Br?nsted acid catalyzed proto-functionalization of enecarbamates and enamides: A convenient route to N,O-acetals

Article abstract of DOI:10.1016/j.tet.2020.131085

N,O-acetals are important structures found in many bioactive natural products, and this unique organic functional group can serve as a useful synthetic precursor to the unstable N-acylimines. In this paper, a convenient route to synthesize N-carbamoyl-N,O

Full text of DOI:10.1016/j.tet.2020.131085

Tetrahedron 76 (2020) 131085
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Brønsted acid catalyzed proto-functionalization of enecarbamates and
enamides: A convenient route to N,O-acetals
a
,
b
,
*
, Zhang Chang-Fei , Hu Xinjun c , Zou Wei , Li Yanli a
a
,
**
a
Ma Xiao-Yan
a
School of Chemical Engineering, Sichuan University of Science & Engineering, Zigong, 643000, PR China
Key Laboratory of Green Chemistry of Sichuan Institutes of Higher Education, Sichuan University of Science and Engineering, Zigong, 643000, PR China
College of Mechanical Engineering, Sichuan University of Science & Engineering, Zigong, 643000, PR China
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 January 2020
Received in revised form
N,O-acetals are important structures found in many bioactive natural products, and this unique organic
functional group can serve as a useful synthetic precursor to the unstable N-acylimines. In this paper, a
convenient route to synthesize N-carbamoyl-N,O-acetals and N-acyl-N,O-acetals from enecarbamates
and enamides in the presence of alcohols as the solvents and nucleophile sources under Brønsted acid
conditions was reported. This strategy could be used to prepare various N,O-acetals from a range of
enecarbamates and enamides with light alcohols, and the products are obtained in good yields (52e98%).
19 February 2020
Accepted 25 February 2020
Available online 19 March 2020
©
2020 Elsevier Ltd. All rights reserved.
Keywords:
N,O-acetal
Brønsted acid
Proto-functionalization
Enecarbamate
Enamide
Alcohol
1
. Introduction
addition of alcohols or phenols to unstable N-benzoylimines [11]
and insertion of aldehydes into N-acyl phthalimides and N-acyl
azoles [12]. Another approach is based on the hydrozirconization of
nitriles followed by acylation and trapping of the acylimine with
alcohols [13]. Recently, electrochemical decarboxylative methox-
N,O-acetals are of great importance due to their role in the
bioactivity of medicinally-relevant molecules and potential appli-
cation as a synthetic building block for the construction of various
nitrogen-containing compounds. There are numerous bioactive
natural products with an N,O-acetal moiety [1] including cytotoxic
agents psymberin (1) [2] and pederin (2) [3] (Fig. 1), and structure-
activity studies demonstrated that the N,O-acetal moiety of 1 and 2
was necessary for potent bioactivity [4]. Additionally, such acetals
have attracted attention as synthetic equivalents to unstable reac-
tive N-acylimines and useful intermediates in organic synthesis [5].
To date, several synthetic routes to N,O-acetals have been
developed. The unique structures can be constructed through
condensation of aldehydes with amides in the presence of titanium
ethoxide [6], methylmagnesium chloride [7], diphenyl phosphate
ylation of N-acetyl-a-amino acids and electrochemical
a-methox-
ylation of N-alkylamides were used to generate N-(
a-methoxyalkyl)
amides [14].
Enamide derivatives are stable enamine surrogates with high
reactivity[15], and functionalization of enamides in the presence of
XtalFluor-E® with alcohols as nucleophilic source yielding N,O-
acetals was reported by Borhan [16]. We also took advantage of
enamide derivatives, and synthesized N,O-acetals using enecarba-
mates and enamides with alcohols catalyzed by Brønsted acid. It is
noteworthy that Toste and coworkers have developed an enantio-
selective oxyfluorination of enamides using chiral phosphoric acid
and Selectfluor[17] (Scheme 1).
[
8], benzotriazole [9] or sodium benzenesulfinate [10], as well as
2. Results and discussion
*
Corresponding author. School of Chemical Engineering, Sichuan University of
Science & Engineering, Zigong, 643000, PR China.
We initiated our studies by running the reactions under 5 mol%
of various Brønsted acid conditions with enecarbamate 1 in the
** Corresponding author.
E-mail addresses: maxy@suse.edu.cn (M. Xiao-Yan), xjhu@suse.edu.cn
(
H. Xinjun).
presence of ethanol as the solvent and nucleophile source. As
https://doi.org/10.1016/j.tet.2020.131085
040-4020/© 2020 Elsevier Ltd. All rights reserved.
0

2
M. Xiao-Yan et al. / Tetrahedron 76 (2020) 131085
Table 2
a
Reaction of enamide derivatives in EtOH to give N,O-acetals
.
Entry
1
Enecarbamate/Enamide [19]
N,O-acetal
Yieldb (%)
90
Fig. 1. Natural compounds containing the N-acyl-N,O-acetal motif.
2
3
4
95
85
98
5
6
7
8
91
63
84
87
9
98
76
Scheme 1. Synthesis of N,O-acetals from enamide derivatives, previous and current
strategies.
