Improved Buchner reaction selectivity in the copper-catalyzed reactions of ethyl 3-arylmethylamino-2-diazo-3-oxopropanoates

Article abstract of DOI:10.1016/j.tet.2017.06.029

Ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates (diazo amidoacetates) generate generally both cyclohepta[c]pyrrolones (Buchner products) and β-lactams (1,4-insertion products), and show obvious N-substituent-controlled chemoselectivity between the intramolecular Buchner reaction and aliphatic 1,4-C-H insertion under the catalysis of copper salts. The less steric N-alkyl substituents in the amide moiety generally favor the aliphatic 1,4-C-H insertion, while the more steric N-alkyl substituents generally favor the Buchner reaction. Compared with rhodium and ruthenium-catalyzed conditions, the current copper-catalyzed conditions improved the Buchner reaction selectivity of ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates.

Full text of DOI:10.1016/j.tet.2017.06.029

Accepted Manuscript
Improved Buchner reaction selectivity in the copper-catalyzed reactions of ethyl 3-
arylmethylamino-2-diazo-3-oxopropanoates
Jing Liu, Jianzhuo Tu, Zhanhui Yang, Chol-Ung Pak, Jiaxi Xu
PII:
S0040-4020(17)30662-2
10.1016/j.tet.2017.06.029
TET 28794
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 24 April 2017
Revised Date: 14 June 2017
Accepted Date: 16 June 2017
Please cite this article as: Liu J, Tu J, Yang Z, Pak C-U, Xu J, Improved Buchner reaction selectivity
in the copper-catalyzed reactions of ethyl 3-arylmethylamino-2-diazo-3-oxopropanoates, Tetrahedron
(2017), doi: 10.1016/j.tet.2017.06.029.
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Improved Buchner reaction selectivity in the
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arylmethylamino-2-diazo-3-oxopropanoates
Jing Liu, Jianzhuo Tu, Zhanhui Yang, Chol-Ung Pak, and Jiaxi Xu*
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of
Science, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China

1
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Tetrahedron
journal homepage: www.elsevier.com
Improved Buchner reaction selectivity in the copper-catalyzed reactions of ethyl
3-arylmethylamino-2-diazo-3-oxopropanoates
Jing Liu, Jianzhuo Tu, Zhanhui Yang, Chol-Ung Pak, and Jiaxi Xu
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology,
Beijing 100029, People’s Republic of China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates (diazo amidoacetates) generate
generally both cyclohepta[c]pyrrolones (Buchner products) and β-lactams (1,4-insertion
products), and show obvious N-substituent-controlled chemoselectivity between the
intramolecular Buchner reaction and aliphatic 1,4-C-H insertion under the catalysis of copper
salts. The less steric N-alkyl substituents in the amide moiety generally favor the aliphatic 1,4-C-
H insertion, while the more steric N-alkyl substituents generally favor the Buchner reaction.
Compared with rhodium and ruthenium-catalyzed conditions, the current copper-catalyzed
conditions improved the Buchner reaction selectivity of ethyl 3-alkyl(arylmethyl)amino-2-diazo-
3-oxopropanoates
Available online
Keywords:
Buchner reaction
Carbenoid
Copper catalyst
Cyclohepta[c]pyrrolone
Diazoamide
Insertion
2017 Elsevier Ltd. All rights reserved
.
Lactam
1. Introduction
under copper catalysis because of the π-π stacking interaction
between the electron-deficient cyano group and the electron-rich
N-arylmethyl group in diazoacetamides11 (Scheme 1).
The reactions of carbenes derived from diazo compounds
provide
a powerful tool to construct synthetically and
In our further studies, we hope to extend our studies on the
reaction of ethyl 3-alkyl(arylmethyl)-2-diazo-3-oxopropanoates
(ethyl diazoamidoacetates) under the copper catalysis and to
improve the intramolecular Buchner reaction selectivity. Herein,
we present the N-substituent-controlled intramolecular Buchner
biologically important organic compounds, especially in the
intramolecular reactions.1 Of particular, we are quite interested in
the intramolecular Buchner reaction2 and aliphatic 1,4-C-H
insertion of substituted diazoacetamides.3 The former gives 9-
azabicyclo[5.3.0]deca-2,4,6-trien-10-one derivatives, 5,7-bicyclic
products, while the latter produces β-lactams for N-
benzyldiazoacetamides. Additionally, the reactions also generate
aliphatic 1,5-C-H insertion to afford γ-lactams4 and aromatic 1,6-
C-H insertion to yield tetrahydroisoquinolinones in some
cases4d,i,5 (Scheme 1). The chemoselectivity between the Buchner
reaction and aliphatic 1,4-C-H insertion has received much
attention.4-9 Previously published results revealed that the
substituents adjacent to the diazo group,4e,f,6 the ligands of
rhodium catalysts,4c,d,6d,7 N-substituents,4b,c,e,f,h,5b,6c,d,e,8 and even
the reaction conditions6e,7b,h,j,9 played important roles in deciding
the chemoselectivity. Ethyl 3-alkyl(arylmethyl)amino-2-diazo-3-
oxopropanoates (N-alkyl-N-arylmethyl-diazoaceamides with α-
ethoxycarbonyl substituent) produced generally β-lactams as
major or sole products under the catalysis of rhodium and
ruthenium catalysts.10 Under these conditions, Buchner products
were obtained in only a few cases with low selectivity. Recently,
our group discovered that the presence of the cyano group
reacion
to
form
ethyl
2-alkyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylates and 1,4-insertion
into aliphatic C-H bonds to yield ethyl trans-β-lactam-3-
carboxylates (Scheme 1).
2. Results and Discussion
Ethyl 3-alkyl(arylmethyl)amino-3-oxopropanoates
1 were
prepared from coupling of ethyl malonyl chloride and N-alkyl-N-
arylmethylamines and further converted into ethyl 3-
alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates 2 by the diazo
transformation with p-acetamidobenzenesulfonyl azide (p-ABSA)
in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as
base (Scheme 2).
adjacent to the diazo group led to a specific Buchner reaction
———
Corresponding author. Tel.: +8610-6443-5565; fax: +8610-6443-5565; e-mail: jxxu@mail.buct.edu.cn

2
Tetrahedron
ACCEPTED MANUSCRIPT
Chemoselectivity in transition metal-catalyzed reactions
Ethyl 2-diazo-3-dibenzylamino-3-oxopropanoate (2a) was
selected as a model substrate to optimize the reaction conditions
under catalysis of different copper salts. At first, Cu(acac)2 was
chosen as the catalyst for the reaction in 1,2-dichloroethane
(DCE) as solvent because they showed excellent efficiency in the
reaction of 2-cyano-2-diazopropanamides.33 The desired product
ethyl 2-benzyl-3-oxo-1,2,3,3a-tetrahydrocyclohepta[c]pyrrole-3a-
carboxylate (3a) was obtained in 27% yield with aliphatic 1,4-C-
H insertion by-product β-lactam 4a in 14% yield after refluxing
overnight (Table 1, entry 1). The yields of both products were
improved in refluxing toluene overnight (Table 1, entry 2).
Further investigation upon various copper catalysts (Table 1,
entries 3–12), including CuBr, CuI, CuCl, Cu(OAc)2·H2O,
R1
N2
R2
Rh, Ru, Cu etc.
N
EWG
O
R3
EWG
O
O
R2
EWG
N
EWG
O
+
+
R1
N
N
R2
R1
R2
Buchner products
1,4-insertion products
1,4-insertion products
R2
R1
R4
N
R2
O
+
N
+
CuSO4·5H2O,
Cu(NO3)2·3H2O,
CuBr2,
Cu(OTf)2,
EWG
EWG
O
CuOTf·1/2C6H6, and CuCl2·2H2O salts, revealed that
CuCl2·2H2O was optimal catalyst, showing a quantitative total
yield and high Buchner reaction selectivity. Changing addition
mode from dropwise to one portion further improved the
selectivity from 72:28 to 75:25 (Table 1, entries 12 and 13).
When the reaction was carried out under open air, similar
selectivity was observed, but the yields decreased obviously,
especially for Buchner product (Table 1, entry 14). Different
solvents were screened. High chemoselectivity was obtained in
refluxing dioxane, but with low total yield (Table 1, entry 15).
Low chemoselectivies and total yields were observed in refluxing
THF and DCM (Table 1, entries 16 and 17). The results indicated
that toluene was good choice of solvent. Different temperatures
were further tested in toluene (Table 1, entries 18−20). Compared
with the reaction in refluxing toluene, yields decreased but
chemoselectivities increased at 100 oC, 80 oC, and 60 oC. Finally,
the reaction was attempted in refluxing toluene without catalyst.
Low yield and chemoselectivity were obtained (Table 1, entry
21). Thus, the optimal conditions (5 mol % CuCl2·2H2O, toluene,
reflux) were ascertained, the best yield of 100% and moderate
chemoselectivity of 75:25 were achieved (Table 1, entry 13).
Although the chemoselectivity was not high, the highest yield of
Buchner product was obtained due to the highest total yield.
aromatic C-H insertion products
1,5-insertion products
Previous work:
Rh/Ru catalysts: Controlled by EWG, ligands of catalysts,
less Buchner products
reaction conditions,
Cu catalysts, EWG = CN: Chemospecific Buchner products
This work:
Cu catalysts: Controlled by N-substituents
Buchner products improved
O
CO2Et
R1
N2
CuII or CuI
R2
+
R1
N
N
EtO2C
R2
O
Buchner products
R3
EtO2C
O
R1
R2
N
R2
N
EtO2C
O
+
+
O
N
CO2Et
aromatic C-H
insertion products
R1
R2
1,4-insertion products
1,4-insertion products
Scheme 1. Transition metal-catalyzed reactions of
diazoacetamides with electron-withdrawing substituents.
Table 1 Optimization of copper catalysts and reaction conditionsa
N2
R1
EDC, DMAP
R2
OH
+
EtO2C
HN
O
R1
R2
p-ABSA, DBU
N
EtO2C
EtO2C
Entry Catalyst
Solvent Time (h) 3a(%)b 4a(%)b
O
O
CO2Et
1
2
3
Cu(acac)2
Cu(acac)2
CuBr
DCE
overnight 27
14
44
57
55
58
54
59
60
50
30
29
28
25
21
7
N2 R1
CuII or CuI
R2
Toluene overnight 35
+
R1
N
N
Toluene
Toluene
Toluene
Toluene
Toluene
4
4
4
4
4
4
4
4
4
4
4
4
4
42
39
41
45
41
39
49
5
50
72
75
65
74
R2
4
CuI
O
Buchner products
5
CuCl
6
7
Cu(OAc)2·H2O
CuSO4·5H2O
EtO2C
O
R3
R1
R2
N
8
Cu(NO3)2·3H2O Toluene
R2
N
EtO2C
O
9
CuBr2
Toluene
Toluene
+
+
O
10
11
12
13c
14d
15
Cu(OTf)2
CuOTf·1/2C6H6 Toluene
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
N
CO2Et
aromatic C-H
insertion products
R1
R2
Toluene
Toluene
Toluene
Dioxane
1,4-insertion products
1,4-insertion products
Scheme 2. Copper-catalyzed reactions of ethyl 3-
alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates.

