Chemoselective synthesis of β-amino ester or β-lactam via sonochemical reformatsky reaction

Article abstract of DOI:10.1002/jccs.201300308

A series of β-amino esters were synthesized by the reaction of N-tosyl aldimine or N-hydroxy aldimine with bromoacetate by sonochemical Reformatsky reaction. The β-N-hydroxyamino ester was obtained and the formed sensitive hydroxylamino functionality was

Full text of DOI:10.1002/jccs.201300308

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Chemoselective Synthesis of b-Amino Ester or b-Lactam via Sonochemical
Reformatsky Reaction
Adam Shih-Yuan Lee,* Yu-Ting Chang and Feng-Yi Su
Department of Chemistry, Tamkang University, Tamsui, New Taipei, Taiwan
(Received: Jun. 22, 2013; Accepted: Sept. 22, 2013; Published Online: Nov. 8, 2013; DOI: 10.1002/jccs.201300308)
A series of b-amino esters were synthesized by the reaction of N-tosyl aldimine or N-hydroxy aldimine
with bromoacetate by sonochemical Reformatsky reaction. The b-N-hydroxyamino ester was obtained
and the formed sensitive hydroxylamino functionality was resistant under the reaction condition. The
b-lactam also was synthesized by the reaction of N-p-methoxy aldimine as reacting substrate under this
sonochemical Reformatsky reaction condition.
Keywords: Sonochemical Reformatsky reaction; N-Hydroxy aldimine; b-N-Hydroxyamino ester;
b-Lactam.
INTRODUCTION
Since the discovery of the addition of zinc ester
acetate with aldimine.13-16 Herewith, we wish to report the
syntheis of b-amino ester by the addition reaction of bro-
moacetate to N-tosyl aldimine and N-hydroxy aldimine un-
der sonochemical Reformatsky reraction condition (Scheme
I).
enolates to aldehydes by Reformatsky in 1887, this poten-
tially useful b-hydroxyalkanoate synthesis has found wide
application in organic synthesis.1,2 Reformatsky reaction
has been recognized as the most useful methods for the for-
mation of carbon–carbon bonds, become a valuable tool in
modern organic synthesis, especially the synthesis of b-
amino acid3,4 and b-Lactam.5,6 The simple and straightfor-
ward preparation of b-amino ester or b-lactam is the addi-
tion of Reformatsky reagent to an aldimine instead of alde-
hyde. In generally, a mixture of b-amino ester and b-lactam
was generated by the reaction of Reformatsky reagent with
aldimine and the complication of the reaction product may
manipulate by the introducing patterns of aldimine, solvent
or temperature.7-9 This reaction was sensitive to the nature
of the nitrogen substituent of the aldimine and a restraining
property of the N-o-methoxyphenyl imine which lead to
sole formation of the b-amino ester was observed and re-
ported.7 To our knowledge, N-hydroxyamino esters could
not be generated from the reaction of bromoacetate with
N-hydroxy aldimine (oxime) by Reformatsky reaction con-
dition because the hydroxyl group was not compatible to
zinc enolate.10 Our laboratory previously developed a sim-
ple and an efficient method for the synthesis of b-amino-
a,b-unsaturated ester by the addition of bromoacetate to
nitrile under a sonochemical Blaise reaction11 which pro-
vide in situ activation of zinc12 without pre-activation of
metal before introduction. Thus, we further investigated
this sonochemical Barbier-type reaction method for the
preparation of b-amino ester by reaction of ethyl bromo-
Scheme I
RESULTS AND DISCUSSIONS
The feasibility of our approach was first tested by
adding ethyl bromoacetate (1.3 mmol) to a mixture of zinc
(3.0 mmol), 1,2-diiodoethane (0.5 mmol) and N-tosyl
aldimine (1.0 mmol) in THF solution (10 mL) and then the
reaction mixture was sonicated for 2 hours followed by
quenching with water and then the reaction mixture was
stirred for 5 minutes (Scheme II). The expected product
b-N-tosylamino ester was obtained with 57% by using wa-
ter as reaction quencher. The yield of b-N-tosylamino ester
was improved to 65% accompanied with b-lactam (5%)
when more acidic solution (1 M HCl) was introduced as
quencher. The better yield (85%) was obtained when 3.5
equivalent of Zn, 1.0 equivalent of 1,2-diiodoethane and
1.6 equivalent of etehyl bromoacetate were introduced un-
der the reaction condition and then quenched with 50%
aqueous NH4Cl solution. Our previously investigations
showed that the reaction mixture of Zn and ICH2CH2I in
THF became acidic solution (pH ~2) under sonication16
* Corresponding author. Tel: +8862-2621-5656 #2543; Fax: +8862-2622-3830; E-mail: adamlee@mail.tku.edu.tw
290
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Chemoselective Synthesis of b-Amino Ester or b-Lactam
Optimization of sonochemical Reformatsky
Scheme II
reaction
which did not promote the formation of b-lactam by further
intramolecular amidation reaction.