1
1
0c
tabulated in Table 1, acetic acid as a weak-acidic catalyst could not
promote the title reaction, while p-toluenesulfonic acid mono-
0
0
hydrate, trifluoroacetic acid and 1,1 -binaphthyl-2,2 -diylhy-
drogenphosphate (BNDHP) provided moderate to good isolated
yields of benzyl (1-ethoxyethyl)carbamate 2. Surprisingly, rela-
tively low yields were obtained when catalyzed by camphor sul-
fonic acid (CSA) and 2M hydrochloric acid, which is probably due to
their enhanced acidity. With considering further research on
enantioselectivity, our best catalyst was determined to be BNDHP
which provided 2 in 81% yield. Then the impact of catalyst dosage
was examined, it was found that optimum yield was obtained with
1c
70
1
1
2c
52
79
3c
Table 1
a
Catalyst optimization for synthesis of benzyl (1-ethoxyethyl)carbamate 2 .
a
Performed with enamide derivative (0.2 mmol) and BNDHP (1.4 mg,
ꢁ
0
.002 mmol) in ethanol (2.0 mL) at 25 C, reactions were stopped after complete
conversion of starting enamide derivatives.
b
Isolated yield.
Entry
Catalyst
CH COOH
Time (h)
Yieldb (%)
c
The ratio of two rotamers was determined by 1H NMR.
1
2
3
4
5
6
3
24
1
3
1
0.5
0.5
NR
73
92
81
30
40
TsOHꢀH
2
O
CF COOH
3
2 mol% of BNDHP after 2 h [18] (see Tables 2 and 3).
BNDHP
CSA
2M HCl
In order to demonstrate the generality of the reaction, a series of
enamide derivatives were synthesized and subjected to the reac-
tion conditions. Enamide derivatives with different acyl groups
a
Performed with 1a (0.2 mmol) and the catalyst (0.005 mmol) in EtOH (2.0 mL) at
C, reactions were stopped after complete conversion of starting enecarbamate
1
t
i
2
3
(R ¼ OBn, O Bu, Ph, Pr, R ¼ R ¼ H) were first investigated, and
ꢁ
2
1
5
gratifyingly, the reactions resulted in the corresponding N-carba-
moyl-N,O-acetals (2a, 2b) and N-acyl-N,O-acetals (2c, 2d) with
a.
b
Isolated yield. NR ¼ no reaction.

M. Xiao-Yan et al. / Tetrahedron 76 (2020) 131085
3
Table 3
Reactions with different alcohols .
denoted in ppm (
solvent acetone-d
d
), and calibrated by using residual undeuterated
a
1
6
(2.05 ppm) for H NMR and acetone-d
6
1
3
(206.26 ppm) for C NMR. The following abbreviations were used
to explain the multiplicities: s ¼ singlet, d ¼ doublet, t ¼ triplet,
br ¼ broad, brs ¼ broad singlet, dt ¼ double triplet, m ¼ multiplet.
The high-resolution mass spectral analysis (HRMS) data were
measured on Thermo Fisher Orbitrap Elite Mass Spectrometer by
Entry
1
NuH
Product
Yield (%)b
56
means of the ESI technique. IR spectra of the compound were
ꢂ1
MeOH
recorded in the range of 400e4000 cm
with a PerkinElmer
Frontier FTIR/NIR spectrometer using KBr pellets.
2
3
iPrOH
EtSH
64
77
4.2. Syntheses of enamide derivatives
The enamide derivatives 1a [20], 1b [20], 1c [16], 1d [16], 1f [21],
g [22], 1h [23], 1i [20], 1k [24]and 1l [24] were prepared according
1
a
to the reported literature procedures.
Performed with 1a (35.6 mg, 0.2 mmol) and BNDHP (1.4 mg, 0.002 mmol) in
ꢁ
alcohol (2.0 mL) at 25 C, reactions were stopped after complete conversion of
starting enecarbamate 1a.
4
.2.1. tert-butyl (Z)-but-1-en-1-ylcarbamate 1e and tert-butyl (E)-
b
Isolated yield.
0
but-1-en-1-ylcarbamate 1e
In a 50 mL flask, formic acid (2.4 mL, 64 mmol) was added to a
solution of n-butylaldehyde (1.4 mL, 10.8 mmol), sodium benze-
nesulfinate (1.64 g, 10.0 mmol) and tert-butyl carbamate
1
t
2
good yields. Besides, enecarbamates 1eꢂ1h (R ¼ O Bu, R ¼ H,
3
n
R ¼ Me, Bn, Bu, Bu) bearing different substituents on the terminal
carbon of the CC double bond were also examined, affording
products 2eꢂ2h in 63%e98% yields. Particularly noteworthy is that
the reaction efficiency of cis-enecarbamate 1e is higher than that of
its isomer trans-enecarbamate 1e′, mostly due to the steric effect.
The reaction is not limited to secondary enecarbamates, as meth-
ylated enecarbamates 1i,1j and cyclic-tertiary enecarbamates 1k,1l
could also result in products with moderate yields, which were
shown to exist as a mixture of amide rotamers by NMR
spectroscopy.