3
16
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
CuCl2·2H2O
-
THF
DCM
Toluene
Toluene
Toluene
Toluene
4
4
4
4
4
4
11
3
3
7
5
1
15
the electron-richer benzyl group as previously reported.
ACCEPTED MANUSCRIPT
17
26
66
35
5
However, two different aliphatic 1,4-C-H insertion product β-
lactams 4ba and 4bb, 4ca and 4cb in these two reactions cannot
be separated due to their similar polarity and property. A series of
3-alkyl(benzyl)amino-2-diazo-3-oxopropanoates 2d-p were
further evaluated. For less bulky 3-benzyl(methyl/propyl)amino-
2-diazo-3-oxopropanoates 2d and 2e, besides Buchner products
3d and 3e and β-lactams 4d and 4e, another class of aliphatic 1,4-
C-H insertion product β-lactams 5d and 5e was obtained (Table
18e
19f
20g
21
37
a Unless otherwise noted, all reactions were performed on 0.4 mmol
scale in 5 mL of the solvent under nitrogen atmosphere. Diazo
compound 2a was dissolved in 5 mL of solvent and added
dropwise. The reaction was monitored by TLC until the starting
material was completely consumed. b Yields were determined by 1H
NMR with 4-iodonitrobenzene as an internal standard. c Diazo
compound 2a was added in one portion. d In open air, diazo
compound 2a was added in one portion. e Conducted at 100 oC. f
Conducted at 80 oC. g Conducted at 60 oC.
2, entries
4
and 5). While, for more bulky 3-
benzyl(isopropyl/tert-butyl)amino-2-diazo-3-oxopropanoates 2f
and 2g, both Buchner products 3f and 3g and β-lactams 4f and 4g
were obtained, respectively, without other aliphatic 1,4-C-H
insertion product β-lactam 5d and aliphatic 1,5-C-H insertion
product γ-lactams (Table 2, entries 6 and 7). Ethyl 3-benzyl(tert-
butyl)amino-2-diazo-3-oxopropanoates
2h-l
with
para-
substituents on the benzyl group generated both Buchner
products 3h-l and β-lactams 4h-l, with Buchner products as
major products in most cases (Table 2, entries 8−12). 3-tert-
Butyl[(3-chlorophenyl)methyl]amino-2-diazo-3-oxopropanoate
2m afforded two different regiomeric Buchner products 3ma and
3mb in a total yield of 25% with a ratio of 64:36 and the
corresponding β-lactam 4m in 64% yield (Table 2, entry 13).
However, 3-tert-butyl[(2-chlorophenyl)methyl]amino-2-diazo-3-
oxopropanoate 2n gave rise to Buchner product 3n only in 61%
After successful optimization of the reaction conditions, we
subsequently investigated the substrate scope. These results were
summarized in Table 2. Ethyl 2-diazo-3-dibenzylamino-3-
oxopropanoate (2a) generated the desired product ethyl 2-benzyl-
3-oxo-1,2,3,3a-tetrahydrocyclohepta[c]pyrrole-3a-carboxylate
(3a) in 75% yield with the corresponding aliphatic 1,4-C-H
insertion product β-lactam 4a in 25% yield (Table 2, entry 1).
Two substituted 2-diazo-3-dibenzylamino-3-oxopropanoates 2b
and
2c
were
also
screened.
Ethyl
3-benzyl[(4-
yield
(Table
2,
entry
14).
3-tert-Butyl[(3,5-
2o
methylphenyl)methyl]amino-2-diazo-3-oxopropanoate (2b) gave
rise to two different Buchner products 3ba and 3bb in the same
yield of 30% with the corresponding aliphatic 1,4-C-H insertion
product β-lactams 4ba and 4bb (Table 2, entry 2). Ethyl 3-
benzyl[(4-chlorophenyl)methyl]amino-2-diazo-3-oxopropanoate
(2c) afforded two different Buchner products in yields of 28%
and 35%, respectively, with the corresponding β-lactams 4ca and
4cb (Table 2, entry 3). The Buchner reaction slightly favored on
dimethylphenyl)methyl]amino-2-diazo-3-oxopropanoate
produced both aliphatic 1,4-C-H insertion product β-lactam 5o in
34% yield and aromatic 1,6-C-H insertion product 6o in 66%
yield (Table 2, entry 15). However, 3-tert-butyl[(2,4-
dimethoxyphenyl)methyl]amino-2-diazo-3-oxopropanoate 2p did
not give Buchner product 3p nor any insertion products (Table 2,
entry 16).
Table 2 Reaction of 2-diazo-3-ethoxy-3-oxopropanamides 2 under the catalysis of CuCl2·2H2O
Yield (%)
Entry R1
R2
3
4
5
6
1
2
CH2Ph
H
3a (75)
3ba (30)
3bb (30)
3ca (28)
3cb (36)
3d (15)
3e (33)
3f (24)
3g (20)
3h (58)
3i (67)
3j (41)
3k (52)
3l (34)
4a (25)
4ba+4bb
(14)
4ca+4cb
(33)
4d (21)
4e (15)
4f (11)
4g (64)
4h (42)
4i (27)
4j (46)
4k (47)
4l (35)
CH2Ph
CH2Ph
4-Me
3
4-Cl
4
5
6
7
8
9
10
11
12
Me
nPr
iPr
H
H
H
H
4-F
4-Cl
4-Br
4-Me
4-OMe
5d (52)
5e (3)
tBu
tBu
tBu
tBu
tBu
tBu
3ma+3mb
(64:36)(25)
3n (61)
3o (0)
13
tBu
3-Cl
4m (64)
14
15
tBu
2-Cl
3,5-
4n (0)
4o (34)
tBu
6o (66)

4
Tetrahedron
ACCEPTED MANUSCRIPT
(Me)2
2,4-
(OMe)2
16
tBu
3p (0)
4p (0)
Structures in Table 2
The results indicate that substrates with less bulky N-alkyl
conditions improved the Buchner products in the reactions of 2-
diazo-3-ethoxy-3-oxopropanamides.
groups undergo not only benzylic aliphatic 1,4-C-H insertion, but
also aliphatic 1,4-C-H insertion on the less steric alkyl groups,
such as methyl and propyl groups, besides the desired Buchner
reaction, because both conformations A and B exist in the
reaction mixture. However, substrates with bulky N-alkyl groups,
for example, isopropyl and tert-butyl groups, exist predominantly
in conformation B, resulting in only occurrence of the benzylic
1,4-C-H insertion besides the desired Buchner reaction (Figure
1). No aliphatic 1,5-C-H insertion was observed under catalysis
of the copper catalyst.
4. Experimental Section
General Information:
Melting points (m.p.) were determined on a Yanaco MP-500
1
melting point apparatus and are uncorrected. H and 13C NMR
spectra were recorded on a Bruker 400 NMR spectrometer at 400
MHz and 100 MHz, respectively, in CDCl3 with TMS as an
internal standard and chemical shifts were reported in ppm. IR
spectra were taken on
a Nicolet AVATAR 330 FT-IR
spectrometer. HRMS spectra were performed on a Bruker
LC/MSD TOF mass spectrometer.
For reactions conducted under anhydrous conditions
glassware was dried in oven at 105 °C prior to use and the
reactions were carried out under a nitrogen atmosphere. Solvents
were refluxed with drying reagents and freshly distilled prior to
use. Dichloromethane (DCM) and 1,2-dichloroethane (DCE)
were dried over calcium hydride. Toluene was refluxed in the
presence of sodium wire with diphenyl ketone as an indicator.
Reagents used were obtained from commercial suppliers and
used without purification. All reactions were followed by thin-
layer chromatography (TLC) where practical, using silica gel
GF254 fluorescent treated silica gel plates, which were visualized
under UV light (254 nm). Column chromatography was
performed on silica gel zcx II (200−300 mesh) with petroleum
ether (PE, 60 oC-90 oC) and ethyl acetate (EA) as the eluent.
Figure 1. Reactive conformations in reaction mixture.
3. Conclusion
The
alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates have been
investigated. They generate generally both
copper-catalyzed
reactions
of
ethyl
3-
cyclohepta[c]pyrrolones (Buchner products) and β-lactams (1,4-
insertion products), showing obvious N-substituent-controlled
chemoselectivity between the intramolecular Buchner reaction
and aliphatic 1,4-C-H insertion. The less bulky N-alkyl
substituents generally predominant the aliphatic 1,4-C-H
insertion, while the more steric N-alkyl substituents generally
prefer the Buchner reaction. Compared with rhodium and
ruthenium-catalyzed conditions, the current copper-catalyzed
4.1. General Procedure for the reductive amination
A primary amine (20 mmol) and aldehyde (20 mmol) were
dissolved in MeOH (50 mL) and the resulting solution was
stirred for 3 hours at room temperature, then NaBH4 (0.90 g, 24
mmol) was added portionwise. After 1 hour, the solution was
added water (50 mL) and extracted with DCM (30 mL) twice.

