MHz,
1
CDCl3) δ: 10.58 (s, 1H), 7.69－7.65 (m, 2H), 7.46－
7.43 (m, 3H), 7.31－7.27 (m, 3H), 7.26－7.24 (m, 1H),
2.04 (s, 3H), 1.78 (q, J＝4.2 Hz, 2H), 1.12 (q, J＝4.4
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 168.6, 168.1,
167.6, 137.2, 130.4, 130.1, 128.7, 128.6, 128.4, 127.5,
121.0, 29.5, 19.1, 16.8. HRMS (ESI) calcd for
C19H17ClN2O3 ([M＋Na]＋) 379.0820, found 379.0796.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(4-
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-mesityl-
cyclopropane-1-carboxamide (3k) The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶6] as a white solid (153.0 mg, 84%), m.p.
1
106－108 ℃; H NMR (400 MHz, CDCl3) δ: 8.36 (s,
1H), 7.59－7.55 (m, 2H), 7.47－7.43 (m, 3H), 6.81 (s,
2H), 2.23 (s, 3H), 2.04 (s, 3H), 1.98 (s, 6H), 1.75 (q, J＝
4.4 Hz, 2H), 1.36 (q, J＝4.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 167.9, 167.8, 166.1, 136.2, 134.7,
131.2, 131.1, 130.2, 128.4, 128.3, 128.1, 29.8, 20.6,
19.2, 17.7, 15.4. HRMS (ESI) calcd for C22H24N2O3 ([M
＋Na]＋) 387.1679, found 387.1687.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(4-
methoxyphenyl)cyclopropane-1-carboxamide
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (146.2
chlorophenyl)cyclopropane-1-carboxamide
(3p)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶6] as a white solid (157.0
mg, 88%), m.p. 79－81 ℃; 1H NMR (400 MHz, CDCl3)
δ: 10.60 (s, 1H), 7.91 (s, 1H), 7.50－7.45 (m, 1H), 7.44
－7.38 (m, 3H), 7.29－7.26 (m, 2H), 7.19 (t, J＝8.2 Hz,
1H), 7.04－7.01 (m, 1H), 2.00 (s, 3H), 1.76 (q, J＝4.2
Hz, 2H), 1.11 (q, J＝4.2 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 168.3, 168.0, 167.8, 139.6, 134.2, 130.3,
130.0, 129.7, 128.3, 127.4, 123.8, 119.8, 117.8, 29.5,
19.0, 16.7. HRMS (ESI) calcd for C19H17ClN2O3 ([M＋
Na]＋) 379.0820, found 379.0821.
(3l)
1
mg, 83%), m.p. 117－119 ℃; H NMR (400 MHz,
CDCl3) δ: 10.04 (s, 1H), 7.58－7.52 (m, 2H), 7.42－
7.38 (m, 3H), 7.34－7.30 (m, 2H), 6.84－6.78 (m, 2H),
3.73 (s, 3H), 2.00 (s, 3H), 1.74 (q, J＝4.2 Hz, 2H), 1.11
(q, J＝4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ:
168.3, 168.0, 167.2, 155.9, 131.7, 130.6, 123.0, 128.3,
127.6, 121.2, 113.8, 55.2, 29.6, 19.1, 16.2. HRMS (ESI)
calcd for C20H20N2O4 ([M＋Na]＋ ) 375.1315, found
375.1304.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(3-
methoxyphenyl)cyclopropane-1-carboxamide (3m)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (137.4
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(2-
chlorophenyl)cyclopropane-1-carboxamide
(3q)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (160.6
mg, 90%), m.p. 73－75 ℃; 1H NMR (400 MHz, CDCl3)
δ: 9.09 (s, 1H), 8.17 (d, J＝8.0 Hz, 1H), 7.52－7.48 (m,
2H), 7.44－7.39 (m, 3H), 7.27 (d, J＝8.0 Hz, 1H), 7.17
(t, J＝7.8 Hz, 1H), 7.00－6.92 (m, 1H), 2.05 (s, 3H),
1.77 (q, J＝4.4 Hz, 2H), 1.35 (q, J＝4.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 167.9, 167.6, 164.9, 134.4,
130.9, 130.3, 128.8, 128.3, 128.0, 127.2, 124.7, 123.5,
1
mg, 78%), m.p. 114－116 ℃; H NMR (400 MHz,
4
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© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—12

Copper(I)-Catalyzed Intramolecular N-N Coupling of Cyclopropyl O-Acyl Ketoximes
122.0, 30.6, 19.2, 16.5. HRMS (ESI) calcd for
C19H17ClN2O3 ([M＋Na]＋) 379.0820, found 379.0817.
Ethyl (E)-4-(1-((acetoxyimino)(phenyl)methyl)-
(400 MHz, CDCl3) δ: 10.33 (s, 1H), 7.84 (d, J＝2.8 Hz,
1H), 7.45 (dd, J＝9.2, 2.8 Hz, 1H), 7.42－7.39 (m, 3H),
7.31－7.25 (m, 2H), 6.83 (d, J＝8.8 Hz, 1H), 3.82 (s,
3H), 2.00 (s, 3H), 1.73 (q, J＝4.2 Hz, 2H), 1.09 (q, J＝
4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 168.4,
168.0, 167.4, 151.3, 132.2, 130.4, 130.0, 128.3, 127.5,
122.0, 122.0, 119.2, 111.9, 56.1, 29.5, 19.1, 16.5.
HRMS (ESI) calcd for C20H19ClN2O4 ([M＋Na]＋ )
409.0926, found 409.0937.
cyclopropane-1-carboxamido)benzoate (3r)
The
product was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶6] as a white solid (159.7 mg,
1
81%), m.p. 94－96 ℃; H NMR (400 MHz, CDCl3) δ:
10.76 (s, 1H), 8.03－7.97 (m, 2H), 7.81－7.76 (m, 2H),
7.46－7.41 (m, 3H), 7.31－7.25 (m, 2H), 4.34 (q, J＝
7.2 Hz, 2H), 2.03 (s, 3H), 1.80 (q, J＝4.4 Hz, 2H), 1.37
(t, J＝7.2 Hz, 3H), 1.12 (q, J＝4.2 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ: 168.6, 168.0, 168.0, 166.3, 142.6,
130.6, 130.4, 130.1, 128.5, 127.6, 125.6, 119.0, 60.7,
29.7, 19.2, 17.1, 14.3. HRMS (ESI) calcd for
C22H22N2O5 ([M＋Na]＋) 417.1421, found 417.1421.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(4-
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-benzyl-
cyclopropane-1-carboxamide (3w) The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶7] as a white solid (131.2 mg, 78%), m.p.