With regard to the nature of the protic nucleophile, other light
alcohols like methanol, 2-propanol and ethanethiol were used to
successfully give the corresponding N,O-acetal and N,S-acetal
products. Noteworthily, the reaction was also applicable to tert
butyl alcohol and benzyl alcohol judging from TLC and the mass
spectrum, however, the products were difficult to separate, which
impelled us to search for new methodology to solve this problem.
(
10.0 mmol) in H
2
O (10 mL) and THF (4 mL). The reaction mixture
ꢁ
was stirred for 24 h at 25 C. The precipitate formed during the
reaction was filtered and washed with water and diethyl ether. tert-
Butyl (1-(phenylsulfonyl)butyl)carbamate was obtained as solid
1
and used in the next step without further purification. H NMR
(
0
1
0
400 MHz, CDCl
3
):
d
¼ 7.92 (d, J ¼ 7.6 Hz, 2H), 7.64e7.52 (m, 3H),
.93 (brs, 1H), 4.86 (td, J ¼ 3.2, 10.8 Hz, 1H), 2.28e2.15 (m, 1H),
.80e1.65 (m, 1H), 1.64e1.52 (m,1H), 1.47e1.42 (m, 1H), 1.21 (s, 9H),
13
.97 ppm (t, J ¼ 7.2 Hz, 3H); C NMR (100 MHz, CDCl
3
):
d
¼ 153.8,
1
367.0, 133.7, 129.2, 129.0, 80.7, 70.5, 28.2, 27.9, 18.7, 13.4 ppm.
tert-Butyl (1-(phenylsulfonyl)butyl)carbamate (3.13
0.0 mmol), dried K CO (5.13 g, 37.2 mmol) and Na SO (6.16 g,
3.4 mmol) in tetrahydrofuran (80 mL) were refluxed for 12 h. The
g,
1
4
2
3
2
4
suspension was cooled to room temprature, the suspension was
filtered through a pad of celite and the filtrate was concentrated.
The reaction mixture was directly purified by silica gel column
chromatography (Hexane/EtOAc ¼ 50:1e20:1 as eluent) to give a
colorless liquid of 1e (479 mg, 28% for two steps) and 1e’ (462 mg,
3
. Conclusion
2
7% for two steps).
1
1e: H NMR (400 MHz, CDCl
3
):
d
¼ 6.38 (t, J ¼ 10 Hz, 1H), 6.13
In conclusion, we have developed a convenient method to
(
1
1
brs, 1H), 4.57 (q, J ¼ 7.2 Hz, 1H), 2.00e1.92 (m, 2H), 1.48 (s, 9H),
synthesize N,O-acetals. Reaction of enecarbamates and enamides
under the Brønsted acid conditions leads to the proto-
functionalization of olefins, yielding N,O-acetals when alcohols
are used as the solvent and nucleophile proton source. The reaction
is efficient with multiple types of enamide derivatives, while the
scope of alcohols is restricted. Efforts toward efficient construction
of N,O-acetals with various alcohols are in progress and will be
reported in due course.
13
.01 ppm (t, J ¼ 7.2 Hz, 3H); C NMR (100 MHz, CDCl ): ¼ 152.8,
3
d
21.5, 109.9, 80.3, 28.3, 18.8, 14.0 ppm.
¼ 6.43 (t, J ¼ 12 Hz, 1H), 6.12
brs, 1H), 5.04e4.92 (m, 2H), 2.04e1.97 (m, 2H), 1.46 (s, 9H),
1
1
3
e’: H NMR (400 MHz, CDCl ): d
(
0
1
13
.98 ppm (t, J ¼ 7.2 Hz, 3H); C NMR (100 MHz, CDCl
3
):
d
¼ 152.9,
22.9, 111.6, 80.1, 28.3, 22.8, 14.4 ppm.
4.2.2. tert-butyl (Z)-methyl(3-phenylprop-1-en-1-yl)carbamate 1j
Sodium hydride (120 mg, 1.5 mmol, 60 wt% in oil) was added to
4
. Experimental section
the magnetically stirred benzyl vinylcarbamate 1h (466 mg,
2
.0 mmol) in anhydrous THF (10 mL) and then iodomethane
ꢁ
4.1. General information
(0.25 ml, 4.0 mmol) was added dropwise to the mixture at 0 C.
After the addition was complete, the mixture was kept at 0 C for
ꢁ
All reactions were monitored by thin-layer chromatography
TLC) on silica gel F254 plates using UV light as visualizing agent (if
30 min and stirred at room temperature. The reaction was moni-
tored by TLC. After the reaction was completed, the reaction
(
applicable), and a solution of phosphomolybdic acid (50 g/L) in
EtOH followed by heating as developing agents. The products were
purified by flash column chromatography on silica gel (200e300
meshes from the Anhui Liangchen Silicon Material Company in
China).
