RuCl3 in poly(ethylene glycol): A highly efficient and recyclable catalyst for the conjugate addition of nitrogen and sulfur nucleophiles

Article abstract of DOI:10.1055/s-2005-870010

The 1,4-conjugate addition of primary, secondary and aromatic amines, thiols, and carbamate to α,β-unsaturated compounds mediated by a catalytic amount (0.5 mol%) of RuCl₃ in poly(ethylene glycol) (PEG) provides the desired β-substituted carbonyls in high yields. In particular, we found that primary aliphatic and aromatic amines produced the single adducts as the sole products in very high yields with RuCl₃-PEG. RuCl ₃-PEG was readily recycled via solvent precipitation with efficient recyclability as evidenced by high yields. Its properties of low sensitivity toward moisture and oxygen, high tolerance of different functional groups, and efficient recyclability make RuCl₃-PEG suitable for both laboratory and industrial scale synthesis of β-substituted carbonyls. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-870010

PAPER
2129
RuCl3 in Poly(ethylene glycol): A Highly Efficient and Recyclable Catalyst for
the Conjugate Addition of Nitrogen and Sulfur Nucleophiles
R
uCl inPoly(ethy
u
lene glycol)
a
as an
E
ffici
x
ent and Recy
i
c
lable
n
Catalyst g Zhang,a,b Yuhong Zhang,*a Leifang Liu,a Hailiang Xu,a Yanguang Wang*a
3
a
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
Fax +86(71)7951512; E-mail: yhzhang@zjuem.zju.edu.cn; E-mail: orgwyg@zju.edu.cn
b
Key Laboratory for Molecular Design and Nutrition Engineering, Ningbo Institute of Technology, Zhejiang University, Ningbo 315100,
P. R. China
Received 21 January 2005; revised 22 March 2005
nitrate-catalyzed versatile Michael reaction was devel-
oped to reduce the complications that characterized the
current standard Michael reaction and was used for facile
preparation of organic compounds of widely different
Abstract: The 1,4-conjugate addition of primary, secondary and ar-
omatic amines, thiols, and carbamate to a,b-unsaturated compounds
mediated by a catalytic amount (0.5 mol%) of RuCl3 in poly(ethyl-
ene glycol) (PEG) provides the desired b-substituted carbonyls in
high yields. In particular, we found that primary aliphatic and aro- structures.13 The studies from Kawatsura and Hartwig for
matic amines produced the single adducts as the sole products in
the transition metal-catalyzed addition of amines to acryl-
very high yields with RuCl3-PEG. RuCl3-PEG was readily recycled
ic acid derivatives indicated that selection of the most ef-
via solvent precipitation with efficient recyclability as evidenced by
fective catalysts depended on the identify of the amine
high yields. Its properties of low sensitivity toward moisture and ox-
and substitution pattern at the unsaturated C=C bond.14
ygen, high tolerance of different functional groups, and efficient re-
cyclability make RuCl3-PEG suitable for both laboratory and
Although great success has been made in aza-Michael re-
industrial scale synthesis of b-substituted carbonyls.
action, several challenges still remained for chemical
Key words: RuCl3, PEG, amines, thiols, conjugate addition
practitioners to grapple with when performing the catalyst
process on scale. First, the relatively high price of noble
metal salts for the addition with carbamates, albeit in cat-
alytic amounts, contributes significantly to the overall
cost of production. Second, the efficient catalyst systems
for the less nucleophilic aromatic amines are still extreme-
ly rare.2f A versatile, air- and moisture-stable, and recycla-
ble catalytic system is highly desirable in aza-Michael
reactions. Poly(ethylene glycol)s (PEGs) are inexpensive
polymers that are readily soluble in some solvents and in-
soluble in a few others solvents, which make them prom-
ising soluble polymeric supports. By using PEG as the
support, the reactions can be carried out under the homo-
geneous conditions and the products and/or catalysts can
be conveniently separated from the reaction mixture via
solvent precipitation.15 As the introduction of cleaner
technologies has become a major concern throughout both
in industry and academia, preparation and application of
recyclable catalysts have become a high priority. The
need for practical and economic methods in large-scale
operations requires the development of efficient and recy-
clable catalytic systems. In this paper, we describe the use
of recyclable RuCl3-PEG as an efficient and versatile cat-
alyst for aza-Michael reaction. The reaction was carried
out under mild condition with high yield in the absence of
solvent and RuCl3-PEG could be readily recycled more
than five times without obvious deactivation. For the first
time, we discovered that the sole single addition products
could be obtained in very high yield with primary aliphat-
ic amines and the aza-Michael addition proceeded
smoothly with various substituted aromatic amines in
RuCl3-PEG system.
b-Amino carbonyl compounds are important intermedi-
ates for a large number of organic compounds and widely
used in the preparation of natural products, chiral auxilia-
ries, and lactams.1 Due to their vast range of applications,
the modification and improvement of the synthesis meth-
od of b-amino carbonyl compounds has been an important
objective in recent years.2 One of the conventional meth-
ods for the preparation of these derivatives is the Mannich
reaction, but this reaction is often limited by long reaction
times and harsh reaction conditions.3 The conjugate addi-
tion of nitrogen nucleophiles to a,b-unsaturated carbonyl
compounds provides an alternative route to construct
these functionalities. However, traditional N-nucleophiles
without special activation were greatly limited to only the
simple primary amines with unsubstituted acrylic com-
pounds.4 Recently, several suitable agents, such as InCl3,5
6
8
9
InBr3, Bi(OTf)3,7 CeCl3-NaI, LiClO4 and copper
salts,10 have been reported to mediate the aza-Michael ad-
dition in both non-aqueous and aqueous solvents. These
processes are mild, less expensive, and environmental
friendly, but they are inactive with less nucleophilic aro-
matic amines and carbamates. More recently, Spencer et
al. reported the palladium-catalyzed11 conjugate addition
of carbamates to enones, which led to the synthesis of
Cbz-protected b-amino ketones. Further investigation by
Kobayashi, et al. demonstrates that several noble metal
salts other than palladium are also effective catalysts for
the Michael addition of enones to carbamates.12 Bismuth
SYNTHESIS 2005, No. 13, pp 2129–2136
x
x.
x
x
.