5
The combined organic layer was dried over anhydrous Na2SO4
and then evaporated under reduced pressure. The crude product
was used in the next step without further purification.
4.2.4. Ethyl 3-(benzyl(methyl)amino)-3-oxopropanoate (1d)
ACCEPTED MANUSCRIPT
1
Yellow oil. 59% yield. H NMR (400 MHz, CDCl3) Major
isomer (62%): δ 7.45 – 7.10 (m, 5H, ArH), 4.62 (s, 2H, CH2),
4.22 (q, J = 7.2 Hz, 2H, CH2), 3.53 (s, 2H, CH2), 2.92 (s, 3H,
CH3), 1.28 (t, J = 7.2 Hz, 3H, CH3). Minor isomer (38%): δ 7.45
– 7.10 (m, 5H, ArH), 4.54 (s, 2H, CH2), 4.18 (q, J = 7.2 Hz, 2H,
CH2), 3.49 (s, 2H, CH2), 2.97 (s, 3H, CH3), 1.25 (t, J = 7.2 Hz,
3H, CH3). 13C NMR (101 MHz, CDCl3) δ 167.6, 167.5, 166.4,
166.2, 136.7, 135.9, 128.9, 128.6, 127.9, 127.8, 127.4, 126.3,
61.4, 53.9, 50.9, 41.6, 41.2, 35.3, 34.0, 14.1, 14.0. IR (DCM) ν
(cm-1): 1736 (C=O), 1654 (C=O). HRMS (ESI) calcd. for
C13H18NO3+ [M+H]+ m/z 236.1281, found 236.1277.
4.2. General Procedure for the synthesis of ethyl 3-
(benzylamino)-3-oxopropanoates using EDC/DMAP as
condensation reagents
To
a
mixture
of
1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide hydrochloride (EDC, 2.88 g,
15 mmol), 4-dimethylaminopyridine (DMAP, 0.183 g, 1.5 mmol)
and the corresponding secondary amine (7.5 mmol) in DCM (20
mL) was added ethyl hydrogen malonate (1.3 mL, 11 mmol). The
reaction mixture was stirred sufficiently at ambient temperature
until amines were disappeared. Then the reaction mixture was
diluted with DCM and washed with brine (2×10 mL). The
organic layer was dried over anhydrous Na2SO4, filtered, and
concentrated. The residue was purified by silica gel
chromatography (petroleum ether/EtOAc, v/v 10:1) to afford pure
amide 1.
4.2.5. Ethyl 3-(benzyl(propyl)amino)-3-oxopropanoate (1e)
1
Yellow oil. 79% yield. H NMR (400 MHz, CDCl3) Major
isomer (56%): δ 7.48 – 7.09 (m, 5H, ArH), 4.64 (s, 2H, CH2),
4.23 (q, J = 7.2 Hz, 2H, CH2), 3.53 (s, 2H, CH2), 3.14 (t, J = 7.6
Hz, 2H, CH2), 1.67 – 1.52 (m, 2H, CH2), 1.30 (t, J = 6.0 Hz, 3H,
CH3), 0.89 (t, J = 7.3 Hz, 3H, CH3). Minor isomer (44%): δ 7.48
– 7.09 (m, 5H, ArH), 4.54 (s, 2H, CH2), 4.17 (q, J = 7.2 Hz, 2H,
CH2), 3.43 (s, 2H, CH2), 3.36 (t, J = 7.6 Hz, 2H, CH2), 1.67 –
1.52 (m, 2H, CH2), 1.26 (t, J = 5.9 Hz, 3H, CH3), 0.88 (t, J = 7.4
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 167.7, 167.6,
166.4, 166.1, 137.1, 136.3, 128.9, 128.5, 127.8, 127.6, 127.2,
126.2, 61.4, 61.3, 51.6, 49.2, 48.1, 47.9, 41.5, 41.1, 21.5, 20.5,
14.04, 14.01, 11.2, 11.1. IR (DCM) ν (cm-1): 1736 (C=O), 1655
4.2.1. Ethyl 3-(dibenzylamino)-3-oxopropanoate (1a)
1
Yellow oil. 47% yield. H NMR (400 MHz, CDCl3) δ 7.44 –
7.05 (m, 10H, ArH), 4.63 (s, 2H, CH2), 4.44 (s, 2H, CH2), 4.20
(q, J = 7.1 Hz, 2H, CH2), 3.54 (s, 2H, CH2), 1.27 (t, J = 7.1 Hz,
3H, CH3). 13C NMR (101 MHz, CDCl3) δ 167.5, 166.7, 136.6,
135.7, 128.9, 128.5, 128.1, 127.8, 127.4, 126.3, 61.5, 50.5, 48.2,
41.3, 14.0. IR (DCM) ν (cm-1): 1738 (C=O), 1652 (C=O). HRMS
(C=O). HRMS (ESI) calcd. for C15H22NO3 [M+H]+ m/z
+
+
(ESI) calcd. for C19H22NO3 [M+H]+ m/z 312.1594, found
264.1594, found 264.1597.
312.1592.
4.2.6. Ethyl 3-(benzyl(isopropyl)amino)-3-oxopropanoate (1f)
4.2.2. Ethyl 3-(benzyl(4-methylbenzyl)amino)-3-oxopropanoate
(1b)
1
Colorless oil. 53% yield. H NMR (400 MHz, CDCl3) Major
isomer (55%): δ 7.41 – 7.14 (m, 5H, ArH), 4.86 (hept, J = 6.8
Hz, 1H, CH), 4.48 (s, 2H, CH2), 4.17 (q, J = 7.2 Hz, 2H, CH2),
3.30 (s, 2H, CH2), 1.26 (t, J = 7.2 Hz, 3H, CH3), 1.14 (t, J = 7.3
Hz, 6H, 2CH3). Minor isomer (45%): δ 7.41 – 7.14 (m, 5H, ArH),
4.57 (s, 2H, CH2), 4.24 (q, J = 7.2 Hz, 2H, CH2), 4.07 (hept, J =
6.7 Hz, 1H, CH), 3.60 (s, 2H, CH2), 1.32 (t, J = 7.2 Hz, 3H,
CH3), 1.14 (t, J = 7.3 Hz, 6H, 2CH3). 13C NMR (101 MHz,
CDCl3) δ 167.8, 167.7, 167.0, 166.0, 138.9, 137.8, 128.8, 128.2,
127.3, 126.7, 126.5, 125.7, 61.4, 61.2, 49.9, 46.4, 46.1, 43.8,
42.0, 41.8, 21.3, 20.0, 14.04, 13.97. IR (DCM) ν (cm-1): 1738
(C=O), 1645 (C=O). HRMS (ESI) calcd. for C15H22NO3+ [M+H]+
m/z 264.1594, found 264.1592.
1
Yellow oil. 83% yield. Major isomer (52%): H NMR (400
MHz, CDCl3) δ 7.37 – 7.23 (m, 4H, ArH), 7.18 – 7.09 (m, 4H,
ArH), 7.02 (d, J = 7.8 Hz, 1H, ArH), 4.60 (s, 2H, CH2), 4.37 (s,
2H, CH2), 4.18 (q, J = 7.1 Hz, 2H, CH2), 3.52 (s, 2H, CH2), 2.31
(s, 3H, CH3), 1.25 (t, J = 7.2 Hz, 3H, CH3). Major isomer (48%):
1H NMR (400 MHz, CDCl3) δ 7.37 – 7.23 (m, 4H, ArH), 7.18 –
7.09 (m, 4H, ArH), 7.02 (d, J = 7.8 Hz, 1H, ArH), 4.57 (s, 2H,
CH2), 4.40 (s, 2H, CH2), 4.18 (q, J = 7.2 Hz, 2H, CH2), 3.50 (s,
2H, CH2), 2.33 (s, 3H, CH3), 1.26 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 167.5, 167.4, 166.62, 166.59, 137.4,
137.0, 136.7, 135.8, 133.5, 132.6, 129.6, 129.1, 128.9, 128.5,
128.1, 128.0, 127.7, 127.3, 126.3, 61.4, 50.23, 50.18, 48.0, 47.8,
41.3, 21.0, 20.9, 14.0. IR (DCM) ν (cm-1): 1738 (C=O), 1651
4.2.7. Ethyl 3-(benzyl(tert-butyl)amino)-3-oxopropanoate (1g).12
(C=O). HRMS (ESI) calcd. for C20H24NO3 [M+H]+ m/z
+
1
Colorless oil. 76% yield. H NMR (400 MHz, CDCl3) δ 7.37
326.1751, found 326.1741.
(t, J = 7.5 Hz, 2H, ArH), 7.31 – 7.18 (m, 3H, ArH), 4.59 (s, 2H,
CH2), 4.18 (q, J = 7.1 Hz, 2H, CH2), 3.37 (s, 2H, CH2), 1.45 (s,
9H, 3CH3), 1.27 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 168.1, 167.7, 138.6, 128.9, 127.2, 125.5, 61.2, 58.4,
49.2, 43.9, 28.6, 14.1.
4.2.3. Ethyl 3-(benzyl(4-chlorobenzyl)amino)-3-oxopropanoate
(1c)
1
Colorless oil. 99% yield. H NMR (400 MHz, CDCl3) Major
isomer (65%): δ 7.38 – 7.25 (m, 5H, ArH), 7.22 – 7.11 (m, 3H,
ArH), 7.07 (d, J = 8.0 Hz, 1H, ArH), 4.55 (s, 2H, CH2), 4.41 (s,
2H, CH2), 4.18 (q, J = 7.1 Hz, 2H, CH2), 3.52 (s, 2H, CH2), 1.26
(t, J = 7.1 Hz, 3H, CH3). Minor isomer (35%): δ 7.38 – 7.25 (m,
5H, ArH), 7.22 – 7.11 (m, 3H, ArH), 7.07 (d, J = 8.0 Hz, 1H,
ArH), 4.58 (s, 2H, CH2), 4.38 (s, 2H, CH2), 4.18 (q, J = 7.1 Hz,
2H, CH2), 3.50 (s, 2H, CH2), 1.26 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 167.4, 167.3, 166.8, 166.6, 139.6,
136.6, 136.3, 135.4, 135.1, 134.2, 133.6, 133.2, 129.4, 129.1,
129.0, 128.9, 128.63, 128.55, 128.5, 128.4, 128.1, 128.0, 127.9,
127.8, 127.7, 127.5, 127.4, 126.3, 64.1, 61.5, 61.4, 50.6, 50.4,
49.9, 48.2, 48.1, 47.6, 41.22, 41.16, 14.0. IR (DCM) ν (cm-1):
4.2.8.
oxopropanoate (1h).
Ethyl
3-(tert-butyl(4-fluorobenzyl)amino)-3-
o
1
White solid, m.p. 78–81 C. 46% yield. H NMR (400 MHz,
CDCl3) δ 7.41 – 7.17 (m, 2H, ArH), 7.16 – 6.94 (m, 2H, ArH),
4.59 (s, 2H, CH2), 4.18 (q, J = 7.2 Hz, 2H, CH2), 3.37 (s, 2H,
CH2), 1.45 (s, 9H, 3CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 167.8, 167.4, 161.7 (d, J = 245.6 Hz),
134.2 (d, J = 3.1 Hz), 126.9 (d, J = 8.0 Hz), 115.6 (d, J = 21.6
Hz), 61.1, 58.2, 48.4, 43.7, 28.4, 13.9. IR (DCM) ν (cm-1): 1742
+
(C=O), 1658 (C=O). HRMS (ESI) calcd. for C16H23FNO3
[M+H]+ m/z 296.1656, found 296.1664.
+
1738 (C=O), 1651 (C=O). HRMS (ESI) calcd. for C19H21ClNO3
[M+H]+ m/z 346.1204, found 346.1207.

6
Tetrahedron
ACCEPTED MANUSCRIPT
+
4.2.9.
Ethyl
3-(tert-butyl(4-chlorobenzyl)amino)-3-
(C=O), 1660 (C=O). HRMS (ESI) calcd. for C16H23ClNO3
oxopropanoate (1i)
[M+H]+ m/z 312.1361, found 312.1362.
o
1
White solid, m.p. 73–76 C. 56% yield. H NMR (400 MHz,
CDCl3) δ 7.35 (d, J = 8.2 Hz, 2H, ArH), 7.18 (d, J = 8.1 Hz, 2H,
ArH), 4.56 (s, 2H, CH2), 4.18 (q, J = 7.1 Hz, 2H, CH2), 3.34 (s,
2H, CH2), 1.44 (s, 9H, 3CH3), 1.27 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 167.9, 167.6, 137.2, 133.0, 129.1,
126.9, 61.3, 58.4, 48.6, 43.9, 28.6, 14.1. IR (DCM): ν (cm-1):
4.2.15. Ethyl 3-(tert-butyl(3,5-dimethylbenzyl)amino)-3-
oxopropanoate (1o)
Colorless oil. 64% yield. 1H NMR (400 MHz, CDCl3) δ 7.02 –
6.68 (m, 4H, ArH), 4.51 (s, 2H, CH2), 4.18 (q, J = 7.1 Hz, 2H,
CH2), 3.37 (s, 2H, CH2), 2.31 (s, 6H, 2CH3), 1.45 (s, 9H, 3CH3),
1.27 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ
168.2, 167.7, 138.6, 138.5, 128.8, 128.5, 126.2, 123.2, 61.2, 58.3,
49.1, 44.0, 28.9, 28.6, 21.3, 14.1. IR (DCM) ν (cm-1): 1742
(C=O), 1654 (C=O). HRMS (ESI) calcd. for C18H28NO3+ [M+H]+
m/z 306.2064, found 306.2059.
+
1735 (C=O), 1648 (C=O). HRMS (ESI) calcd. for C16H23ClNO3
[M+H]+ m/z 312.1361, found 312.1358.
4.2.10.
oxopropanoate (1j)
Ethyl
3-((4-bromobenzyl)(tert-butyl)amino)-3-
1
White solid, m.p. 79−80 °C. 71% yield. H NMR (400 MHz,
CDCl3) δ 7.50 (d, J = 8.5 Hz, 2H, ArH), 7.12 (d, J = 8.5 Hz, 2H,
ArH), 4.54 (s, 2H, CH2), 4.18 (q, J = 7.1 Hz, 2H, CH2), 3.34 (s,
2H, CH2), 1.44 (s, 9H, 3CH3), 1.27 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 168.0, 167.6, 137.8, 132.1, 127.3,
121.1, 61.4, 58.5, 48.7, 43.9, 28.6, 14.1. IR (DCM) ν (cm-1): 1741
4.2.16.
oxopropanoate (1p)
Ethyl
3-(tert-butyl(2,4-dimethoxybenzyl)amino)-3-
1
White solid, m.p. 93–96 °C. 20% yield. H NMR (400 MHz,
CDCl3) δ 7.12 (d, J = 8.4 Hz, 1H, ArH), 6.50 (dd, J = 8.4, 2.3 Hz,
1H, ArH), 6.45 (d, J = 2.3 Hz, 1H, ArH), 4.44 (s, 2H, CH2), 4.18
(q, J = 7.2 Hz, 2H, CH2), 3.81 (s, 6H, 2CH3), 3.33 (s, 2H, CH2),
1.44 (s, 9H, 3CH3), 1.26 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101
MHz, CDCl3) δ 168.3, 168.0, 160.1, 156.9, 126.9, 119.0, 103.9,
98.5, 61.1, 58.1, 55.4, 55.2, 44.2, 43.8, 28.4, 14.1. IR (DCM) ν
(cm-1): 1740 (C=O), 1654 (C=O). HRMS (ESI) calcd. for
C18H28NO5+ [M+H]+ m/z 338.1962, found 338.1963.
+
(C=O), 1655 (C=O). HRMS (ESI) calcd. for C16H23BrNO3
[M+H]+ m/z 356.0856, found 356.0858.
4.2.11.
Ethyl
3-(tert-butyl(4-methylbenzyl)amino)-3-
oxopropanoate (1k)
Yellow oil. 63% yield. 1H NMR (400 MHz, CDCl3) δ 7.18 (d,
J = 8.0 Hz, 2H, ArH), 7.11 (d, J = 8.0 Hz, 2H, ArH), 4.55 (s, 2H,
CH2), 4.17 (q, J = 7.2 Hz, 2H, CH2), 3.37 (s, 2H, CH2), 2.35 (s,
3H, CH3), 1.45 (s, 9H, 3CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 168.2, 167.7, 136.9, 135.6, 129.6,
125.4, 61.2, 58.3, 49.0, 44.0, 29.1, 28.6, 21.0, 14.1. IR (DCM) ν
(cm-1): 1742 (C=O), 1652 (C=O). HRMS (ESI) calcd. for
C17H26NO3+ [M+H]+ m/z 292.1907, found 292.1910.
4.3. General Procedure for the synthesis of ethyl 3-
(benzylamino)-2-diazo-3-oxopropanoates 2
To a solution of 1 (5 mmol) in dry DCM (20 mL) was added
p-ABSA (1.32 g, 5.5 mmol) and DBU (5.5 mmol, 0.82 mL) at 0
oC. The resulting mixture was stirred for 18 hours at room
temperature. Filtrated to remove the solid. The solvent was
removed under reduced pressure and the residue was purified by
silica gel column chromatography to afford the pure product 2.
4.2.12.
Ethyl
3-(tert-butyl(4-methoxybenzyl)amino)-3-
oxopropanoate (1l)13
4.3.1. Ethyl 2-diazo-3-(dibenzylamino)-3-oxopropanoate (2a).7d
Colorless oil. 39% yield. 1H NMR (400 MHz, CDCl3) δ 7.14
(d, J = 8.7 Hz, 2H, ArH), 6.97 – 6.78 (m, 2H, ArH), 4.53 (s, 2H,
CH2), 4.18 (q, J = 7.1 Hz, 2H, CH2), 3.81 (s, 3H, CH3), 3.38 (s,
1
Yellow oil. 76% yield. H NMR (400 MHz, CDCl3) δ 7.38–
7.12 (m, 10H, ArH), 4.51 (s, 4H, 2CH2), 4.25 (q, J = 7.2 Hz, 2H,
CH2), 1.28 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3)
δ 162.4, 162.3, 136.2, 128.6, 127.7, 127.5, 66.8, 61.4, 50.3, 14.3.
2H, CH2), 1.44 (s, 9H, 3CH3), 1.27 (t, J = 7.1 Hz, 3H, CH3). 13
NMR (101 MHz, CDCl3) δ 168.2, 167.7, 158.8, 130.5, 126.6,
C
114.3, 61.2, 58.3, 55.3, 48.6, 43.9, 28.6, 14.1. IR (DCM) ν (cm-1):
4.3.2.
oxopropanoate (2b)
Ethyl
3-(benzyl(4-methylbenzyl)amino)-2-diazo-3-
+
1742 (C=O), 1659 (C=O). HRMS (ESI) calcd. for C17H26NO4
[M+H]+ m/z 308.1856, found 308.1859.
1
Yellow oil. 95% yield. H NMR (400 MHz, CDCl3) δ 7.34 –
7.24 (m, 3H, ArH), 7.18 – 7.11 (m, 4H, ArH), 7.04 (d, J = 8.0
Hz, 2H, ArH), 4.49 (s, 2H, CH2), 4.45 (s, 2H, CH2), 4.24 (q, J =
7.1 Hz, 2H, CH2), 2.33 (s, 3H, CH3), 1.27 (t, J = 7.1 Hz, 3H,
CH3). 13C NMR (101 MHz, CDCl3) δ 162.4, 162.2, 137.2, 136.3,
133.1, 129.3, 128.6, 127.8, 127.7, 127.5, 66.8, 61.4, 50.1, 21.1,
14.3. IR (DCM) ν (cm-1): 2127 (C=N=N), 1709 (C=O), 1626
4.2.13.
oxopropanoate (1m)
Ethyl
3-(tert-butyl(3-chlorobenzyl)amino)-3-
Colorless oil. 65% yield. 1H NMR (400 MHz, CDCl3) δ 7.40 –
7.18 (m, 3H, ArH), 7.13 (d, J = 7.4 Hz, 1H, ArH), 4.58 (s, 2H,
CH2), 4.17 (q, J = 7.1 Hz, 2H, CH2), 3.34 (s, 2H, CH2), 1.44 (s,
9H, 3CH3), 1.26 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 167.8, 167.5, 140.9, 134.8, 130.1, 127.4, 125.6, 123.5,
61.2, 58.3, 48.6, 43.8, 28.5, 13.9. IR (DCM) ν (cm-1): 1736
+
(C=O). HRMS (ESI) calcd. for C20H22N3O3 [M+H]+ m/z
352.1656, found 352.1647.
+
(C=O), 1655 (C=O). HRMS (ESI) calcd. for C16H23ClNO3
[M+H]+ m/z 312.1361, found 312.1362.
4.3.3.
Ethyl
3-(benzyl(4-chlorobenzyl)amino)-2-diazo-3-
oxopropanoate (2c)
4.2.14.
Ethyl
3-(tert-butyl(2-chlorobenzyl)amino)-3-
1
Yellow oil. 93% yield. H NMR (400 MHz, CDCl3) δ 7.35 –
7.28 (m, 5H, ArH), 7.18 – 7.10 (m, 4H, ArH), 4.48 (s, 2H, CH2),
4.46 (s, 2H, CH2), 4.26 (q, J = 7.1 Hz, 2H, CH2), 1.28 (t, J = 7.2
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 162.5, 162.3,
136.0, 134.8, 133.4, 129.2, 128.8, 128.7, 127.8, 127.7, 67.0, 61.6,
50.7, 49.7, 14.4. IR (DCM) ν (cm-1): 2130 (C=N=N), 1709
oxopropanoate (1n)
Colorless oil. 76% yield. 1H NMR (400 MHz, CDCl3) δ 7.51 –
7.30 (m, 3H, ArH), 7.28 – 7.07 (m, 1H, ArH), 4.61 (s, 2H, CH2),
4.18 (q, J = 7.1 Hz, 2H, CH2), 3.30 (s, 2H, CH2), 1.46 (s, 9H,
3CH3), 1.27 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ = 167.9, 167.9, 135.9, 131.8, 129.7, 128.5, 127.3,
127.0, 61.3, 58.4, 47.2, 43.8, 28.4, 14.1. IR (DCM) ν (cm-1): 1742
+
(C=O), 1626 (C=O). HRMS (ESI) calcd. for C19H19ClN3O3
[M+H]+ m/z 372.1109, found 372.1114.