4
mixture was partitioned between saturated aqueous NH Cl and
ethyl acetate. The organic layer was separated and the aqueous
layer was extracted with ethyl acetate (50 mL ꢃ 3). The combined
2 4
organic layers were washed with water, dried over Na SO , and
concentrated. The residue was purified by flash column chroma-
1H NMR and 13C NMR spectra were recorded in acetone-d
so-
lution on a Bruker AM 400 MHz instrument. Chemical shifts were
tography with petroleum ether/EtOAc (20:1) to give corresponding
6
1
product 1j as white solid (356 mg, 72%). H NMR (400 MHz, CDCl
3
):

4
M. Xiao-Yan et al. / Tetrahedron 76 (2020) 131085
d
¼ 7.32e7.17 (m, 5H), 6.30 (brs, 1H), 5.10 (q, J ¼ 7.6 Hz, 1H), 3.45 (d,
4.4.6. tert-butyl (1-ethoxypropyl)carbamate 2f
13
1
J ¼ 7.2 Hz, 2H), 3.08 (s, 3H), 1.49 ppm (s, 9H); C NMR (100 MHz,
H NMR (400 MHz, acetone-d
6
):
d
¼ 6.21 (brs,1H), 4.81e4.73 (m,
CDCl ):
3
3
d
¼ 154.6, 140.3, 129.3, 128.4, 128.2, 126.0, 118.6, 80.4, 36.0,
1H), 3.66e3.54 (m, 1H), 3.47e3.36 (m, 1H), 1.68e1.58 (m, 1H),
1.48e1.48 (m, 1H), 1.41 (s, 9H), 1.11 (t, J ¼ 6.8 Hz, 3H), 0.89 ppm (t,
3.1, 28.3 ppm.
13
J ¼ 7.6 Hz, 3H); C NMR (100 MHz, acetone-d
6
):
d
¼ 156.7, 83.6,
7
1
9.0, 68.2, 63.2, 28.7, 15.7, 10.0 ppm; IR: ῡ ¼ 3340, 2975, 2923, 1704,
4
.4. General experimental procedure for BNDHP catalyzed proto-
ꢂ1
518, 1367, 1175, 1082 cm
;
HRMS (ESI): m/z calcd for
functionalization of enamide derivatives
þ
C
10
H21NO
3
Na: 226.1414; found: 226.1411 [MþNa] .
To a solution of enecarbamate 1a, 1d-1l or enamide 1b, 1c
4
.4.7. tert-butyl (1-ethoxyhexyl)carbamate 2g
(
0
0.2 mmol) in alcohol (2.0 mL) was added the BNDHP (1.4 mg,
1
ꢁ
H NMR (400 MHz, acetone-d
.91e4.77 (m, 1H), 3.66e3.53 (m, 1H), 3.48e3.34 (m, 1H), 1.68e1.58
6
):
d
¼ 6.21 (d, J ¼ 6.8 Hz, 1H),
.002 mmol), and the reaction mixture was stirred at 25 C. When
4
the starting materials disappeared as judged by TLC, the solvent
was removed under reduced pressure. The residue was purified by
flash column chromatography on silica gel eluting with petroleum
ether/EtOAc to afford the product 2a-2o.
(m, 1H), 1.57e1.48 (m, 1H), 1.41 (m, 9H), 1.38e1.26 (m, 6H), 1.10 (t,
1
3
J ¼ 7.2 Hz, 3H), 0.88 ppm (t, J ¼ 6.4 Hz, 3H); C NMR (100 MHz,
acetone-d ):
¼ 156.6, 82.3, 79.0, 63.2, 36.3, 32.4, 28.8, 25.8, 23.5,
5.8, 14.5 ppm, IR: ῡ ¼ 2931, 2866, 1702, 1518, 1368, 1248, 1174,
6
d
1
ꢂ1
1085 cm ; HRMS (ESI): m/z calcd for C13
H
27NO
3
Na: 268.1883;
4
.4.1. Benzyl (1-ethoxyethyl)carbamate 2a
þ
found: 268.1880 [MþNa] .
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 7.46e7.24 (m, 5H), 6.74 (brs,
1
(
(
H), 5.14e5.06 (m, 1H), 5.08 (s, 2H), 3.63e3.52 (m, 1H), 3.49e3.38
4
.4.8. tert-butyl (1-ethoxy-3-phenylpropyl)carbamate 2h
13
m, 1H), 1.30 (d, J ¼ 6.0 Hz, 3H), 1.10 ppm (t, J ¼ 6.8 Hz, 3H); C NMR
1
H NMR (400 MHz, acetone-d
J ¼ 8.8 Hz,1H), 4.96e4.80 (m,1H), 3.68e3.56 (m,1H), 3.49e3.56 (m,
H), 2.69 (t, J ¼ 7.6 Hz, 2H), 2.01e1.81 (m, 2H), 1.43 (s, 9H), 1.14 ppm
6
):
d
¼ 7.35e7.11 (m, 5H), 6.35 (d,
100 MHz, acetone-d ):
6
d
¼ 156.8, 138.2, 129.2, 128.6 {One carbon
signal for CH overlapped}, 79.2, 66.5, 63.1, 21.9, 15.6 ppm; IR:
1
ꢂ1
ῡ ¼ 3324, 3035, 1706, 1530, 1452, 1333, 1242, 1090 cm ; HRMS
13
(
1
t, J ¼ 7.2 Hz, 3H); C NMR (100 MHz, acetone-d
6
):
d
¼ 156.6, 142.8,
(
[
ESI): m/z calcd for C12
H17NO
3
Na: 246.1101; found: 246.1096
29.4, 129.3, 126.7, 81.7, 79.1, 63.3, 38.1, 32.4, 28.7, 15.8 ppm; IR:
þ
MþNa] .