N-Hydroxyamino esters have been used as synthetic
intermediates and present some applications in organic
synthesis.17-20 In order to afford N-hydroxyamino ester, we
investigated N-hydroxy aldimine under this sonochemical
Reformatsky reaction condition. The results showed that
the N-hydroxyamino ester was obtained as only product
when N-hydroxy aldimine was used as reacting substrate
under the reaction condition (Table 1, entry 4). To under-
stand and expand the scope for synthesis of b-N-tosyl-
amino and N-hydroxyamino ester by this Reformatsky re-
action, a series of N-tosyl aldimines and N-hydroxy aldi-
mines were prepared and investigated under this sono-
chemical Reformatsky reraction condition. The results are
shown in Table 1, the N-hydroxyamino esters were ob-
tained as only product when N-hydroxy aldimines were in-
troduced under the reaction condition. While N-tosyl aldi-
mine was used as reacting substrate, in most examples, the
b-N-tosylamino esters were obtained as only product ex-
cept entries 4, 5 and 7 in Table 1. It is also worthy to know
that the formation yield of b-lactam was lower than 3% for
these cases. The higher yields of N-hydroxyamino esters
were obtained when alkyl oximes was used as reacting sub-
strate compared to alkyl N-tosylimines (Table 1, entries
1-3). The much higher yields of aryl b-N-tosylamino esters
were obtained when aryl N-tosylimines were used as react-
ing substrate which compared to aryl oximes (Table 1, en-
tries 4-10).
III). The experimental results showed that b-N-p-methoxy-
amino ester was generated as the major product when H2O
and 50% NH4Cl were used as quencher under the reaction
condition. The b-lactam with 96% yield could be obtained
as the sole product when quenching with more acidic solu-
tion (2M HCl) to the reaction mixture under this sono-
Optimization of N-methoxy imine as re-
Scheme III
acting substrate
A previous report showed that b-lactam was formed
as the only product with one-step process when N-p-meth-
oxy imine was used as reacting substrate by using activated
zinc granules and dioxane as solvent under ultrasound.21
Thus, we further investigated the reaction of N-p-methoxy
imine under this sonochemical reaction condition (Scheme
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291

Article
Lee et al.
chemical reaction condition. The b-lactam was success-
fully synthesized by using N-p-methoxy aldimine as react-
ing substrate and quenched with 2 M HCl solution under
this sonochemical Reformatsky reaction condition.
Our experimental results showed that chemoselectiv-
ity of this sonochemical Reformatsky reraction which rely
on the introduction of N-substituted aldimine patterns. The
consequently intramolecular amidation was completed
when N-p-methoxy aldimine was used as reacting substrate
under the reaction condition without further introducing
amidating agent.