73－75 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.53 (s, 1H),
7.44－7.38 (m, 5H), 7.28－7.19 (m, 3H), 7.10－7.05
(m, 2H), 4.40 (d, J＝5.6 Hz, 2H), 1.99 (s, 3H), 1.68 (q,
J＝4.2 Hz, 2H), 1.24 (q, J＝4.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 169.5, 168.0, 166.2, 137.9, 131.1,
130.1, 128.3, 127.9, 127.3, 127.0, 43.9, 29.6, 19.2, 15.6.
bromophenyl)cyclopropane-1-carboxamide
(3s)
The product was isolated by flash chromatography [el-
uent: V(EtOAc)∶V(PE)＝1∶7] as a white solid (162.5
mg, 81%), m.p. 68－70 ℃; 1H NMR (400 MHz, CDCl3)
δ: 10.57 (s, 1H), 7.63－7.58 (m, 2H), 7.44－7.40 (m,
3H), 7.40－7.36 (m, 2H), 7.29－7.26 (m, 2H), 2.01 (s,
3H), 1.76 (q, J＝4.2 Hz, 2H), 1.10 (q, J＝4.4 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ: 168.5, 168.0, 167.6,
137.6, 131.6, 130.4, 130.0, 128.4, 127.5, 121.3, 116.3,
29.6, 19.1, 16.7. HRMS (ESI) calcd for C19H17BrN2O3
([M＋Na]＋) 423.0315, found 423.0314.
HRMS (ESI) calcd for C20H20N2O3 ([M ＋ Na] ＋
)
359.1366, found 359.1351.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-butyl-
cyclopropane-1-carboxamide (3x) The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
1
V(PE)＝1∶7] as a yellow oil (136.1 mg, 94%); H
NMR (400 MHz, CDCl3) δ: 7.37－7.32 (m, 5H), 7.28 (s,
1H), 3.18－3.11 (m, 2H), 1.95 (s, 3H), 1.57 (q, J＝4.2
Hz, 2H), 1.37－1.28 (m, 2H), 1.19－1.11 (m, 2H), 1.08
(q, J＝4.2 Hz, 2H), 0.77 (t, J＝7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 169.3, 168.0, 167.1, 131.1, 130.0,
128.2, 127.8, 39.8, 31.00, 29.4, 19.7, 19.1, 15.4, 13.5.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(4-
fluorophenyl)cyclopropane-1-carboxamide (3t) The
product was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (141.3 mg,
83%), m.p. 93－95 ℃; H NMR (400 MHz, CDCl3) δ:
HRMS (ESI) calcd for C17H22N2O3 ([M ＋ Na] ＋
)
1
10.43 (s, 1H), 7.68－7.62 (m, 2H), 7.44－7.40 (m, 3H),
7.32－7.28 (m, 2H), 6.97 (t, J＝8.6 Hz, 2H), 2.01 (s,
3H), 1.75 (q, J＝4.2 Hz, 2H), 1.11 (q, J＝4.2 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ: 168.5, 168.1, 167.5,
158.9 (d, J＝241 Hz), 134.6 (d, J＝2.7 Hz), 130.4,
130.0, 128.3, 127.5, 121.3 (d, J＝7.8 Hz), 115.3 (d, J＝
22.2 Hz), 29.5, 19.1, 16.5. HRMS (ESI) calcd for
C19H17FN2O3 ([M＋Na]＋) 363.1115, found 363.1115.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(4-
(trifluoromethyl)phenyl)cyclopropane-1-carbox-
amide (3u) The product was isolated by flash chro-
matography [eluent: V(EtOAc)∶V(PE)＝1∶7] as a
white solid (158.1 mg, 81%), m.p. 57－59 ℃; 1H NMR
(400 MHz, CDCl3) δ: 10.87 (s, 1H), 7.85 (d, J＝8.8 Hz,
2H), 7.55 (d, J＝8.8 Hz, 2H), 7.46－7.41 (m, 3H), 7.29
－7.25 (m, 2H), 2.02 (s, 3H), 1.79 (q, J＝4.4 Hz, 2H),
1.12 (q, J＝4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ:
168.6, 168.1, 168.1, 141.6, 130.3, 130.1, 128.4, 127.5,
126.0 (q, J＝3.5 Hz), 125.6, 125.5, 125.3, 122.8, 119.5,
29.6, 19.1, 17.0. HRMS (ESI) calcd for C20H17F3N2O3
([M＋Na]＋) 413.1083, found 413.1083.
325.1523, found 325.1508.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-cyclo-
hexylcyclopropane-1-carboxamide (3y) The product
was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (139.6 mg,
1
85%), m.p. 47－49 ℃; H NMR (400 MHz, CDCl3) δ:
7.35 (s, 5H), 7.1 (d, J＝7.2 Hz, 1H), 3.70－3.57 (m,
1H), 1.97 (s, 3H), 1.75－1.65 (m, 2H), 1.62－1.52 (m,
4H), 1.52－1.44 (m, 1H), 1.28－1.17 (m, 2H), 1.12－
1.08 (m, 2H), 1.06－0.98 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ: 168.2, 168.0, 167.2, 131.2, 130.0, 128.2,
127.8, 48.7, 32.4, 29.5, 25.2, 24.5, 19.2, 15.4. HRMS
(ESI) calcd for C19H24N2O3 ([M＋Na]＋ ) 351.1679,
found 351.1667.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(tert-
butyl)cyclopropane-1-carboxamide (3z) The prod-
uct was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶7] as a white solid (136.1 mg,
1
90%), m.p. 53－55 ℃; H NMR (400 MHz, CDCl3) δ:
7.36 (s, 5H), 6.74 (s, 1H), 1.97 (s, 3H), 1.52 (q, J＝4.2
Hz, 2H), 1.16 (s, 9H), 1.11 (q, J＝4.2 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 168.1, 167.9, 166.7, 131.5,
130.0, 128.2, 127.8, 51.3, 30.2, 28.3, 19.2, 15.0. HRMS
(ESI) calcd for C17H22N2O3 ([M＋Na]＋ ) 325.1523,
found 325.1514.
(E)-1-((Acetoxyimino)(phenyl)methyl)-N-(3-
chloro-4-methoxyphenyl)cyclopropane-1-carbox-
amide (3v) The product was isolated by flash chro-
matography [eluent: V(EtOAc)∶V(PE)＝1∶7] as a
white solid (164.3 mg, 85%), m.p. 69－71 ℃; 1H NMR
(Z)-2-((Acetoxyimino)(phenyl)methyl)-N-(4-
Chin. J. Chem. 2016, XX, 1—12
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
5

Zhang et al.
FULL PAPER
chlorophenyl)butanamide (3a') The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶7] as a yellow oil (163.2 mg, 91%); H
NMR (400 MHz, CDCl3) δ: 9.34 (s, 1H), 7.61 (d, J＝
8.8 Hz, 2H), 7.42－7.36 (m, 3H), 7.33－7.29 (m, 2H),
7.22 (d, J＝8.8 Hz, 2H), 3.67 (t, J＝7.2 Hz, 1H), 2.03 (s,
3H), 2.01－1.98 (m, 1H), 1.92－1.82 (m, 1H), 0.96 (t,
J＝7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 168.5,
167.8, 167.3, 136.6, 131.1, 130.1, 128.9, 128.7, 128.3,
329.1260, found 329.1254.
