Efficient synthesis of β-oxoalkyl carbamates from carbon dioxide, internal propargylic alcohols, and secondary amines catalyzed by silver salts and DBU

Article abstract of DOI:10.1055/s-0029-1218675

The three-component reaction of internal propargylic alcohols with secondary amines and carbon dioxide proceeded smoothly in the presence of a catalyst system comprising a silver salt and 1,8-diazabicyclo[5.4.0]undec-7-ene in 1,4-dioxane at 90 °C to give the corresponding β-oxoalkyl carbamates in good to high yields. The counterion of the silver salt had little effect on the reaction whereas the nature of the organic base had a marked influence. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218675

PAPER
1433
Efficient Synthesis of b-Oxoalkyl Carbamates from Carbon Dioxide, Internal
Propargylic Alcohols, and Secondary Amines Catalyzed by Silver Salts and
DBU
b
-Oxoalkyl Car
b
h
s
aorong Qi, Liangbin Huang, Huanfeng Jiang*
School of Chemistry and Chemical Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640,
P. R. of China
Fax +86(20)87112906; E-mail: jianghf@scut.edu.cn
Received 14 December 2009; revised 21 January 2010
As part of our continuous efforts to fix carbon dioxide
Abstract: The three-component reaction of internal propargylic al-
chemically,9 we found that b-oxopropyl carbamates could
cohols with secondary amines and carbon dioxide proceeded
smoothly in the presence of a catalyst system comprising a silver
salt and 1,8-diazabicyclo[5.4.0]undec-7-ene in 1,4-dioxane at 90 °C
be synthesized efficiently through coupling of propargylic
alcohols, secondary amines, and carbon dioxide in the ab-
to give the corresponding b-oxoalkyl carbamates in good to high sence of any added catalyst or organic solvent under com-
pressed carbon dioxide.10 In our further explorations of
yields. The counterion of the silver salt had little effect on the reac-
tion whereas the nature of the organic base had a marked influence.
the scope of this reaction, we also found that only terminal
Key words: amines, carbamates, carbon dioxide, catalysis, propar-
gylic alcohols
propargylic alcohols could be used and that internal prop-
argylic alcohols showed almost no conversion into the de-
sired products. This suggested that internal propargylic
alcohols are less active than terminal ones and that they
Chemical fixation of carbon dioxide into valuable organic may need activating by an active catalyst.
compounds is of great interest in connection with the pro-
With the goal of broadening the scope of the method, we
tection of the environment and the utilization of carbon re-
sources.1 Carbon dioxide is abundant, nontoxic,
nonflammable, and renewable. There are many possibili-
ties for using carbon dioxide as a safe and cheap C1 feed-
stock in organic synthesis. One of the most important
methods in this field is the direct synthesis of carbamates,
in which carbon dioxide is used as a clean and safe starting
material to replace toxic phosgene or isocyanates.2 Organ-
ic carbamates are very important precursors that are wide-
ly used in agriculture as pesticides, fungicides, and
herbicides; in pharmacology as pharmaceuticals; and in
the chemical industry as intermediates.3 Carbamates are
also useful as protective groups for amine functions in
peptide synthesis.4
examined the reactions of several inactive internal propar-
gylic alcohols with secondary amines and carbon dioxide
catalyzed by silver salts and 1,8-diazabicyclo[5.4.0]un-
dec-7-ene (DBU), in which various internal propargylic
alcohols were activated and converted into the corre-
sponding b-oxoalkyl carbamates in good to high yields
(Scheme 1).
R2
R3
O
R2
AgOAc, DBU
1,4-dioxane
R12NH
+
R4
OH
R12N
+
CO2
O
R4
R3
O
2
3
1
2a: R2–R3 = -[CH2]5-, R4 = Ph
2b: R2 = R3 = Me, R4 = Ph
1a: diethylamine
1b: dipropylamine
1c: dibutylamine
1d: diallylamine
1e: pyrrolidine
The one-pot, three-component, coupling reaction of prop-
argylic alcohols, secondary amines, and carbon dioxide is
a promising route to b-oxoalkyl carbamates. Although a
number of catalysts have been developed for this reaction,
including ruthenium complexes,5 iron complexes,6 and
lanthanide chlorides,7 their activity and/or selectivity is
low, and only terminal propargylic alcohols have been in-
vestigated for use in these reactions. Copper complexes
that are based on macrocycles containing a ferrocene
group show a high activity for terminal propargylic alco-
hols, but when the internal propargylic alcohol 2-methyl-
4-phenylbut-3-yn-2-ol was subjected to the reaction, the
yield of carbamate fell sharply.8
2c: R2 = Me, R3 = H, R4 = Ph
2d: R2–R3 = -[CH2]5-, R4 = Me
2e: R2 = R3 = Me, R4 = 4-MeOC6H4
2f: R2 = R3 = H, R4 = Ph
1f: morpholine
Scheme 1 Synthesis of b-oxoalkyl carbamates from internal pro-
pargylic alcohols, secondary amines, and carbon dioxide
We first examined the reaction of diethylamine (1a) with
1-(phenylethynyl)cyclohexanol (2a) and carbon dioxide
under various conditions, and the results of these studies
are presented in Table 1. We have previously shown that
internal propargylic alcohols activated by silver salts can
react with primary amines and carbon dioxide to afford 4-
alkylidene-1,3-oxazolidin-2-ones.9f However, silver salts,
such as silver acetate, alone did not catalyze the corre-
sponding reaction of internal propargylic alcohols to give
the corresponding carbamates under 2 MPa of CO2 at
50 °C (Table 1, entry 1). To our delight however, when 30
mol% of DBU was added, the reaction took place and the
SYNTHESIS 2010, No. 9, pp 1433–1440
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x
.