with silica gel and ethyl acetate/hexane as eluent. Ethyl-3-tosyl-
aminooctanoate (Table 1, Entry 1): 1H-NMR: d 0.90 (3H, t, J =
7.3 Hz), 1.13-1.24 (7H, m), 1.32-1.48 (4H, m), 2.34 (3H, s), 2.68
(1H, dd, J = 15.1, 4.0 Hz), 2.76 (1H, dd, J = 15.1, 5.1 Hz),
3.11-3.20 (1H, m), 3.97 (2H, q, J = 7.3 Hz), 5.09 (1H, NH, d, J =
7.2 Hz), 7.13 (2H, d, J = 6.7 Hz), 7.68 (2H, d, J = 6.7 Hz). 13C-
NMR: d 13.8, 14.0, 22.9, 24.6, 26.7, 27.2, 38.1, 53.6, 59.9, 125.4,
135.7, 136.3, 142.1, 169.7. Ethyl-3-hydroxyaminooctanoate
(Table 1, Entry 1): 1H-NMR: d 0.89 (3H, t, J = 7.1), 1.13-1.24
(7H, m), 1.32-1.49 (4H, m), 2.72 (1H, dd, J = 14.7, 4.2 Hz), 2.80
(1H, dd, J = 14.7, 5.3 Hz), 4.17 (2H, q, J = 7.1 Hz), 7.41 (1H, NH,
br). 13C-NMR: d 13.8, 14.1, 25.1, 25.8, 26.8, 27.4, 39.9, 55.8,
70.1, 170.1. Ethyl-3-tosylamino-4-octenoate (Table 1, Entry
2): 1H-NMR: d 0.87 (3H, t, J = 7.4), 1.09-1.58 (5H, m), 2.10 (2H,
dt, J = 5.8, 6.4 Hz), 2.31-2.53 (5H, m), 3.81-3.87 (1H, m), 4.04
(2H, t, J = 7.4 Hz), 5.02 (1H, NH, d, J = 7.1 Hz), 6.48 (1H, dt, J =
15.1, 5.4 Hz), 7.18 (2H, d, J = 6.8 Hz), 7.41 (1H, dd, J = 15.1, 5.8
Hz), 7.70 (2H, d, J = 6.8 Hz). 13C-NMR: d 14.4, 23.0, 24.9, 35.2,
40.3, 59.5, 60.3, 125.3, 135.6, 136.2, 142.3, 169.7. Ethyl-3-hy-
droxyamino-4-octenoate (Table 1, Entry 2): 1H-NMR: d 0.90
(3H, t, J = 7.0), 1.25-1.51 (5H, m), 2.19 (1H, m), 2.35-2.61 (3H,
m), 3.97-4.02 (1H, m), 4.17 (2H, q, J = 7.0 Hz), 6.69 (1H, dd, J =
14.8, 5.7 Hz), 7.32 (1H, NH, br), 7.42 (1H, dt, J = 14.8, 6.1 Hz).
113C-NMR: d 14.9, 25.9, 36.1, 45.9, 62.2, 70.7, 123.1, 132.3,
170.3. Ethyl-3-hydroxyamino-3-cyclohexylpropionate (Table
1, Entry 3): 1H-NMR: d 1.06-1.45 (9H, m), 1.51-1.80 (4H, m),
1.95 (1H, m), 2.51-2.69 (2H, m), 3.39-3.47 (1H, m), 4.14 (2H, q, J
= 7.1 Hz), 7.11 (1H, NH, br). 13C-NMR (75.5 MHz, CDCl3) d
14.1, 22.5, 22.8, 23.1, 29.8, 46.0, 56.7, 70.2, 170.8. Ethyl-3-
As a conclusion, we demonstrate here an efficient
method for the synthesis of b-N-tosylamino esters from ex-
tensively applied N-tosyl aldimines via sonochemical
Reformatsky reaction. N-Hydroxy aldimine (oxime) as re-
acting substrate leads to the formation of b-N-hydroxy-
amino ester as sole product under this sonochemical reac-
tion condition. The b-N-hydroxyamino ester was afforded
by Reformatsky reaction of N-hydroxy aldimine as react-
ing substrate without protection of reactive hydroxyl func-
tionality
EXPERIMENTAL
General: All reagents were purchased from Aldrich and
Riedel-deHaen and all were used directly without further purifi-
cation. The 1H NMR (proton nuclear magnetic resonance) spectra
were recorded at 300 MHz (Bruker-AC300P) with deuteriochlo-
roform (CDCl3, Aldrich 99.8 atom% D) as the solvent and the in-
ternal standard. The 13C NMR (carbon nuclear magnetic reso-
nance) spectra were recorded at 75.5 MHz (Bruker-AC300P) with
CDCl3 as the solvent and the internal standard. Chemical shifts
are reported in parts per million and resonance patterns are re-
ported with the notations of either s (singlet), d (doublet), t (trip-
let), q (quartet), or m (multiplet). Coupling constant (J) are re-
ported in hertz (Hz).