5-(4-Chlorophenyl)-7-(4-methoxyphenyl)-5,6-
diazaspiro[2.4]hept-6-en-4-one (7c) The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶8] as a white solid (89.2 mg, 92%), m.p.
1
1
101－103 ℃; H NMR (400 MHz, CDCl3) δ: 8.05－
8.00 (m, 2H), 7.57－7.52 (m, 2H), 7.41－7.35 (m, 2H),
6.96－6.92 (m, 2H), 3.85 (s, 3H), 2.11 (q, J＝4.4 Hz,
2H), 1.90 (q, J＝4.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 172.7, 161.2, 157.7, 137.3, 129.9, 128.8,
127.3, 122.9, 119.8, 114.4, 55.4, 33.0, 21.1. HRMS (ESI)
calcd for C18H15ClN2O2 ([M＋Na]＋) 349.0714, found
349.0710.
127.3, 120.9, 55.8, 24.1, 19.2, 11.6. HRMS (ESI) calcd
＋
for C19H19ClN2O3 ([M ＋ Na] ) 381.0976, found
381.0976.
(E)-1-(1-(Acetoxyimino)ethyl)-N-(4-methoxy-
phenyl)cyclopropane-1-carboxamide (3b')
product was isolated by flash chromatography [eluent:
The
5-(4-Chlorophenyl)-7-(p-tolyl)-5,6-diazaspiro-
[2.4]-hept-6-en-4-one (7d) The product was isolated
by flash chromatography [eluent: V(EtOAc)∶V(PE)＝
1∶8] as a yellow solid (90.4 mg, 97%), m.p. 100－
102 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.06－7.99 (m,
2H), 7.47 (d, J＝8.4 Hz, 2H), 7.39－7.34 (m, 2H), 7.22
(d, J＝8.0 Hz, 2H), 2.38 (s, 3H), 2.10 (q, J＝4.4 Hz,
2H), 1.88 (q, J＝4.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 172.7, 157.9, 140.6, 137.2, 129.8, 129.6,
128.8, 127.4, 125.6, 119.8, 33.0, 21.3, 21.1. HRMS (ESI)
calcd for C18H15ClN2O ([M＋Na]＋) 333.0765, found
333.0764.
V(EtOAc)∶V(PE)＝1∶8] as a white solid (124.8 mg,
1
86%), m.p. 64－69 ℃; H NMR (400 MHz, CDCl3) δ:
10.12 (s, 1H), 7.55 (d, J＝9.2 Hz, 2H), 6.83 (d, J＝9.2
Hz, 2H), 3.76 (s, 3H), 2.22 (s, 3H), 1.92 (s, 3H), 1.69 (q,
J＝4.2 Hz, 2H), 1.21 (q, J＝4.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 167.8, 167.1, 166.2, 156.0, 131.8,
121.3, 113.9, 55.3, 29.5, 19.3, 15.5, 14.1. HRMS (ESI)
calcd for C15H18N2O4 ([M＋Na]＋ ) 313.1159, found
313.1137.
(E)-1-(1-(Acetoxyimino)ethyl)-N-(4-chloro-
phenyl)-cyclopropane-1-carboxamide (3c')
product was isolated by flash chromatography [eluent:
The
5-(4-Chlorophenyl)-7-(m-tolyl)-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7e) The product was isolated
by flash chromatography [eluent: V(EtOAc)∶V(PE)＝
1∶8] as a yellow solid (83.0 mg, 89%), m.p. 84－
V(EtOAc)∶V(PE)＝1∶8] as a white solid (132.6 mg,
1
86%): m.p. 81－83 ℃; H NMR (400 MHz, CDCl3) δ:
1
10.78 (s, 1H), 7.63 (d, J＝8.8 Hz, 2H), 7.23 (d, J＝8.8
Hz, 2H), 2.22 (s, 3H), 1.87 (s, 3H), 1.71 (q, J＝4.4 Hz,
2H), 1.22 (q, J＝4.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 167.7, 167.5, 165.8, 137.2, 128.6, 128.5,
121.0, 29.2, 19.2, 16.1, 13.5. HRMS (ESI) calcd for
C14H15ClN2O3 ([M＋Na]＋) 317.0663, found 317.0646.
7-(4-Methoxyphenyl)-5-phenyl-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7a) The product was isolated
by flash chromatography [eluent: V(EtOAc)∶V(PE)＝
1∶8] as a yellow solid (78.4 mg, 89%), m.p. 107－
109 ℃; 1H NMR (400 MHz, CDCl3) δ: 8.06 (d, J＝8.0
Hz, 2H), 7.55 (d, J＝8.8 Hz, 2H), 7.43 (t, J＝7.8 Hz,
2H), 7.20 (t, J＝7.4 Hz, 1H), 6.93 (d, J＝8.8 Hz, 2H),
3.83 (s, 3H), 2.09 (q, J＝4.2 Hz, 2H), 1.89 (q, J＝4.4
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.7, 161.0,
157.4, 138.6, 128.8, 127.2, 124.8, 123.1, 118.8, 114.3,
55.3, 32.9, 20.9. HRMS (ESI) calcd for C18H16N2O2 ([M
＋Na]＋) 315.1104, found 315.1100.
86 ℃; H NMR (400 MHz, CDCl3) δ: 8.07－8.00 (m,
2H), 7.46 (s, 1H), 7.39－7.35 (m, 2H), 7.31－7.29 (m,
2H), 2.40 (s, 3H), 2.10 (q, J＝4.4 Hz, 2H), 1.89 (q, J＝
4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.6,
158.1, 138.7, 137.2, 131.1, 130.1, 129.8, 128.7, 126.5,
122.7, 119.8, 33.1, 21.4, 21.1. HRMS (ESI) calcd for
C18H15ClN2O ([M＋Na]＋) 333.0765, found 333.0761.
5,7-Bis(4-chlorophenyl)-5,6-diazaspiro[2.4]hept-
6-en-4-one (7f) The product was isolated by flash
chromatography [eluent: V(EtOAc)∶V(PE)＝1∶8] as
a white solid (90.4 mg, 91%), m.p. 136－138 ℃; 1H
NMR (400 MHz, CDCl3) δ: 8.02－7.97 (m, 2H), 7.53 (d,
J＝8.8 Hz, 2H), 7.43－7.37 (m, 4H), 2.10 (q, J＝4.4 Hz,
2H), 1.93 (q, J＝4.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 172.5, 156.8, 137.1, 136.5, 130.2, 129.3,
128.9, 128.8, 127.0, 119.9, 33.0, 21.2. HRMS (ESI)
calcd for C17H12Cl2N2O ([M＋Na]＋) 353.0219, found
353.0219.