2
0
0
5
Our initial studies focused on the reaction between prima-
ry aliphatic amines and acrylonitrile. The molar ratio of
acrylonitrile to amine was 1:1. n-Butylamine was chosen
Advanced online publication: 13.07.2005
DOI: 10.1055/s-2005-870010; Art ID: F01405SS
© Georg Thieme Verlag Stuttgart · New York

2130
H. Zhang et al.
PAPER
to test the reactivity of RuCl3 in CH2Cl2 at room tempera- With this new finding, the aza-Michael reactions of vari-
ture for three hours. The catalyst amounts reported in the ous a,b-unsaturated carbonyl compounds with n-butyl-
literatures were around 10 mol%.14 We found that RuCl3 amine were then investigated. The results revealed that
was an efficient catalyst for the aza-Michael addition re- both a,b-unsaturated ester and a,b-unsaturated ketone
action and 0.5 mol% of RuCl3 was sufficient to get high gave the sole single addition products with excellent yield
yields. A mixture of 65% single addition product and 35% in RuCl3-PEG (Table 1, entries 2,3), but longer reaction
double addition product was generated in CH2Cl2 time was needed. Again, a mixture of single and double
(Table 1, entry 1).11 Other solvents such as DMSO, THF, addition products was formed with a,b-unsaturated ester
and toluene were found to have a minor effect on the poor in CH2Cl2. (Table 1, entry 2) However, it was noticed that
chemoselectivity. However, the aza-Michael reaction was the single Michael addition was obtained with cyclohex-
not only carried out effectively in PEG2000 under the 2-en-1-one in CH2Cl2 (Table 1, entry 4). Employing i-
same reaction condition, but also produced only the single PrNH2 as the source of primary aliphatic amine in combi-
addition product in high yield when CH2Cl2 was displaced nation with RuCl3-PEG system afforded the desired sole
(Table 1, entry 1).
single addition products, which further confirmed that
RuCl3-PEG system was effective as catalyst for use in
Table 1 RuCl3-PEG-Catalyzed Aza-Michael Addition of a,b-Unsaturated Carbonyls with Primary Aliphatic Amines
R1
R1
H
N
R1
R1
R
NH2
+
+
R
EWG
EWG
EWG R
EWG
A
B
EWG = COR, COOR, CN
R1 = H, CH3
Entry
Amine
Unsaturated compound
Time (h)
Yield (%)a, Product
PEG2000b
CH2Cl2c (A:B)
98 (65:35)
1
2
CN
3
8
98, a1
96, a2
NH2
95 (55:45)
OEt
O
3
4
8
8
92, a3
96, a4
93
96
OEt
O
O
5
6
3
8
98, a5
90, a6
98 (70:30)
91 (62:38)
NH2
CN
OEt
O
7
8
87, a7
85
OEt
O
8
9
3
8
8
96, a8
92, a9
92, a10
97 (85:15)
93 (87:13)
93
NH2
CN
OEt
O
10
OEt
O
11
12
8
3
87, a11
91, a12
89
O
93 (90:10)
CN
NH2
13
14
8
8
90, a13
89, a14
92 (91:9)
87
OEt
O
OEt
O
a Isolated yield and all the compounds were identified by MS and 1H NMR spectroscopy.
b PEG2000 as reaction solvent.
c CH2Cl2 as solvent.
Synthesis 2005, No. 13, 2129–2136 © Thieme Stuttgart · New York

PAPER
RuCl3 in Poly(ethylene glycol) as an Efficient and Recyclable Catalyst
2131
Table 2 RuCl3-PEG-Catalyzed Aza-Michael Addition of a,b-Un-
saturated Carbonyls with Aromatic Amines
high chemoselective aza-Michael addition (Table 1, en-
tries 5–7). The mechanism of the high chemoselectivity of
Ru-PEG system is not clear yet but may be related with
the coordination properties of PEG.
Entry
Amine
Unsaturated Time (h) Yield (%),a
compound
Product
The studies about the coordination and conformation in
PEG system containing metal ions16,17 revealed that PEG
were either wrapped around the metal ions forcing the
ether oxygens to point inwards and coordinate to metal
ions mimicking crown ethers, or coordinated with the
metal ions by the terminal OH group. The coordination ef-
fect of PEG was even stronger than crown ethers. In the
Ru-PEG system, it is possible that the long chains of PEG,
either leaving one end dangling or forcing unusual coordi-
nation geometries, leave no room around ruthenium ions
for the relatively bulky adducts of primary amines to pro-
ceed with the further addition.
NH2
1
2
8
8
96, b1
CN
92, b2
OEt
O
3
4
12
12
87, b3
98, b4
O
NH2
CN
CH3O
5
12
97, b5
OEt
O
6
7
12
24
91, b6
91, b7
O
Compared with aliphatic amines, the aromatic amines as
the nucleophiles show considerably less reactivity due to
the transformation of nitrogen lone-pair electrons to the
aromatic ring. Therefore, many catalysts that are success-
fully employed in aza-Michael addition with aliphatic
amines failed to work with aromatic amines. For example,
NH2
CN
O2N
8
9
24
24
81, b8
87, b9
OEt
O
O
10
Cu(OTf)2 was reported to be effective in the conjugate
a Isolated yield and all the compounds were identified by MS and
NMR spectroscopy.
addition of aliphatic amines to a,b-unsaturated carbonyls,
but the aromatic amines were not subjected to the addition
in the same conditions.
InCl3 and Bi(OTf)3 also showed the inactivity in aza-
Michael addition with aromatic amines although they are
efficient in the Michael addition with aliphatic amines.5,7
We evaluated the aza-Michael reaction with respect to the
substituted aromatic amines and the results are presented
in Table 2. It is seen that all the reactions examined led to
good conversions, albeit with different reaction time.
Aniline and more reactive p-methoxyaniline delivered the
desired products with excellent yields (Table 2, entries 1–
6). Reactions involving deactivated p-nitroaniline afford-
ed a good isolated yield, but longer reaction times were re-
quired (Table 2, entries 7–12). These results clearly
indicate that RuCl3-PEG works well with both electron-
poor and electron-rich aromatic amines. All the reaction
products of aromatic amines with a,b-unsaturated carbon-
yls were single addition adducts.