7
4.3.4. Ethyl 3-(benzyl(methyl)amino)-2-diazo-3-oxopropanoate
(2d)
Hz, 2H, ArH), 4.56 (s, 2H, CH2), 4.23 (q, J = 7.1 Hz, 2H, CH2),
ACCEPTED MANUSCRIPT
1.37 (s, 9H, 3CH3), 1.28 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101
MHz, CDCl3) δ 163.4, 162.4, 138.8, 131.7, 128.5, 121.1, 61.3,
59.0, 51.0, 28.8, 14.4. IR (DCM) ν (cm-1): 2124 (C=N=N), 1707
1
Yellow oil. 93% yield. H NMR (400 MHz, CDCl3) δ 7.49 –
7.13 (m, 5H, ArH), 4.60 (s, 2H, CH2), 4.26 (q, J = 7.1 Hz, 2H,
CH2), 2.91 (s, 3H, CH3), 1.29 (t, J = 7.1 Hz, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 162.3, 162.1, 136.4, 128.6, 127.8, 127.5,
66.5, 61.4, 52.9, 36.0, 14.4. IR (DCM) ν (cm-1): 2125 (C=N=N),
+
(C=O), 1654 (C=O). HRMS (ESI) calcd. for C16H21BrN3O3
[M+H]+ m/z 382.0761, found 382.0764.
4.3.11. Ethyl 3-[tert-butyl(4-methylbenzyl)amino]-2-diazo-3-
+
1709 (C=O), 1626 (C=O). HRMS (ESI) calcd. for C13H16N3O3
oxopropanoate (2k)
[M+H]+ m/z 262.1186, found 262.1182.
o
1
Yellow crystals, m.p. 73–76 C. 76% yield. H NMR (400
MHz, CDCl3) δ 7.13 (d, J = 8.0 Hz, 2H, ArH), 7.08 (d, J = 8.0
Hz, 2H, ArH), 4.58 (s, 2H, CH2), 4.23 (q, J = 7.2 Hz, 2H, CH2),
2.33 (s, 3H, CH3), 1.38 (s, 9H, 3CH3), 1.28 (d, J = 7.2 Hz, 3H,
CH3). 13C NMR (101 MHz, CDCl3) δ 163.2, 162.6, 137.0, 136.5,
129.3, 126.7, 61.2, 58.8, 51.3, 28.8, 21.0, 14.4. IR (DCM) ν (cm-
1): 2123 (C=N=N), 1709 (C=O), 1629 (C=O). HRMS (ESI)
calcd. for C17H24N3O3+ [M+H]+ m/z 318.1812, found 318.1811.
4.3.5. Ethyl 3-(benzyl(propyl)amino)-2-diazo-3-oxopropanoate
(2e)
1
Yellow oil. 84% yield. H NMR (400 MHz, CDCl3) δ 7.74 –
7.05 (m, 5H, ArH), 4.61 (s, 2H, CH2), 4.26 (q, J = 7.1 Hz, 2H,
CH2), 3.25 (t, J = 7.4 Hz, 2H, CH2), 1.63 – 1.54 (m, 2H, CH2),
1.29 (t, J = 7.1 Hz, 3H, CH3), 0.86 (t, J = 7.4 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 162.5, 161.9, 136.7, 128.6, 127.49,
127.47, 66.4, 61.4, 50.7, 48.9, 20.7, 14.4, 11.1. IR (DCM) ν (cm-
1): 2124 (C=N=N), 1708 (C=O), 1625 (C=O). HRMS (ESI)
calcd. for C15H20N3O3+ [M+H]+ m/z 290.1499, found 290.1502.
4.3.12. Ethyl 3-[tert-butyl(4-methoxybenzyl)amino]-2-diazo-3-
oxopropanoate (2l).13
1
Yellow oil. 95% yield. H NMR (400 MHz, CDCl3) δ 7.11 (d,
4.3.6.
oxopropanoate (2f)
Ethyl
3-(benzyl(isopropyl)amino)-2-diazo-3-
J = 8.7 Hz, 2H, ArH), 6.95 – 6.76 (m, 2H, ArH), 4.55 (s, 2H,
CH2), 4.23 (q, J = 7.1 Hz, 2H, CH2), 3.80 (s, 3H, CH3), 1.37 (s,
9H, 3CH3), 1.29 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 163.2, 162.6, 158.8, 131.4, 128.0, 114.0, 68.1, 61.2,
58.8, 55.3, 51.1, 28.7, 14.4.
1
Yellow oil. 98% yield. H NMR (400 MHz, CDCl3) δ 7.40 –
6.83 (m, 5H, ArH), 4.54 (s, 2H, CH2), 4.36 – 4.07 (m, 3H, CH &
CH2), 1.30 (t, J = 7.1 Hz, 3H, CH3), 1.23 (d, J = 6.7 Hz, 6H,
2CH3). 13C NMR (101 MHz, CDCl3) δ 162.6, 161.7, 138.3,
128.4, 126.9, 126.7, 66.8, 61.3, 50.9, 45.9, 21.0, 14.4. IR (DCM)
ν (cm-1): 2121 (C=N=N), 1707 (C=O), 1623 (C=O). HRMS
4.3.13. Ethyl 3-(tert-butyl(3-chlorobenzyl)amino)-2-diazo-3-
oxopropanoate (2m)
o
1
Yellow crystals, m.p. 63–67 C. 73% yield. H NMR (400
MHz, CDCl3) δ 7.31 – 7.22 (m, 2H, ArH), 7.19 (s, 1H, ArH),
7.10 (d, J = 7.1 Hz, 1H, ArH), 4.59 (s, 2H, CH2), 4.23 (q, J = 7.2
Hz, 2H, CH2), 1.39 (s, 9H, 3CH3), 1.29 (t, J = 7.2 Hz, 3H, CH3).
13C NMR (101 MHz, CDCl3) δ 163.3, 162.4, 141.8, 134.6, 129.9,
127.5, 126.9, 124.9, 61.3, 59.1, 51.1, 28.8, 14.4. IR (DCM) ν
(cm-1): 2125 (C=N=N), 1708 (C=O), 1630 (C=O). HRMS (ESI)
calcd. for C16H21ClN3O3+ [M+H]+ m/z 338.1266, found 338.1258.
(ESI) calcd. for C15H20N3O3 [M+H]+ m/z 290.1499, found
+
290.1498.
4.3.7.
Ethyl
3-(benzyl(tert-butyl)amino)-2-diazo-3-
oxopropanoate (2g).12,13
1
Yellow crystals, m.p. 95–96 °C. 72% yield. H NMR (400
MHz, CDCl3) δ 7.40 – 7.14 (m, 5H, ArH), 4.62 (s, 2H, CH2),
4.23 (q, J = 7.2 Hz, 2H, CH2), 1.39 (s, 9H, 3CH3), 1.28 (t, J = 7.2
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 163.3, 162.6,
139.6, 128.7, 127.3, 126.8, 61.3, 58.9, 51.6, 28.8, 14.4.
4.3.14. Ethyl 3-[tert-butyl(2-chlorobenzyl)amino]-2-diazo-3-
oxopropanoate (2n)
1
4.3.8.
Ethyl
3-(tert-butyl(4-fluorobenzyl)amino)-2-diazo-3-
Yellow oil. 66% yield. H NMR (400 MHz, CDCl3) δ 7.38 –
oxopropanoate (2h)
7.17 (m, 4H, ArH), 4.75 (s, 2H, CH2), 4.23 (q, J = 7.2 Hz, 2H,
CH2), 1.41 (s, 9H, 3CH3), 1.28 (t, J = 7.0 Hz, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 163.6, 162.6, 136.8, 132.2, 129.9, 128.6,
128.4, 126.8, 61.3, 59.1, 49.0, 28.7, 14.4. IR (DCM) ν (cm-1):
2124 (C=N=N), 1708 (C=O), 1631 (C=O). HRMS (ESI) calcd.
for C16H21ClN3O3+ [M+H]+ m/z 338.1266, found 338.1267.
o
1
Yellow crystals, m.p. 90–93 C. 90% yield. H NMR (400
MHz, CDCl3) δ 7.17 (dd, J = 8.4, 5.3 Hz, 2H, ArH), 7.02 (t, J =
8.6 Hz, 2H, ArH), 4.58 (s, 2H, CH2), 4.24 (q, J = 7.1 Hz, 2H,
CH2), 1.38 (s, 9H, 3CH3), 1.29 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 163.3, 162.4, 162.0 (d, J = 246.0 Hz),
135.3 (d, J = 3.2 Hz), 128.4 (d, J = 8.0 Hz), 115.5 (d, J = 21.5
Hz), 61.3, 58.9, 50.9, 28.8, 14.4. IR (DCM) ν (cm-1): 2125
(C=N=N), 1707 (C=O), 1654 (C=O). HRMS (ESI) calcd. for
C16H21FN3O3+ [M+H]+ m/z 322.1567, found 322.1571.
4.3.15. Ethyl 3-(tert-butyl(3,5-dimethylbenzyl)amino)-2-diazo-3-
oxopropanoate (2o)
o
1
Yellow crystals, m.p. 176–181 C. 78% yield. H NMR (400
MHz, CDCl3) δ 6.89 (s, 1H, ArH), 6.79 (s, 2H, ArH), 4.55 (s, 2H,
CH2), 4.23 (q, J = 7.1 Hz, 2H, CH2), 2.29 (s, 6H, 2CH3), 1.40 (s,
9H, 3CH3), 1.28 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 163.1, 162.6, 139.5, 138.2, 128.8, 124.4, 67.9, 61.2,
58.9, 51.5, 28.8, 21.3, 14.4. IR (DCM) ν (cm-1): 2122 (C=N=N),
4.3.9.
Ethyl 3-[tert-butyl(4-chlorobenzyl)amino]-2-diazo-3-
oxopropanoate (2i).13
o
1
Yellow crystals, m.p. 54–56 C. 99% yield. H NMR (400
MHz, CDCl3) δ 7.30 (d, J = 8.4 Hz, 2H, ArH), 7.14 (d, J = 8.4
Hz, 2H, ArH), 4.58 (s, 2H, CH2), 4.23 (q, J = 7.2 Hz, 2H, CH2),
1.38 (s, 9H, 3CH3), 1.29 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (101
MHz, CDCl3) δ 163.4, 162.4, 138.2, 133.1, 128.8, 128.2, 61.3,
59.0, 51.0, 28.8, 14.4.
+
1709 (C=O), 1630 (C=O). HRMS (ESI) calcd. for C18H26N3O3
[M+H]+ m/z 332.1969, found 332.1971.
4.3.16. Ethyl 3-(tert-butyl(2,4-dimethoxybenzyl)amino)-2-diazo-
3-oxopropanoate (2p)
o
4.3.10. Ethyl 3-[(4-bromobenzyl)(tert-butyl)amino]-2-diazo-3-
Yellow crystals, m.p. 54-58 C. 91% yield. 1H NMR (400
oxopropanoate (2j)
MHz, CDCl3) δ 7.09 – 7.03 (m, 1H, ArH), 6.47 – 6.41 (m, 2H,
ArH), 4.53 (s, 2H, CH2), 4.24 (q, J = 7.1 Hz, 2H, CH2), 3.80 (s,
3H, CH3), 3.77 (s, 3H, CH3), 1.33 (s, 9H, 3CH3), 1.29 (t, J = 7.1
o
1
Yellow crystals, m.p. 54–57 C. 94% yield. H NMR (400
MHz, CDCl3) δ 7.46 (d, J = 8.4 Hz, 2H, ArH), 7.08 (d, J = 8.4