7-(4-Methoxyphenyl)-5-(p-tolyl)-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7b) The product was isolated
by flash chromatography [eluent: V(EtOAc)∶V(PE)＝
1∶8] as a yellow solid (83.6 mg, 91%), m.p. 105－
107 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.92 (d, J＝8.4
Hz, 2H), 7.57－7.52 (m, 2H), 7.23 (d, J＝8.0 Hz, 2H),
6.94－6.90 (m, 2H), 3.83 (s, 3H), 2.36 (s, 3H), 2.07 (q,
J＝4.4 Hz, 2H), 1.87 (q, J＝4.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 172.5, 160.9, 157.2, 136.3, 134.4,
129.3, 127.1, 123.1, 118.8, 114.2, 55.2, 32.8, 20.9, 20.8.
5,7-Diphenyl-5,6-diazaspiro[2.4]hept-6-en-4-one
(7g) The product was isolated by flash chromatog-
raphy [eluent: V(EtOAc)∶V(PE)＝1∶8] as a white
1
solid (74.0 mg, 94%), m.p. 57－59 ℃; H NMR (400
MHz, CDCl3) δ: 8.09－8.02 (m, 2H), 7.64－7.58 (m,
2H), 7.48－7.41 (m, 5H), 7.22 (t, J＝7.4 Hz, 1H), 2.12
(q, J＝4.4 Hz, 2H), 1.92 (q, J＝4.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ: 172.8, 157.7, 138.6, 130.5, 130.2,
128.9, 128.8, 125.8, 125.0, 118.8, 33.1, 20.9. HRMS
(ESI) calcd for C17H14N2O ([M+Na]+) 285.0998, found
285.0985.
HRMS (ESI) calcd for C19H18N2O2 ([M ＋ Na] ＋
)
6
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© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—12

Copper(I)-Catalyzed Intramolecular N-N Coupling of Cyclopropyl O-Acyl Ketoximes
7-Phenyl-5-(p-tolyl)-5,6-diazaspiro[2.4]hept-6-en-
4-one (7h) The product was isolated by flash chroma-
tography [eluent: V(EtOAc)∶V(PE)＝1∶8] as a white
1∶8] as a yellow solid (80.7 mg, 92%), m.p. 74－
76 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.70 (t, J＝4.0
Hz, 1H), 7.68 (d, J＝8.0 Hz, 1H), 7.61－7.58 (m, 2H),
7.43 (q, J＝1.6 Hz, 3H), 7.33 (t, J＝8.6 Hz, 1H), 6.77
(dd, J＝8.4, 2.4 Hz, 1H), 3.85 (s, 3H), 2.11 (q, J＝4.4
Hz, 2H), 1.90 (q, J＝4.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 172.7, 159.9, 157.5, 139.7, 130.4, 130.1,
129.6, 128.9, 125.7, 104.3, 55.3, 33.1, 20.9. HRMS (ESI)
calcd for C18H16N2O2 ([M＋Na]＋ ) 315.1104, found
315.1094.
1
solid (79.6 mg, 96%), m.p. 108－110 ℃; H NMR
(400 MHz, CDCl3) δ: 7.96－7.92 (m, 2H), 7.63－7.58
(m, 2H), 7.44－7.40 (m, 3H), 7.24 (d, J＝8.4 Hz, 2H),
2.37 (s, 3H), 2.09 (q, J＝4.4 Hz, 2H), 1.89 (q, J＝4.4
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 157.4,
136.1, 134.5, 130.5, 130.0, 129.2, 128.8, 125.6, 118.8,
32.9, 20.9, 20.8. HRMS (ESI) calcd for C18H16N2O ([M
＋Na]＋) 299.1155, found 299.1149.
5-(2-Methoxyphenyl)-7-phenyl-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7n) The product was isolated
by flash chromatography [eluent: V(EtOAc)∶V(PE)＝
1∶8] as a yellow solid (77.2 mg, 88%), m.p. 127－
129 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.59－7.53 (m,
2H), 7.44 (d, J＝7.6 Hz, 1H), 7.42－7.34 (m, 4H), 7.04
(t, J＝7.8 Hz, 2H), 3.85 (s, 3H), 2.10 (q, J＝4.4 Hz, 2H),
1.91 (q, J＝4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ:
173.5, 157.6, 155.0, 130.7, 129.8, 129.8, 128.7, 128.4,
126.0, 125.7, 120.6, 112.3, 55.9, 31.6, 20.5. HRMS (ESI)
calcd for C18H16N2O2 ([M＋Na]＋ ) 315.1104, found
315.10095.
7-Phenyl-5-(m-tolyl)-5,6-diazaspiro[2.4]hept-6-en-
4-one (7i) The product was isolated by flash chroma-
tography [eluent: V(EtOAc)∶V(PE)＝1∶8] as a yel-
1
low solid (77.1 mg, 93%): m.p. 81－83 ℃; H NMR
(400 MHz, CDCl3) δ: 7.62－7.55 (m, 2H), 7.46－7.40
(m, 4H), 7.35－7.28 (m, 3H), 2.36 (s, 3H), 2.15 (q, J＝
4.4 Hz, 2H), 1.94 (q, J＝4.4 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 173.2, 157.6, 136.1, 135.0, 131.1,
130.6, 129.9, 128.8, 128.3, 126.6, 126.4, 125.5, 31.7,
20.6, 18.4. HRMS (ESI) calcd for C18H16N2O ([M＋
Na]＋) 299.1155, found 299.1150.
7-Phenyl-5-(o-tolyl)-5,6-diazaspiro[2.4]hept-6-en-
4-one (7j) The product was isolated by flash chroma-
tography [eluent: V(EtOAc)∶V(PE)＝1∶7] as a yel-
low oil (73.8 mg, 89%); 1H NMR (400 MHz, CDCl3) δ:
7.90－7.87 (m, 2H), 7.65－7.58 (m, 2H), 7.46－7.41
(m, 3H), 7.33 (t, J＝7.8 Hz, 1H), 7.04 (d, J＝7.8 Hz,
1H), 2.42 (s, 3H), 2.10 (q, J＝4.2 Hz, 2H), 1.90 (q, J＝
4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.7,
157.5, 138.6, 138.4, 130.4, 130.0, 128.8, 128.6, 125.8,
125.7, 119.4, 116.0, 33.0, 21.5, 20.8. HRMS (ESI) calcd
for C18H16N2O ([M＋Na]＋) 299.1155, found 299.1143.
