One-pot Synthesis, Crystal structure, and Bioactivity of N-Phenoxyacetyl-2,4,5-trisubstituted-1,3-oxazolidines

Article abstract of DOI:10.1002/jhet.2706

N-phenoxyacetyl-1,3-oxazolidine derivatives were synthesized by the cyclization and acylation with β-amino alcohol, ketone, and phenoxyacetyl chloride as the starting materials. All compounds were characterized by IR, ¹H NMR, ¹³C NMR, ESI-MS, and elemental analysis. The configuration of 4a was determined by X-ray crystallography. The preliminary biological tests showed that all products could protect soybean against injury caused by 2,4-D butylate to some extent.

Full text of DOI:10.1002/jhet.2706

Month 2016 One-pot Synthesis, Crystal structure, and Bioactivity of N-Phenoxyacetyl-
2,4,5-trisubstituted-1,3-oxazolidines
*
Ying Fu, Wen-Geng Chen, Yu-Wen Hou, Bin Wang, Li-Xia Zhao, and Fei Ye
Department of Applied Chemistry, Northeast Agricultural University, Harbin 150030, China
*
E-mail: yefei@neau.edu.cn
Received April 8, 2016
DOI 10.1002/jhet.2706
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
N-phenoxyacetyl-1,3-oxazolidine derivatives were synthesized by the cyclization and acylation with
β-amino alcohol, ketone, and phenoxyacetyl chloride as the starting materials. All compounds were
1
characterized by IR, H NMR, 13C NMR, ESI-MS, and elemental analysis. The configuration of 4a was
determined by X-ray crystallography. The preliminary biological tests showed that all products could protect
soybean against injury caused by 2,4-D butylate to some extent.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
[3 + 2] cycloaddition of azomethine ylides and carbonyl
compounds [22–24], palladium catalyzed [3 + 2] cycload-
dition reactions, Lewis acid-catalyzed [3+ 2] cycloaddition
reactions of aziridines [25,26], or others [27–30]. Recently,
Yoon’s group has reported an efficient method for
establishing 1,3-oxazolidines through iron-catalyzed or
copper-catalyzed aminohydroxylation of olefins [31–33].
As part of our work on nitrogen-containing heterocyclic
compounds [34–36], herein we reported one-pot synthesis
of a series of novel N-phenoxyacetyl-1,3-oxazolidines 4
via cyclization and acylation without any expensive
reagent or catalyst (Scheme 3). The configuration of 4a
was further determined by X-ray crystallography. The
bioactivity determination of the N-phenoxyacetyl-1,3-
oxazolidine derivatives was carried out on soybean from
the injury of 2,4-D butylate.
Oxazolidine derivatives have made them attractive
targets for synthesis with their structural diversity and
biological importance [1]. Oxazolidines are pharmacophores,
embedded within the core of potent antitumor
tetrahydroisoquinoline natural products [2–4]. They are
endowed a large spectrum of biological activities,
including remarkable anti-inflammatory, antibacterial
agent, antihypertensive, α1-adrenoceptor antagonists,
antiplasmodial, and inhibitors of the epidermal growth
factor receptor. 1,3-Oxazolidine derivatives were also
widely applied in organic synthesis, chiral auxiliaries, drug
design, or prodrugs [5–7]. They also acted as the ligands in
asymmetric catalysis and as a host molecule for the
incorporation of guest molecules or ions [8–10]. Some
reports indicated that N-dichloroacetyl oxazolidine
derivatives were investigated as herbicide safeners, which
effectively protected maize against the injury of
thiocarbamate and chloroacetanilide herbicides [11,12].
Structure–activity relationship (SAR) was very important
in the search for biological activity because it provided
useful information about chemical substituents, which are
necessary for the target bioactivity [13,14]. Based on the
SAR, isoxadifen-ethyl, which was combined with the
structural features of 5-phenyl-4,5-dihydroisoxazole-3-
ethyl ester and the safener diphenyl acid, possesses strong
security to rice (Scheme 1). Recently, many successful
cases using strategies of active substructure combination
and bioisosteric replacement have been reported [15].
In view of the facts mentioned previously, the novel
target molecules N-phenoxyacetyl-1,3-oxazolidine deriva-
tives were designed and synthesized based on the SAR
[16] and active substructure combination keeping the
oxazolidine as the parent skeleton structure (Scheme 2).