1
tosylamino-3-phenylpropionate (Table 1, Entry 4): H-NMR:
d 1.13 (3H, t, J = 7.2 Hz), 2.37 (3H, s), 2.73 (1H, dd, J = 15.8, 5.9
Hz), 2.83 (1H, dd, J = 15.8, 6.4 Hz), 4.01 (2H, q, J = 7.2 Hz), 4.73
(1H, q, J = 6.6 Hz), 5.65 (1H, NH, d, J = 7.6 Hz), 7.09-7.23 (7H,
m), 7.61 (2H, d, J = 6.8 Hz). 13C-NMR: d 13.9, 21.4, 41.4, 54.4,
60.8, 126.4, 127.0, 127.6, 128.4, 129.3, 137.5, 139.3, 143.1,
170.5. HRMS: m/z 348.1271 (2.2, M+1) (calcd. for C18H21NO4S,
M+1, 348.1270). MS: m/z 348 (2.2), 262 (42), 261 (73), 260
(base), 194 (12), 191 (90), 177 (16), 164 (13), 157 (21), 156 (27),
146 (44), 139 (20), 135 (15), 118 (10), 106 (12), 105 (24), 104
(73), 103 (25), 92 (30), 91 (72), 77 (18), 65 (24). Ethyl-3-hy-
droxyamino-3-phenylpropionate (Table 1, Entry 4): 1H-NMR:
d 1.26 (3H, t, J = 7.0 Hz), 2.70 (1H, dd, J = 16.1, 5.0 Hz), 2.78
(1H, dd, J = 16.1, 6.4 Hz), 4.19 (2H, q, J = 7.0 Hz), 5.14 (1H, dd, J
= 8.5, 5.0 Hz), 7.27-7.45 (6H, m). 13C-NMR: d 14.1, 43.3, 60.9,
70.3, 125.7, 128.4, 142.5, 150.3, 172.4. Ethyl-3-(toluene-4-sul-
fonylamino)-3-(4-methoxyphenyl)-propionate (Table 1, Entry
5): 1H-NMR: d 1.13 (3H, t, J = 7.3 Hz), 2.38 (3H, s), 2.68 (1H, dd,
A Representative Procedure for Synthesis of b-N-hy-
droxyamino ester: Ethyl bromoacetate (1.6 mmol) was added to
a solution of zinc (3.5 mmol), 1,2-diiodoethane (1.0 mmol) and
N-hydroxy aldimine (1.0 mmol) in anhydrous THF (10 mL) and
the reaction mixture was sonicated in a commercial ultrasonic
cleaning bath22 (Elma-T490DH, 50 kHz) for two hours at around
43 oC. After the sonication, an aqueous 50% NH4Cl (8.0 mL) was
added and stirred for 5 to 30 minutes. The reaction mixture was
extracted with ethyl acetate (10 mL ´3) and the combined organic
layer was washed with brine (20 mL), dried with MgSO4, filtered,
and then the organic solvent was removed under reduced pres-
sure. Further purification was achieved on a flash chromatograph
292
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Chemoselective Synthesis of b-Amino Ester or b-Lactam
J = 15.1, 6.2 Hz), 2.80 (1H, dd, J = 15.1, 6.6 Hz), 3.74 (3H, s),
4.01 (2H, q, J = 7.3 Hz), 4.67 (1H, dd, J = 7.3, 6.6 Hz), 5.61 (1H,
NH, d, J = 7.3 Hz), 6.70 (2H, d, J = 8.7 Hz), 7.01 (2H, d, J = 8.7
Hz), 7.17 (2H, d, J = 8.4 Hz), 7.59 (2H, d, J = 8.4 Hz). 13C-NMR: d
14.2, 21.4, 42.4, 57.1, 62.6, 66.0, 118.9, 126.3, 128.8, 129.1,