5-Mesityl-7-phenyl-5,6-diazaspiro[2.4]hept-6-en-
4-one (7k) The product was isolated by flash chroma-
tography [eluent: V(EtOAc)∶V(PE)＝1∶7] as a white
5-(4-Chlorophenyl)-7-phenyl-5,6-diazaspiro[2.4]-
hept-6-en-4-one (7o) The product was isolated by
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
8] as a white solid (84.6 mg, 95%), m.p. 90－92 ℃; 1H
NMR (400 MHz, CDCl3) δ: 8.03 (d, J＝9.2 Hz, 2H),
7.59 (q, J＝2.0 Hz, 2H), 7.47－7.42 (m, 3H), 7.41－
7.36 (m, 2H), 2.12 (q, J＝4.4 Hz, 2H), 1.91 (q, J＝4.4
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.7, 157.9,
137.2, 130.3, 130.3, 129.9, 129.0, 128.8, 125.8, 119.8,
33.1, 21.1. HRMS (ESI) calcd for C17H13ClN2O ([M＋
Na]＋) 319.0609, found 319.0610.
5-(3-Chlorophenyl)-7-phenyl-5,6-diazaspiro[2.4]-
hept-6-en-4-one (7p) The product was isolated by
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
7] as a white solid (80.1 mg, 90%), m.p. 70－72 ℃; 1H
NMR (400 MHz, CDCl3) δ: 8.11 (t, J＝2.0 Hz, 1H),
8.03－8.00 (m, 1H), 7.63－7.57 (m, 2H), 7.47－7.41
(m, 3H), 7.34 (t, J＝8.2 Hz, 1H), 7.17 (dd, J＝8.0, 1.2
Hz, 1H), 2.13 (q, J＝4.4 Hz, 2H), 1.92 (q, J＝4.2 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ: 172.8, 158.0,
139.6, 134.5, 130.4, 130.2, 129.9, 129.0, 125.8, 124.9,
118.6, 116.5, 33.2, 21.2. HRMS (ESI) calcd for
C17H13ClN2O ([M＋Na]＋) 319.0609, found 319.0604.
5-(2-Chlorophenyl)-7-phenyl-5,6-diazaspiro[2.4]-
hept-6-en-4-one (7q) The product was isolated by
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
8] as a yellow solid (69.5 mg, 78%), m.p. 87－89 ℃;
1H NMR (400 MHz, CDCl3) δ: 7.60－7.51 (m, 4H),
7.44－7.40 (m, 3H), 7.39－7.32 (m, 2H), 2.15 (q, J＝
4.4 Hz, 2H), 1.95 (dd, J＝4.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 173.2, 158.2, 134.9, 131.8, 130.5,
130.4, 130.1, 129.7, 128.9, 128.9, 127.4, 125.8, 31.8,
20.7. HRMS (ESI) calcd for C17H13ClN2O ([M＋Na]＋)
319.0609, found 319.0600.
1
solid (74.9 mg, 82%), m.p. 103－105 ℃; H NMR
(400 MHz, CDCl3) δ: 7.60－7.57 (m, 2H), 7.45－7.38
(m, 3H), 6.98 (s, 2H), 2.33 (s, 3H), 2.22 (s, 6H), 2.16 (q,
J＝4.2 Hz, 2H), 1.94 (q, J＝4.2 Hz, 2H); 13C NMR (100
MHz, CDCl3) δ: 173.4, 157.7, 138.8, 136.4, 132.5,
130.8, 129.9, 129.1, 128.9, 125.5, 31.4, 21.1, 20.3, 18.0.
HRMS (ESI) calcd for C20H20N2O ([M ＋ Na] ＋
)
327.1468, found 327.1460.
5-(4-Methoxyphenyl)-7-phenyl-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7l) The product was isolated by
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
7] as a yellow oil (81.6 mg, 93%); 1H NMR (400 MHz,
CDCl3) δ: 7.95－7.89 (m, 2H), 7.60－7.57 (m, 2H),
7.45－7.39 (m, 3H), 6.99－6.93 (m, 2H), 3.82 (s, 3H),
2.10 (q, J＝4.2 Hz, 2H), 1.89 (q, J＝4.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 172.4, 157.5, 156.9, 132.0,
130.5, 130.0, 128.9, 125.7, 120.7, 113.9, 55.4, 32.9,
20.8. HRMS (ESI) calcd for C18H16N2O2 ([M＋Na]＋)
315.1104, found 315.1088.
5-(3-Methoxyphenyl)-7-phenyl-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7m) The product was isolated
by flash chromatography [eluent: V(EtOAc)∶V(PE)＝
Ethyl 4-(4-oxo-7-phenyl-5,6-diazaspiro[2.4]hept-
6-en-5-yl)benzoate (7r) The product was isolated by
Chin. J. Chem. 2016, XX, 1—12
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
7

Zhang et al.
FULL PAPER
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
7] as a white solid (79.2 mg, 79%), m.p. 120－122 ℃;
1H NMR (400 MHz, CDCl3) δ: 8.2－8.16 (m, 2H), 8.15
－8.09 (m, 2H), 7.64－7.59 (m, 2H), 7.48－7.43 (m,
3H), 4.38 (q, J＝7.2 Hz, 2H), 2.15 (q, J＝4.4 Hz, 2H),
1.95 (q, J＝4.4 Hz, 2H), 1.41 (t, J＝7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 173.1, 166.2, 158.4, 142.3,
130.6, 130.5, 130.3, 129.1 126.5, 126.0, 117.8, 60.9,
33.2, 21.2, 14.4. HRMS (ESI) calcd for C20H18N2O3
([M＋Na]＋) 357.1210, found 357.1208.
5-(4-Bromophenyl)-7-phenyl-5,6-diazaspiro[2.4]-
hept-6-en-4-one (7s) The product was isolated by
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
8] as a white solid (89.1 mg, 87%), m.p. 80－82 ℃; 1H
NMR (400 MHz, CDCl3) δ: 8.02－7.93 (m, 2H), 7.62－
7.56 (m, 2H), 7.54－7.49 (m, 2H), 7.48－7.42 (m, 3H),
2.11 (q, J＝4.4 Hz, 2H), 1.90 (q, J＝4.4 Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 172.7, 157.9, 137.6, 131.7,
130.3, 130.2, 128.9, 125.8, 120.1, 117.7, 33.1, 21.1.
HRMS (ESI) calcd for C17H13BrN2O ([M ＋ Na] ＋ )
363.1003, found 363.1001.