1,3-Oxazolidines were usually prepared by condensation
of β-amino alcohols with aldehydes or ketones [17–21], the
RESULTS AND DISCUSSION
The synthetic route was depicted in Scheme 3. Amino
alcohols 1 were cyclization with ketones 2 to generate
oxazolidines 3 with benzene as solvent [34]. The acylation
of oxazolidine and phenoxyacetyl chloride was achieved
by using anhydrous K2CO3 as the attaching acid agent at
0–5°C. As oxazolidine easily transformed to Schiff base
in the presence of alkali over 18°C [34], anhydrous
K2CO3 was selected as the attaching acid agent rather than
triethylamine. The yields of 4 compounds were obtained in
45–85%. The substitute group structure affected the yields
significantly. When R1 and R2 were ꢀCH3, the steric
hindrance was weak. So the yields of 4b and 4c were high,
which were 85% and 80%, respectively. The steric
hindrance effects caused by R3 and R4 are more obvious
than effects produced by R1 and R2. It can be seen that
the yield of 4d was 45% due to steric hindrance effects
caused by the size increasing the of the groups R3 and
© 2016 Wiley Periodicals, Inc.

Y. Fu, W.-G. Chen, Y.-W. Hou, B. Wang, L.-X. Zhao, and F. Ye
Vol 000
Scheme 1. Design of isoxadifen-ethyl. [Color figure can be viewed in the
online issue, which is available at wileyonlinelibrary.com.]
The single crystal of 4a was obtained by dissolving it in
ethanol and light petroleum, followed by slow evaporation.
The molecular structure and the packing view of 4a were
shown in Figures 1 and 2, respectively. It was obvious that
there was π-p-π-p-π large conjunctive effect between C9,
N1, C8, N2, C7, O1, and benzene, which resulted in
shorter bond length of N1-C9 [1.464(3)], N1-C8 [1.347
(3)] than the typical C-N bond length [1.472(2)Å]. No
significant π-π interactions were found in the crystal
structure. The compound contained an original benzene
ring (plane I) and a new five-member ring, plane II, which
were made up of N1, C9, C10, C11, and O3 atoms. Plane I
[C1, C2, C3, C4, C5, and C6] made a dihedral angle of
13.4° with plane II. Plane II looked like an envelope shape
with C9 deviated from the plane.
All the novel N-phenoxyacetyl oxazolidine derivatives
were evaluated for their protection of soybean against the
injury of 2,4-D butylate at the concentration of 462ga.i./
hm2 (Table 1). Compounds 4a–k showed some recovery
rate for plant height, plant fresh weight, root length, and
root fresh weight. The recovery rates of the plant index
indicated that the synthesized compounds except 4f, 4g,
and 4i led to good activity. They might be used as the
candidate of herbicide because they are similar as phenoxy
acid herbicide. Among the compounds tested, compound
4c showed the best activity against the injury of 2,4-D
butylate. But the activity against the injury of 2,4-D
butylate synthesized is inferior to R-28725.
Scheme 2. Structure of the target compounds. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
R4, which were ꢀCH3 and ꢀCH2CH3, respectively. It was
similar of 4e with R3 and R4 being ꢀCH2CH3 and ꢀCH3
separately.
EXPERIMENTAL
Melting points were obtained on a Beijing Taike melting
point apparatus (X-4) and are uncorrected. The IR spectra
(wave numbers in cm–1) were taken on a KJ-IN-27G
The structures of compounds 4a–k were characterized by
1
infrared (IR), Hꢀ, and 13C NMR, elemental analysis, and
infrared spectrophotometer (KBr). The H NMR and 13C
1
MS. In the IR spectra, a characteristic carbonyl band at
1
around 1660cmꢀ1 proved the presence of C=O. The H
NMR spectra were performed on Bruker AVANCE
300 MHz, with CDCl3 or DMSO-d6 as the solvent and
TMS as the internal standard. Mass spectra were obtained
on Finigan Ion trap mass spectrometer. All reagents were
of analytical grade.