8
Tetrahedron
ACCEPTED MANUSCRIPT
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 163.7, 162.9,
160.4, 158.9, 129.9, 119.3, 103.8, 98.6, 61.1, 58.1, 55.5, 55.3,
48.3, 28.4, 14.4. IR (DCM) ν (cm-1): 2120 (C=N=N), 1708
4.4.5. Ethyl trans-1-benzyl-4-(4-methylphenyl)azetidin-2-one-3-
carboxylate (4ba) and ethyl trans-1-(4-methylbenzyl)-4-
phenylazetidin-2-one-3-carboxylate (4bb)
+
(C=O), 1632 (C=O). HRMS (ESI) calcd. for C18H26N3O5
4ba and 4bb cannot be separated due to similar polarity and
property. Yellow oil. H NMR (400 MHz, CDCl3) δ 7.38 – 7.28
[M+H]+ m/z 364.1867, found 364.1880.
1
4.4. General Procedure for the reaction of ethyl 3-
(m, 6H, ArH), 7.19 – 7.04 (m, 12H, ArH), 4.86 (d, J = 15.2 Hz,
1H in CH2), 4.84 (d, J = 15.2 Hz, 1H in CH2),4.68 (d, J = 2.3 Hz,
1H, CH), 4.66 (d, J = 2.3 Hz, 1H, CH), 4.23 (m, 4H, 2CH2), 3.91
– 3.87 (m, 2H, 1H in CH2 & 1H in CH2), 3.79 (d, J = 15.2 Hz, 1H
in CH2), 3.76 (d, J = 15.1 Hz, 1H in CH2), 2.36 (s, 3H, CH3), 2.33
(s, 3H, CH3), 1.29 (t, J = 7.1 Hz, 6H, 2CH3). 13C NMR (101
MHz, CDCl3) δ 166.9, 166.8, 162.5, 162.3, 139.0, 137.5, 136.1,
134.8, 132.9, 131.6, 129.8, 129.4, 129.1, 129.0, 128.8, 128.24,
128.21, 127.8, 126.8, 126.7, 63.5, 63.4, 61.77, 61.76, 56.9, 44.7,
44.5, 21.2, 21.1, 14.1. IR (DCM) ν (cm-1): 1764 (C=O), 1732
alkyl(arylmethyl)amino-2-diazo-3-oxopropanoates
the catalysis of CuCl2·2H2O
2 under
A two-necked flask charged with 5 mol% CuCl2·2H2O (3.4 mg,
0.02 mmol) was added dry toluene (5 mL) under N2 atmosphere
and then the solution was heated to reflux. A solution of
diazoamidoacetate 2 (0.4 mmol) in 5 mL of dry toluene was
added. Upon addition, the solution was refluxed for another 4
hours. Then the internal standard 4-iodonitrobenzene was added.
The solvent was removed under reduced pressure and the residue
was purified by preparative TLC to afford the products 3 and 4.
+
(C=O). HRMS (ESI) calcd. for C20H22NO3 [M+H]+ m/z
324.1594, found 324.1595.
4.4.1.
Ethyl
2-benzyl-3-oxo-1,2,3,3a-
4.4.6.
Ethyl
2-benzyl-6-chloro-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3a).7d
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3ca)
Colorless crystals, m.p. 97–100 °C. 1H NMR (400 MHz,
CDCl3) δ 7.34 – 6.22 (m, 5H, ArH), 6.54 – 6.32 (m, 3H, 3CH),
6.23 (d, J = 5.2 Hz, 1H, CH), 5.65 (d, J = 9.4 Hz, 1H, CH), 4.79
(d, J = 14.9 Hz, 1H in CH2), 4.44 (d, J = 14.8 Hz, 1H in CH2),
4.27 (d, J = 15.0 Hz, 1H in CH2), 4.15 – 4.00 (m, 2H, CH2), 4.00
(d, J = 15.0 Hz, 1H in CH2), 1.15 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 171.0, 167.7, 135.5, 130.4, 129.8,
128.7, 128.3, 128.1, 127.9, 127.8, 122.4, 120.5, 61.7, 59.9, 50.2,
46.7, 14.0.
o
1
White solid, m.p. 149-151 C. H NMR (400 MHz, CDCl3) δ
7.37 – 7.23 (m, 5H, ArH), 6.61 (d, J = 6.9 Hz, 1H, CH), 6.44 (dd,
J = 10.3, 1.5 Hz, 1H, CH), 6.13 (ddd, J = 6.8, 2.0, 2.0 Hz, 1H,
CH), 5.68 (d, J = 10.3 Hz, 1H, CH), 4.78 (d, J = 14.9 Hz, 1H in
CH2), 4.43 (d, J = 14.8 Hz, 1H in CH2), 4.25 (d, J = 15.1 Hz, 1H
in CH2), 4.18 (dq, J = 10.7, 7.1 Hz, 1H in CH2), 4.05 (dq, J =
10.7, 7.1 Hz, 1H in CH2), 3.97 (d, J = 15.1 Hz, 1H in CH2), 1.18
(t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 170.3,
167.4, 135.3, 135.2, 131.0, 129.9, 128.8, 128.0, 127.9, 126.9,
123.8, 119.0, 62.2, 59.7, 50.1, 46.8, 13.9. IR (DCM) ν (cm-1):
4.4.2. Ethyl trans-1-benzyl-4-phenylazetidin-2-one-3-carboxylate
+
(4a).7d,14
1743 (C=O), 1693 (C=O). HRMS (ESI) calcd. for C19H19ClNO3
[M+H]+ m/z 344.1048, found 344.1050.
1
Colorless oil. H NMR (400 MHz, CDCl3) δ 7.37 – 7.18 (m,
4.4.7.
Ethyl
2-(4-chlorobenzyl)-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3cb)
10H, ArH), 4.87 (d, J = 15.2 Hz, 1H in CH2), 4.70 (s, 1H, CH),
4.24 (q, J = 7.2 Hz, 2H, CH2), 3.91 (s, 1H, CH), 3.83 (d, J = 15.3
Hz, 1H in CH2), 1.29 (t, J = 7.2 Hz, 3H, CH3). 13C NMR (101
MHz, CDCl3) δ 166.7, 162.4, 135.9, 134.6, 129.1, 129.0, 128.7,
128.2, 127.8, 126.7, 63.4, 61.8, 57.0, 44.8, 14.1.
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.4 Hz,
2H, ArH), 7.21 (d, J = 8.4 Hz, 2H, ArH), 6.53 – 6.40 (m, 3H,
3CH), 6.24 (d, J = 5.7 Hz, 1H, CH), 5.63 (d, J = 9.8 Hz, 1H,
CH), 4.77 (d, J = 15.0 Hz, 1H in CH2), 4.38 (d, J = 15.0 Hz, 1H
in CH2), 4.26 (dd, J = 14.9, 2.2 Hz, 1H in CH2), 4.14 – 3.92 (m,
3H, CH2 & 1H in CH2), 1.15 (t, J = 7.1 Hz, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 171.2, 167.7, 134.1, 133.7, 130.1, 130.0,
129.3, 129.0, 128.4, 128.2, 122.3, 120.7, 61.8, 59.8, 50.2, 46.1,
14.0. IR (DCM) ν (cm-1): 1747 (C=O), 1698 (C=O). HRMS (ESI)
calcd. for C19H19ClNO3+ [M+H]+ m/z 344.1048, found 344.1050.
4.4.3.
Ethyl
2-benzyl-6-methyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3ba)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.09 (m, 5H,
ArH), 6.21 (d, J = 6.2 Hz, 2H, 2CH), 5.65 – 5.59 (m, 2H, 2CH),
4.78 (d, J = 14.9 Hz, 1H in CH2), 4.73 (d, J = 14.7 Hz, 1H in
CH2), 4.24 (d, J = 14.9 Hz, 1H in CH2), 4.15 – 3.93 (m, 3H, CH2
& 1H in CH2), 2.02 (s, 3H, CH3), 1.14 (t, J = 7.1 Hz, 3H, CH3).
13C NMR (101 MHz, CDCl3) δ 171.1, 168.0, 139.1, 137.5, 135.5,
132.4, 131.3, 130.5, 129.8, 128.7, 128.3, 128.0, 127.9,125.3,
122.3, 120.4, 61.6, 59.9, 50.1, 46.6, 24.4, 13.9. IR (DCM) ν (cm-
1): ν = 1747 (C=O), 1698 (C=O). HRMS (ESI) calcd. for
C20H22NO3+ [M+H]+ m/z 324.1594, found 324.1599.
4.4.8. Ethyl trans-1-benzyl-4-(4-chlorophenyl)azetidin-2-one-3-
carboxylate (4ca) and ethyl trans-1-(4-chlorobenzyl)-4-
phenylazetidin-2-one-3-carboxylate (4cb)
4ca and 4cb cannot be separated from the copper-catalyzed
reaction mixture. They cannot be separated each other and were
obtained from the Rh2(OAc)4-catalyzed reaction for verifying
4.4.4.
Ethyl
2-(4-chlorobenzyl)-3-oxo-1,2,3,3a-
1
their structures. 63% yield. Yellow oil. Major (71%): H NMR
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3bb)
(400 MHz, CDCl3) δ 7.39 – 7.23 (m, 7H, ArH), 7.11 (d, J = 8.4
Hz, 2H, ArH), 4.80 (d, J = 15.3 Hz, 1H, 1H in CH2), 4.69 (d, J =
2.4 Hz, 2H, CH), 4.24 (qd, J = 7.1, 2.1 Hz, 1H, CH2), 3.92 (d, J =
2.3 Hz, 1H, CH), 3.82 (d, J = 15.4 Hz, 1H, 1H in CH2), 1.30 (t, J
= 7.1 Hz, 3H, CH3). Minor (29%): 1H NMR (400 MHz, CDCl3) δ
7.39 – 7.23 (m, 7H, ArH), 7.11 (d, J = 8.4 Hz, 2H, ArH), 4.78 (d,
J = 14.8 Hz, 1H, 1H in CH2), 4.69 (d, J = 2.4 Hz, 2H, CH), 4.24
(qd, J = 7.1, 2.1 Hz, 1H, CH2), 3.87 (d, J = 2.2 Hz, 1H, CH), 3.83
(d, J = 15.3 Hz, 1H, 1H in CH2), 1.30 (t, J = 7.1 Hz, 3H, CH3).
13C NMR (101 MHz, CDCl3) δ 166.7, 166.5, 162.3, 162.1, 135.7,
134.5, 133.7, 133.2, 129.8, 129.5, 129.3, 129.11, 129.09, 128.9,
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.09 (m, 4H,
ArH), 6.51 – 6.37 (m, 3H, 3CH), 6.28 (d, J = 10.1 Hz, 1H, CH),
6.10 (d, J = 6.5 Hz, 1H, CH), 4.42 (d, J = 9.4 Hz, 1H in CH2),
4.38 (d, J = 9.2 Hz, 1H in CH2), 4.24 (d, J = 14.9 Hz, 1H in
CH2),4.15 – 3.93 (m, 3H, CH2 and 1H in CH2), 2.33 (s, 3H, CH3),
1.14 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ
170.9, 168.0, 137.5, 135.5, 132.4, 129.8, 129.4, 128.2, 127.9,
127.7, 121.3, 120.2, 61.5, 59.4, 50.0, 46.4, 21.0, 13.9. IR (DCM)
ν (cm-1): ν = 1747 (C=O), 1698 (C=O). HRMS (ESI) calcd. for
C20H22NO3+ [M+H]+ m/z 324.1594, found 324.1599.