5-(4-Fluorophenyl)-7-phenyl-5,6-diazaspiro[2.4]-
hept-6-en-4-one (7t) The product was isolated by
flash chromatography [eluent: V(EtOAc)∶V(PE)＝1∶
8] as a yellow solid (75.7 mg, 90%), m.p. 97－99 ℃;
1H NMR (400 MHz, CDCl3) δ: 8.05－7.99 (m, 2H),
7.61－7.57 (m, 2H), 7.46－7.41 (m, 3H), 7.15－7.07
(m, 2H), 2.12 (q, J＝4.4 Hz, 2H), 1.90 (q, J＝4.4 Hz,
2H); 13C NMR (100 MHz, CDCl3) δ: 172.5, 159.8 (d,
J＝242.6 Hz), 157.8, 134.8 (d, J＝2.7 Hz), 130.3, 130.2,
128.9, 125.7, 120.5 (d, J＝7.9 Hz), 115.4 (d, J＝22.4
Hz), 33.0, 21.0. HRMS (ESI) calcd for C17H13FN2O ([M
＋Na]＋) 303.0904, found 303.0894.
hept-6-en-4-one (7w) and 5w The mixture of 7w and
5w was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶8] as a white solid and the
1
yield of 7w was calculated according to the H NMR
(ca. 45.6 mg, 55%); 1H NMR (400 MHz, CDCl3) δ: 7.51
－7.46 (m, 2H), 7.43－7.41 (m, 2H), 7.39－7.32 (m,
5H), 7.31－7.28 (m, 1H), 5.04 (s, 2H), 2.03 (q, J＝4.2
Hz, 2H), 1.83 (q, J＝4.6 Hz, 2H); 13C NMR (100 MHz,
CDCl3) δ: 174.0, 157.3, 136.7, 130.7, 129.8, 128.9,
128.5, 128.2, 127.5, 125.5, 48.6, 20.3, 15.3. HRMS (ESI)
calcd for C18H16N2O ([M＋Na]＋ ) 299.1155, found
299.1155.
Mixture of 5-butyl-7-phenyl-5,6-diazaspiro[2.4]-
hept-6-en-4-one (7x) and 5x The mixture of 7x and
5x was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶8] as a yellow oil and the yield
of 7x was calculated according to the 1H NMR (ca. 51.6
1
mg, 71%); H NMR (400 MHz, CDCl3) δ: 7.51－7.46
(m, 2H), 7.39－7.34 (m, 3H), 3.82 (t, J＝7.2 Hz, 2H),
1.99 (q, J＝4.4 Hz, 2H), 1.78 (q, J＝4.4 Hz, 2H), 1.77
－172 (m, 2H), 1.39－1.35 (m, 2H), 0.94 (t, J＝7.4 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 173.9, 156.9,
130.8, 129.6, 128.8, 125.4, 44.5, 30.6, 20.0, 19.8, 13.6.
HRMS (ESI) calcd for C15H18N2O ([M ＋ Na] ＋
)
265.1311, found 265.1301.
Mixture of 5-cyclohexyl-7-phenyl-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7y) and 5y The mixture of 7y
and 5y was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶8] as a white solid and the
yield of 7s was calculated according to the 1H NMR (ca.
1
47.5 mg, 59%); H NMR (400 MHz, CDCl3) δ: 7.51－
7.47 (m, 2H), 7.39－7.34 (m, 3H), 4.22－4.11 (m, 1H),
1.99 (q, J＝4.4 Hz, 2H), 1.90－1.81 (m, 6H), 1.78 (q,
J＝4.2 Hz, 2H), 1.54－1.44 (m, 2H), 1.28－1.18 (m,
2H); 13C NMR (100 MHz, CDCl3) δ: 173.3, 156.5,
129.5, 128.7, 128.5, 125.5, 53.1, 35.3, 31.2, 25.5, 20.0,
15.2. HRMS (ESI) calcd for C17H20N2O ([M＋Na]＋)
291.1468, found 291.1459.
7-Phenyl-5-(4-(trifluoromethyl)phenyl)-5,6-diaza-
spiro[2.4]hept-6-en-4-one (7u) The product was iso-
lated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶8] as a white solid (90.2 mg, 91%), m.p. 88
1
－90 ℃; H NMR (400 MHz, CDCl3) δ: 8.23 (d, J＝
8.8 Hz, 2H), 7.68 (d, J＝8.8 Hz, 2H), 7.61 (q, J＝2.0 Hz,
2H), 7.47－7.44 (m, 3H), 2.15 (q, J＝4.4 Hz, 2H), 1.94
(q, J＝4.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ:
173.1, 158.4, 141.3, 130.5, 130.2, 129.0, 128.7, 126.1 (q,
J＝3.7 Hz), 125.9, 118.2, 33.2, 21.3. HRMS (ESI) calcd
for C18H13F3N2O ([M＋Na]＋) 353.0872, found 35.0873.
5-(3-Chloro-4-methoxyphenyl)-7-phenyl-5,6-
diazaspiro[2.4]hept-6-en-4-one (7v) The product was
isolated by flash chromatography [eluent: V(EtOAc)∶
V(PE)＝1∶8] as a white solid (84.3 mg, 86%), m.p.
Mixture of 5-(tert-butyl)-7-phenyl-5,6-diazaspiro-
[2.4]hept-6-en-4-one (7z) and 5z The mixture of 7z
and 5z was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶8] as a yellow solid and the
yield of 7z was calculated according to the 1H NMR (ca.
1
17.0 mg, 23%); H NMR (400 MHz, CDCl3) δ: 7.56 (t,
J＝7.4 Hz, 3H), 7.48 (dd, J＝7.2, 3.6 Hz, 2H), 1.95 (q,
J＝4.2 Hz, 2H), 1.70 (q, J＝4.2 Hz, 2H), 1.59 (s, 9H);
13C NMR (100 MHz, CDCl3) δ: 174.1, 155.0, 133.2 (s),
128.7, 128.5, 125.3, 51.7, 36.1, 28.3, 14.9. HRMS (ESI)
calcd for C15H18N2O ([M＋Na]＋ ) 243.1492, found
240.1491.
2-Benzoyl-N-phenylbutanamide (5a') The prod-
uct was isolated by flash chromatography [eluent:
V(EtOAc)∶V(PE)＝1∶8] as a white solid (31.7 mg,
35%); 1H NMR (400 MHz, CDCl3) δ: 8.83 (s, 1H), 8.05
(d, J＝7.6 Hz, 2H), 7.65 (t, J＝7.2 Hz, 1H), 7.55－7.50
(m, 4H), 7.30－7.26 (m, 2H), 4.43 (t, J＝7.2 Hz, 1H),
2.20－2.03 (m, 2H), 1.03 (t, J＝7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 200.8, 167.0, 136.2, 134.4, 129.3,
1
135－137 ℃; H NMR (400 MHz, CDCl3) δ: 8.08 (d,
J＝2.4 Hz, 1H), 7.94 (dd, J＝8.8, 2.6 Hz, 1H), 7.61－
7.56 (m, 2H), 7.47－7.40 (m, 3H), 6.97 (d, J＝9.2 Hz,
1H), 3.91 (s, 3H), 2.12 (q, J＝4.4 Hz, 2H), 1.90 (q, J＝
4.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.4,
157.9, 152.3, 132.4, 130.3, 130.2, 129.0, 125.8, 122.5,
121.1, 118.2, 111.9, 56.3, 33.0, 21.0. HRMS (ESI) calcd
＋
for C18H15ClN2O2 ([M ＋ Na] ) 349.0714, found
349.0709.