ꢂ1
ῡ ¼ 2976, 2931, 1702, 1499, 1368, 1248, 1170, 1086 cm ; HRMS
(ESI): m/z calcd for C16
H25NO
3
Na: 302.1727; found: 302.1721
þ
4
.4.2. tert-butyl (1-ethoxyethyl)carbamate 2b
[MþNa] .
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 6.31 (brs,1H), 5.07e4.94 (m,
1
H), 3.61e3.50 (m, 1H), 3.46e3.36 (m, 1H), 1.41 (s, 9H), 1.25 (d,
4.4.9. Benzyl (1-ethoxyethyl)(methyl)carbamate 2i
13
1
J ¼ 6 Hz, 3H), 1.10 ppm (t, J ¼ 6.8 Hz, 3H); C NMR (100 MHz,
H
NMR (400 MHz, acetone-d
6
):
d
¼
7.53e7.20 (m,
acetone-d
6
):
d
¼ 156.2, 78.9, 78.6, 63.0, 28.6, 21.9, 15.7 ppm; IR:
5H þ 5H ꢃ 0.7), 5.58e5.51 (m, 1H), 5.51e5.43 (m, 1H ꢃ 0.7),
ꢂ1
ῡ ¼ 3341, 2979, 2932, 1703, 1520, 1367, 1156, 1091 cm ; HRMS
5.21e5.09 (m, 2H þ 2H ꢃ 0.7), 3.43e3.24 (m, 2H þ 2H ꢃ 0.7), 2.76
(
[
ESI): m/z calcd for C
9
H19NO
3
Na: 212.1257; found: 212.1255
(s, 3H), 2.74 (s, 3H ꢃ 0.7), 1.24 (s, 3H), 1.22 (s, 3H ꢃ 0.7),
þ
13
MþNa] .
1.14e1.07 ppm (m, 3H þ 3H ꢃ 0.7); C NMR (100 MHz, acetone-d
6
):
d
¼ 156.9, 156.3, 138.4, 138.3, 129.4, 128.9, 128.8, 128.7 {Two carbon
signals for CH overlapped}, 82.3 {One carbon signal for CH over-
lapped}, 67.6, 67.4, 63.3, 63.2, 26.5, 26.4, 19.8, 19.44, 15.5 {One
carbon signal for CH
4
.4.3. N-(1-ethoxyethyl)benzamide 2c
1
H NMR (400 MHz, acetone-d
dt, J ¼ 30.8, 7.6 Hz, 2H), 7.45 (brs, 1H), 5.60e5.52 (m, 1H),
.66e3.57 (m, 1H), 3.54e3.45 (m, 1H), 1.38 (d, J ¼ 6.0 Hz, 3H),
6
):
d
¼ 7.94 (d, J ¼ 7.2 Hz, 3H), 7.49
3
overlapped} ppm, IR: ῡ ¼ 2980, 1706, 1449,
(
3
1
d
ꢂ1
1404, 1328, 1139, 1107, 1083 cm ; HRMS (ESI): m/z calcd for
1
3
C
13
H19NO
3
Na: 260.1257; found: 260.1255 [MþNa]þ.
.12 ppm (t, J ¼ 7.2 Hz, 3H); C NMR (100 MHz, acetone-d
6
):
¼ 167.34, 135.5, 132.2, 129.2, 128.2, 77.3, 63.5, 21.9, 15.6 ppm; IR:
ꢂ1
4.4.10. tert-butyl (1-ethoxy-3-phenylpropyl)(methyl)carbamate 2j
ῡ ¼ 3308, 2980, 1645, 1530, 1488, 1282, 1095, 698 cm ; HRMS
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 7.40e7.06 (m, 5H þ 5H),
(
[
ESI): m/z calcd for C11
H15NO
2
Na: 216.0995; found: 216.0992
þ
5.37 (t, J ¼ 6.4 Hz, 1H), 5.20 (t, J ¼ 6.4 Hz, 1H), 3.48e3.38 (m, 2H),
MþNa] .