Preparation of 2,4,5-trisubstituted-3-phenoxyacetyl-1,3-
Amino alcohols 1 (0.03 mol) and ketone
(0.03 mol) 2 were added in 35mL benzene, and the
NMR spectra of 4a–k exhibited that the aromatic protons ap-
peared at the region 6.88–7.33ppm, which also confirmed
the accomplishment of the acylation. It was the characteristic
of oxazolidine. In the 13C NMR spectra of the synthesized
compounds, the signals observed in the region were δ
95–100ppm, δ 60–65ppm, and δ 45–50ppm accounting
for the signals of the three carbons oxazolidine ring.
oxazolidines.
Scheme 3. The route for synthesis of the title compounds.
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Synthesis and Bioactivity of N-Phenoxyacetyl oxazolidines
Figure 1. Molecular structure for compound 4a. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
reaction was stirred for 1 h under 30–35°C. Then, the
mixture was heated to reflux until water was stripped off,
followed by cooling to 20–25°C and addition of 1 g
anhydrous K2CO3. Afterwards, 4.2 mL (0.03 mol) of
phenoxyacetyl chloride was added dropwise with stirring.
Stirring was continued for 1 h. The organic phase was
washed until pH= 7. The organic layer was dried over
magnesium sulfate anhydrous and vacuum distillation
solvent. Compounds 4a, 4c, 4d, 4f, 4h, 4j, and 4k were
recrystallized with ethanol and light petroleum until the
white crystals were obtained. Compounds 4b, 4e, 4i, and
4 g were separated on silica gel by column
chromatography [V (EtOAc):V (light petroleum) =1:3].
The physical and spectra data of the compounds 4a–k are
as follows:
N-Phenoxyacetyl-2,2-dimethyl-1,3-oxazolidine (4a). White
solid. Yield 5.36 g (76%). m.p. 89–90°C. IR: ν 2880–
2979, 1666 (C = O), 1421–1588; 1H NMR (CDCl3): δ
Figure 2. Packing view of the compound 4a. [Color figure can be
viewed in the online issue, which is available at wileyonlinelibrary.com.]
6.88–7.26 (m, 5H, Ar-H), 4.53 (s, 2H, O-CH2-C = O),
Table 1
Effect of detoxification of compounds 4a–k to growth index of soybeana,b,c
.
Recovery of plant
height (%)
Recovery of plant
weight (%)
Recovery of root
length (%)
Recovery of
root weight (%)
Compound
R-28725
4a
4b
4c
4d
4e
4f
4g
4h
74.46
57.19
47.48
56.47
59.35
44.60
13.67
1.80
59.71
ꢀ1.44
52.52
14.39
101.11
65.63
57.45
75.25
65.35
73.64
46.05
ꢀ15.24
90.60
15.90
65.29
79.98
67.69
46.67
65.64
125.12
65.64
48.72
65.49
43.85
6.69
56.64
53.59
27.53
4.92
ꢀ6.39
14.26
18.19
41.89
5.41
ꢀ20.51
1.538
18.46
4i
4j
4k
ꢀ32.82
51.79
69.74
aData are means of three replicates.
Treat with compounds ꢀTreat with 2;4-D butylate
cWater treated was used as contrast.
bRecovery Rateð%Þ ¼
.
Contrast ꢀ Treat with 2;4-D butylate
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Y. Fu, W.-G. Chen, Y.-W. Hou, B. Wang, L.-X. Zhao, and F. Ye
Vol 000
3.95–3.98 (t, J = 2.0 Hz, 2H, C-CH2-O), 3.59–3.62 (t,
J = 1.0 Hz, 2H, N-CH2-C), 1.54 (s, 6H, 2 × CH3-C); 13C
NMR (CDCl3): δ 164.61, 157.84, 129.60, 129.60,
121.66, 114.57, 114.57, 95.29, 68.59, 63.52, 45.04,
24.26, 24.26. ESI-MS m/z: 236 [M + H+]. Anal. calcd for
C13H17NO3: C, 66.36; H, 7.28; N, 5.95%; Found: C,
66.42; H, 7.35; N, 5.86%.