129.4, 137.5, 139.3, 159.2, 177.1. HRMS: m/z 377.1314 (1.7)
(calcd. for C19H23NO5S, 377.1297). MS: m/z 377 (1.7), 291 (12),
290 (66), 223 (17), 222 (base), 161 (13), 155 (40), 137 (27), 135
(26), 134 (57), 133 (12), 91 (55), 77 (12), 65 (13). Ethyl-3-hy-
droxyamino-3-(4-methoxyphenyl)propionate (Table 1, Entry
5): 1H-NMR: d 1.26 (3H, t, J = 7.2), 2.74 (1H, dd, J = 15.2, 4.9
Hz), 2.83 (1H, dd, J = 15.2, 5.8 Hz), 3.75 (3H, s), 4.17 (2H, q, J =
7.2 Hz), 5.01 (1H, m), 6.84 (2H, d, J = 8.7 Hz), 7.14 (2H, d, J = 8.7
Hz), 7.41 (1H, NH, br). 13C-NMR: d 14.6, 45.9, 62.3, 66.4, 73.0,
119.3, 128.6, 130.2, 144.9, 162.1, 177.9. Ethyl-3-tosylamino-3-
(4-nitrophenyl)propionate (Table 1, Entry 6): 1H-NMR: d 1.23
(3H, t, J = 7.4 Hz), 2.39 (3H, s), 2.73 (1H, dd, J = 15.2, 5.9 Hz),
2.82 (1H, dd, J = 15.2, 6.5 Hz), 4.27 (2H, q, J = 7.4 Hz), 5.06 (1H,
dd, J = 7.2, 6.5 Hz), 5.98 (1H, NH, d, J = 7.2 Hz), 7.32 (2H, d, J =
8.3 Hz), 7.76 (2H, d, J = 8.7 Hz), 7.91 (2H, d, J = 8.3 Hz), 8.24
(2H, d, J = 8.7 Hz). 13C-NMR: d 14.0, 21.5, 41.9, 55.9, 61.0,
123.8, 126.2, 127.9, 129.4, 138.1, 142.2, 144.2, 158.2, 173.7.
Ethyl-3-hydroxyamino-3-(4-nitrophenyl)propionate (Table 1,
Entry 6): 1H-NMR: d 1.30 (3H, t, J = 7.0 Hz), 2.39 (3H, s), 2.78
(1H, dd, J = 15.0, 5.1 Hz), 2.82 (1H, dd, J = 15.0, 6.0 Hz), 4.23
(2H, q, J = 7.0 Hz), 5.42 (1H, dd, J = 8.2, 6.0 Hz), 7.74 (1H, d, J =
8.7 Hz), 8.02 (1H, NH, br), 8.23 (2H, d, J = 8.7 Hz). 13C-NMR: d
14.1, 46.4, 61.9, 72.0, 123.7, 129.1, 145.0, 161.8, 177.2. Ethyl-
3-tosylamino-3-(4-fluorophenyl)propionate (Table 1, Entry
7): 1H-NMR: d 1.07 (3H, t, J = 7.1 Hz), 2.31 (3H, s), 2.65 (1H, dd,
J = 15.3, 4.9 Hz), 2.73 (1H, dd, J = 15.3, 5.5 Hz), 3.96 (2H, q, J =
7.1 Hz), 4.73 (1H, dd, J = 8.0, 5.5 Hz), 6.25 (1H, NH, d, J = 8.0
Hz), 6.77 (2H, dd, J = 16.2, 8.7 Hz), 7.02-7.24 (4H, br), 7.53 (2H,
d, J = 8.3Hz). 13C-NMR: d 14.1, 21.9, 42.7, 56.0, 62.2, 117.8,
126.1, 128.4, 129.6, 136.9, 140.0, 159.9, 175.4. MS: m/z 279 (10),
278 (55), 211 (13), 210 (base), 164 (19), 155(70), 122 (42),
121(12), 91 (83), 65(13). Ethyl-3-hydroxyamino-3-(4-fluoro-
phenyl)propionate (Table 1, Entry 7): 1H-NMR: d 1.26 (3H, t, J
= 7.3 Hz), 2.65 (1H, dd, J = 15.3, 5.3 Hz), 2.85 (1H, dd, J = 15.3,
6.4 Hz), 4.13 (2H, q, J = 7.3 Hz), 5.30 (1H, dd, J = 8.1, 6.4 Hz),
7.07 (2H, m), 7.56 (2H, m), 7.92 (1H, NH, br). 13C-NMR: d 14.8,
46.8, 61.9, 72.1, 124.1, 126.4, 130.2, 146.0, 177.9. HRMS: m/z