3
2
6
.37e3.26 (m, 2H), 2.68 (s, 6H), 2.66e2.50 (m, 4H), 2.02e1.89 (m,
H), 1.88e1.73 (m, 2H), 1.47 (s, 9H), 1.40 (s, 9H), 1.19e1.11 ppm (m,
4
.4.4. N-(1-ethoxyethyl)isobutyramide 2d
13
H); C NMR (100 MHz, acetone-d
6
):
d
¼ 156.7, 155.9, 142.8, 142.6,
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 7.35 (brs, 1H), 5.35e5.23
1
8
29.5, 129.4, 126.9 {Three carbon signals for CH overlapped}, 85.1,
4.6, 80.1, 79.9, 63.3, 63.1, 35.7, 35.5, 32.3, 32.1, 28.8 {One carbon
(
1
m, 1H), 3.57e3.46 (m, 1H), 3.44e3.33 (m, 1H), 2.50e2.37 (m, 1H),
13
.23 (d, J ¼ 6.0 Hz, 3H), 1.11e1.04 ppm (m, 9H); C NMR (100 MHz,
signal for CH
3
overlapped}, 27.1, 26.2, 15.59, 15.55 ppm; IR:
acetone-d
6
):
d
¼ 177.4, 76.1, 63.0, 35.6, 21.8, 20.1, 19.7, 15.5 ppm; IR:
ꢂ1
ῡ ¼ 2975, 1698, 1452, 1396, 1342, 1258, 1145, 1084 cm ; HRMS
ꢂ1
ῡ ¼ 3437, 3289.74, 2976, 1650, 1542, 1444, 1380, 1098 cm ; HRMS
(
[
ESI): m/z calcd for C17
MþNa] .
H27NO
3
Na: 316.1883; found: 316.1890
(
[
ESI): m/z calcd for C
8
H17NO
2
Na: 182.1151; found: 182.1149
þ
þ
MþNa] .
4
.4.11. tert-butyl 2-ethoxypyrrolidine-1-carboxylate 1k
1
4
.4.5. tert-butyl (1-ethoxybutyl)carbamate 2e
H NMR (400 MHz, acetone-d
6
):
d
¼ 5.07 (s, 1H), 5.01 (s, 1H),
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 6.21 (brs, 1H), 4.86 (dd,
3.50e3.31 (m, 4H), 3.22e3.10 (m, 4H), 1.90e1.78 (m, 2H), 1.75e1.59
13
J ¼ 15.6, 6.4 Hz, 1H), 3.64e3.54 (m, 1H), 3.46e3.36 (m, 1H),
(m, 6H), 1.32 (s, 18H), 1.02e0.93 ppm (m, 6H); C NMR (100 MHz,
acetone-d ):
¼ 155.6, 154.7, 88.1, 87.9, 79.8, 79.6, 64.0, 63.8, 46.7,
46.2, 33.8, 33.2, 28.7 {One carbon signal for CH overlapped}, 23.6,
1.67e1.55 (m, 1H), 1.54e1.31 (m, 3H), 1.41 (s, 9H), 1.10 (t, J ¼ 6.8 Hz,
3
d
6
d
13
H), 0.90 ppm (t, J ¼ 7.6, 3H); C NMR (100 MHz, acetone-d
6
):
3
¼ 156.6, 82.0, 78.9, 63.2, 38.3, 28.7, 19.2, 15.7, 14.1 ppm; IR:
22.6, 16.0 {One carbon signal for CH
3
overlapped} ppm; IR:
ꢂ1
ꢂ1
ῡ ¼ 2968, 2934, 1704, 1518, 1368, 1252, 1174, 1084 cm ; HRMS
ῡ ¼ 3438, 2975, 1702, 1454, 1388, 1253, 1169, 1094 cm ; HRMS
(
[
ESI): m/z calcd for C11
MþNa] .
H23NO
3
Na: 240.1570; found: 240.1568
(ESI): m/z calcd for C11
[MþNa] .
H21NO
3
Na: 238.1414; found: 238.1420
þ
þ

M. Xiao-Yan et al. / Tetrahedron 76 (2020) 131085
5
4
.4.12. tert-butyl 2-ethoxyazepane-1-carboxylate 1l
References
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 5.41 (t, J ¼ 8.0 Hz, 1H), 5.30
[
1] a) R.A. Mosey, P.E. Floreancig, Nat. Prod. Rep. 29 (2012) 980;
b) M.L. Sznaidman, S.M. Hecht, Org. Lett. 3 (2001) 2811;
c) J.C. Rech, P.E. Floreancig, Org. Lett. 5 (2003) 1495;
(
(
t, J ¼ 8.0 Hz, 1H ꢃ 0.8), 3.65e3.31 (m, 3H þ 3H ꢃ 0.8), 2.96e2.86
m, 1H þ 1H ꢃ 0.8), 2.21e2.13 (m, 1H þ 1H ꢃ 0.8), 1.77 (d, J ¼ 12.8,
1
9
4
8
2
2
H þ 1H ꢃ 0.8), 1.63e1.44 (m, 4H þ 4H ꢃ 0.8); 1.46 (s,
d) N. Shangguan, S. Kiren, L. Williams, J. Org. Lett. 9 (2007) 1093.
2] a) R.H. Cichewicz, F.A. Valeriote, P. Crews, Org. Lett. 6 (2004) 1951;
[
H þ 9H ꢃ 0.8), 1.35e1.28 (m, 1H þ 1H ꢃ 0.8), 1.17e1.04 ppm (m,
1
3
b) G.R. Pettit, J.-P. Xu, J.-C. Chapuis, R.K. Pettit, L.P. Tackett, D.L. Doubek,
J.N.A. Hooper, J.M. Schmidt, J. Med. Chem. 47 (2004) 1149.