N-phenoxyacety-2,2,5-trimethyl-1,3-oxazolidine (4b). White
solid. Yield 6.35 g (85%). m.p. 62–63°C. IR: ν 2989–2851,
1671 (C = O), 1426–1597. 1H NMR (CDCl3): δ 6.93–7.33
(m, 5H, Ar-H), 4.57 (s, 2H, O-CH2-C = O), 4.21–4.28 (m,
1H, C-CH-O), 3.77–3.82 (m, 1H, N-CH2-C),3.14–3.20 (t,
J = 2.3 Hz, 1H, N-CH2-C), 1.58–1.62 (d, J = 3.8 Hz, 6H,
2 × CH3), 1.33–1.35 (d, J = 1.5 Hz, 3H, CH3). 13C NMR
(CDCl3): δ 164.48, 157.85, 129.64, 129.64, 121.71,
114.60, 114.60, 95.67, 70.64, 68.73, 51.84, 25.80, 23.83,
17.94. ESI-MS m/z: 250 [M + 1]. Anal. calcd for
C14H19NO3: C, 67.45; H, 7.68; N, 5.62%; Found: C,
67.52; H, 7.55; N, 5.76%.
N-phenoxyacety-2,2,4,5-tetramethyl-1,3-oxazolidine (4c). White
solid. Yield 6.32 g (80%). m.p. 53–54°C. IR: ν 2900–2973,
1644–1660 (C = O), 1425–1599. 1H NMR (CDCl3): δ
6.94–7.33 (m, 5H, Ar-H), 4.58–4.71 (d, J = 6.8 Hz, 2H,
O-CH2-C = O), 4.20–4.23 (m, 1H, C-CH-O), 4.03–4.07
(m, 1H, N-CH-C), 1.69 (s, 3H, CH3), 1.58 (s, 3H, CH3),
1.21–1.27 (m, 6H, 2 × CH3). 13C NMR (CDCl3): δ
164.24, 157.09, 129.60, 129.60, 121.68, 114.77, 114.77,
94.88, 72.89, 67.96, 55.14, 27.12,23.50,15.64,14.31;
ESI-MS m/z: 264 [M + 1]. Anal. calcd for C15H21NO3: C,
68.42; H, 8.04; N, 5.32%; Found: C, 68.53; H, 8.14; N,
5.25%.
N-phenoxyacety-2,2,4-trimethyl-5-ethyl-1,3-oxazolidine
(4d). White solid. Yield 3.74 g (45%). m.p. 170–171°C.
IR: ν 2884–2971, 1646–1661 (C = O), 1422–1599. 1H
NMR (CDCl3): δ 6.94–7.32 (m, 5H, Ar-H), 4.58–4.71 (m,
2H, O-CH2-C = O), 4.03–4.10 (m, 1H, N-CH-C), 3.93–
3.98 (m, 1H, C-CH-O), 1.51–1.73 (m, 8H, 2 N-C-CH3,
CH2-C), 1.20–1.23 (d, J = 2.3 Hz, 3H, N-C-CH3), 0.98–
1.03 (t, J = 1.5Hz, 3H, O-C-C-CH3). 13C NMR (CDCl3):
δ 164.18, 158.09, 129.61, 129.61, 121.68, 114.78, 114.78,
94.85, 78.80, 67.89, 54.32, 27.11, 23.47, 22.04, 15.50,
10.36. ESI-MS m/z: 278 [M + 1]. Anal. calcd for
C16H23NO3: C, 69.29; H, 8.36; N, 5.05%; Found: C,
69.21; H, 8.44; N, 5.15%.
278 [M+ 1]. Anal. calcd for C16H23NO3: C, 69.29; H,
8.36; N, 5.05%; Found: C, 69.33; H, 8.48; N, 5.01%.
N-phenoxyacety-2,2-dimethyl-4-ethyl-1,3-oxazolidine
(4f). White solid. Yield 4.11 g (52%). m.p. 64–65°C. IR:
ν 2891–2977, 1666 (C =O), 1417–1599; 1H NMR
(CDCl3): δ 6.94–7.31 (m, 5H, Ar-H), 4.58–4.71 (m, 2H,
O-CH2-C = O), 3.89–3.94 (m, 3H, N-CH-CH2-O), 1.64–
1.79 (m, 5H, N-C-CH3, CH2-C), 1.54 (s, 3H, N-C-CH3),
0.95–0.99 (t, J = 2.0 Hz, 3H, CH3). 13C NMR (CDCl3): δ
164.54, 158.03, 129.60, 129.60, 121.68, 114.68, 114.68,
95.71, 68.05, 66.97, 58.15, 27.38, 26.47, 22.91, 10.80.
ESI-MS m/z: 264 [M +1]. Anal. calcd for C15H21NO3: C,
68.42; H, 8.04; N, 5.32%; Found: C, 68.48; H, 8.12; N,
5.26%.