227.0949 (6.2) (calcd. for C11H14FNO3, 227.0958). MS: m/z 227
(6.2), 210 (24), 195 (21), 181 (19), 179 (36), 153 (51), 149 (53),
140 (20), 139 (28), 125 (49), 124 (92), 123 (base), 122 (80), 121
(36), 111 (21), 109 (67), 101 (23), 97 (27), 96 (29), 95 (63), 75
(28), 71 (34). Ethyl-3-tosylamino-3-furan-2-yl-propionate
(Table 1, Entry 8): 1H-NMR: d 1.23 (3H, t, J = 6.9 Hz), 2.40 (3H,
s), 2.79 (1H, dd, J = 15.1, 5.8 Hz), 2.88 (1H, dd, J = 15.1, 6.3 Hz),
4.14 (2H, q, J = 6.9 Hz), 4.77-4.86 (1H, m), 5.58 (1H, NH, d, J =
8.7 Hz), 6.01 (1H, d, J = 3.3 Hz), 6.15 (1H, d, J = 3.0 Hz), 7.17-
7.25 (3H, m), 7.67 (1H, d, J = 8.1 Hz). 13C-NMR: d 13.9, 21.6,
41.2, 54.1, 60.9, 107.1, 117.5, 126.6, 129.4, 137.3, 138.9, 141.3,
158.8, 175.1. MS: m/z 250 (19), 182 (base), 171 (24), 155 (43), 91
(77), 65 (11). Ethyl-3-hydroxyamino-3-furan-2-yl-propionate
(Table 1, Entry 8): 1H-NMR: d 1.26 (3H, t, J = 6.6 Hz), 2.79 (1H,
dd, J = 15.0, 5.5 Hz), 2.86 (1H, dd, J = 15.0, 6.5 Hz), 4.22 (2H, q, J
= 6.6 Hz), 4.90-4.99 (1H, m), 6.46 (1H, d, J = 2.1 Hz), 6.62 (1H, d,
J = 3.3 Hz), 7.12 (1H, d, J = 2.1 Hz), 7.32 (1H, NH, br). 13C-NMR:
d 14.4, 40.4, 59.9, 71.9, 109.8, 117.1, 143.9, 162.1, 176.0. HRMS:
m/z 199.0827 (2.1) (calcd. for C9H13NO4, 199.0845). MS: m/z 199
(2.1), 181 (9), 175 (9), 167 (23), 165 (10), 149 (13), 125 (12), 121
(28), 120 (14), 111 (base), 108 (10), 101 (12), 97 (32), 95 (82), 94
(21), 81 (10), 71 (10). Ethyl-3-tosylamino-3-thiophen-2-yl-pro-
pionate (Table 1, Entry 9): 1H-NMR d 1.18 (3H, t, J = 7.3 Hz),
2.37 (3H, s), 2.79 (1H, dd, J = 14.5, 5.3 Hz), 2.85 (1H, dd, J =
14.5, 6.1 Hz), 4.01 (2H, q, J = 7.3 Hz), 4.95 (1H, ddd, J = 8.5, 6.1,
5.3 Hz), 5.73 (1H, NH, d, J = 8.5 Hz), 6.75-6.82 (2H, m), 7.10
(1H, d, J = 1.5 Hz), 7.24 (2H, d, J = 8.4 Hz), 7.69 (1H, d, J = 8.4
Hz). 13C-NMR: d 14.1, 21.8, 41.2, 56.5, 60.7, 124.7, 125.4, 126.0,
126.9, 130.0, 137.4, 139.9, 143.2, 174.7. MS: m/z 266 (33), 199
(12), 198 (base), 155 (31), 152 (11), 110 (19), 91 (42). Ethyl-3-
hydroxyamino-3-thiophen-2-yl-propionate (Table 1, Entry
9): 1H-NMR: d 1.28 (3H, t, J = 7.3 Hz), 2.79 (1H, dd, J = 15.1, 5.4
Hz), 2.85 (1H, dd, J = 15.1, 6.6 Hz), 4.18 (2H, q, J = 7.3 Hz), 5.45
(1H, ddd, J = 8.4, 6.6, 5.4 Hz), 6.84 (1H, d, J = 1.6 Hz), 7.11 (1H,
d, J = 1.8 Hz), 7.41 (1H, d, J = 1.6 Hz), 7.65 (1H, NH, br). 13C-
NMR: d 14.4, 42.5, 61.5, 71.9, 125.1, 126.7, 127.7, 143.5, 175.9.