9
128.79, 128.76, 128.2, 127.91, 127.86, 126.7, 63.5, 63.4, 61.85,
61.82, 57.1, 56.3, 50.1, 46.8, 44.9, 44.1, 14.1, 13.9. IR (DCM) ν
(cm-1): 1765 (C=O), 1731 (C=O). HRMS (ESI) calcd. for
C19H19ClNO3+ [M+H]+ m/z 344.1048, found 344.1056.
2.4 Hz, 1H, CH), 3.63 (d, J = 2.1 Hz, 1H, CH), 1.78 – 1.69 (m,
ACCEPTED MANUSCRIPT
1H in CH2), 1.50 – 1.40 (m, 1H in CH2), 1.30 (t, J = 7.1 Hz, 3H,
CH3), 0.88 (t, J = 7.4 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3)
δ 167.5, 162.1, 135.2, 128.8, 128.0, 127.8, 61.6, 59.0, 56.3, 44.8,
24.9, 14.1, 9.2. IR (DCM) ν (cm-1): 1766 (C=O), 1737 (C=O).
HRMS (ESI) calcd. for C15H20NO3+ [M+H]+ m/z 262.1438, found
262.1434.
4.4.9.
Ethyl
2-methyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3d)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.49 – 6.39 (m, 3H,
3CH), 6.31 (s, 1H, CH), 5.60 (d, J = 9.7 Hz, 1H, CH), 4.40 (d, J
= 15.0 Hz, 1H in CH2), 4.12 (d, J = 14.9 Hz, 1H in CH2), 4.05 (q,
J = 7.1 Hz, 2H, CH2), 3.00 (s, 3H, CH3), 1.14 (t, J = 7.1 Hz, 3H,
CH3). 13C NMR (101 MHz, CDCl3) δ 171.7, 168.1, 130.7, 129.8,
128.5, 127.7, 122.7, 120.4, 61.8, 52.8, 30.0, 29.7, 14.0. IR
(DCM) ν (cm-1): 1708 (C=O), 1650 (C=O). HRMS (ESI) calcd.
for C13H16NO3+ [M+H]+ m/z 234.1125, found 234.1122.
4.4.15.
Ethyl
2-isopropyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3f)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.47 – 6.39 (m, 3H,
3CH), 6.32 (d, J = 3.8 Hz, 1H, CH), 5.60 (d, J = 10.3 Hz, 1H,
CH), 4.48 (hept, J = 6.8 Hz, 1H, CH), 4.34 (dd, J = 14.7, 2.4 Hz,
1H in CH2), 4.14 – 3.96 (m, 3H, 1H in CH2 & CH2), 1.23 (d, J =
6.8 Hz, 3H, CH3), 1.19 (d, J = 6.8 Hz, 3H, CH3), 1.14 (t, J = 7.1
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 170.2, 167.9,
131.1, 129.7, 128.3, 127.8, 122.6, 120.5, 61.6, 60.5, 45.7, 43.4,
19.7, 19.5, 14.0. IR (DCM) ν (cm-1): 1751 (C=O), 1698 (C=O).
HRMS (ESI) calcd. for C15H20NO3+ [M+H]+ m/z 262.1438, found
262.1441.
4.4.10.
Ethyl
trans-1-methyl-4-phenylazetidin-2-one-3-
carboxylate (4d).15
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.46 – 7.33 (m, 5H,
ArH), 4.82 (d, J = 2.2 Hz, 1H, CH), 4.27 (q, J = 7.2 Hz, 1H in
CH2), 4.26 (q, J = 7.2 Hz, 1H in CH2), 3.89 (d, J = 2.2 Hz, 1H,
CH), 3.45 (s, 3H, CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3).
4.4.16.
carboxylate (4f)
Ethyl
trans-1-isopropyl-4-phenylazetidin-2-one-3-
4.4.11. Ethyl 1-benzyl-2-oxoazetidine-3-carboxylate (5d)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.40 – 7.36 (m, 5H,
ArH), 4.84 (d, J = 2.3 Hz, 1H, CH), 4.30 – 4.17 (m, 2H, CH2),
3.80 (d, J = 2.3 Hz, 1H, CH), 3.77 (hept, J = 6.8 Hz, 1H, CH),
1.30 (t, J = 7.1 Hz, 3H, CH3), 1.30 (d, J = 6.8 Hz, 3H, CH3), 1.04
(d, J = 6.7 Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 167.0,
162.1, 137.9, 128.4, 126.8, 126.6, 62.7, 61.7, 56.3, 45.7, 21.0,
20.3, 14.1. IR (DCM) ν (cm-1): 1763 (C=O), 1729 (C=O). HRMS
1
Colorless oil. H NMR (400 MHz, CDCl3) δ 7.42 – 7.29 (m,
5H, ArH), 4.49 (d, J = 15.2 Hz, 1H in CH2), 4.42 (d, J = 15.2 Hz,
1H in CH2), 4.27 (qd, J = 7.2, 1.7 Hz, 2H, CH2), 4.05 (dd, J =
5.3, 2.6 Hz, 1H, CH), 3.49 (dd, J = 5.7, 2.6 Hz, 1H in CH2), 3.29
(t, J = 5.5 Hz, 1H in CH2), 1.33 (t, J = 7.1 Hz, 3H, CH3). 13
C
NMR (101 MHz, CDCl3) δ 167.4, 162.3, 134.8, 128.9, 128.1,
127.9, 61.7, 54.1, 46.3, 41.7, 14.1. IR (DCM) ν (cm-1): 1762
(C=O), 1721 (C=O). HRMS (ESI) calcd. for C13H16NO3+ [M+H]+
m/z 234.1125, found 234.1129.
+
(ESI) calcd. for C15H20NO3 [M+H]+ m/z 262.1438, found
262.1434.
4.4.17.
Ethyl
2-tert-butyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3g)
4.4.12.
Ethyl
2-propyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3e)
o
1
White solid, m.p. 80–83 C. H NMR (400 MHz, CDCl3) δ
6.47 – 6.39 (m, 3H, 3CH), 6.26 (dd, J = 4.6, 2.4 Hz, 1H, CH),
5.60 – 5.58 (m, 1H, CH), 4.46 (dd, J = 14.9, 2.3 Hz, 1H in CH2),
4.24 (dd, J = 14.9, 1.6 Hz, 1H in CH2), 4.11 (dq, J = 10.7, 7.1 Hz,
1H in CH2), 4.00 (dq, J = 10.7, 7.1 Hz, 1H in CH2), 1.46 (s, 9H,
3CH3), 1.15 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 170.8, 168.1, 131.4, 129.6, 128.3, 127.7, 123.1, 120.1,
61.5, 61.2, 54.7, 49.5, 27.4, 14.0. IR (DCM) ν (cm-1): 1746
(C=O), 1722 (C=O). HRMS (ESI) calcd. for C16H22NO3+ [M+H]+
m/z 276.1594, found 276.1600.
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.49 – 6.40 (m, 3H,
3CH), 6.31 (d, J = 4.1 Hz, 1H, CH), 5.60 (d, J = 9.6 Hz, 1H,
CH), 4.41 (dd, J = 14.9, 2.3 Hz, 1H in CH2), 4.11 (dd, J = 14.9,
2.3 Hz, 1H in CH2), 4.10 – 4.00 (m, 2H, CH2), 3.52 (dt, J = 14.0,
7.1 Hz, 1H in CH2), 3.28 (dt, J = 14.0, 6.9 Hz, 1H in CH2), 1.68 –
1.58 (m, 2H, CH2), 1.14 (t, J = 7.1 Hz, 3H, CH3), 0.94 (t, J = 7.4
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 170.8, 167.9,
130.9, 129.8, 128.4, 127.8, 122.7, 120.4, 61.6, 60.0, 50.5, 44.3,
20.3, 14.0, 11.0. IR (DCM) ν (cm-1): 1746 (C=O), 1705 (C=O).
HRMS (ESI) calcd. for C15H20NO3+ [M+H]+ m/z 262.1438, found
262.1439.
4.4.18.
Ethyl
trans-1-(tert-butyl)-4-phenylazetidin-2-one-3-
carboxylate (4g).14,15
4.4.13.
carboxylate (4e)
Ethyl
trans-1-propyl-4-phenylazetidin-2-one-3-
Colorless crystals, m.p. 91–94 oC. 1H NMR (400 MHz,
CDCl3) δ 7.39 – 7.32 (m, 5H, ArH), 4.85 (d, J = 2.3 Hz, 1H, CH),
4.27 – 4.19 (m, 2H, CH2), 3.69 (d, J = 2.2 Hz, 1H, CH), 1.29 (t, J
= 7.6 Hz, 3H, CH3), 1.27 (s, 9H, 3CH3). 13C NMR (101 MHz,
CDCl3) δ 167.1, 162.1, 139.1, 128.9, 128.7, 126.6, 62.5, 61.6,
56.4, 55.1, 28.0, 14.1.
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.45 – 7.30 (m, 5H,
ArH), 4.84 (d, J = 2.1 Hz, 1H, CH), 4.25 (qd, J = 7.1, 2.5 Hz, 2H,
CH2), 3.84 (d, J = 2.0 Hz, 1H, CH), 3.44 (dt, J = 14.0, 7.3 Hz, 1H
in CH2), 2.84 (dt, J = 14.0, 6.7 Hz, 1H in CH2). 1.56 – 1.47 (m,
2H, CH2), 1.30 (t, J = 7.1 Hz, 3H, CH3), 0.92 (t, J = 7.4 Hz, 3H,
CH3). 13C NMR (101 MHz, CDCl3) δ 167.0, 162.5, 136.5, 129.1,
129.0, 126.7, 63.4, 61.8, 57.3, 42.7, 20.9, 14.1, 11.4. IR (DCM) ν
(cm-1): 1766 (C=O), 1731 (C=O). HRMS (ESI) calcd. for
C15H20NO3+ [M+H]+ m/z 262.1438, found 262.1438.
4.4.19.
Ethyl
2-tert-butyl-6-fluoro-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3h)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.39 (ddd, J = 10.9,
9.4, 1.8 Hz, 1H, CH), 6.17 – 6.14 (m, 2H, 2CH), 5.75 (dd, J =
10.6, 5.1 Hz, 1H, CH), 4.44 (d, J = 14.9 Hz, 1H in CH2), 4.19 (d,
J = 15.5 Hz, 1H in CH2), 4.17 – 4.10 (m, 1H in CH2), 4.03 (dq, J
= 10.7, 7.1 Hz, 1H in CH2), 1.46 (s, 9H, 3CH3), 1.17 (t, J = 7.1
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 170.1, 167.8, 161.2
(d, J = 245.2 Hz), 128.2 (d, J = 3.7 Hz), 125.6 (d, J = 13.7 Hz),
122.7 (d, J = 36.6 Hz), 116.8 (d, J = 11.7 Hz), 109.1 (d, J = 28.1
4.4.14. Ethyl trans-1-benzyl-4-ethylazetidin-2-one-3-carboxylate
(5e)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.37 – 7.28 (m, 5H,
ArH), 4.71 (d, J = 15.4 Hz, 1H in CH2), 4.23 (q, J = 7.1 Hz, 2H,
CH2), 4.13 (d, J = 15.5 Hz, 1H in CH2), 3.71 (ddd, J = 8.3, 4.3,