N-phenoxyacety-2-methyl-2,4-diethyl-1,3-oxazolidine
(4g). White solid. Yield 3.99 g (48%). m.p. 85–87°C. IR:
1
ν 2881–2976, 1643–1659 (C = O), 1415–1599; H NMR
(CDCl3): δ 6.92–7.32 (m, 5H, Ar-H), 4.52–4.71 (m, 2H,
O-CH2-C = O), 3.82–3.97 (m, 3H, N-CH-CH2-O), 1.97–
2.19 (m, 2H, N-C-CH2-C), 1.61–1.76 (m, 2H, CH2-C),
1.49 (s, 3H, N-C-CH3), 0.81–1.06 (m, 6H, 2 ×CH3). 13C
NMR (CDCl3): δ 164.59, 158.09, 129.62, 129.62, 121.69,
114.70, 114.70, 98.37, 67.99, 66.92, 58.16, 30.69, 27.76,
21.14, 11.08, 8.28. ESI-MS m/z: 278 [M + 1]. Anal. calcd
for C16H23NO3: C, 69.29; H, 8.36; N, 5.05%; Found: C,
69.22; H, 8.45; N, 5.13%.
N-phenoxyacety-2,2,4-triethyl-1,3-oxazolidine (4h). White
solid. Yield 5.24 g (60%). m.p. 59–60°C. IR: ν 2878–2968,
1647 (C = O), 1421–1599; 1H NMR (CDCl3): δ 6.92–7.32
(m, 5H, Ar-H), 4.58–4.73 (m, 2H, O-CH2-C = O), 4.98–
4.03 (m, 1H, N-CH-C), 3.80–3.89 (m, 2H, O-CH2-C),
1.68–2.21 (m, 6H, 3CH2-C), 0.93–0.98 (t, J = 3.0 Hz, 3H,
CH3), 0.81–0.88 (m, 6H, 2 × CH3). 13C NMR (CDCl3): δ
164.59, 158.03, 129.63, 129.63, 121.66, 114.62, 114.62,
101.09, 67.91, 67.86, 58.06, 28.12, 27.90, 27.49, 11.20,
8.28, 8.18. ESI-MS m/z: 292 [M + 1]. Anal. calcd for
C17H25NO3: C, 70.07; H, 8.65; N, 4.81%; Found: C,
69.98; H, 8.72; N, 4.77%.
N-phenoxyacetyl-2-methyl-2-n-propyl-4-ethyl-1,3-oxazolidine
(4i). White solid. Yield 5.15g (59%). m.p. 79–81°C. IR: ν
2879–2962, 1642 (C = O), 1420–1598. 1H NMR (CDCl3):
δ 6.92–7.33 (m, 5H, Ar-H), 4.57–4.71 (m, 2H, O-CH2-
C = O), 3.84–3.87 (m, 3H, N-CH-CH2-O), 2.03–1.40 (m,
6H, 3 ×CH2-C), 1.49 (s, 3H, CH3), 0.88–0.98 (m, 6H,
2 × CH3). 13C NMR (CDCl3): δ 164.55, 158.08, 129.61,
129.61, 121.68, 114.70, 114.70, 98.01, 67.99, 66.94,
58.14, 40.22, 27.76, 21.36, 17.23, 14.16, 11.08. ESI-MS
m/z: 292 [M +1]. Anal. calcd for C17H25NO3: C, 70.07;
H, 8.65; N, 4.81%; Found: C, 70.15; H, 8.76; N, 4.70%.