Mixture of 5-benzyl-7-phenyl-5,6-diazaspiro[2.4]-
8
www.cjc.wiley-vch.de
© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—12

Copper(I)-Catalyzed Intramolecular N-N Coupling of Cyclopropyl O-Acyl Ketoximes
129.0, 129.0, 128.7, 121.3, 121.2, 56.9, 27.1, 12.0.
worthy that compound 6g cannot cyclize to the corre-
HRMS (ESI) calcd for C13H14N2O2 ([M ＋ Na] ＋
)
sponding pyrazolone 7g under our optimal conditions
(Table 1, Entry 2), and most of 6g was recovered at
present.[9c]
324.0762, found 324.0766.
Mixture of 5-(4-methoxyphenyl)-7-methyl-5,6-
diazaspiro[2.4]hept-6-en-4-one (7b') and 5b' The
mixture of 7b' and 5b' was isolated by flash chroma-
tography [eluent: V(EtOAc)∶V(PE)＝1∶10] as a yel-
low solid and the yield of 7b' was calculated according
to the 1H NMR (ca: 57.8 mg, 84%); 1H NMR (400 MHz,
CDCl3) δ: 7.81－7.76 (m, 2H), 6.94－6.89 (m, 2H),
3.79 (s, 3H), 1.94 (s, 3H), 1.77－1.71 (m, 2H), 1.66－
1.61 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 172.1,
156.7, 132.0, 121.8, 120.5, 113.9, 55.4, 33.6, 18.6, 12.5.
HRMS (ESI) calcd for C13H14N2O2 ([M ＋ Na] ＋ )
253.0947, found 253.0947.
NaOAc (2.0 equiv.)
HONH2 HCl (2.0 equiv.)
HO
Ph
O
O
N
O
Ph
Ph
Ph
N
N
V(EtOH):V(H2O) = 25:1
H
H
reflux
6g
5g
AcO
Ph
TEA (2.0 equiv.)
AcCl (1.5 equiv.)
N
O
Ph
(3)
CH2Cl2, 0 oC
N
H
3g
Mixture of 5-(4-chlorophenyl)-7-methyl-5,6-
diazaspiro[2.4]hept-6-en-4-one (7c') and 5c' The
mixture of 7c' and 5c' was isolated by flash chromatog-
raphy [eluent: V(EtOAc)∶V(PE)＝1∶10] as a yellow
solid and the yield of 7c' was calculated according to
the H NMR (ca: 52.8 mg, 75%); H NMR (400 MHz,
CDCl3) δ: 7.95－7.88 (m, 2H), 7.38－7.32 (m, 2H),
1.97 (s, 3H), 1.81－1.74 (m, 2H), 1.71－1.65 (m, 2H);
13C NMR (100 MHz, CDCl3) δ: 172.36, 160.05, 129.57,
128.75, 121.36, 119.58, 33.7, 18.91, 12.52. HRMS (ESI)
calcd for C12H11ClN2O ([M＋Na]＋) 257.0452, found
257.0452.
With the optimized conditions in hand (Table 1, En-
try 2), the scope of this intramolecular N-N cyclization
using different O-acetyl oximes 3 was then investigated
(Table 2). It was found that satisfactory yields of 7a－7f
(89%－97%) were obtained when starting materials (3a
－3f) with various aryl substituents (R1) were employed
for the reactions, and no deprotection by-products 5a－
5f were detected by means of HRMS and 1H NMR. The
variation of the R2 group was then examined. The re-
sults revealed that the reaction was well tolerant
1
1
Table 1 Survey of the reaction conditionsa
Results and Discussion
With this assumption in mind, compound 1-(1- (ace-
toxyimino)ethyl)-N-phenylcyclopropane-1-carbox-
amide (3g), which could be easily synthesized from
1-benzoyl-N-phenylcyclopropane-1-carboxamide (5g)
via an intermediate product 1-((hydroxyimino)(phenyl)-
methyl)-N-phenylcyclopropane-1-carboxamide (6g) by
a two-step reaction following the literatures (Eq. 3),[6,9]
was selected as the model compound to evaluate its
ability to give the seven-membered ring compound 4g.
After many attempts, however, compound 5,7-diphenyl-
5,6-diazaspiro[2.4]hept-6-en-4-one (7g) instead of 4g
was isolated in the yield of 94% when we treated 3g
with CuBr (10 mol%) at 100 ℃ in toluene for 2 h (Ta-
ble 1, Entry 2). The yield of 7g was reduced when the
reaction was performed at a higher or lower temperature
(120 or 80 ℃) (Table 1, Entries 1 and 3). Similar result
was also observed in case of increasing the amount of
catalyst (Table 1, Entry 4). However, the reaction could
not afford 7g in the absence of CuBr catalyst, and 89%
of 3g was recovered (Table 1, Entry 5). Other copper
salts including CuCl, CuI, Cu2O, CuBr2, Cu(OAc)2 and
CuSO4•5H2O were screened against the reaction. They
were less effective than CuBr for the desired reaction
(Table 1, Entries 6－11). The reaction was also tested
against various solvents, including DMF, DMSO, xy-
lene, 1,4-dioxane, and EtOH. The experiments disclosed
that they were all found to be less efficient than toluene
for the conversion (Table 1, Entries 12－16). It is note-
Entry Cat. (equiv.)
T/℃ Time/h Solvent Yield of 7a/%
1
2
3
4
5
6
7
8
9
CuBr (0.1)
CuBr (0.1)
CuBr (0.1)
CuBr (0.2)
CuBr (0)
120 1
100 2
80 12
100 1.5
100 2
100 5
100 8
100 24
100 1
100 20
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMF
91
94
81
90
0b
CuCl (0.1)
CuI (0.1)
92
87
75c
82
80
18d
0e
Cu2O (0.1)
CuBr2 (0.1)
10 Cu(OAc)2 (0.1)
11 CuSO4·5H2O (0.1) 100 24
12
13
14
15
16
CuBr (0.1)
CuBr (0.1)
CuBr (0.1)
CuBr (0.1)
CuBr (0.1)
100 24
100 8.0
100 4.0
100 6.0
100 24
DMSO
xylene
77
85
74
42f
1,4-dioxane
EtOH
a Unless otherwise indicated, all reactions were carried out with 3
(0.3 mmol) in 3 mL solvent; b 89% of 3g was recovered; 8% of
c
3g was recovered; d 65% of 3g was recovered; e A trace amount of
f
3g and complex mixture was observed; 13% of 3g was recov-
ered.
Chin. J. Chem. 2016, XX, 1—12
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9

Zhang et al.
FULL PAPER
towards various aryl bearing the electron-donating
groups (EDG’s) (e.g., Me and OMe) and electron-with-
drawing groups (EWG’s) (e.g., Cl, Br, F, CF3 and CO2Et)
at the ortho-, meta- or para-position on the phenyl ring.