[3] a) M. Pavan, G. Bo, Physiol. Comp. Oecol. 3 (1953) 307;
b) C. Cardani, D. Ghiringhelli, R. Mondelli, A. Quilico, Tetrahedron Lett. 6
(1965) 2537;
H þ 4H ꢃ 0.8); C NMR (100 MHz, acetone-d
6
):
d
¼ 156.8, 155.6,
5.2, 84.3, 80.0, 79.6, 62.9, 62.8, 41.4, 40.9, 36.0, 35.7, 30.84, 30.77,
9.1, 28.71, 28.67, 28.5, 23.6, 23.5, 15.71, 15.69 ppm; IR: ῡ ¼ 2975,
ꢂ1
930, 1698, 1472, 1414, 1366, 1162, 1081 cm ; HRMS (ESI): m/z
c) A. Furusaki, T. Watanabe, T. Matsumoto, M. Yanagiya, Tetrahedron Lett. 9
(1968) 6301;
d) R. Narquizian, P.J. Kocienski, The Role of Natural Products in Drug Discov-
ery, vol. 32, Springer Berlin Heidelberg, 2000, p. 25.
þ
calcd for C13
H25NO
3
Na: 266.1727; found: 266.1725 [MþNa] .
4.4.13. Benzyl (1-methoxyethyl)carbamate 2m
[4] S. Wan, F. Wu, J.C. Rech, M.E. Green, R. Balachandran, W.S. Horne, B.W. Day,
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 7.45e7.26 (m, 5H), 6.76 (brs,
P.E. Floreancig, J. Am. Chem. Soc. 133 (2011) 16668.
[5] P. Gizecki, R. Dhal, C. Poulard, P. Gosselin, G. Dujardin, J. Org. Chem. 68 (2003)
4338.
1
H), 5.09 (s, 2H), 5.02e4.93 (m, 1H), 3.24 (s, 3H), 1.29 ppm (t,
13
J ¼ 6.0 Hz, 3H); C NMR (100 MHz, acetone-d
6
):
d
¼ 156.9, 138.2,
[6] M. Li, B. Luo, Q. Liu, Y. Hu, A. Ganesan, P. Huang, S. Wen, Org. Lett. 16 (2014)
129.2, 128.7 {One carbon signal for CH overlapped}, 80.8, 66.6, 55.0,
10.
2
1.5 ppm; IR: ῡ ¼ 3330, 2939, 1709, 1528, 1454, 1337, 1246,
[7] J. Halli, K. Hofman, T. Beisel, G. Manolikakes, Eur. J. Org Chem. (2015) 4624.
[8] Y. Zhang, Y. Dai, G. Li, X. Cheng, Synlett 25 (2014) 2644.
ꢂ1
1080 cm ; HRMS (ESI): m/z calcd for C11
H15NO
3
Na: 232.0944;
[
9] a) A.R. Katritzky, J. Pernak, W.-Q. Fan, F. Saczewski, J. Org. Chem. 56 (1991)
439;
b) A.R. Katritzky, W.-Q. Fan, M. Black, J. Pernak, J. Org. Chem. 57 (1992) 547.
þ
found: 232.0944 [MþNa] .
4
[
[
10] a) J.A. Murry, D.E. Frantz, A. Soheili, R. Tillyer, E.J.J. Grabowski, P.J. Reider,
J. Am. Chem. Soc. 123 (2001) 9696;
4
.4.14. Benzyl (1-isopropoxyethyl)carbamate 2n
1
H NMR (400 MHz, acetone-d
H), 5.25e5.14 (m, 1H), 5.08 (s, 2H), 3.90e3.75 (m, 1H), 1.27 (d,
6
):
d
¼ 7.51e7.19 (m, 5H), 6.72 (s,
b) S. Lou, P.N. Moquist, S.E. Schaus, J. Am. Chem. Soc. 129 (2007) 15398;
c) N. George, M. Bekkaye, G. Masson, J. Zhu, Eur. J. Org Chem. (2011) 3695;
d) P. Gizecki, R. Ait Youcef, C. Poulard, R. Dhal, G. Dujardin, Tetrahedron Lett.
1
1
3
J ¼ 5.6 Hz, 3H), 1.09 ppm (dd, J ¼ 20.8, 5.2 Hz, 6H); C NMR
45 (2004) 9589.
(
100 MHz, acetone-d ):
6
d
¼ 156.8, 138.3, 129.3, 128.7 {One carbon
11] a) G. Li, F.R. Fronczek, J.C. Antilla, J. Am. Chem. Soc. 130 (2008) 12216;
signal for CH overlapped}, 77.1, 68.3, 66.6, 23.9, 22.6, 22.0 ppm; IR:
b) S. Vellalath, I. Cꢀ ori ꢁc , B. List, Angew. Chem. Int. Ed. 49 (2010) 9749.
ꢂ1
ῡ ¼ 3342, 2976, 1710, 1526, 1330, 1241, 1084, 986 cm ; HRMS (ESI):
[12] R.N. Enright, J.L. Grinde, L.I. Wurtz, M.S. Paeth, T.R. Wittman, E.R. Cliff,
Y.T. Sankari, L.T. Henningsen, C. Tan, J.D. Scanlon, P.H. Willoughby, Tetrahe-
dron 72 (2016) 6397.