10
Tetrahedron
ACCEPTED MANUSCRIPT
Hz), 61.9, 61.1, 54.9, 49.5, 27.4, 13.9. IR (DCM) ν (cm-1): 1745
Colorless oil. 1H NMR (400 MHz, CDCl3) δ 6.24 (d, J = 10.1
Hz, 1H, CH), 6.21 (d, J = 6.5 Hz, 1H, CH), 6.13 (d, J = 6.6 Hz,
1H, CH), 5.56 (d, J = 10.1 Hz, 1H, CH), 4.43 (d, J = 14.8 Hz, 1H
in CH2), 4.20 (d, J = 14.7 Hz, 1H in CH2), 4.13 (dq, J = 10.7, 7.1
Hz, 1H in CH2), 3.98 (dq, J = 10.8, 7.1 Hz, 1H in CH2), 2.02 (s,
3H, CH3), 1.46 (s, 9H, 3CH3), 1.14 (t, J = 7.1 Hz, 3H, CH3). 13C
NMR (101 MHz, CDCl3) δ 171.0, 168.4, 138.9, 131.0, 129.2,
125.2, 122.1, 119.8, 61.4, 60.8, 54.7, 49.3, 27.4, 24.5, 14.0. IR
(DCM) ν (cm-1): 1762 (C=O), 1730 (C=O). HRMS (ESI) calcd.
for C17H24NO3+ [M+H]+ m/z 290.1751, found 290.1751.
+
(C=O), 1701 (C=O). HRMS (ESI) calcd. for C16H21FNO3
[M+H]+ m/z 294.1500, found 294.1500.
4.4.20. Ethyl trans-1-(tert-butyl)-4-(4-fluorophenyl)azetidin-2-
one-3-carboxylate (4h)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.41 – 7.35 (m, 2H,
ArH), 7.07 (t, J = 8.6 Hz, 2H, ArH), 4.84 (d, J = 2.2 Hz, 1H,
CH), 4.28 – 4.17 (m, 2H, CH2), 3.66 (d, J = 2.3 Hz, 1H, CH),
1.30 (t, J = 7.1 Hz, 3H, CH3), 1.26 (s, 9H, 3CH3). 13C NMR (101
MHz, CDCl3) δ 167.0, 162.8 (d, J = 248.0 Hz), 162.0, 135.0 (d, J
= 3.3 Hz), 128.3 (d, J = 8.3 Hz), 116.0 (d, J = 21.8 Hz), 62.6,
61.8, 55.7, 55.2, 28.1, 14.1. IR (DCM) ν (cm-1): 1761 (C=O),
4.4.26. Ethyl trans-1-(tert-butyl)-4-(4-methylphenyl)azetidin-2-
one-3-carboxylate (4k)
1728 (C=O). HRMS (ESI) calcd. for C16H21FNO3 [M+H]+ m/z
294.1500, found 294.1504.
Colorless crystals, m.p. 106-108 °C. 1H NMR (400 MHz,
CDCl3) δ 7.28 (d, J = 8.1 Hz, 2H, ArH), 7.18 (d, J = 7.9 Hz, 2H,
ArH), 4.81 (d, J = 2.2 Hz, 1H, CH), 4.28 – 4.16 (m, 2H, CH2),
3.67 (d, J = 2.2 Hz, 1H, CH), 2.36 (s, 3H, CH3), 1.28 (t, J = 7.1
Hz, 3H, CH3), 1.26 (s, 9H, 3CH3). 13C NMR (101 MHz, CDCl3) δ
167.2, 162.2, 138.6, 136.1, 129.6, 126.6, 62.5, 61.6, 56.3, 55.1,
28.1, 21.1, 14.1. IR (DCM) ν (cm-1): 1762 (C=O), 1730 (C=O).
HRMS (ESI) calcd. for C17H24NO3+ [M+H]+ m/z 290.1751, found
290.1751.
+
4.4.21.
Ethyl
2-tert-butyl-6-chloro-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3i)
1
Yellow crystals, m.p. 77–80 °C. H NMR (400 MHz, CDCl3)
δ 6.61 (d, J = 6.9 Hz, 1H, CH), 6.40 (d, J = 10.3 Hz, 1H, CH),
6.16 (d, J = 6.9 Hz, 1H, CH), 5.63 (d, J = 10.3 Hz, 1H, CH), 4.44
(d, J = 15.1 Hz, 1H in CH2), 4.28 – 4.12 (m, 3H, CH2 & 1H in
CH2), 1.46 (s, 9H, 3CH3), 1.17 (t, J = 7.1 Hz, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 170.1, 166.9, 135.0, 132.0, 129.6, 126.9,
124.5, 118.6, 62.6, 61.8, 55.3, 49.4, 28.1, 14.1. IR (DCM) ν (cm-
1): 1700 (C=O), 1654 (C=O). HRMS (ESI) calcd. for
C16H21ClNO3+ [M+H]+ m/z 310.1204, found 310.1203.
4.4.27.
Ethyl
2-(tert-butyl)-6-methoxy-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3l)
1
Yellow oil. H NMR (400 MHz, CDCl3) δ 6.27 (dd, J = 10.7,
2.1 Hz, 1H, CH), 6.13 (d, J = 7.2 Hz, 1H, CH), 5.73 (d, J = 10.6
Hz, 1H, CH), 5.61 (d, J = 7.1 Hz, 1H, CH), 4.42 (d, J = 14.1 Hz,
1H in CH2), 4.26 – 4.09 (m, 3H, 1H in CH2 & CH2), 3.60 (s, 3H,
CH3), 1.45 (s, 9H, 3CH3), 1.15 (t, J = 7.1 Hz, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 171.3, 166.6, 159.4, 131.1, 129.8, 129.3,
127.9, 114.4, 61.9, 58.2, 55.3, 52.3, 43.4, 27.6, 14.0. IR (DCM) ν
(cm-1): ν = 1701 (C=O), 1654 (C=O). HRMS (ESI) calcd. for
C17H24NO4+ [M+H]+ m/z 306.1700, found 306.1698.
4.4.22. Ethyl trans-1-(tert-butyl)-4-(4-chlorophenyl)azetidin-2-
one-3-carboxylate (4i).16
Colorless crystals, m.p. 77–80 °C. 1H NMR (400 MHz,
CDCl3) δ 7.36 – 7.33 (m, 4H, ArH), 4.83 (d, J = 2.2 Hz, 1H, CH),
4.02 (dq, J = 10.8, 7.1 Hz, 2H, CH2), 3.65 (d, J = 2.3 Hz, 1H,
CH), 1.26 (m, 12H, 4CH3). 13C NMR (101 MHz, CDCl3) δ 167.7,
162.0, 137.8, 134.6, 129.2, 128.0, 61.6, 55.7, 54.9, 49.4, 27.4,
13.9.
4.4.28. Ethyl trans-1-(tert-butyl)-4-(4-methoxyphenyl)azetidin-2-
one-3-carboxylate (4l).17
4.4.23.
Ethyl
2-tert-butyl-6-bromo-3-oxo-1,2,3,3a-
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.6 Hz,
2H, ArH), 6.90 (d, J = 8.6 Hz, 2H, ArH), 4.80 (d, J = 2.0 Hz, 1H,
CH), 4.23 (qd, J = 7.2, 3.2 Hz, 2H, CH2), 3.82 (s, 3H, CH3), 3.67
(d, J = 2.2 Hz, 1H, CH). 1.29 (t, J = 7.2 Hz, 3H, CH3), 1,26 (s,
9H, 3CH3). 13C NMR (101 MHz, CDCl3) δ 167.2, 162.1, 159.8,
130.9, 127.9, 114.3, 62.5, 61.6, 56.0, 55.3, 55.1, 28.1, 14.1.
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3j)
White crystals, m.p. 94–97 °C. 1H NMR (400 MHz, CDCl3) δ
6.86 (d, J = 6.8 Hz, 1H, CH), 6.53 (dd, J = 10.2, 1.0 Hz, 1H,
CH), 6.12 (ddd, J = 6.8, 2.0, 2.0 Hz, 1H, CH), 5.54 (d, J = 10.2
Hz, 1H, CH), 4.42 (d, J = 15.3 Hz, 1H in CH2), 4.27 – 4.14 (m,
2H, 2CH2), 4.03 (dq, J = 10.7, 7.1 Hz, 1H in CH2), 1.47 (s, 9H,
3CH3), 1.20 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 170.0, 167.7, 132.5, 131.4, 130.6, 124.43, 124.39,
119.3, 61.9, 61.0, 54.9, 49.4, 27.4, 14.0. IR (DCM) ν (cm-1): 1767
4.4.29.
Ethyl
2-tert-butyl-7-chloro-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3ma)
White crystals, m.p. 83–87 °C. 1H NMR (400 MHz, CDCl3) δ
6.61 (d, J = 7.0 Hz, 1H, CH), 6.39 – 6.30 (m, 2H, 2CH), 6.27 (d,
J = 1.9 Hz, 1H, CH), 4.46 (dd, J = 15.4, 2.5 Hz, 1H in CH2), 4.23
(dd, J = 15.3, 2.0 Hz, 1H in CH2), 4.15 – 4.03 (m, 2H, CH2), 1.46
(s, 9H, 3CH3), 1.17 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101
MHz, CDCl3) δ 170.1, 167.4, 133.5, 133.1, 128.1, 126.3, 123.3,
122.1, 61.8, 55.0, 53.4, 49.2, 27.4, 14.0. IR (DCM) ν (cm-1): ν =
+
(C=O), 1733 (C=O). HRMS (ESI) calcd. for C16H21BrNO3
[M+H]+ m/z 354.0699, found 354.0702.
4.4.24. Ethyl trans-1-(tert-butyl)-4-(4-bromophenyl)azetidin-2-
one-3-carboxylate (4j)
Colorless crystals, m.p. 80-82 °C. 1H NMR (400 MHz,
CDCl3) δ 7.54 – 7.50 (m, 2H, ArH), 7.32 – 7.25 (m, 2H, ArH),
4.82 (d, J = 2.2 Hz, 1H, CH), 4.23 (qd, J = 7.0, 2.8 Hz, 2H, CH2),
3.64 (d, J = 2.2 Hz, 1H, CH), 1.270 (t, J = 7.0 Hz, 3H, CH3),
1.266 (s, 9H, 3CH3). 13C NMR (101 MHz, CDCl3) δ 166.9,
162.0, 138.4, 132.2, 128.3, 122.7, 62.4, 61.7, 55.7, 48.3, 28.0,
14.1. IR (DCM) ν (cm-1): 1767 (C=O), 1733 (C=O). HRMS (ESI)
calcd. for C16H21BrNO3+ [M+H]+ m/z 354.0699, found 354.0702.
+
1747 (C=O), 1698 (C=O). HRMS (ESI) calcd. for C16H21ClNO3
[M+H]+ m/z 310.1204, found 310.1208.
4.4.30.
Ethyl
2-tert-butyl-4-chloro-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3mb)
White crystals, m.p. 83–87 °C. 1H NMR (400 MHz, CDCl3) δ
6.61 (d, J = 7.0 Hz, 1H, CH), 6.38 (m, 2H, 2CH), 6.27 (d, J = 1.9
Hz, 1H), 6.21 – 6.15 (m, 1H, CH), 5.75 (s, 1H, CH), 4.41 (dd, J =
15.4, 2.4 Hz, 1H in CH2), 4.23 (dd, J = 15.4, 1.9 Hz, 1H in CH2),
4.15 – 4.03 (m, 2H, CH2), 1.45 (s, 9H, 3CH3), 1.17 (t, J = 7.1, 3.0
Hz, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 169.5, 167.4,
4.4.25.
Ethyl
2-tert-butyl-6-methyl-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3k)