Table 3 RuCl3-PEG-Catalyzed Aza-Michael Addition of a,b-Un-
saturated Carbonyls with Secondary Amines
Entry
Amine
Unsaturated Time (h)
compound
Yield (%),a
Product
1
2
3
6
~100, c1
97, c2
CN
NH
10
12
OEt
OEt
O
O
89, c3
4
5
6
6
10
10
99, c4
98, c5
91, c6
CN
NH
O
OEt
O
O
OEt
O
The aza-Michael reaction of several secondary amines is
presented in Table 3. The results demonstrate that the
RuCl3-PEG catalytic system is highly efficient with sec-
ondary amines. Variation in the structures of secondary
aliphatic amines has little effect on the addition, in all the
cases good conversions were observed (Table 3, entries
1–9).
7
8
9
10
12
12
85, c7
97, c8
94, c9
NH
CN
OEt
O
a Isolated yield and all the compounds were identified by MS and
NMR spectroscopy.
Extension of this method with thiols also gives the aza-
Michael addition products in excellent yields (Table 4,
entries 1–6). Both aliphatic and aromatic thiols gave de-
sired products in excellent yields. The reactivity of acry-
lonitrile, ethyl acrylate, and cyclohex-2-en-1-one with a
carbamate was also examined. The catalyst system ap-
peared to be completely ineffective for the aza-Michael
addition of acrylonitrile and ethyl acrylate with carbam-
ate. Only cyclohex-2-en-1-one delivered the desired aza-
Michael addition product in good yield after the prolonga-
tion of reaction time (Table 4, entry 7).
Synthesis 2005, No. 13, 2129–2136 © Thieme Stuttgart · New York

2132
H. Zhang et al.
PAPER
Table 4 RuCl3-PEG-Catalyzed Michael Addition of a,b-Unsaturat-
ed Carbonyls with Thiols and Carbamate
metals because their strong tendency to poison these cata-
lysts. Probing the catalyst performance by yield provides
evidence of the excellent stability of the catalyst, as the
yield remains almost constant over the reaction cycles.
Entry
Unsaturated
compound
Thiol/
Carbamate
Time (h) Yield (%)a,
Product
In conclusion, we have established a highly efficient
RuCl3-PEG catalytic system that allow the formation of
the sole single addition products derived from both ali-
phatic and aromatic primary amines in aza-Michael addi-
tion under mild conditions. The application of various
a,b-unsaturated carbonyls in combination with primary
and secondary amines, thiols, and carbamate, permits a
variety of substituted b-amino- or thio- carbonyls to be
produced involving only air-stable chemicals. The simple
reaction protocol that does not require high pressure and
solvents makes this reaction a superior alternative to the
existing protocols.
1
2
3
8
8
94, d1
92, d2
89, d3
SH
CN
OEt
O
12
O
4
5
12
8
93, d4
92, d5
SH
HS
CN
OEt
O
6
7
8
87, d6
89, d7
O
24
O
H2N
O
All reactions were monitored by TLC on gel F254 plates. 1H NMR
and 13C NMR spectra were recorded on a Bruker Advance 500 spec-
trometer, using CDCl3 as solvent and TMS as internal standard.
Mass spectroscopy data was obtained on a Bruker Esquire-LC with
electrospray (ESI-MS) measurements. IR data were recorded at
Nicolet 5DX FT-IR using KBr optics. Elemental analyses were per-
formed in the ThermoFinnigan Flash EA1112 measurements. All
compounds were characterized by IR, 1H NMR, and MS data. New
a Isolated yield and all the compounds were identified by MS and
NMR spectroscopy.
The results presented above reveal that RuCl3-PEG sys-
tem is efficient in the aza-Michael addition with aliphatic
and aromatic amines, aromatic and aliphatic thiols, and
carbamate. The observation that both PEG and RuCl3 are
insoluble in diethyl ether allows us to explore the possibil-
ity to reuse PEG and the expensive RuCl3 by extraction of
the reaction media with diethyl ether. We evaluated the re-
cyclability of RuCl3-PEG catalyst for the addition of ethyl
acrylate with n-butylamine, aniline, and benzenethiol. Be-
cause ethyl acrylate is inactive to aza-Michael addition
with the carbamate, we chose cyclohex-2-enone as the ad-
dition substrate with carbamate for the recycle (Table 5,
entry 4).
1
compounds (b6, b9, d6) were characterized by IR, H NMR, 13C
NMR, MS and elemental analyses.
RuCl3-Catalyzed 1,4-Conjugate Addition Reactions; General
Procedure
RuCl3·H2O (0.011 g, 0.05 mmol) was added to a mixture of PEG
(average MW 2000, 4 g), amine (10 mmol) and the appropriate a,b-
unsaturated compound (10–15 mmol). Reaction under N2 was re-
quired with aromatic amines to avoid the oxidation of the substrates.
The reaction mixture was kept at 50 °C for 3–24 h by magnetic stir-
ring and then cooled to r.t. After the reaction, the solution was
poured into Et2O (20 mL), then the solution was kept cooling in a
refrigerator for 30 min to aid precipitation. The precipitate was
washed with further portions of Et2O, and the washings were com-
bined with the initial filtrate. The combined Et2O phases were
washed several times with H2O and dried (MgSO4). After filtration
and removal of the solvent, the product was dried under vacuum.
Further purification was not needed when acrylonitrile and acrylate
were used as the substrates. The crude products derived from cyclo-
hex-2-en-1-one and methyl methacrylate were purified by flash
Table 5 shows the results of reusing the catalytic system
for five times. The efficient recyclability of the catalytic
system is manifest from the almost constant and high ad-
dition yields over the various reaction cycles. It is worth
to note that the catalytic system was successfully recycled
in the Michael addition with benzenethiol. Thiols are dif-
ficult to use in the catalytic systems containing transition
Table 5 Recyclability Effect of RuCl3-PEG Catalyst in Aza-Michael Addition Reaction
Entry
Unsaturated compound
Amine/Thiol/Carbamate
Recycle number/Product Yield (%)a
1
2
3
4
5
1
2
3
4
95
96
90
92
90
OEt
O
NH2
NH2
92
92
89
90
92
87
93
90
88
91
90
86
90
88
85
SH
O
O
H2N
O
a Isolated yield.
Synthesis 2005, No. 13, 2129–2136 © Thieme Stuttgart · New York

PAPER
RuCl3 in Poly(ethylene glycol) as an Efficient and Recyclable Catalyst
IR (neat): 3356, 2960, 2926, 1741, 1471, 1386, 1190 cm–1.