HRMS: m/z 215.0609 (4.5) (calcd. for C9H13NO3S, 215.0616).
MS: m/z 215 (4.5), 198 (5), 137 (10), 127 (68), 113 (12), 112 (13),
111 (base), 110 (15), 109 (11), 97 (13), 84 (17), 83 (15), 57 (10).
Ethyl-3-hydroxyamino-3-indol-3-yl-propionate (Table 1, En-
1
try 10): H-NMR: d 1.23 (3H, t, J = 6.5 Hz), 2.78 (1H, dd, J =
15.1, 5.5 Hz), 2.90 (1H, dd, J = 15.1, 6.8 Hz), 4.23 (2H, q, J = 6.5
Hz), 5.48-5.56 (1H, m), 7.20 (1H, m), 7.31 (1H, ArNH, br), 7.55
(1H, J = 6.4 Hz), 7.68 (1H, d, J = 6.4 Hz), 7.73-7.83 (2H, m), 8.18
(1H, NH, br). 13C-NMR: d 13.8, 41.3, 60.8, 71.0, 113.8, 114.6,
120.8, 123.4, 123.7, 125.6, 132.9, 139.8, 175.2. Ethyl-3-(4-
methoxy-phenyl)-3-(4-methoxy-phenylamino)-propionate
(Scheme III): 1H-NMR: d 1.18 (1H, t, J = 7.2 Hz), 2.76 (2H, d, J
= 6.9 Hz), 3.70 (3H, s), 3.77 (3H, s), 4.13 (2H, q, J = 7.2 Hz), 4.71
(1H, t, J = 6.9 Hz), 6.54 (2H, d, J = 12.3 Hz), 6.69 (2H, d, J = 10.2
Hz), 6.85 (2H, d, J = 10.2 Hz), 7.27 (2H, d, J = 12.3 Hz). 13C-
NMR: d 14.1, 42.4, 56.1, 62.6, 64.5, 65.8, 118.9, 128.1, 128.8,
J. Chin. Chem. Soc. 2014, 61, 290-294
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Article
Lee et al.
9. Shankar, B. B.; Kirkup, M. P.; McCombie, S. W.; Clader, J.
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19, 916.
129.1, 129.4, 138.6, 155.6, 159.2, 176.1. 1-(4-Methoxy-phenyl)-
1
4-phenyl-azetidin-2-one (Scheme III): H-NMR: d 2.92 (1H,
dd, J = 15.3, 2.1 Hz), 3.52 (1H, dd, J = 15.3, 4.8 Hz), 3.74 (3H, s),
3.81 (3H, s), 4.93 (1H, dd, J = 4.8, 2.1 Hz), 6.78 (2H, d, J = 9.1
Hz), 6.91 (2H, d, J = 6.3 Hz), 7.23 (2H, d, J = 9.1 Hz), 7.29 (2H, d,
J = 6.3 Hz). 13C-NMR: d 45.6, 52.3, 53.8, 53.9, 112.6, 112.9,
116.5, 125.6, 128.5, 129.8, 154.2, 158.0, 162.5.
11. Lee, A. S.-Y.; Cheng, R.-Y.; Pan, O.-G. Tetrahedron Lett.
1997, 38, 443.
12. The ZnI2 and ethene were generated form Zn powder and
1,2-diiodoethane under sonication.
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hedron Lett. 2006, 47, 7085.
ACKNOWLEDGMENTS
14. Lee, A. S.-Y.; Chu, S.-F.; Chang, Y.-T.; Wang, S.-H. Tetra-
hedron Lett. 2004, 45, 1551.
We thank the National Science Council in Taiwan
(NSC 98-2119-M-032-002-MY3) and Tamkang Univer-
sity for financial support.
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J. Chin. Chem. Soc. 2014, 61, 290-294