þ
m/z calcd for C13
3
H19NO Na: 260.1257; found: 260.1259 [MþNa] .
[13] S. Wan, M.E. Green, J.-H. Park, P.E. Floreancig, Org. Lett. 9 (2007) 5385.
ꢁ
4
.4.15. Benzyl (1-(ethylthio)ethyl)carbamate 2
[14] a) J. Adamek, R. Mazurkiewicz, A. Pazdzierniok-Holewa, M. Grymel, A. Kuznik,
K. Zielinska, J. Org. Chem. 79 (2014) 2765;
1
H NMR (400 MHz, acetone-d
6
):
d
¼ 7.52e7.19 (m, 5H), 6.72 (d,
b) R. Mazurkiewicz, J. Adamek, A. Pazdzierniok-Holewa, K. Zielinska,
W. Simka, A. Gajos, K. Szymura, J. Org. Chem. 77 (2012) 1952;
c) T. Tajima, H. Kurihara, T. Fuchigami, J. Am. Chem. Soc. 129 (2007) 6680.
J ¼ 6.4 Hz, 1H), 5.13e5.14 (m, 3H), 2.70e2.59 (m, 1H), 2.56e2.46 (m,
1
3
1
H), 1.44 (d, J ¼ 6.8 Hz, 3H), 1.21 ppm (t, J ¼ 7.6 Hz, 3H); C NMR
[15] (For recent reviews on the enamide chemistry, see:) a) R. Matsubara,
(
100 MHz, acetone-d ):
6
d
¼ 156.4, 138.2, 129.2, 128.7 {One carbon
S. Kobayashi, Acc. Chem. Res. 41 (2008) 292;
b) D.R. Carbery, Org. Biomol. Chem. 6 (2008) 3455;
signal for CH overlapped}, 66.7, 52.4, 24.8, 22.6, 15.5 ppm; IR:
ꢂ1
ῡ ¼ 3320, 1700, 1524, 1452, 1326, 1226, 1066, 1029 cm ; HRMS
c) L. Lefort, J.A.F. Boogers, T. Kuilman, R.J. Vijn, J. Janssen, H. Straatman, J.G. de
Vries, A.H.M. de Vries, Org. Process Res. Dev. 14 (2010) 568;
d) K. Gopalaiah, H.B. Kagan, Chem. Rev. 111 (2011), 4599;
e) G.R. Dake, Synlett 23 (2012) 814;
f) T. Kuranaga, Y. Sesoko, M. Inoue, Nat. Prod. Rep. 31 (2014) 514;
g) N. Gigant, L. Chausset-Boissarie, I. Gillaizeau, Chem. Eur J. 20 (2014) 7548;
h) G. Bernadat, G. Masson, Synlett 25 (2014) 2842;
(
[
ESI): m/z calcd for C12
MþNa] .
2
H17NO SNa: 262.0872; found: 262.0873
þ
Acknowledgments
i) X. Liu, K. Zheng, X. Feng, Synthesis 46 (2014) 2241;
j) M.-X. Wang, Chem. Commun. 51 (2015) 6039;
k) T. Courant, G. Dagousset, G. Masson, Synthesis 47 (2015) 1799.
16] Y. Yi, H. Gholami, M.G. Morrow, B. Borhan, Org. Biomol. Chem. 15 (2017) 9570.
17] T. Honjo, R.J. Phipps, V. Rauniyar, F.D. Toste, Angew. Chem. Int. Ed. 51 (2012)
This work was financially supported by NSFC, China (21901174),
the Opening Project of Material Corrosion and Protection Key
Laboratory of Sichuan Province, China (2018CL04), the Cooperation
Project of Wuliangye Group Co., Ltd. and Sichuan University of
Science & Engineering, China (CXY2019ZR003), the Opening Proj-
ect of Key Laboratory of Green Chemistry of Sichuan Institutes of
Higher Education, China (LZJ1806), and the Science and Technology
Department of Sichuan Province, China (2019YFG0174).
[
[
9684.
[18] (The details was shown in the supporting information).
19] Enamide derivatives were prepared according to the reported literature
procedures excepting 1e, vol. 1e’ and 1j.
[
[
20] S. Chanthamath, D.T. Nguyen, K. Shibatomi, S. Iwasa, Org. Lett. 15 (2013) 772.
[21] A.J. Boyington, C.P. Seath, A.M. Zearfoss, Z. Xu, N.T. Jui, J. Am. Chem. Soc. 141
́
́
(
2019) 4147.
́
[
[
22] M. Terada, K. Sorimachi, J. Am. Chem. Soc. 129 (2007) 292.
23] T. Hashimoto, H. Nakatsu, Y. Takiguchi, K. Maruoka, J. Am. Chem. Soc. 135
Appendix A. Supplementary data
́
́
(2013) 16010.
[24] D.F. Oliveira, P.C.M.L. Miranda, C.R.D. Correia, J. Org. Chem. 64 (1999) 6646.
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2020.131085.