x
x
.2
0
1
0
Advanced online publication: 11.02.2010
DOI: 10.1055/s-0029-1218675; Art ID: F23909SS
© Georg Thieme Verlag Stuttgart · New York

1434
C. Qi et al.
PAPER
desired product, 1-(phenylacetyl)cyclohexyl diethylcar- time seem to favor the reaction. A yield of 89% was ob-
bamate (3a) was obtained in 28% yield (entry 2), along tained when the reaction was performed at 90 °C for 15 h
with (4Z)-4-benzylidene-1,3-dioxaspiro[4.5]decan-2-one, (entries 2, 4-6). However increasing the temperature from
which was formed by incorporation of carbon dioxide into 90 °C to 110 °C led to a marked decrease in yield as a re-
2a and obtained in 40% isolated yield.11 A control exper- sult of decomposition of product 2a to give cyclohex-
iment showed that DBU alone did not catalyze the reac- anone and benzaldehyde as major byproducts (entry 7).
tion (entry 3). The presence of both the silver salt and The effect of the solvent was also evaluated (entries 6, 9-
DBU is therefore required for the reaction to occur. Rais- 11). The use of 1,4-dioxane as the solvent gave a higher
ing the reaction temperature and prolonging the reaction yield than was obtained in toluene, dichloromethane, or
Table 1 Optimization of the Synthesis of 1-(Phenylacetyl)cyclohexyl Diethylcarbamate (3a) by the Reaction of Diethylamine (1a), 1-(Phe-
nylethynyl)cyclohexanol (2a) and Carbon Dioxide
O
AgOAc, DBU
+
CO2
Et2NH
+
Et2N
O
OH
O
Entrya
1
Catalyst
AgOAc
AgOAc
none
Base
Solvent
Temp(°C)
50
Time (h)
10
10
10
15
15
15
15
15
15
15
15
15
15
24
15
15
15
15
15
15
15
15
15
15
15
Yield (%)b
none
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
toluene
0
28
0
2
DBU
DBU
DBU
DBU
DBU
DBU
none
50
3
50
4
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgNO3
AgBF4
Ag2CO3
AgOAc
AgOAc
AgOAc
AgOAc
FeCl3
50
43
73
89
76
13
82
70
86
62
68
41
85
84
84
17
15
21
10
0
5
70
6
90
7
110
90
8
9
DBU
DBU
DBU
DBU
DBU
none
90
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
CH2Cl2
90
THF
90
none
90
nonec
90
nonec
120
90
DBU
DBU
DBU
DABCO
DMAP
pyrridine
Et3N
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
90
90
90
90
90
90
DBU
DBU
DBU
DBU
90
PdCl2
90
0
SnCl2
90
0
CuCl
90
27
a Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), catalyst (0.075 mmol), base (0.15 mmol), solvent (1.5 mL), CO2 (2 MPa).
b Isolated yield.
c The reaction was performed under 8 MPa of CO2 without any additional organic solvent.
Synthesis 2010, No. 9, 1433–1440 © Thieme Stuttgart · New York

PAPER
b-Oxoalkyl Carbamates
1435
tetrahydrofuran. Moreover, a lower yield was also ob-
tained when the reaction was carried out under neat or su-
percritical conditions (entries 12-13). Note that even at
higher temperature or in supercritical carbon dioxide, the
presence of DBU appears to be necessary to obtain satis-
factory results (entries 8, 14). For example, in the absence
of DBU at 90 °C in 1,4-dioxane, the reaction gave only a
13% yield of the carbamate, and most of the alcohol 2a re-
mained unreacted and could be recovered (entry 8).
We also investigated the catalytic activities of several oth-
er silver salts such as silver nitrate, silver tetrafluorobo-
rate, and silver carbonate (entries 15-17) and we found
that the counterion of the silver salt had little effect on the
reaction. On the other hand, the nature of the organic base
had a marked effect on the reaction. Replacement of DBU
with other organic bases such as 1,4-diazabicy-
clo[2.2.2]octane (DABCO), 4-(N,N-dimethylamino)pyri-
dine (DMAP), pyridine, or triethylamine led to marked
reductions in the yield, and large amounts of unreacted al-
cohol were recovered (entries 18-21). With other metal
salts such as iron(III) chloride, palladium(II) chloride,
tin(II) chloride, or copper(I) chloride as catalysts, trace or
low yields of the product were obtained and most of the
alcohol remained unreacted (entries 22-25). Therefore,
the optimum reaction conditions are as follows: diethyl-
amine (1a, 0.5 mmol), 1-(phenylethynyl)cyclohexanol
(2a, 0.5 mmol), 1,4-dioxane (1.5 mL), AgOAc (0.075
mmol), DBU (0.15 mmol), a temperature of 90 °C, a CO2
pressure of 2 MPa, and a reaction time of 15 hours.