N-phenoxyacetyl-2-methyl-2-isobutyl-4-ethyl-1,3-oxazolidine
(4j). White solid. Yield 5.59 g (61%). m.p. 84–85°C. IR:
ν 2865–2984, 1649 (C=O), 1415–1598; 1H NMR (CDCl3):
δ 6.91–7.32 (m, 5H, Ar-H), 4.56–4.70 (m, 2H, O-CH2-
C = O), 3.80–3.98 (m, 3H, N-CH-CH2-O), 2.10–2.16 (m,
N-phenoxyacety-2,2,5-trimethyl-4-ethyl-1,3-oxazolidine
(4e). White solid. Yield 4.16 g (50%). m.p. 50–51°C. IR:
1
ν 2983–2937, 1641–1664 (C = O), 1421–1598; H NMR
(CDCl3): δ 6.93–7.33 (m, 5H, Ar-H), 4.55–4.71 (m, 2H,
O-CH2-C = O), 4.08–4.22 (m, 1H, N-CH-C), 3.66–3.84
(m, 1H, C-CH-O), 1.56–1.65 (m, 8H, 2 × N-C-CH3, CH2-
C), 1.23–1.32 (m, 3H, O-C-CH3), 0.96–1.04 (m, 3H,
CH3). 13C NMR (CDCl3): δ 165.50, 157.80, 129.64,
129.64, 121.72, 114.54, 114.54, 96.11, 68.59, 63.96,
60.54, 27.28, 24.04, 21.24, 14.42, 11.68. ESI-MS m/z:
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Synthesis and Bioactivity of N-Phenoxyacetyl oxazolidines
[3] Williams, R. M.; Glinka, T.; Flanagan, M. E.; Gallegos, R.;
Coffman, H.; Pei, D. J Am Chem Soc 1992, 114, 733.
[4] Tomita, F.; Takahashi, K.; Tamaoki, T. J Antibiot 1984,
37, 1268.
[5] Ren, Q. Y.; Mo, W. Y.; Gao, L.; He, H. W.; Gu, Y. C.
J Heterocyclic Chem 2010, 47, 171.
[6] Xing, X.; Fichera, A.; Kumar, K. Org Lett 2001, 3, 1285.
[7] Vasse, J. L.; Joosten, A.; Denhez, C.; Szymoniak, J. Org Lett
2005, 7, 4887.
1H, CH-C), 1.67–1.86 (m, 4H, 2 ×CH2-C), 1.51 (s, 3H,
N-C-CH3), 0.91–0.99 (m, 9H, 3CH3). 13C NMR (CDCl3):
δ 164.64, 158.07, 129.61, 129.61, 121.65, 114.69, 114.69,
98.45, 68.02, 67.05, 57.97, 46.32, 27.61, 24.70, 23.91,
21.46, 11.08. ESI-MS m/z: 306 [M+ H+]. Anal. calcd for
C18H27NO3: C, 70.79; H, 8.91; N, 4.59%; Found: C,
70.86; H, 8.88; N, 4.45%.
[8] Kang, B. M.; Miller, A. W.; Goyal, S.; Nguyen, S. T. Chem
Commun 2009, 3928.
[9] Beckmann, J.; Duthie, A.; Reeske, G.; Schurmann, M. Organ-
ometallics 2005, 24, 3629.
[10] Sato, M.; Uehara, F.; Sato, K.; Yamaguchi, M.; Kabuto, C.
J Am Chem Soc 1999, 121, 8270.
[11] Czech, B. P.; Kus, P.; Stetson, C. M.; Dalley, N. K.; Bartsch,
R. A. Tetrahedron 2007, 63, 1360.
[12] Hastings, C. J.; Pluth, M. D.; Biros, S. M.; Bergman, R. G.;
Raymond, K. N. Tetrahedron 2008, 64, 8362.
[13] Buono, D. D.; Scarponi, L.; Espen, L. Phytochemistry 2007,
68, 2614.
[14] Hatzios, K. K.; Burgos, N. Weed Sci 2004, 52, 454.
[15] Guan, A. Y.; Liu, C. L.; Yang, X. P.; Dekeyser, M. Chem Rev
2014, 114, 7079.
[16] Yenne, S. P.; Hatzios, K. K. J Agric Food Chem 1990, 38,
1950.
[17] Jeon, Y. M.; Kim, D.; Mirkin, C. A.; Golen, J. A.; Rheingold,
A. L. Tetrahedron 2008, 64, 8428.
[18] Padwa, A.; Dent, W. J Org Chem 1987, 52, 235.
[19] Hosomi, A.; Miyashiro, Y.; Yoshida, R.; Tominaga, Y.;
Yanagi, T.; Hojo, M. J Org Chem 1990, 55, 5308.
[20] Wittland, C.; Arend, M.; Risch, N. Synthesis 1996, 367.
[21] Lee, S. H.; Yang, J.; Han, T. D. Tetrahedron Lett 2001,
42, 3487.
[22] Hayashi, T.; Yamamoto, A.; Ito, Y. Tetrahedron Lett 1988,
29, 99.