2133
chromatography on a silica gel column to give the pure products.
During the treatment with Et2O, the RuCl3-PEG precipitated from
the solvent. Further the precipitated RuCl3-PEG was readily reused
in the recycle experiments.
1H NMR (500 MHz, CDCl3): d = 4.12 (q, J = 7.2 Hz, 2 H), 2.9 (m,
1 H), 2.88 (t, J = 6.35 Hz, 2 H), 2.54 (t, J = 6.35 Hz, 2 H), 1.27 (t,
J = 7.2 Hz, 3 H), 1.06 (d, J = 6.15 Hz, 6 H).
ESI-MS: m/z = 160 (M + H)+.
3-Butylaminopropionitrile (a1)9
A 25-mL round-bottomed flask was charged with PEG2000 (4 g),
n-butylamine (0.73 g, 0.01 mol), acrylonitrile (0.53 g, 0.01 mol) and
RuCl3⋅H2O (0.011 g, 0.05 mmol). The mixture was heated at 50 °C
for 3 h. After completion of the reaction (TLC), the solution was al-
lowed to cool. Et2O (2 × 25 mL) was added, the mixture stirred for
5 min, and then kept in a refrigerator for 10 min and filtered. The
volatiles were removed in vacuo; yield: 1.23 g (98%); oil.
2-Methyl-3-Isopropylaminopropionic Acid Methyl Ester (a7)19
From isopropylamine (0.59 g, 0.01 mol), methyl methacrylate (1.02
g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.48 g
(93%); oil.
IR (neat): 2957, 2933, 1736, 1621, 1462, 1196 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.69 (s, 3 H), 2.86 (m, 1 H), 2.76
(m, 1 H), 2.60 (m, 2 H), 1.21 (s, 1 H), 1.17 (d, J = 7.2 Hz, 2 H), 1.03
(d, J = 6.2 Hz, 6 H).
IR (neat): 3443, 2961, 2916, 2253, 1735, 1465, 1356, 1191 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.9 (t, J = 6.64 Hz, 2 H), 2.6 (t,
J = 7.14 Hz, 2 H), 2.5 (t, J = 6.65 Hz, 2 H), 1.44–1.48 (m, 2 H),
1.33–1.37 (m, 2 H), 0.9 (t, J = 7.3 Hz, 3 H).
ESI-MS: m/z = 160 (M + H)+.
3-Benzylaminopropionitrile (a8)10
ESI-MS: m/z = 127 (M + H)+.
From benzylamine (1.07 g, 0.01 mol), acrylonitrile (0.53 g, 0.01
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.53 g (96%); oil.
3-Butylaminopropionic Acid Ethyl Ester (a2)9
IR (neat): 3334, 2927, 2845, 2247, 1602, 1454, 1126 cm–1.
From n-butylamine (0.73 g, 0.01 mol), ethyl acrylate (1.0 g, 0.01
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.67 g (96%); oil.
1H NMR (500 MHz, CDCl3): d = 7.31–7.34 (m, 2 H), 7.24–7.32 (m,
3 H), 3.8 (s, 2 H), 2.8 (m, 2 H), 2.5 (m, 2 H).
IR (neat): 3410, 2959, 2872, 1736, 1457, 1366, 1184 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.1 (q, J = 7.5 Hz, 2 H), 2.8 (t,
J = 6.8 Hz, 2 H), 2.9 (t, J = 7.2 Hz, 2 H), 2.53–2.65 (m, 2 H), 1.4
(m, 2 H), 1.22–1.25 (m, 5 H), 1.2 (t, J = 7.5 Hz, 3 H).
ESI-MS: m/z = 161 (M + H)+.
3-Benzylaminopropionic Acid Ethyl Ester (a9)9
ESI-MS: m/z = 174 (M + H)+.
From benzylamine (1.07 g, 0.01 mol), ethyl acrylate (1.5 g, 0.01
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.9 g (92%); oil.
2-Methyl-3-butylaminopropionic Acid Methyl Ester (a3)9
From n-butylamine (0.73 g, 0.01 mol), methyl methacrylate (1.02 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.60 g
(92%); oil.
IR (neat): 3377, 2981, 2828, 1732, 1603, 1495, 1028 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.26 (m, 2 H), 7.06 (m, 3 H), 4.06
(q, J = 7.2 Hz, 2 H), 3.64 (s, 2 H), 2.9–3.1 (m, J = 6.2 Hz, 2 H),
2.61–2.65 (t, J = 6.15 Hz, 2 H), 1.23–1.27 (t, J = 7.2 Hz, 3 H).
IR (neat): 2957, 2933, 1736, 1621, 1462, 1196 cm–1.
ESI-MS: m/z = 208 (M + H)+.
1H NMR (500 MHz, CDCl3): d = 3.68 (s, 3 H), 2.8 (m, 1 H), 2.5 (m,
4 H), 1.45 (m, 2 H), 1.43 (m, 2 H), 1.15 (d, J = 6.4 Hz, 3 H), 0.88 (t,
J = 6.5 Hz, 3 H).
3-Benzylamino-2-methylpropionic Acid Methyl Ester (a10)10
From 1-phenylethylamine (1.21 g, 0.01 mol), methyl methacrylate
(1.02 g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.90
g (93%); oil.
ESI-MS: m/z = 174 (M + H)+.
3-Butylaminocyclohexanone (a4)18
IR (neat): 2952, 2848, 1736, 1603, 1495, 1454, 1196 cm–1.
From n-butylamine (0.73 g, 0.01 mol), cyclohex-2-en-1-one (0.96
g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude prod-
uct was purified by flash chromatography on a silica gel column
(eluent: hexanes–EtOAc, 4:1); yield: 1.62 g (96%).
1H NMR (500 MHz, CDCl3): d = 7.3 (m, 3 H), 7.2 (m, 2 H), 3.7 (s,
2 H), 3.6 (s, 3 H), 2.8 (m, 1 H), 2.6 (m, 2 H), 1.5 (s, 1 H), 1.1 (d,
J = 6.6 Hz, 3 H).
ESI-MS: m/z = 208 (M + H)+.
IR (neat): 3364, 2971, 1701, 1495, 1449, 1374, 1050 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.67 (m, 1 H), 2.9 (m, 1 H), 2.3–
2.5 (m, 4 H), 2.17–2.25 (m, 6 H), 1.68–1.72 (m, 4 H), 0.9 (t, J = 7.3
Hz, 3 H).
3-Benzylaminocyclohexanone (a11)10
From benzylamine (1.07 g, 0.01 mol), cyclohex-2-en-1-one (0.96 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude product
was purified by flash chromatography on a silica gel column (elu-
ent: hexanes–EtOAc, 4:1); yield: 1.7 g (89%).
ESI-MS: m/z = 192 (M + Na)+.
3-Isopropylaminopropionitrile (a5)19
IR (neat): 3355, 2960, 2926, 1705, 1601, 1586, 1290 cm–1.
From isopropylamine (0.59 g, 0.01 mol), acrylonitrile (0.53 g, 0.01
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.0 g (98%); oil.
1H NMR (500 MHz, CDCl3): d = 7.31–7.34 (m, 4 H), 7.24 (m, 1 H),
4.5 (s, 1 H), 3.80 (s, 2 H), 3.7 (s, 1 H), 2.8 (m, 1 H), 2.01–2.47 (m,
5 H), 1.68 (m, 2 H).
IR (neat): 2960, 2926, 2246, 1736, 1466, 1376, 1191 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.8 (t, J = 6.55 Hz, 2 H), 2.75 (m,
1 H), 2.4 (t, J = 6.55 Hz, 2 H), 1.01 (d, J = 6.2 Hz, 6 H).
ESI-MS: m/z = 226 (M + Na)+.
3-(1-Phenylethylamino)propionitrile (a12)9
From 1-phenylethylamine (1.21 g, 0.01 mol), acrylonitrile (0.53 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.56 g
(91%); oil.
ESI-MS: m/z = 113 (M + H)+.
3-Isopropylaminopropionic Acid Ethyl Ester (a6)19
From isopropylamine (0.59 g, 0.01 mol), ethyl acrylate (1.5 g, 0.015
mol), RuCl3⋅H2O (0.011g, 0.05 mmol); yield: 1.0 g (91%); oil.
IR (neat): 3322, 3018, 2966, 2914, 2247, 1493, 1132 cm–1.
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IR (neat): 3356, 2960, 2826, 2245, 1611, 1386, 1090 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.30–7.34 (m, 4 H), 7.23–7.26 (m,
1 H), 3.78–3.38 (m, J = 6.5 Hz, 1 H), 2.6–2.8 (m, 2 H), 2.39–2.43
(m, 2 H), 1.52 (s, 1 H), 1.35–1.36 (d, J = 6.6 Hz, 3 H).
1H NMR (500 MHz, CDCl3): d = 6.79–6.81 (d, J = 7.0 Hz, 2 H),
6.59–6.61 (d, J = 7.0 Hz, 2 H), 3.75 (s, 3 H), 3.45–3.47 (m, J = 6.48
Hz, 2 H), 2.5–2.6 (t, J = 6.48 Hz, 2 H).
ESI-MS: m/z = 175 (M + H)+.
ESI-MS: m/z = 177 (M + H)+.
3-(1-Phenylethylamino)propionic Acid Ethyl Ester (a13)9
From 1-phenylethylamine (1.21 g, 0.01 mol), ethyl acrylate (1.0 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.94 g
(90%); oil.
3-(4-Methoxyphenylamino)propionic Acid Ethyl Ester (b5)21
From 4-methoxyaniline (1.23 g, 0.01 mol), ethyl acrylate (1.0 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 2.0 g (92%);
yellow solid.
IR (neat): 3356, 2961, 2921, 1738, 1611, 1090 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.27–7.28 (m, 4 H), 7.19–7.20 (m,
1 H), 4.0–4.1 (q, J = 7.0 Hz, 2 H), 3.73–3.74 (q, J = 6.5 Hz, 1 H),
2.65–2.73 (m, 2 H), 2.41–2.43 (m, 2 H), 1.72 (s, 1 H), 1.30–1.31 (d,
J = 6.5 Hz, 3 H), 1.19–1.31 (t, J = 7.1 Hz, 3 H).
IR (neat): 3359, 2926, 2831, 1624, 1513, 1228, 1020 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.8–6.81 (d, J = 7.1 Hz, 2 H),
6.50–6.60 (d, J = 7.1 Hz, 2 H), 4.9 (s, 1 H), 4.2–4.25 (q, J = 7.2 Hz,
2 H), 3.84 (s, 3 H), 3.48–3.51 (q, J = 6.15 Hz, 2 H), 2.60–2.62 (t,
J = 6.15 Hz, 2 H), 1.23–1.27 (t, J = 7.2 Hz, 3 H).
ESI-MS: m/z = 222 (M + H)+.
ESI-MS: m/z = 224 (M + H)+.
2-Methyl-3-(1-phenylethylamino)propionic Acid Methyl Ester
(a14)9
From 1-phenylethylamine (1.21 g, 0.01 mol), methyl methacrylate
(1.02 g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.97
g (89%); oil.
3-(4-Methoxyphenylamino)cyclohexanone (b6)
From 4-methoxyaniline (1.23 g, 0.01 mol), cyclohex-2-en-1-one
(0.96 g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude
product was purified by flash chromatography on a silica gel col-
umn (eluent: hexanes–EtOAc, 4:1); yield: 1.99 g (91%).
IR (neat): 2950, 2840, 1735, 1603, 1495, 1454, 1196 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.2 (m, 2 H), 7.18 (m, 3 H), 3.6 (s,
3 H), 2.9 (m, 3 H), 2.85 (m, 2 H), 2.63 (m, 2 H), 1.25 (s, 1 H), 1.14
(d, J = 6.6 Hz, 3 H).
IR (neat): 3360, 2924, 2831, 1714, 1613, 1217, 1029 cm–1.
1H NMR (500 MHz, CDCl3): d = 6.8 (d, J = 6.9 Hz, 2 H), 6.6 (d,
J = 7.0 Hz, 2 H), 4.62 (s, 1 H), 3.75 (s, 3 H), 3.65 (m, 1 H), 2.98 (m,
1 H), 2.20–2.56 (m, 5 H), 1.68–1.70 (m, 2 H).
ESI-MS: m/z = 223 (M + H)+.
13C NMR (125 MHz, CDCl3): d = 21.0, 32.84, 43.19, 49.07, 52.30,
56.0, 112.81, 122.65, 135.44, 151.67, 208.24.
3-Phenylaminopropionitrile (b1)20
From aniline (0.93 g, 0.01 mol), acrylonitrile (0.53 g, 0.01 mol), and
RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.4 g (96%); oil.
ESI-MS: m/z = 242 (M + Na)+.
IR (neat): 3356, 2960, 2926, 2245, 1471, 1366, 1080 cm–1.
Anal. Calcd for C13H17NO2: C, 71.21; H, 7.81. Found: C, 71.32; H,
7.75.
1H NMR (500 MHz, CDCl3): d = 7.19–7.24 (m, 2 H), 6.75–6.78 (m,
1 H), 6.6–6.62 (d, J = 7.8 Hz, 2 H), 3.48–3.51 (t, J = 6.5 Hz, 2 H),
2.60–2.62 (t, J = 6.5 Hz, 2 H).
3-(4-Nitrophenylamino)propionitrile (b7)20
From 4-nitroaniline (1.38 g, 0.01 mol), acrylonitrile (0.795 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.73 g (91%);
yellow.
ESI-MS: m/z = 147 (M + H)+.
Phenylaminoacetic Acid Ethyl Ester (b2)20
From aniline (0.93 g, 0.01 mol), ethyl acrylate (1.0 g, 0.01 mol), and
RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.74 g (92%); oil.
IR (neat): 3369, 2968, 2243, 1603, 1601, 1435, 1176, 1091 cm–1.
1H NMR (500 MHz, CDCl3): d = 8.1 (d, J = 9.1 Hz, 2 H), 6.8 (d,
J = 9.1 Hz, 2 H), 3.51–3.53 (t, J = 6.5 Hz, 2 H), 2.56–2.59 (t, J = 6.5
Hz, 2 H).
IR (neat): 3355, 2960, 2916, 1740, 1571, 1386 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.16–7.24 (m, 2 H), 6.69–6.72 (m,
1 H), 6.61–6.62 (d, J = 7.7 Hz, 2 H), 4.02–4.17 (q, J = 7.15 Hz, 2
H), 4.02 (s, 1 H), 3.43–3.45 (t, J = 6.3 Hz, 2 H), 2.59–2.61 (t, J = 6.3
Hz, 2 H), 1.24–1.27 (t, J = 7.15 Hz, 3 H).
ESI-MS: m/z = 192 (M + H)+.
3-(4-Nitrophenylamino)propionic Acid Ethyl Ester (b8)21
From 4-nitroaniline (1.38 g, 0.01 mol), ethyl acrylate (1.0 g, 0.01
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.9 g (81%); yel-
low.
ESI-MS: m/z = 194 (M + H)+.
3-Phenylaminocyclohexanone (b3)8
IR (neat): 3392, 2985, 2926, 1723, 1607, 1503 cm–1.
From aniline (0.93 g, 0.01 mol), cyclohex-2-en-1-one (0.96 g, 0.01
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude product was
purified by flash chromatography on a silica gel column (eluent:
hexanes–EtOAc, 4:1); yield: 1.64 g (87%).
1H NMR (500 MHz, CDCl3): d = 8.0 (d, J = 9.0 Hz, 2 H), 6.5 (d,
J = 9.0 Hz, 2 H), 4.9 (s, 1 H), 4.15–4.19 (q, J = 7.15 Hz, 2 H), 3.52–
3.56 (q, J = 6.2 Hz, 2 H), 2.62–2.65 (t, J = 6.2 Hz, 2 H), 1.25–1.28
(t, J = 7.15 Hz, 3 H).
IR (neat): 3346, 2896, 1711, 1471, 1386, 1090 cm–1.
ESI-MS: m/z = 239 (M + H)+.
1H NMR (500 MHz, CDCl3): d = 7.29–7.34 (m, 4 H), 7.24 (m, 1 H),
4.6 (s, 1 H), 3.7 (s, 1 H), 2.8 (d, J = 4.2 Hz, 1 H), 2.35–2.47 (m, 3
H), 2.06–2.10 (m, 2 H), 1.77–1.80 (m, 2 H).
3-(4-Nitrophenylamino)cyclohexanone (b9)
From 4-nitroaniline (1.38 g, 0.01 mol), cyclohex-2-en-1-one (0.96
g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude prod-
uct was purified by flash chromatography on a silica gel column
(eluent: hexane–EtOAc, 4:1); yield: 1.88 g (87%).
ESI-MS: m/z = 212 (M + Na)+.
3-(4-Methoxyphenylamino)propionitrile (b4)21
From 4-methoxyaniline (1.23 g, 0.01 mol), acrylonitrile (0.53 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.7 g (98%);
yellow solid.
IR (neat): 3378, 2998, 1714, 1601, 1396, 1177, 1092 cm–1.
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1H NMR (500 MHz, CDCl3): d = 8.0 (d, J = 9.1 Hz, 2 H), 6.5 (d,
J = 9.1 Hz, 2 H), 4.6 (s, 1 H), 3.9 (s, 1 H), 2.82–2.85 (d, J = 4.2 Hz,
1 H), 2.47 (m, 1 H), 2.35–2.38 (m, 2 H), 2.10 (m, 1 H), 2.06–2.09
(m, 1 H), 1.77–1.80 (m, 2 H).
(2-Methyl-3-morpholin-4-yl)propionic Acid Methyl Ester (c6)7
From morpholine (0.87 g, 0.01 mol), methyl methacrylate (1.02 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.69 g
(91%).
13C NMR (125 MHz, CDCl3): d = 22.2, 30.84, 41.17, 48.07, 52.08,
111.75, 126.72, 138.72, 151.66, 208.59.
IR (neat): 2954, 2854, 1739, 1458, 1119 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.69 (s, 3 H), 3.66 (m, 4 H), 2.68–
2.71 (dm, 2 H), 2.62–2.64 (dm, 4 H), 2.28–2.32 (m, 1 H), 1.14–1.15
(d, J = 6.8 Hz, 3 H).
ESI-MS: m/z = 257 (M + Na)+.
Anal. Calcd for C12H14N2O3: C, 61.53; H, 6.02. Found: C, 61.67; H,
5.89.
ESI-MS: m/z = 188 (M + H)+.
(3-Piperidin-1-yl)propionitrile (c1)9
(3-Morpholin-4-yl)cyclohexanone (c7)
From morpholine (0.87 g, 0.01 mol), cyclohex-2-en-1-one (0.96 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.6 g (85%);
oil.
From piperidine (0.85 g, 0.01 mol), acrylonitrile (0.795 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.4 g (~100%);
oil.
IR (neat): 2933, 2856, 2806, 2243, 1436, 1126 cm–1.
IR (neat): 2950, 2855, 1520, 1040 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.65–2.68 (m, 2 H), 2.48–2.51 (m,
2 H), 2.42 (m, 4 H), 1.56–1.60 (m, 4 H), 1.42–1.45 (m, 2 H).
1H NMR (500 MHz, CDCl3): d = 3.7 (t, J = 4.6 Hz, 4 H), 3.4 (m, 1
H), 2.3 (t, J = 4.6 Hz, 4 H), 2.63–2.76 (m, 1 H), 2.34–2.37 (m, 3 H),
2.12–1.27 (m, 2 H), 1.6–1.7 (m, 2 H).
ESI-MS: m/z = 139 (M + H)+.
13C NMR (125 MHz, CDCl3): d = 22.1, 31.0, 38.2, 48.3, 52.3, 56.2,
72.8, 208.5.
(3-Piperidin-1-yl)propionic Acid Ethyl Ester (c2)9
From piperidine (0.85 g, 0.01 mol), ethyl acrylate (1.5 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.81 g (97%); oil.
ESI-MS: m/z = 206 (M + Na)+.
Anal. Calcd for C10H17NO2: C, 65.54; H, 9.35. Found: C, 65.66; H,
9.75.
IR (neat): 2936, 2855, 2806, 1736, 1436 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.11–4.15 (m, 2 H), 2.64–2.67 (m,
2 H), 2.48–2.51 (m, 2 H), 2.39 (m, 4 H), 1.54–1.58 (m, 4 H), 1.42–
1.43 (m, 2 H), 1.24–1.26 (m, 3 H).
3-Dibutylaminopropionitrile (c8)11
From dibutylamine (1.29 g, 0.01 mol), acrylonitrile (0.795 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.76 g (97%); oil.
ESI-MS: m/z = 186 (M + H)+.
IR (neat): 2958, 2872, 2801, 2256, 1453 cm–1.
(2-Methyl-3-piperidin-1-yl)propionic Acid Methyl Ester (c3)9
From piperidine (0.85 g, 0.01 mol), methyl methacrylate (1.02 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.69 g
(89%); oil.
1H NMR (500 MHz, CDCl3): d = 3.50 (t, J = 7.2 Hz, 2 H), 3.25 (t,
J = 7.6 Hz, 4 H), 2.60 (t, J = 7.2 Hz, 2 H), 1.5–1.6 (m, 4 H), 1.32–
1.36 (m, 4 H), 0.95 (t, J = 7.5 Hz, 6 H).
ESI-MS: m/z = 183 (M + H)+.
IR (neat): 2932, 2854, 2797, 1743, 1461 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.68 (s, 3 H), 2.62–2.67 (m,
J = 6.9 Hz, 1 H), 2.58–2.60 (m, 1 H), 2.32–2.37 (dm, 4 H), 2.25–
2.28 (m, 1 H), 1.50–1.54 (m, 4 H), 1.39–1.44 (m, 2 H), 1.12 (d,
J = 6.9 Hz, 3 H).
3-Dibutylaminopropionic Acid Ethyl Ester (c9)11
From dibutylamine (1.29 g, 0.01 mol), ethyl acrylate (1.5 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.44 g (90%); oil.
IR (neat): 2958, 2922, 1738, 1461, 1366 cm–1.
ESI-MS: m/z = 186 (M + H)+.
1H NMR (500 MHz, CDCl3): d = 4.09–4.12 (m, 2 H), 2.75–2.76 (m,
2 H), 2.35–2.43 (m, 6 H), 1.30–1.41 (m, 4 H), 1.22–1.30 (m, 7 H),
0.87–0.91 (m, 6 H).
(3-Morpholin-4-yl)propionitrile (c4)7
From morpholine (0.87 g, 0.01 mol), acrylonitrile (0.795 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.38 g (99%); oil.
ESI-MS: m/z = 230 (M + H)+.
IR (neat): 2952, 2856, 2806, 1440, 1089 cm–1.
3-Phenylthiopropionitrile (d1)6
1H NMR (500 MHz, CDCl3): d = 3.71–3.72 (t, J = 4.5 Hz, 4 H),
2.66–2.69 (t, J = 6.9 Hz, 2 H), 2.52–2.53 (t, J = 6.87 Hz, 2 H),
2.49–2.52 (t, J = 4.5 Hz, 4 H).
From benzenethiol (1.1 g, 0.01), acrylonitrile (0.795 g, 0.015 mol),
and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.53 g (94%); oil.
IR (neat): 2924, 2853, 1574, 1486, 1279, 1084, 1022 cm–1.
ESI-MS: m/z = 141 (M + H)+.
1H NMR (500 MHz, CDCl3): d = 7.41–7.42 (m, 2 H), 7.32–7.35 (m,
2 H), 7.27 (m, 1 H), 3.10–3.13 (t, J = 7.2 Hz, 2 H), 2.56–2.59 (t,
J = 7.2 Hz, 2 H).
(3-Morpholin-4-yl)propionic Acid Ethyl Ester (c5)7
From morpholine (0.87 g, 0.01 mol), ethyl acrylate (1.5 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.8 g (96%); oil.
ESI-MS: m/z = 164 (M + H)+.
IR (neat): 2951, 2856, 1732, 1453, 1108 cm–1.
3-Phenylthiopropionic Acid Ethyl Ester (d2)22
1H NMR (500 MHz, CDCl3): d = 4.12–4.16 (q, J = 7.07, 2 H), 3.69–
3.70 (t, J = 4.16 Hz, 4 H), 2.67–2.70 (t, J = 7.18 Hz, 2 H), 2.49–
2.51 (t, J = 7.20 Hz, 2 H), 2.46–2.48 (t, J = 4.16 Hz, 4 H), 1.24–
1.27 (t, J = 7.07 Hz, 3 H).
From benzenethiol (1.07 g, 0.01 mol), ethyl acrylate (1.5 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.9 g (92%); oil.
IR (neat): 2919, 1734, 1664, 1508, 1176, 1020 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.36 (m, 2 H), 7.21 (m, 3 H), 4.1
(m, 2 H), 3.14 (t, J = 6.4 Hz, 2 H), 2.75 (t, J = 6.4 Hz, 2 H), 1.2 (t,
J = 7.2 Hz, 3 H).
ESI-MS: m/z = 188 (M + H)+.
ESI-MS: m/z = 232 (M + Na)+.
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3-Phenylthiocyclohexanone (d3)22
References
From benzenethiol (1.07 g, 0.01 mol), cyclohex-2-en-1-one (0.96 g,
0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude product
was purified by flash chromatography on a silica gel column (elu-
ent: hexanes–EtOAc, 4:1); yield: 1.84 g (89%).
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IR (neat): 2924, 1728, 1674, 1418, 1266, 1041 cm–1.
1H NMR (500 MHz, CDCl3): d = 7.4 (m, 2 H), 7.2 (m, 3 H), 3.4 (m,
1 H), 2.6 (d, J = 4.3 Hz, 1 H), 2.30–2.37 (m, 3 H), 2.12 (m, 2 H),
1.68 (m, 2 H).
ESI-MS: m/z = 230 (M + Na)+.
3-[2-(2-Cyanoethylsulfanyl)ethylsulfanyl]propionitrile (d4)23
From dithioglycol (0.94 g, 0.01 mol), acrylonitrile (0.795 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield: 1.86 g (93%); oil.
IR (neat): 2976, 2927, 1732, 1451, 1372, 1182 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.85–2.91 (m, 8 H), 2.76–2.77 (m,
2 H), 2.66–2.67 (m, 2 H).
ESI-MS: m/z = 201 (M + H)+.
3-[2-(2-Ethoxycarbonylethylsulfanyl)ethylsulfanyl]propionic
Acid Ethyl Ester (d5)24
From dithioglycol (0.94 g, 0.01 mol), ethyl acrylate (1.5 g, 0.015
mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol); yield 2.7g (92%); oil.
IR (neat): 2924, 1745, 1503, 1350, 1128, 1028 cm–1.
1H NMR (500 MHz, CDCl3): d = 4.1 (t, J = 6.8 Hz, 4 H), 2.81–2.83
(m, 8 H), 2.67 (m, 4 H), 1.2 (t, J = 7.3 Hz, 6 H).
ESI-MS: m/z = 295 (M + H)+.
3-[2-(2-Ethoxycarbonylethylsulfanyl)ethylsulfanyl]cyclohex-
anone (d6)
From dithioglycol (0.94 g, (0.01 mol), cyclohex-2-en-1-one (1.92 g,
0.02 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The crude product
was purified by flash chromatography on a silica gel column (elu-
ent: hexanes–EtOAc, 4:1); yield: 2.7 g (95%).
(11) Wabnitz, T. C.; Spencer, J. B. Tetrahedron Lett. 2002, 43,
3891.
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4, 1319.
IR (neat): 2847, 1710, 1453, 1411, 1216 cm–1.
(13) Srivastava, N.; Banik, K. J. Org. Chem. 2003, 68, 2109.
(14) Kawatsura, M.; Hartwig, J. F. Organometallics 2001, 20,
1960.
(15) (a) Bergbreiter, D. E.; Osburn, P. L.; Liu, Y. S. J. Am. Chem.
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Green Chem. 2001, 3, 146. (c) Chandrasekhar, S.;
Narsihmulu, Ch.; Sultana, S. Sh.; Reddy, N. R. Org. Lett.
2002, 4, 4399.
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1995, 36, 4471.
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1996, 35, 6964.
1H NMR (500 MHz, CDCl3): d = 3.1 (m, 2 H), 2.7 (s, 4 H), 2.69 (m,
2 H), 2.38 (m, 6 H), 2.1 (m, 4 H), 1.7 (m, 4 H).
13C NMR (125 MHz, CDCl3): d = 24.28, 30.87, 31.79, 41.05, 43.26,
48.29, 208.66.
ESI-MS: m/z = 309 (M + Na)+.
Anal. Calcd for C14H22O2S2: C, 58.70; H, 7.74. Found: C, 58.82; H,
7.60.
(3-Oxocyclohexyl)carbamic Acid Ethyl Ester (d7)25
From carbamic acid methyl ester (0.75 g, 0.01 mol), cyclohex-2-en-
1-one (0.96 g, 0.01 mol), and RuCl3⋅H2O (0.011 g, 0.05 mmol). The
crude product was purified by flash chromatography on a silica gel
column (eluent: hexanes–EtOAc, 4:1); yield: 1.7 g (85%).
(18) Xu, L.-W.; Li, L.; Xia, C.-G. Helv. Chim. Acta 2004, 87,
1522.
(19) Alcria, M.; Norio, I.; Makoto, S.; Tomoko, M. Chem.
Pharm. Bull. 1999, 47, 246.
IR (neat): 2964, 2924, 1706, 1536, 1449, 1245, 1056 cm–1.
(20) Heiniger, S. A. J. Org. Chem. 1957, 22, 1213.
(21) Merchant, J. R.; Chothia, D. S. J. Chem. Soc., Perkin Trans.
1 1972, 932.
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Abstr. 1998, 129, 224895.
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Abstr. 1960, 56, 1952.
(25) Xu, L.; Xia, C.-G. Tetrahedron Lett. 2004, 45, 4507.
1H NMR (500 MHz, CDCl3): d = 4.1 (t, J = 7.4 Hz, 2 H), 3.78 (m,
1 H), 2.6 (m, 1 H), 2.0–2.3 (m, 5 H), 1.6 (m, 2 H), 1.2 (m, 3 H).
ESI-MS: m/z = 208 (M + Na)+.
Acknowledgment
We thank the support received from the Natural Science Foundation
of China (No. 20373061) as well as the Teaching and Research
Award Program for Outstanding Young Teachers in Higher Educa-
tion Institutions of MOE, P.R.C.
Synthesis 2005, No. 13, 2129–2136 © Thieme Stuttgart · New York