11
134.3, 132.3, 130.2, 129.1, 121.1, 119.6, 61.9, 61.0, 59.7, 49.4,
Reference
ACCEPTED MANUSCRIPT
27.4, 14.0. IR (DCM) ν (cm-1): ν = 1747 (C=O), 1698 (C=O).
+
HRMS (ESI) calcd. for C16H21ClNO3 [M+H]+ m/z 310.1204,
1. For recent reviews, see (a) Lombard, F. J.; Coster, M. J. Org. Biomol.
Chem. 2015, 13, 6419-6431. (b) Egger, J.; Carreira, E. M. Nat. Product
Rep. 2014, 31, 449-455. (c) Ohfune, Y.; Shinada, T. Eur. J. Org.
Chem. 2005, 5127-5143.
found 310.1208.
4.4.31. Ethyl trans-1-(tert-butyl)-4-(3-chlorophenyl)azetidin-2-
one-3-carboxylate (4m)
2. (a) Li, J. J. Name reactions, 4th. ed., Springer-Verlag, Berlin
Heidelberg, 2009, pp.78-79; and references cited therein. (b) Reisman,
S. E.; Nani, R. R.; Levin, S. Synlett 2011, 2437-2442.
3. For reviews, see: (a) Davies, H. M. L.; Beckwith, R. E. J. Chem. Rev.
2003, 103, 2861-2903. (b) Dong, K. Y.; Qiu, L. H.; Xu, X. F. Curr.
Org. Chem. 2016, 20, 29-40.
4. (a) Brown, P.; Southgate, R. Tetrahedron Lett. 1986, 27, 247-250. (b)
Doyle, M. P.; Shanklin, M. S.; Oon, S.-M.; Pho, H. Q.; Heidet, F. R. v.
d.; Veal, W. R. J. Org. Chem. 1988, 53, 3384-3386. (c) Doyle, M. P.;
Taunton, J.; Pho, H. Q. Tetrahedron Lett. 1989, 30, 5397-5400. (d)
Doyle, M. P.; Pieters, R. J.; Taunton, J.; Pho, H. Q.; Padwa, A.;
Hertzog, D. L.; Precedo, L. J. Org. Chem. 1991, 56, 820-829. (e) Gois,
P. M. P.; Afonso, C. A. M. Eur. J. Org. Chem. 2003, 19, 3798-3810.
(f) Yoon, C. H.; Nagle, A.; Chen, C.; Gandhi, D.; Jung, K. W. Org.
Lett. 2003, 5, 2259-2262. (g) Martin, C.; Belderrain, T.R.; Perez, P. J.
Org. Biomol. Chem. 2009, 7, 4777-4781. (h) Zhang, B.; Wee, A. G. H.
Org. Lett. 2010, 12, 5386-5389. (i) Lo, V. K. Y.; Guo, Z.; Choi, M. K.
W.; Yu, W. Y.; Huang, J. S.; Che, C. M. J. Am. Chem. Soc. 2012, 134,
7588-7591.
1
Yellow crystals, m.p. 74–77 °C. H NMR (400 MHz, CDCl3)
δ 7.39 (s, 1H, ArH), 7.34 – 7.28 (m, 3H, ArH), 4.82 (d, J = 2.3
Hz, 1H, CH), 4.27 – 4.21 (m, 2H, CH2), 3.66 (d, J = 2.3 Hz, 1H,
CH), 1.30 (t, J = 7.2 Hz, 3H, CH3), 1.28 (s, 9H, 3CH3). 13C NMR
(101 MHz, CDCl3) δ 166.8, 161.9, 141.5, 135.0, 130.3, 128.9,
126.8, 124.6, 62.5, 61.8, 55.7, 55.3, 28.1, 14.1. IR (DCM) ν (cm-
1): ν = 1766 (C=O), 1731 (C=O). HRMS (ESI) calcd. for
C16H21ClNO3+ [M+H]+ m/z 310.1204, found 310.1209.
4.4.32.
Ethyl
2-tert-butyl-8-chloro-3-oxo-1,2,3,3a-
tetrahydrocyclohepta[c]pyrrole-3a-carboxylate (3n)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 6.48 – 6.36 (m, 3H,
3CH), 5.70 (d, J = 9.9 Hz, 1H, CH), 4.33 (d, J = 16.2 Hz, 1H in
CH2), 4.23 (d, J = 16.0 Hz, 1H in CH2), 4.13 (dq, J = 10.7, 7.1
Hz, 1H in CH2), 4.03 (dq, J = 10.8, 7.1 Hz, 1H in CH2), 1.48 (s,
9H, 3CH3), 1.16 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 166.9, 162.5, 130.4, 129.6, 129.4, 127.3, 127.2, 125.8,
61.7, 55.2, 49.6, 27.9, 27.4, 14.1. IR (DCM) ν (cm-1): ν = 1709
5. (a) Doyle, M. P.; Shanklin, M. S.; Pho, H.-Q.; Mahapatro, S. N. J. Org.
Chem. 1988, 53, 1017-1022. (b) Etkin, N.; Babu, S. D.; Fooks, C. J.;
Durst, T. J. Org. Chem. 1990, 55, 1093-1096. (c) Park, C. P.; Nagle,
A; Yoon, C. H.; Chen, C. L.; Jung, K. W. J. Org. Chem. 2009, 74,
6231-6236.
+
(C=O), 1659 (C=O). HRMS (ESI) calcd. for C16H21ClNO3
6. (a) Wee, A. G. H.; Liu, B.; Zhang, L. J. Org. Chem. 1992, 57, 4404-
4414. (b) Davies, H. M. L.; Antoulinakis, E. G. J. Organomet. Chem.
[M+H]+ m/z 310.1204, found 310.1206.
2001, 617−618, 47-55. (c) Yoon, C. H.; Zaworotko, M. J.; Moulton,
4.4.33. Ethyl trans-1-(tert-butyl)-4-(3,5-dimethylphenyl)azetidin-
B.; Jung, K. W. Org. Lett. 2001, 3, 3539-3542. (d) Gois, P. M. P.;
Afonso, C. A. M. Eur. J. Org. Chem. 2004, 3773-3788. (e) Ring, A;
Ford, A.; Maguire, A. R. Tetrahedron Lett. 2016, 57, 5399-5406 .
7. (a) Padwa, A.; Austin, D. J.; Hornbuckle, S. F.; Semones, M. A.;
Doyle, M. P.; Protopopova, M. N. J. Am. Chem. Soc. 1992, 114, 1874-
1876. (b) Padwa, A.; Austin, D. J.; Price, A. T.; Semones, M. A.;
Doyle, M. P.; Protopopova, M. N.; Winchester, W. R.; Tran, A. J. Am.
Chem. Soc. 1993, 115, 8669-8680. (c) Brown, D. S.; Elliott, M. C.;
Moody, C. J.; Mowlem, T. J.; Marinoand, J. P.; Padwa, A. J. Org.
Chem. 1994, 59, 2447-2455. (d) Miah, S.; Slawin, A. M. Z.; Moody, C.
J.; Sheehan, S. M.; Marino, J. P.; Semones, M. A.; Padwa, A.;
Richards, I. C.; Tetrahedron 1996, 52, 2489-2514. (e) Prein, M.;
Manley, P. J.; Padwa, A. Tetrahedron 1997, 53, 7777-7794. (f)
Moody, C. J.; Miah, S.; Slawin, A. M. Z.; Mansfield, D. J.; Richards, I.
C. Tetrahedron 1998, 54, 9689-9700. (g) Chen, Z. L.; Chen, Z. Y.;
Jiang, Y. Z.; Hu, W. H. Tetrahedron 2005, 61, 1579-1586. (h)
Candeias, N. R.; Gois, P. M. P.; Afonso, C. A. M. J. Org. Chem. 2006,
71, 5489-5497. (i) Xu, X.; Deng, Y.; Yim, D. N.; Zavalij, P. Y.; Doyle,
M. P. Chem. Sci. 2015, 6, 2196-2201. (j) Padwa, A.; Zou, Y. J. Org.
Chem. 2015, 80, 1802-1808.
8. (a) Doyle, M. P.; Protopopova, M. N.; Winchester, W. R.; Daniel, K.
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2-one-3-carboxylate (4o)
Yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.00 – 6.96 (m, 3H,
ArH), 4.76 (d, J = 2.2 Hz, 1H, CH), 4.22 (qd, J = 7.1, 4.8 Hz, 2H,
CH2), 3.67 (d, J = 2.2 Hz, 1H, CH), 2.32 (s, 6H, 2CH3), 1.28 (t, J
= 7.1 Hz, 3H, CH3), 1.28(s, 9H, 3CH3). 13C NMR (101 MHz,
CDCl3) δ 167.3, 162.2, 138.6, 134.2, 130.3, 129.1, 124.3, 123.3,
62.5, 61.6, 56.5, 48.7, 29.7, 28.1, 21.2, 14.1. IR (DCM) ν (cm-1):
ν = 1732 (C=O), 1716 (C=O). HRMS (ESI) calcd. for
C18H26NO3+ [M+H]+ m/z 304.1907, found 304.1903.
4.4.34.
Ethyl
2-(tert-butyl)-5,7-dimethyl-3-oxo-1,2,3,4-
tetrahydroisoquinoline-4-carboxylate (6o)
1
Colorless oil. H NMR (400 MHz, CDCl3) δ 6.96 (s, 1H,
ArH), 6.86 (s, 1H, ArH), 4.65 (s, 1H, CH), 4.63 (d, J = 15.8 Hz,
1H in CH2), 4.42 (d, J = 15.1 Hz, 1H in CH2), 4.11 (q, J = 7.1 Hz,
2H, CH2), 2.37 (s, 3H, CH3), 2.30 (s, 3H, CH3), 1.53 (s, 9H,
3CH3), 1.22 (t, J = 7.1 Hz, 3H, CH3). 13C NMR (101 MHz,
CDCl3) δ 168.8, 167.2, 137.2, 135.8, 133.3, 130.3, 127.1, 124.2,
61.5, 57.9, 54.8, 47.4, 28.2, 21.0, 18.7, 14.0. IR (DCM) ν (cm-1):
ν = 1735 (C=O), 1655 (C=O). HRMS (ESI) calcd. for
C18H26NO3+ [M+H]+ m/z 304.1907, found 304.1910.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (No. 21572017).
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Mo, S. Y.; Li, X. H.; Xu, J. X. J. Org. Chem. 2014, 79, 9186-9195.
12. Kim, M. H.; Choi, S. H.; Lee, Y. J.; Lee, J.; Nahm, K.; Jeong, B. S.;
Park, H. G.; Jew, S. S.; Chem. Commun. 2009, 7, 782–784.
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Chem., 2006, 71, 815-818.
Supplementary Material
1
Copies of H and 13C NMR spectra of unknown products 1, 2, 3,
1
4, 5, and 6, copies of H NMR spectra of some representative
crude reaction mixtures. The Supplementary Material is available
free of charge on http://dx. doi: 10.1021/xxxxxx.
16. Yang, Z. H.; Li, S. Q.; Zhang, Z.; Xu, J. X. Org. Biomol. Chem. 2014,
12, 9822-9830.
17. Lo, K. Y.; Thu, H. Y.; Chan, Y. M.; Lam, T. L.; Yu, W. Y.; Che, C. M.
Synlett. 2012, 23, 2753-2757.

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Tetrahedron
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