Compounds 7g－7v were isolated in moderate to good
yields (78%－96%). It is noteworthy that ortho-chloro-
substituted compound 3q afforded a byproduct 5q (8%).
Furthermore, the starting materials (3w－3z) with ali-
phatic substituent R2 also afforded the deprotection
products 5w－5z besides the desired 7w－7z. And the
yields showed an increasing tendency with the increas-
ing steric hindrance of the substituents. Similar results
were also observed for the starting materials 3b'－3c'
and 3a'. Accordingly, several control experiments were
conducted, using 3q as the model compound, in order to
minimise the amout of the deprotection products 5.
However, it was found that the reaction still produced
5q in the yield of 23%, along with 7q in 66% yield,
when we treated 3q under the optimized conditions in
anhydrous toluene in the N2 atomphere after 5 h. Addi-
tionally, the other two control experiments also showed
that the yields of compounds 5q and 7q had almost no
change when the reaction was performed in the presence
of 4Å molecular sieves in anhydrous toluene in the N2
atomphere or under open air in the presence of 10 equiv.
of water. It was deduced according to these observations
that the deprotection product 5 was unlikely formed
during the work-up stage, and may be from the reaction
period.
Table 2 Extension of the reaction scopea
MeO
N
MeO
Ph
Cl
MeO
N
N
Cl
N
N
N
N
N
O
O
O
O
7a: 1 h, 89%
7d: 2.5 h, 97%
7b: 1 h, 91%
7c: 1 h, 92%
Cl
Cl
Cl
N
N
N
Ph
N
Ph
N
N
N
Ph
N
N
Ph
N
O
O
O
O
O
7g: 2 h, 94%
7e: 2 h, 89%
7h: 3.5 h, 96%
7i: 2.5 h, 93%
MeO
7f: 3 h, 91%
OMe
N
N
Ph
Ph
N
N
N
Ph
N
Ph
Ph
Ph
N
N
N
N
OMe
O
O
O
O
O
7j: 3 h, 89%b
7n: 2 h, 88%
7k: 2 h, 82%
7l: 1.5 h, 93%
7m: 2.5 h, 92%
Cl
Cl
CO2Et
Br
N
N
N
N
N
N
Ph
N
Ph
Ph
N
Ph
N
N
Cl
O
O
O
O
O
7q: 5 h, 78%c
7r: 4 h, 79%b
OMe
Cl
7o: 3.5 h, 95%
7p: 5 h, 90%
7s: 3 h, 87%
Bn
CF3
N
F
N
Bu-n
N
N
N
Ph
Ph
N
N
N
Ph
Ph
Ph
Ph
N
N
O
O
O
O
O
7w+5w: 3 h, 69%
7x+5x: 3 h, 82%
7v: 3 h, 86%
7u: 4 h, 91%
7t: 2.5 h, 90%
N
N
N
N
Cl
N
N
Ph
OMe
Ph
Ph
N
O
N
O
N
N
O
O
O
7c'+5c': 4 h, 90% (5:1)d,f
7b'+5b': 1 h, 92% (10:1)d,f
7a'+5a': 0.5 h, 35% (0:1)d,e
7y+5y: 6 h, 78%
7z+5z: 6 h, 75%
a Unless otherwise indicated, all of the reactions were carried out with 3 (0.3 mmol) and CuBr (4.3 mg, 0.03 mmol) in toluene (3 mL) at
100 ℃. b Reaction was performed in N2. c 8% of 5q was obtained. d The mixture of 7 and 5 could not be separated due to their same po-
larity, and the ratio of compounds 7 and 5 provided in the bracket was determined based on the 1H NMR. e The reaction was performed at
100 ℃. f The reaction was performed at 120 ℃.
10
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© 2016 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2016, XX, 1—12

Copper(I)-Catalyzed Intramolecular N-N Coupling of Cyclopropyl O-Acyl Ketoximes
Limited extension was concerned on these starting
materials of which methylene position was substituted
by alkyl because the O-acetyl oxime derivatives are dif-
ficult to prepare under the current conditions. Obviously,
they are competitive reactions of the N-N coupling
reaction and hydrolysis. It was deduced that, compara-
tively, these compounds which are easily to hydrolyze
(such as 3q and 3w－3c') will generate the byproducts
5.[10] However, the hydrolyzate 5 could not be com-
pletely inhibited when we performed the reaction under
the optimized conditions with 3q in an ultra-dried tolu-
ene (H2O＜0.3‰). Radical trapping experiments were
also conducted to determine whether a radical process
was involved in this reaction using 2,2,6,6-tetramethyl-
1-piperidinyloxy (TEMPO) radical scavenger. It was
found that the reactions proceed smoothly to give 7g in
69% and 62% yields in the presence of the 1 and 10
equiv. TEMPO, respectively. The observed results sug-
gested that a radical process may not be involved in the
transformation.[11] In addition, the experiments using
CuII catalysts suggested that a CuIII species might be
involved in this transformation (Table 1, Entries 8－10).
A plausible mechanism for this reaction was proposed
based on these results of the current study and infor-
mation from the literature (Scheme 1).[12] Oxidative ad-
ditions to N－O bonded species are precedential.[13]
Accordingly, we deduced that the oxidative addition of
the O-acetyl oximes 3 to the CuI catalyst occurred first
to form the CuIII species A.[11b,14] Oxime acetates acted
not only as a substrate, but also as an oxidant, thus the
reaction needs no additional oxidants or additives. Then,
the putative organo-copper(III) intermediate A formed
the desired product 7 via the reductive elimination reac-
tion and simultaneously released one molecule of
AcOH.[11b,14] Alternatively, intermediate A underwent
hydrolysis pathway to give the by-product 5, the proce-
dure is similar to those of several previous related
works.[11a]
ile synthesis of spiro-fused pyrazolin-5-ones has been
developed. The reaction uses readily available O-acetyl
oximes acting not only as a substrate, but also as an ox-
idant, without additional oxidants or additives, and pro-
ceeds under non-basic and non-oxidizing conditions
thus complementing existing N-N bond forming reac-
tions.
Acknowledgement
We thank the National Natural Science Foundation
of China (Nos. 21272057 and 21372065), Young Back-
bone Teachers Fund of Henan (No. 2014GGJS-049),
Key Project of Henan Educational Committee (No.
14A150053, 14A150019, 14B150042, and 15A150015),
Science & Technology Innovation Talents in Universi-
ties of Henan Province (No. 17HASTIT002), Outstand-
ing Young Talent Cultivation Project Funding of Henan
Normal University (No. 14YR002), the Program of
Foundation and Frontier Technology Research of Henan
Province (No. 122300410296) and Open Project of Jilin
Province Key Laboratory of Organic Functional Molec-
ular Design & Synthesis (No. 130028651).
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R2
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R2
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Chin. J. Chem. 2016, XX, 1—12
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www.cjc.wiley-vch.de
11

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FULL PAPER
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12
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