Figure 1 X-ray crystal structure of 3a; ellipses are shown at the
30% probability level
zylidene-1,3-dioxaspiro[4.5]decan-2-one was obtained in
18% yield (entry 7). Other internal tertiary propargylic al-
cohols (2b, 2d, and 2e), a secondary propargylic alcohol
(2c), and a primary propargylic alcohol (2f) also under-
went reaction with various secondary amines to give the
corresponding products in good-to-high yields (entries 8-
19). Note that the less-hindered alkyne 2f did not react
with 1g to afford the desired product under the optimized
conditions but instead gave the cyclic carbonate 4-ben-
zylidene-1,3-dioxolan-2-one in 8% yield (entry 20).
On the basis of previous reports5a,b,9e,f,10,13 and our experi-
mental results, a plausible mechanism for the reaction is
postulated in Scheme 2. Firstly, the Z-alkylidene cyclic
carbonate 6 is formed through incorporation of carbon di-
oxide into the internal propargylic alcohol in the presence
of silver acetate and 1,8-diazabicyclo[5.4.0]undec-7-ene
via 4 and 5. The carbonate 6 then undergoes nucleophilic
addition with the secondary amine to give the intermedi-
ate 7, which tautomerizes to give the corresponding car-
bamate 3.
A single crystal of product 3a was obtained by slow crys-
tallization from a mixture of petroleum ether and ethyl
acetate, and its structure was established by single-crystal
X-ray analysis (Figure 1).
With the optimized reaction conditions in hand, we ex-
tended the process to a variety of internal propargylic al-
cohols and secondary amines. Some representative
examples are listed in Table 2. The reaction between 1-
(phenylethynyl)cyclohexanol (2a) and various secondary
amines12 1a–f occurred smoothly to give desired b-
oxoalkylcarbamate in yields of 80–93% (Table 2, entries
1-6). However, when bulky diisopropylamine (1g) was
subjected to the reaction, none of the desired carbamate
was detected and the cyclic carbonate (4Z)-4-ben-
In conclusion, we have developed a convenient and effi-
cient one-pot synthesis of b-oxoalkyl carbamates from
carbon dioxide as a starting material. Cooperation be-
tween the silver salt and 1,8-diazabicyclo[5.4.0]undec-7-
ene is a key factor in activating the transformation. This
study extends the range of substrates that can be used in
R2
R2
R3
O
R3
O
O
R2
O
O
DBU
Ag
R4
OH
O
+
CO2
Ag
R3
AgOAc
R4
DBUH
DBUH
R4
5
2
4
– DBU
– AgOAc
O
R2
R3
R2
O
O
R12NH
O
O
R12N
R12N
R4
O
R4
O
R3
R2
R3
R4
OH
O
3
7
6
Scheme 2 Proposed mechanism for the formation of carbamates
Synthesis 2010, No. 9, 1433–1440 © Thieme Stuttgart · New York

1436
C. Qi et al.
PAPER
the three-component reaction of propargylic alcohols, efficient chemical transformations of carbon dioxide into
secondary amines, and carbon dioxide. Further studies on valuable fine chemicals are ongoing in our laboratory.
Table 2 Reactions of Various Propargylic Alcohols, Secondary Amines, and Carbon Dioxide in the Presence of Silver Acetate and 1,8-Di-
azabicyclo[5.4.0]undec-7-ene
R2
R3
O
R2
AgOAc, DBU
R12NH
+
R4
OH
R12N
+
CO2
O
R4
R3
1,4-dioxane
90 °C, 15 h
O
1
2
3
Entrya
Amine
Propargylic alcohol
Conversionb Product
(%)
Yieldc
(%)
O
HO
HO
1
2
1a
1b
2a
quant
99
3a
3b
89
88
NH
N
O
O
O
2a
2a
2a
NH
N
O
O
O
HO
HO
3
4
1c
98
3c
85
93
N
O
O
NH
O
1d
quant
3d
N
O
NH
O
O
HO
HO
HO
5
6
1e
1f
2a
2a
98
97
3e
3f
80
74
NH
N
O
O
O
O
NH
N
O
O
O
O
O
O
7
8
9
1g
1a
1b
2a
2b
2b
98
97
98
3g
3h
3i
0
87
88
NH
NH
N
N
O
O
OH
O
O
N
O
NH
OH
OH
O
O
N
O
10
1c
2b
97
3j
85
NH
O
Synthesis 2010, No. 9, 1433–1440 © Thieme Stuttgart · New York

PAPER
b-Oxoalkyl Carbamates
1437
Table 2 Reactions of Various Propargylic Alcohols, Secondary Amines, and Carbon Dioxide in the Presence of Silver Acetate and 1,8-Di-
azabicyclo[5.4.0]undec-7-ene (continued)
R2
R3
O
R2
AgOAc, DBU
R12NH
+
R4
OH
R12N
+
CO2
O
R4
R3
1,4-dioxane
90 °C, 15 h
O
1
2
3
Entrya
Amine
Propargylic alcohol
Conversionb Product
(%)
Yieldc
(%)
O
11
1d
2b
99
3k
86
N
O
OH
NH
O
O
12
13
1e
1a
2b
2c
91
90
3l
82
87
NH
NH
OH
N
O
O
O
3m
N
O
O
OH
O
N
O
14
15
16
1b
1d
1a
2c
2c
92
97
93
3n
3o
3p
82
90
89
NH
O
OH
OH
O
N
O
O
NH
O
HO
2d
NH
N
O
N
O
O
O
HO
17
1c
2d
quant
3q
84
NH
O
O
18
19
1a
1d
2e
quant
74
3r
3s
70
73
NH
MeO
OH
N
O
O
O
OMe
N
O
O
2f
2f
NH
O
OH
OH
20
1g
12
3t
0
NH
N
O
O
a Reaction conditions: secondary amine (0.5 mmol), alcohol (0.5 mmol), AgOAc (0.075 mmol), DBU (0.15 mmol), 1,4-dioxane (1.5 mL), CO2
(2 MPa), 90 °C, 15 h.
b Determined by GC analysis.
c Isolated yield.
1H NMR spectra were recorded on a Bruker DRX-400 spectrometer
with CDCl3 as the solvent and TMS as the internal standard. GC
analyses were performed on a GC-7900 chromatograph with a
flame-ionization detector and equipped with an AT.SE-30 capillary
column (internal diameter = 0.32 mm, length = 30 m). Mass spectra
were recorded on a Shimadzu GCMS–QP5050A mass spectrometer
operating at an ionization voltage of 70 eV and equipped with a DB-
WAX capillary column (internal diameter = 0.25 mm, length = 30
Synthesis 2010, No. 9, 1433–1440 © Thieme Stuttgart · New York

1438
C. Qi et al.
PAPER
MS (70 eV): m/z (%) = 373 [M+], 282, 156 (100), 109, 91, 58.
m). IR spectra were recorded on a Bruker Tensor 27 spectrometer.
Melt points were recorded on a Büchi B-545 instrument. All starting
materials and catalysts were commercially purchased and used
without further purification. Crystallographic data for compound 3a
have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publications CCDC 764657; copies can be
obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(1223)336033 or email:
deposit@ccdc.cam.ac. uk].
Anal. Calcd for C23H35NO3: C, 73.96; H, 9.44; N, 3.75. Found: C,
73.83; H, 9.60; N, 3.82.
1-(Phenylacetyl)cyclohexyl Diallylcarbamate (3d)
Orange oil.
IR (KBr): 3077, 3027, 2936, 2860, 1695, 1457, 1413, 1295, 929,
770, 704 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.20–1.28 (m, 1 H), 1.48–1.57 (m,
2 H), 1.62–1.70 (m, 5 H), 2.11–2.15 (m, 2 H), 3.76 (s, 2 H), 3.91 (d,
J = 5.6 Hz, 2 H), 3.97 (d, J = 5.6 Hz, 2 H), 5.16–5.23 (m, 4 H),
5.78–5.86 (m, 2 H), 7.19–7.28 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 21.5, 25.1, 31.3, 42.1, 49.0, 49.1,
85.2, 116.9, 117.2, 126.6, 128.2, 129.9, 133.2, 133.4, 134.9, 154.6,
206.9.
Carbamates 3; General Procedure
A 15 mL poly(tetrafluoroethylene) reaction vessel was charged
with secondary amine 1 (0.5 mmol), propargylic alcohol 2 (0.5
mmol), AgOAc (0.075 mmol), and DBU (0.015 mmol). The vessel
was loaded into a stainless-steel autoclave with a pressure-regulat-
ing system, and the autoclave was sealed. CO2 was introduced from
a cylinder and the reaction was carried out at the selected tempera-
ture under magnetic stirring for the required reaction time. A con-
stant pressure of CO2 was maintained during the reaction. When the
reaction was complete, the vessel was cooled in an ice bath and the
pressure was slowly released to atmospheric pressure. The residual
material was extracted with Et2O. The products were purified by
column chromatography [silica gel, petroleum–EtOAc (10:1)], and
identified by MS and 1H and 13C NMR spectrometry.
MS (70 eV): m/z (%) = 341 [M+], 250, 124 (100), 91, 41.
Anal. Calcd for C21H27NO3: C, 73.87; H, 7.97; N, 4.10. Found: C,
73.75; H, 8.11; N, 4.23.
1-(2-Phenylacetyl)cyclohexyl Pyrrolidine-1-carboxylate (3e)
White solid; mp 116–117 °C.
IR (KBr): 2937, 2869, 1691, 1417, 1333, 1253, 1093, 718 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.20–1.27 (m, 1 H), 1.52–1.58 (m,
2 H), 1.64–1.71 (m, 5 H), 1.89–1.98 (m, 4 H), 2.14–2.17 (m, 2 H),
3.43 (t, J = 6.8 Hz, 2 H), 3.51 (q, J = 6.8 Hz, 2 H), 3.85 (s, 2 H),
7.21–7.32 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 21.5, 24.9, 25.2, 25.8, 31.4, 42.3,
46.1, 46.2, 84.5, 126.5, 128.2, 129.9, 135.0, 153.6, 207.5.
1-(Phenylacetyl)cyclohexyl Diethylcarbamate (3a)
White solid; mp 74–75 °C.
IR (KBr): 2935, 2863, 1695, 1427, 1274, 1132, 987, 772, 702 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.16 (t, J = 7.2 Hz, 3 H), 1.22–
1.28 (m, 4 H), 1.50–1.55 (m, 2 H), 1.63–1.71 (m, 5 H), 2.11–2.14
(m, 2 H), 3.32 (q, J = 7.2 Hz, 2 H), 3.41 (q, J = 7.2 Hz, 2 H), 3.77
(s, 2 H), 7.20–7.30 (m, 5 H).
MS (70 eV): m/z (%) = 315 [M+], 224, 98 (100), 70, 55, 28.
13C NMR (100 MHz, CDCl3): d = 13.4, 14.2, 21.3, 24.9, 31.1, 41.5,
41.7, 41.9, 84.4, 126.3, 128.1, 129.6, 134.8, 154.2, 207.1.
Anal. Calcd for C19H25NO3: C, 72.35; H, 7.99; N, 4.44. Found: C,
72.22; H, 8.08; N, 4.31.
MS (70 eV): m/z (%) = 317 [M+], 226, 100 (100), 72, 44, 28.
1-(Phenylacetyl)cyclohexyl Morpholine-4-carboxylate (3f)
White solid; mp 102–103 °C.
IR (KBr): 2932, 2857, 1694, 1426, 1234, 1119, 765, 700 cm–1.
Anal. Calcd for C19H27NO3: C, 71.89; H, 8.57; N, 4.41. Found: C,
71.78; H, 8.64; N, 4.52.
1H NMR (400 MHz, CDCl3): d = 1.19–1.26 (m, 1 H), 1.47–1.53 (m,
2 H), 1.64–1.71 (m, 5 H), 2.11–2.14 (m, 2 H), 3.47-3.61 (m, 4 H),
3.69–3.72 (m, 4 H), 3.79 (s, 2 H), 7.20–7.31 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 21.6, 25.1, 31.3, 42.3, 43.9, 44.8,
66.7, 85.1, 126.6, 128.3, 129.8, 134.7, 153.9, 206.8.
1-(Phenylacetyl)cyclohexyl Dipropylcarbamate (3b)
Orange oil.
IR (KBr): 2935, 2867, 1791, 1432, 1245, 1170, 766 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.92 (t, J = 7.2 Hz, 3 H), 1.00 (t,
J = 7.2 Hz, 3 H), 1.22–1.28 (m, 1 H), 1.56–1.73 (m, 11 H), 2.13–
2.16 (m, 2 H), 3.26 (q, J = 7.2 Hz, 2 H), 3.33 (q, J = 7.2 Hz, 2 H),
3.80 (s, 2 H), 7.22–7.33 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 11.1, 21.2, 21.3, 21.6, 25.0, 31.2,
41.9, 48.8, 49.3, 84.4, 126.3, 128.1, 129.6, 134.9, 154.2, 207.2.
MS (70 eV): m/z (%) = 331 [M+], 240, 114 (100), 91, 70, 42, 28.
Anal. Calcd for C19H25NO4: C, 68.86; H, 7.60; N, 4.23. Found: C,
68.98; H, 7.42; N, 4.32.
MS (70 eV): m/z (%) = 345 [M+], 254, 128 (100), 109, 91, 43.
1,1-Dimethyl-2-oxo-3-phenylpropyl Diethylcarbamate (3h)
Orange oil.
IR (KBr): 2980, 1699, 1430, 1284, 1154, 1060, 775, 722 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.15–1.20 (m, 6 H), 1.48 (s, 6 H),
3.25–3.48 (m, 4 H), 3.79 (s, 2 H), 7.20–7.31 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 13.6, 14.2, 24.0, 41.7, 41.9, 42.1,
83.2, 126.6, 128.3, 129.8, 134.8, 154.7, 206.9.
Anal. Calcd for C21H31NO3: C, 73.01; H, 9.04; N, 4.05. Found: C,
73.28; H, 8.91; N, 4.13.
1-(Phenylacetyl)cyclohexyl Dibutylcarbamate (3c)
Orange oil.
IR (KBr): 2938, 2870, 1684, 1427, 1260, 1107, 766, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.93 (t, J = 7.2 Hz, 3 H), 1.00 (t,
J = 7.2 Hz, 3 H), 1.20–1.48 (m, 5 H), 1.50–1.75 (m, 11 H), 2.10–
2.14 (m, 2 H), 3.27 (q, J = 7.6 Hz, 2 H), 3.35 (q, J = 7.6 Hz, 2 H),
3.78 (s, 2 H), 7.22–7.31 (m, 5 H).
MS (70 eV): m/z (%) = 277 [M+], 186, 100 (100), 72, 28.
Anal. Calcd for C16H23NO3: C, 69.29; H, 8.36; N, 5.05. Found: C,
69.01; H, 8.55; N, 5.12.
13C NMR (100 MHz, CDCl3): d = 13.9, 19.9, 20.1, 21.5, 25.1, 30.2,
31.0, 31.3, 42.0, 47.1, 47.2, 84.6, 126.5, 128.2, 129.8, 135.0, 154.7,
207.2.
1,1-Dimethyl-2-oxo-3-phenylpropyl Dipropylcarbamate (3i)
Orange oil.
IR (KBr): 2966, 2875, 1694, 1466, 1423, 1250, 1148, 727 cm–1.
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b-Oxoalkyl Carbamates
1439
1H NMR (400 MHz, CDCl3): d = 0.89 (t, J = 7.2 Hz, 3 H), 0.94 (t,
J = 7.2 Hz, 3 H), 1.48 (s, 6 H), 1.55–1.65 (m, 4 H), 3.20–3.26 (m, 4
H), 3.79 (s, 2 H), 7.21–7.31 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 11.1, 21.2, 21.8, 23.9, 42.0, 48.8,
49.3, 83.2, 126.6, 128.2, 129.8, 134.9, 155.1, 206.8.
1-Methyl-2-oxo-3-phenylpropyl Dipropylcarbamate (3n)
Orange oil.
IR (KBr): 2964, 1701, 1428, 1245, 1167, 1095, 703 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.90 (t, J = 8.0 Hz, 6 H), 1.35 (d,
J = 8.0 Hz, 3 H), 1.55–1.65 (m, 4 H), 3.15–3.27 (m, 4 H), 3.81 (s, 2
H), 5.13 (q, J = 8.0 Hz, 1 H), 7.21–7.31 (m, 5 H).
MS (70 eV): m/z (%) = 305 [M+], 214, 128 (100), 86, 43.
Anal. Calcd for C18H27NO3: C, 70.79; H, 8.91; N, 4.59. Found: C,
71.01; H, 8.88; N, 4.51.
13C NMR (100 MHz, CDCl3): d = 11.1, 16.5, 21.2, 21.8, 45.2, 48.8,
49.3, 74.9, 126.9, 128.5, 129.6, 133.5, 155.5, 206.2.
MS (70 eV): m/z (%) = 291 [M+], 200, 128 (100), 91, 43, 28.
1,1-Dimethyl-2-oxo-3-phenylpropyl Dibutylcarbamate (3j)
Orange oil.
Anal. Calcd for C17H25NO3: C, 70.07; H, 8.65; N, 4.81. Found: C,
69.76; H, 8.78; N, 4.92.
IR (KBr): 2965, 2868, 1696, 1465, 1252, 1152, 1150, 772, 727
cm–1.
1H NMR (400 MHz, CDCl3): d = 0.92 (t, J = 7.2 Hz, 3 H), 0.97 (t,
J = 7.2 Hz, 3 H), 1.30–1.37 (m, 4 H), 1.48 (s, 6 H), 1.51–1.58 (m, 4
H), 3.22–3.29 (m, 4 H), 3.79 (s, 2 H), 7.22–7.31 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 13.8, 19.9, 23.9, 30.2, 30.9, 42.0,
46.8, 47.1, 83.2, 126.6, 128.2, 129.8, 134.9, 155.1, 206.8.
1-Methyl-2-oxo-3-phenylpropyl Diallylcarbamate (3o)
Orange oil.
IR (KBr): 3076, 2986, 2931, 1707, 1420, 1244, 1098, 928, 706
cm–1.
1H NMR (400 MHz, CDCl3): d = 1.35 (d, J = 7.2 Hz, 3 H), 3.80 (s,
2 H), 3.89 (d, J = 5.6 Hz, 4 H), 5.13–5.18 (m, 5 H), 5.77–5.81 (m, 2
H), 7.18–7.33 (m, 5 H).
MS (70 eV): m/z (%) = 333 [M+], 242, 156 (100), 91, 57, 29.
Anal. Calcd for C20H31NO3: C, 72.04; H, 9.37; N, 4.20. Found: C,
71.84; H, 9.48; N, 4.25.
13C NMR (100 MHz, CDCl3): d = 16.5, 45.2, 48.7, 49.2, 75.3,
116.9, 117.3, 127.0, 128.5, 129.6, 133.1, 133.3, 133.4, 155.3, 205.9.
MS (70 eV): m/z (%) = 287 [M+], 196, 124 (100), 91, 41.
1,1-Dimethyl-2-oxo-3-phenylpropyl Diallylcarbamate (3k)
Orange oil.
Anal. Calcd for C17H21NO3: C, 71.06; H, 7.37; N, 4.87. Found: C,
71.17; H, 7.32; N, 4.78.
IR (KBr): 3076, 3026, 2973, 2866, 1698, 1465, 1250, 1151, 1150,
772, 726 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.49 (s, 6 H), 3.78 (s, 2 H), 3.94
(d, J = 4.8 Hz, 4 H), 5.15–5.19 (m, 4 H), 5.75–5.83 (m, 2 H), 7.20–
7.31 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 23.9, 42.1, 49.0, 49.2, 83.7,
116.8, 117.3, 126.6, 128.3, 129.8, 133.2, 133.4, 134.9, 154.9, 206.7.
1-Propionylcyclohexyl Diethylcarbamate (3p)
Orange oil.
IR (KBr): 2937, 2868, 1700, 1431, 1272, 1070, 778 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.98 (t, J = 4.0 Hz, 3 H), 1.01–
1.18 (m, 6 H), 1.38–1.50 (m, 2 H), 1.56–1.62 (m, 6 H), 2.02–2.10
(m, 2 H), 2.39 (q, J = 4.0 Hz, 2 H), 3.21–3.31 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 8.0, 13.4, 14.2, 21.2, 25.1, 28.4,
31.4, 41.6, 41.7, 84.2, 154.3, 210.7.
MS (70 eV): m/z (%) = 301 [M+], 210, 124 (100), 91, 65, 41, 28.
Anal. Calcd for C18H23NO3: C, 71.73; H, 7.69; N, 4.65. Found: C,
71.42; H, 7.78; N, 4.66.
MS (70 eV): m/z (%) = 255 [M+], 226, 198, 100 (100), 72, 57, 28.
Anal. Calcd for C14H25NO3: C, 65.85; H, 9.87; N, 5.49. Found: C,
65.54; H, 9.99; N, 5.62.
1,1-Dimethyl-2-oxo-3-phenylpropyl Pyrrolidine-1-carboxylate
(3l)
White solid; mp 74–75 °C
IR (KBr): 2975, 2876, 1688, 1405, 1153, 1056, 769, 729 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.50 (s, 6 H), 1.85–1.93 (m, 4 H),
3.37–3.44 (m, 4 H), 3.83 (s, 2 H), 7.21–7.31 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 24.2, 24.9, 25.7, 42.3, 46.1, 83.1,
126.6, 128.2, 129.8, 134.8, 153.8, 207.1.
MS (70 eV): m/z (%) = 275 [M+], 184, 98 (100), 55, 41.
1-Propionylcyclohexyl Dibutylcarbamate (3q)
Orange oil.
IR (KBr): 2938, 2866, 1699, 1461, 1226, 1134, 772 cm–1.
1H NMR (400 MHz, CDCl3) d = 0.91 (t, J = 8.0 Hz, 3 H), 0.96 (t,
J = 8.0 Hz, 3 H), 1.05 (s, 3 H), 1.20–1.42 (m, 8 H), 1.44–1.67 (m, 8
H), 2.02–2.10 (m, 2 H), 2.43 (q, J = 8.0 Hz, 2 H), 3.20 (t, J = 8.0 Hz,
2 H), 3.28 (t, J = 8.0 Hz, 2 H).
Anal. Calcd for C16H21NO3: C, 69.79; H, 7.69; N, 5.09. Found: C,
69.97; H, 7.59; N, 5.12.
13C NMR (100 MHz, CDCl3): d = 8.1, 13.8, 19.9, 20.1, 21.5, 25.2,
28.4, 30.1, 30.9, 31.4, 47.0, 47.1, 84.3, 154.7, 210.8.
MS (70 eV): m/z (%) = 311 (M+), 282, 254, 156 (100), 100, 57, 29.
1-Methyl-2-oxo-3-phenylpropyl Diethylcarbamate (3m)
Orange oil.
IR (KBr): 2980, 1700, 1433, 1274, 1171, 1087, 773, 707 cm–1.
Anal. Calcd for C18H33NO3: C, 69.41; H, 10.68; N, 4.50. Found: C,
69.13; H, 10.81; N, 4.55.
1H NMR (400 MHz, CDCl3): d = 1.14–1.18 (m, 6 H), 1.35 (d,
J = 7.2 Hz, 3 H), 3.32–3.34 (m, 4 H), 3.81 (s, 2 H), 5.14 (q, J = 7.2
Hz, 1 H), 7.19–7.33 (m, 5 H).
3-(4-Methoxyphenyl)-1,1-dimethyl-2-oxo-propyl Diethylcar-
bamate (3r)
Orange oil.
13C NMR (100 MHz, CDCl3): d = 13.4, 14.0, 16.5, 41.4, 42.0, 45.3,
IR (KBr): 2980, 1698, 1430, 1250, 1157, 782 cm–1.
74.8, 126.9, 128.5, 129.6, 133.5, 155.0, 206.2.
1H NMR (400 MHz, CDCl3): d = 1.13–1.22 (m, 6 H), 1.48 (s, 6 H),
3.32 (t, J = 6.8 Hz, 4 H), 3.73 (s, 3 H), 3.77 (s, 2 H), 6.83–6.85 (m,
2 H), 7.13–7.15 (m, 2 H).
MS (70 eV): m/z (%) = 263 [M+], 172, 100 (100), 72, 44, 28.
Anal. Calcd for C15H21NO3: C, 68.42; H, 8.04; N, 5.32. Found: C,
68.69; H, 7.93; N, 5.41.
Synthesis 2010, No. 9, 1433–1440 © Thieme Stuttgart · New York

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C. Qi et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 13.6, 24.0, 41.2, 41.7, 41.9, 55.2,
(3) (a) Vauthey, I.; Valot, F.; Gozzi, C.; Fache, F.; Lemaire, M.
Tetrahedron Lett. 2000, 41, 6347. (b) Wu, T. T.; Huang, J.;
Arrington, N. D.; Dill, G. M. J. Agric. Food Chem. 1987, 35,
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(d) Adams, P.; Baron, F. A. Chem. Rev. 1965, 65, 567.
(4) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; Wiley: New York, 1999, 315–318.
(5) (a) Sasaki, Y.; Dixneuf, P. H. J. Org. Chem. 1987, 52, 4389.
(b) Burncau, C.; Dixneuf, P. H. Tetrahedron Lett. 1987, 28,
2005. (c) Sasaki, Y. JP 62061961(A), 1987; Chem. Abstr.
1988, 108, 204234.
(6) Kim, T. J.; Kwon, K. H.; Kwon, S. C.; Baeg, J. O.; Shim, S.
C.; Lee, D. H. J. Organomet. Chem. 1990, 389, 205.
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J. Bull. Korean Chem. Soc. 1990, 11, 467.
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83.1, 113.8, 126.9, 128.1, 130.7, 154.7, 158.4, 207.3.
MS (70 eV): m/z (%) = 307 [M+], 186, 162, 121, 100 (100), 72, 44,
29.
Anal. Calcd for C17H25NO4: C, 66.43; H, 8.20; N, 4.56. Found: C,
66.29; H, 7.95; N, 4.62.
2-Oxo-3-phenylpropyl Diallylcarbamate (3s)
Orange oil.
IR (KBr): 3076, 2928, 1708, 1460, 1417, 1244, 1097, 929, 761, 700
cm–1.
1H NMR (400 MHz, CDCl3): d = 3.73 (s, 2 H), 3.90 (d, J = 5.6 Hz,
4 H), 4.71 (s, 2 H), 5.15–5.18 (m, 4 H), 5.74–5.79 (m, 2 H), 7.20–
7.35 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 46.1, 48.7, 49.2, 68.5, 116.9,
117.3, 127.0, 128.7, 129.4, 132.9, 133.0, 133.2, 155.3, 202.3.
MS (70 eV): m/z (%) = 273 [M+] 182, 124 (100), 91, 41, 27.
(9) (a) Qi, C. R.; Jiang, H. F.; Wang, Z. Y.; Zou, B.; Yang, S. R.
Synlett 2007, 255. (b) Qi, C. R.; Jiang, H. F.; Wang, Z. Y.;
Zou, B. Chin. J. Chem. 2007, 25, 1051. (c) Qi, C. R.; Jiang,
H. F.; Liu, H. L.; Yang, S. R.; Zou, B. Gaodeng Xuexiao
Huaxue Xuebao 2007, 28, 1084; Chem. Abstr. 2007, 148,
538111. (d) Jiang, H. F.; Wang, A. Z.; Liu, H. L.; Qi, C. R.
Eur. J. Org. Chem. 2008, 2309. (e) Jiang, H.; Zhao, J.;
Wang, A. Synthesis 2008, 763. (f) Jiang, H. F.; Zhao, J. W.
Tetrahedron Lett. 2009, 50, 60.
(10) Qi, C. R.; Jiang, H. F. Green Chem. 2007, 9, 1284.
(11) (4Z)-4-Benzylidene-1,3-dioxaspiro[4.5]decan-2-one could
be quantitatively transformed into 3a by treatment with
Et2NH (1 equiv) in 1,4-dioxane at 90 °C for 15 h.
(12) When a primary amine(butylamine) was used under the
same conditions, 4-benzylidene-3-butyl-1-oxa-3-
Anal. Calcd for C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found: C,
69.94; H, 7.23; N, 5.31.
Acknowlegment
The authors thank the National Natural Science Foundation of Chi-
na (Nos. 20625205, 20772034 and 20932002), the Doctoral Fund of
the Ministry of Education of China (20090172110014), and the
Guangdong Natural Science Foundation (No. 8451064101000236)
for financial support.
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Synthesis 2010, No. 9, 1433–1440 © Thieme Stuttgart · New York