[23] Shim, J. G.; Yamamoto, Y. Tetrahedron Lett 1999, 40, 1053.
[24] Inman, G. A.; Butler, D. C. D.; Alper, H. Synlett 2001, 914.
[25] Yadav, V. K.; Sriramurthy, V. J Am Chem Soc 2005, 127,
16366.
[26] Kang, Y. F.; Wang, R.; Liu, L.; Da, C. S.; Yan, W. J.; Xu, Z.
Q. Tetrahedron Lett 2005, 46, 863.
[27] Huo, C. D.; Wei, R.; Zhang, W.; Yang, L.; Liu, Z. L. Synlett
2005, 161.
[28] Sriramurthy, V.; Barcan, G. A.; Kwon, O. J Am Chem Soc
2007, 129, 12928.
N-phenoxyacetyl-3-ethyl-1-oxa-4-aza-spiro-4,5-noncane
(4k). White solid. Yield 6.91 g (76%). m.p. 79–81°C. IR:
ν 2865–2954, 1665 (C = O), 1421–1598. 1H NMR
(CDCl3): δ 6.92–7.32 (m, 5H, Ar-H), 4.51–4.70 (m, 2H,
O-CH2-C = O), 3.87 (s, 3H, N-CH-CH2-O), 1.46–2.72 (m,
10H, -(CH2)5-), 1.21-1.31 (m, 1H, CH2-C), 0.93–0.98 (t,
J =3.0 Hz, 3H, CH3). 13C NMR (CDCl3): δ 164.65,
158.11, 129.60, 129.60, 121.63, 114.70, 114.70, 97.28,
68.11, 66.65, 58.12, 34.85, 29.46, 27.61, 24.57, 23.33,
23.23, 10.94. ESI-MS m/z: 304 [M+ H+]. Anal. calcd for
C18H25NO3: C, 71.26; H, 8.31; N, 4.62%; Found: C,
71.18; H, 8.37; N, 4.59%.
X-ray data collection and structure refinement for 4a. The
X-ray data were collected on a Bruker AXS II CCD area-
detector diffractometer using graphite monochromated
Mo Ka radiation (λ = 0.071073 nm) at 298(2) K. The
structure was solved by direct methods using SHELXS-
97 and refined by full-matrix least squares on F2 using
full-matrix least-squares procedures. Minimum and
maximum, final electron density were ꢀ0.124 and
0.162 eÅꢀ3. Symmetry equivalent reflections were used
to optimize crystal shape and size. Crystallographic data
have been deposited at the Cambridge Crystallographic
Data Centre as supplementary publication number CCDC
942879. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK [fax: +44(1223)336033 or
e-mail: deposit@ccdc.cam.ac.uk].
[29] Purushothaman, S.; Raghunathan, R. Tetrahedron Lett 2009,
50, 6848.
[30] Mohammadizadeh, M. R.; Firoozi, N. Tetrahedron Lett 2010,
51, 2467.
[31] Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. J Am Chem Soc
2008, 130, 6610.
[32] Michaelis, D. J.; Shaffer, C. J.; Yoon, T. P. J Am Chem Soc
2007, 129, 1866.
Acknowledgments. This work was supported by the National Nature
Science Foundation of China (No. 31401787), the Natural Science
Foundation of Heilongjiang Province (No. B201303), the
Research Science Foundation in Technology Innovation of
Harbin (No. 2015RAYXJ010), and the Young Talents Project of
Northeast Agricultural University (No. 14QC38).
[33] Williamson, K. S.; Yoon, T. P. J Am Chem Soc 2010, 132,
4570.
[34] Fu, Y.; Fu, H. G.; Ye, F.; Mao, J.-D.; Wen, X. T. Synth
Commun 2009, 39, 2454.
REFERENCES AND NOTES
[35] Ye, F.; Yang, L.; Li, H. T.; Fu, Y.; Xu, W. J. J Heterocycl
Chem 2010, 47, 229.
[36] Gao, S.; Fu, Y.; Zhao, L. X.; Xing, Z. Y.; Ye, F. Heterocycles
2012, 85, 903.
[1] Shaghafi, M. B.; Grote, R. E.; Jarvo, E. R. Org Lett 2011,
13, 5188.
[2] Scott, J. D.; Williams, R. M. Chem Rev 2002, 102, 1669.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet