A one-pot, two step synthesis of 2,2-disubstituted 1-nitroalkenes

Article abstract of DOI:10.1016/S0040-4020(03)00754-3

The reactions of ketones 1a-o, nitromethane 2, and a stoichiometric amount of piperidine 3a or ethylenediamine 3b in the presence of mercaptan 6a in THF or CH₃CN solution give high yields of β-nitrosulfides 7a-o. The latter can be oxidized by 8

Full text of DOI:10.1016/S0040-4020(03)00754-3

Tetrahedron 59 (2003) 4979–4992
A one-pot, two step synthesis of 2,2-disubstituted 1-nitroalkenes
Yeong-Jiunn Jang,a Wen-Wei Lin,a Yuh-Kuo Shih,a Ju-Tsung Liu,b Ming-Hsing Hwangc
and Ching-Fa Yaoa
,
*
aDepartment of Chemistry, National Taiwan Normal University 88, Sec. 4, Tingchow Road, Taipei 116, Taiwan, ROC
bArmy Force of Military Police School, P.O. Box 90092 Wugu, Taipei 248, Taiwan, ROC
cApplied Life Science and Health, Chia Nan University of Pharmacy and Science 60, Sec. 1, Erh-Ten Road, Jen-Te, Tainan 717,
Taiwan, ROC
Received 10 March 2003; accepted 8 May 2003
Abstract—The reactions of ketones 1a–o, nitromethane 2, and a stoichiometric amount of piperidine 3a or ethylenediamine 3b in the
presence of mercaptan 6a in THF or CH3CN solution give high yields of b-nitrosulfides 7a–o. The latter can be oxidized by 8a (m-CPBA or
m-CPBA/AcOH) at 08C, 8b (H2O2/AcOH), or 8c (H2O2) at room temperature, thus generating b-nitroalkylsulfoxides 9a–o, which then
undergo elimination to produce medium to high yields of 2,2-disubstituted-1-nitroalkenes 5a–o, when refluxed in a solution of ClCH2CH2Cl
(1,2-dichloroethane). After preparation from 1a–o, 2, 3, and 6a, 7a–o were oxidized with 8a, 8b, or 8c in a mixture of CH3CN and
ClCH2CH2Cl to generate b-nitrosulfoxides 9a–o, which then underwent elimination under refluxing under one-pot conditions. Compounds
14 and 15g were also prepared using 13, 2, 3b, and 6, in a similar manner. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
a Dean–Stark trap to continuously remove water during the
refluxing. In addition, unreacted ketones 1 are sometimes
recovered, because they are not consumed completely due
to the reversibility of the reaction. In this paper, we wish to
report on an alternate, improved, facile, and useful method
for preparing 7 without the need for a Dean–Stark
apparatus, and develop an extension of the earlier study,
in which an improved methodology for the one-pot
synthesis of nitroalkenes 5 was described. The overall
synthesis involves the use of ketones 1, nitromethane 2,
various bases 3, mercaptans 6, and various oxidization
reagents 8, using a number of solvents such as DMF
(dimethylformamide), ClCH2CH2Cl (1,2-dichloroethane),
THF (tetrahydronfuran), or CH3CN (acetonitrile) or a
mixture of CH3CN–ClCH2CH2Cl under similar reaction
conditions (Scheme 1).
Nitro-olefins are useful intermediates and important struc-
tural units in organic synthesis.1 – 6 Nitroalkenes are
typically prepared by a nitro-aldol approach by reacting
nitroalkanes with carbonyl compounds, such as aldehydes,
followed by dehydration of the 2-nitroalcohols.7 – 12
Unfortunately, the Henry reaction is impractical for the
preparation of 2,2-disubstituted-1-nitroalkenes because it is
reversible when ketones are used.13,14 Tamura et al.
employed N,N-dimethylethylenediamine to drive the con-
densation of ketones with nitroalkanes, but the major
products were b,g-unsaturated tautomers.15 Our previous
study16 reported that some 2,2-disubstituted-1-nitroalkenes
can be prepared by the reaction of ketones 1, nitromethane
2, piperidine 3a, a mercaptan 6, and m-chloroperoxybenzoic
acid (m-CPBA) 8a-1, which is an amalgamation of
Carroll’s17 and Trost’s18,19 work, involving a nitro-aldol
addition to generate the intermediate tertiary b-nitro
alcohols 4, the dehydration of 4 to give nitroalkenes 5
(reversible), the conjugate addition of the mercaptan 6 to 5
to yield b-nitrosulfides 7, the oxidation of 7 with m-CPBA
8a-1 to form b-nitrosulfoxides 9 and, finally, a b-elimin-
ation to give 5. Although medium to high yields of
intermediate 7 can be prepared by the reaction of 1 with
2, 6, and a catalytic amount of 3a using benzene as the
solvent,16,17 this method is not only lengthy but also requires
2. Results and discussion
In some preliminary tests, a variety of solvents such as
DMF, ClCH2CH2Cl, THF, and CH3CN and bases such as
piperidine 3a and ethylenediamine 3b were examined. Only
43% yield of 7f and small amounts of unreacted ketone were
observed when cyclopentanone 1f was reacted with 2 and 3a
in the presence of benzyl mercaptan 6a in DMF solution at
1008C (oil bath temperature) for 3 h (entry 11 of Table 1).
The solution became black in color and only traces of 7f
remained when the reaction time was increased to 8 h under
similar conditions (entry 12). Similarly, a 64% yield of 7f
and traces of unreacted 1f were observed when the same
Keywords: ketone; mercaptan; nitro-olefin; hydrogen peroxide; one-pot.
*
Corresponding author. Tel.: þ886-2-29309092; fax: þ886-2-29324249;
e-mail: cheyaocf@scc.ntnu.edu.tw
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00754-3

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Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
Scheme 1.
reaction was conducted in ClCH2CH2Cl solution at reflux
for 36 h (entry 13). However, 7f was produced in 94% yield
when refluxing THF or CH3CN was used as the solvent for a
period of 12 h (entry 14) or 4 h (entry 15). These results
indicate that the use of THF or CH3CN as a solvent in
preparing intermediate 7 is desirable, compared to benzene,
DMF, or ClCH2CH2Cl. Based on the above observation,
ketones 1a–e and 1g–l, respectively, were also reacted with
2 and 6a in the presence of 3a or b in THF or CH3CN
solution under similar conditions, using different reaction
times to give 7a–e and 7g–l. The complete experimental
data are shown in Table 1.
reactions. Different solvents may affect the same reaction to
different extents even under similar reaction conditions. In
comparing the data in Table 1 to our previous study in which
benzene was used as a solvent,16 we conclude that both THF
and CH3CN are superior solvents for the preparation of 7
and the use of a base, such as 3a or b also leads to
dramatically improved yields. According to Table 1, similar
and different characteristics are also observed when THF or
CH3CN is used as a solvent. Concerning the similarities, the
first observation is that high yields of 7 can be obtained
within a few hours under gentle reflux. As a result, this
reaction is best controlled by an appropriate choice of
solvent. The second observation is the reaction rate. For
example, the use of CH3CN and THF as a solvent results in a
Solvents frequently play an important role in chemical

Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
4981
Table 1. The preparation of b-nitrosulfides 7 from the reaction of keontes 1,
nitromethane 2, base 3, and mercaptan 6a (4 equiv.) in THF, CH3CN, DMF,
or ClCH2CH2Cl solution under refluxing condition
conditions.16 However, 68 or 83% of 7h was generated
when 1h was reacted with 2, 3b, and 6a in THF or CH3CN
solution under refluxing for only 15 or 12 h (entries 18 and
19). For cyclooctanone 1i, 67 or 51% (entries 20 and 21) of
7i was generated in THF or CH3CN solution under similar
conditions and only traces were observed when benzene was
used. Using acetophenone 1l, although only 5 or 23% of the
expected product 7l was generated in THF or CH3CN for 60
or 12 h (entries 26 and 27 of Table 1), no product was
detected when the reaction was conducted in benzene or 1,2-
dichloroethane. A possible explanation for this is that the
presence of steric hindrance between the ketone and
nucleophiles inhibits the reaction, especially in the case of
benzene or 1,2-dichloroethane.
Entry
1
2
(equiv.) (equiv.) (equiv.)
Base
Solvent
Time
(h)
7
Yield
(%)a
1
2
3
4
5
6
7
8
1ab
1.0
1.0
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
3a (2.0) THF
12 7a
7a
18 7b
7b
60 7c
12 7c
60 7d
13 7d
24 7e
14 7e
96
97
82
95
42
44
52
59
94
95
43
1ab
3a (2.0) CH3CN
3b (1.0) THF
3b (1.0) CH3CN
3b (2.0) THF
3b (2.0) CH3CN
3b (2.0) THF
3b (1.5) CH3CN
3b (1.0) THF
3b (1.0) CH3CN
3a (1.0) DMF
3a (1.0) DMF
5
1b (1.0)
1b (1.0)
1c (1.0)
1c (1.0)
1d (1.0)
1d (1.0)
1e (1.0)
1e (1.0)
1f (1.0)
1f (1.0)
1f (1.0)
1f (1.0)
1f (1.0)
1g (1.0)
1g (1.0)
1h (1.0)
1h (1.0)
1i (1.0)
1i (1.0)
1j (1.0)
1j (1.0)
1k (1.0)
1k (1.0)
1l (1.0)
1l (1.0)
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
3
8
7f
7f Tracec
Our previous study found that 7 can be oxidized by
m-CPBA 8a-1 in CH2Cl2 and then undergo elimination in a
CCl4 solution to give product 5.16 However, the experi-
mental procedures are tedious and the reaction is incomplete
under these conditions. Then we examined the use of 1,2-
dichloroethane ClCH2CH2Cl (bp 83–848C) as the solvent.16
b-Nitrosulfides 7 was oxidized by 8a-1 at 08C for 0.5–1 h
and then underwent elimination after refluxing for 3–4 h in
a ClCH2CH2Cl solution to give high yields of 5. Compared
to our previous report,16 the use of ClCH2CH2Cl is actually
superior to the use of CH2Cl2 or CCl4 at certain steps. The
change in solvent not only simplifies the experimental
procedures but also increases the yields dramatically, as
shown in Table 2.
3a (1.0) ClCH2CH2Cl 36 7f
64
94
94
71
96
68
83
67
51
98d
98d
97
98
5
3a (2.0) THF
3a (2.0) CH3CN
3a (2.0) THF
3a (2.0) CH3CN
3b (2.0) THF
3b (2.0) CH3CN
3b (2.0) THF
3b (1.0) CH3CN
3b (2.0) THF
3b (2.0) CH3CN
3b (1.25) THF
3b (1.25) CH3CN
3b (3.0) THF
3b (3.0) CH3CN
12 7f
7f
12 7g
7g
4
4
15 7h
12 7h
51 7i
8
7i
12 7j
12 7j
24 7k
16 7k
60 7l
12 7l
23
a
Isolated yield.
Excess amount.
Messy result.
EþZ isomers.
b
c
d
It has been reported that sulfide compounds can be oxidized
by peroxy acid21,22 or by hydrogen peroxide H2O2 in certain
solvents in the presence of acid and a catalyst or by various
other oxidizing agents to generate a sulfoxide.23 – 28
According to literature reports21,22 and the results in
Table 2, peroxyacetic acid, generated from acetic acid and
hydrogen peroxide,29 could be used to replace 8a-1
(m-CPBA). When 7g was reacted with 8b, prepared from
14 equiv. of acetic acid and 5 equiv. of 35% H2O2, in
ClCH2CH2Cl solution at room temperature for 1 h, followed
by refluxing for 4 h, 90% of the expected product 5g and
traces of unidentified products were obtained (entry 7 of
Table 3). This indicates that acetic acid is first oxidized by
H2O2 to generate peroxyacetic acid29 and then oxidizes 7g
to produce intermediate 9g which finally undergoes
decrease in the reaction time from a few days to a few hours,
compared to the use of benzene. A possible explanation for
these two features, high yield and high reaction rate, is the
superior water-solvation ability of these two solvents. In the
reaction process, when the intermediate 4 dehydrates to
form the intermediate 5 and one water molecule, these two
water-soluble solvents can solvate this water molecule well,
separate it from 5 and prevent the occurrence of retro-Henry
reaction. At this stage, the mercaptan 6 will trap the
intermediate 5 without any difficulty to produce high yield
of 7. Concerning the differences between CH3CN and THF,
the yields are always higher and the reaction rate is also
much faster when the reaction is conducted in CH3CN. A
possible explanation is that CH3CN is a more polar solvent
with an empirical solvent polarity of ET (30) (46.7) and a
dielectric constant of 1(38) compared to THF, with a
polarity of ET(30) (37.4) and a dielectric constant of
1(7.6).20 Solvent polarity is important in terms of the
solubility of the reactants, but also because they have an
effect on the nucleophilicity of anions that are involved in
nucleophilic additions.
Table 2. The preparation of 2,2-disubstituted-1-nitroalkenes 5 from
b-nitrosulfides 7 and 8a-1 (1.1 equiv. of m-CPBA) in 1,2-dichloroethane
solution at 08C and then under refluxing condition
Entry
7
08C Time (h)
Reflux time (h)
5
Yield (%)a
1
2
3
4
5
6
7
8
7a
7b
7c
7d
7e
7f
7g
7h
7i
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
3
3
3
3
3
3
3
3
3
4
4
4
5a
5b
5c
5d
5e
5f
5g
5h
5i
85
95b
96
87b
94b
94
In addition to the above advantages, this improved method
is also useful for preparing steric b-nitro sulfides, such as 7
with a bulky group in the molecule which is not easily
prepared in benzene solution. For example, when cyclo-
heptanone 1h was reacted with 2 and thiophenol in the
presence of 3a in benzene under reflux for 70 h, no product
was generated, and only 22% of the product was obtained
when allyl mercaptan was used for 70 h under similar
96
95
91
98b
94b
93
9
10
11
12
7j
7k
7l
5j
5k
5l
1
1
a
Isolated yield.
EþZ isomers.
b

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Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
Table 3. The preparation of 2,2-disubstituted-1-nitroalkenes 5 from
b-nitrosulfides 7 and 8b [H2O2 (5 equiv.)/AcOH (14 equiv.)] in 1,2-
dichloroethane solution at room temperature (1 h) and then under refluxing
condition (4 h)
The strategy of this involved preparing 5 from 1, 2, 3, 6a,
and 8 in a one-pot synthesis and without the isolation of 7.
Ketones 1g and k were chosen as cyclic and acyclic
examples to test this methodology. After generating 7g from
the reaction of 1g, 2, 3, and 6a in THF solution as shown in
Eq. (1), 4 equiv. of 8a-1 was directly added to the solution at
08C and the temperature was then increased to room
temperature for 1 h followed by refluxing for 4 h to give
20% of 5g and only minor amounts of unreacted 7g (entry
15 of Table 5). Similarly, 36% of 5g and negligible
unreacted 7g were also observed when the same reaction
was conducted in CH3CN solution (entry 16 of Table 5).
Only traces of product 5k were generated and unreacted 7k
was largely recovered when 1k was conducted in THF or
CH3CN solution (entries 25 and 26 of Table 5). Based on the
results shown in Tables 2–4 in which the oxidation of 7 with
8 in ClCH2CH2Cl solution gave high yields of 5, ClCH2-
CH2Cl was added to the CH3CN solution at a volume ratio
of CH3CN to ClCH2CH2Cl of 3 to 4. The yield of 5g was
increased to 95% and that of 5k was also improved and
increased to 24% and no intermediate 7g or k remained in
the solution (entries 14 and 24 of Table 5). Given the low
yield of 5k, it is possible that some 5k might have been
destroyed by base 3b after its formation. To prove this
assumption, after 7k was generated from the first step,
14 equiv. of acetic acid AcOH was added to the solution to
neutralize 3b and 8a-1 was then added to the solution to
oxidize 7k in the CH3CN–ClCH2CH2Cl mixture, as
described above. As expected, the yield of product 5k was
increased to 97% (entry 23 of Table 5). Based on this result,
either m-CPBA or m-CPBA/AcOH was used as an oxidant
in subsequent experiments. In addition to 5g and k,
nitroalkene 5 were also prepared from ketone 1 under
similar procedures and conditions, as shown in Table 5.
Entry
7
5
Yield (%)a
Entry
7
5
Yield (%)a
1
2
3
4
5
6
7a
7b
7c
7d
7e
7f
5a
5b
5c
5d
5e
5f
97
60b
94
96b
47b
36
7
8
9
10
11
12
7g
7h
7i
7j
7k
7l
5g
5h
5i
5j
5k
5l
90
91
88
96b
49b
70
a
Isolated yield.
EþZ isomers.
b
elimination to yield 5g as described above. In addition to
substrate 7g, other substrates such as 7a–f and 7h–l were
also reacted with 8b to yield 5a–f and 5h–l under similar
conditions, as shown in Table 3.
Although 8a or b is able to oxidize 7 to 9 efficiently, organic
acid by-product generated, such as m-chlorobenzoic acid
which is environmentally harmful or acetic acid remained in
the mixture and this increases a difficulty in the purification
of the final nitroalkenes 5. To avoid these disadvantages,
hydrogen peroxide 8c (5 equiv.) was used to oxidize 7
directly in ClCH2CH2Cl solution under similar conditions.
Fortunately, a nearly quantitative yield of 9 was produced in
most cases and the end products were very clean compared
to the use of 8a or b. These results also suggest that the
presence of m-chlorobenzoic acid or acetic acid is actually
undesirable in the final product, as shown in Table 4.
Based on the results in Tables 1–4, we conclude that the use
ð1Þ
of pure 7 and oxidization agent 8 in ClCH2CH2Cl solution
generate high yields of 5. However, one serious problem
was found during the column purification of 7, the
unpleasant odor of traces of mercaptan 6 that remained in
the crude mixture. To solve this problem, we combined the
first step in the generation of 7 and the second step in the
oxidization of 7 by 8 to develop an alternate methodology.
As shown in Table 5, the yields of 5c (30 and 17%), 5d (51
and 47%), 5i (21 and 5%), and 5l (11 and 4%) were all not
high when m-CPBA or m-CPBA/AcOH were used as
oxidants, but these results can be explained by the low
yields of 7c (44%), 7d (59%), 7i (51%), and 7l (23%) in the
first step (entries 6, 8, 21, 27 of Table 1) so that the total
yields are low to medium (entries 5– 8, 19, 20, 27, and 28 of
Table 5). Another possibility is that the presence of other
compounds in the mixture also underwent side reactions
thus decreasing the yield of 5.
Table 4. The preparation of 2,2-disubstituted-1-nitroalkenes 5 from
b-nitrosulfides 7 and 8c (5 equiv. of H2O2) in 1,2-dichloroethane solution
at room temperature (1 h) and then under refluxing condition (4 h)
After the use of 8a as an oxidization reagent to obtain
the figures shown in Table 5, the next trial was to use
8b (AcOH/H2O2) in the cosolvent of CH3CN–ClCH2CH2Cl
solution (Eq. (2)). As expected, 5–90% yields of 5
were generated under similar procedures and
conditions (Table 6). Although the yields of 5c (24%),
5d (37%), 5i (38%), and 5l (5%) were, again, not
high (entries 3, 4, 9, 12 of Table 6) and are similar to
Table 5, these results also can be explained by the rationale
as above.
Entry
7
5
Yield (%)a
Entry
7
5
Yield (%)a
1
2
3
4
5
6
7a
7b
7c
7d
7e
7f
5a
5b
5c
5d
5e
5f
97
93b
94
96b
90b
95
7
8
9
10
11
12
7g
7h
7i
7j
7k
7l
5g
5h
5i
5j
5k
5l
97
95
95
96b
97b
70
a
Isolated yield.
EþZ isomers.
b

Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
4983
Table 5. One-pot synthesis of 5 from 1, 2, 3, and 6a in CH3CN or THF and then reaction with m-CPBA/AcOH or m-CPBA after adding ClCH2CH2Cl as a
cosolvent if necessary
Entry
1
3 (equiv.)
Solvent
AcOH (equiv.)
m-CPBA (equiv.)
Reflux (h)
5
Yield (%)a
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1c
1c
1d
1d
1e
1e
1f
3a (2.0)
3a (2.0)
3b (1.0)
3b (1.0)
3b (3.0)
3b (3.0)
3b (1.5)
3b (1.5)
3b (1.0)
3b (1.0)
3a (0.5)
3a (0.5)
3a (0.5)
3a (0.5)
3a (0.5)
3a (0.5)
3b (1.0)
3b (1.0)
3b (1.0)
3b (1.0)
3b (1.5)
3b (1.5)
3b (1.0)
3b (1.0)
3b (1.0)
3b (1.0)
3b (2.0)
3b (2.0)
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
THF
14
–
14
–
35
–
14
–
14
–
14
–
14
–
–
–
14
–
14
–
18
–
14
–
–
–
21
–
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
5
4
4
4
4
4
6
4
4
4
4
4
3
3
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
5a
5a
5b
5b
5c
5c
5d
5d
5e
5e
5f
98
80
89b (1.4:1)c
39b (1.5:1)c
30
17
51b (1.1:1)c
47b (1.1:1)c
92b (1.9:1)c
28b (1.8:1)c
85
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
1f
5f
83
96
95
20d
36d
70
1g
1g
1g
1g
1h
1h
1i
1i
1j
1j
1k
1k
1k
1k
1l
5g
5g
5g
5g
5h
5h
5i
5i
5j
5j
5k
5k
5k
5k
5l
CH3CN
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
THF
47
21e
5f
60b (1.6:1)c
54b (1.6:1)c
97b (1:1)c
24b (1:1)c
Traced
Traced
11b (1.2:1)c
4b (1.1:1)c
CH3CN
CH3CN/ClCH2CH2Cl
CH3CN/ClCH2CH2Cl
1l
5l
Volume ratio of CH3CN–ClCH2CH2Cl¼3:4.
a
Isolated yield.
EþZ isomers.
b
c
Ratio between E and Z isomers measured by the crude NMR before purification.
Unreacted b-nitrosulfides 7 were recovered.
d
e
f
65% of 11.
57% of 11.
Table 7. One-pot synthesis of 2,2-disubstituted-1-nitroalkenes 5 from 1, 2,
3, and 6a in CH3CN and then reaction with 8c (H2O2) in a mixture of
CH3CN and ClCH2CH2Cl
Table 6. One-pot synthesis of 2,2-disubstituted-1-nitroalkenes 5 from 1, 2,
3, and 6a in CH3CN and then reaction with 8b (H2O2/AcOH) in a mixture
of CH3CN and ClCH2CH2Cl
Entry
1
Base 3
(equiv.)
H2O2
(equiv.)
Reflux (h)
5
Yield (%)a
Entry
1
Base 3
(equiv.) (equiv.) (equiv.)
AcOH
H2O2
Reflux
(h)
5
Yield
(%)a
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
3a (2.0)
3b (0.5)
3b (3.0)
3b (1.5)
3b (1.0)
3a (0.5)
3a (0.5)
3b (1.0)
3b (1.0)
3b (1.5)
3b (1.0)
3b (2.0)
10
13
15
10
15
10
10
15
5.0
13
15
15
3
3
3
4
3
3.5
3.5
3
4
4
5a
5b
5c
5d
5e
5f
5g
5h
5i
70
90b (1.6:1)c
35
Trace
1
2
3
4
5
6
7
8
1a 3a (2.0)
1b 3b (0.5)
1c 3b (3.0)
1d 3b (1.5)
1e 3b (1.0)
1f 3a (0.5)
1g 3a (0.5)
1h 3b (1.0)
14
18
35
21
21
14
14
21
14
18
21
21
10
13
15
10
15
10
10
15
5.0
13
15
15
3
3
3
4
3
3.5
3.5
3
4
4
5a 90
5b 69b (1.5:1)c
5c 24
96b (1.8:1)c
91
87
5d 37b (1.1:1)c
5e 70b (1.9:1)c
5f 76
23d
5g 73
5h 53
9
Traced
31b (1.5:1)c
56b (1:1)c
15b (1.1:1)c
10
11
12
1j
1k
1l
5j
5k
5l
9
1i
3b (1.0)
5i
38
10
11
12
1j 3b (1.5)
1k 3b (1.0)
5j 18b (1.6:1)c
5k 73b (1:1)c
3
4
3
4
1l
3b (2.0)
5l
5b (1.1:1)c
Volume ratio of CH3CN–ClCH2CH2Cl¼3:4.
a
Isolated yield.
EþZ isomers.
Volume ratio of CH3CN–ClCH2CH2Cl¼3:4.
b
a
Isolated yield.
EþZ isomers.
c
b
ratio between E and Z isomers measured by the crude NMR before
purification.
b,g-Unsaturated tautomer is the major products.
c
Ratio between E and Z isomers measured by the crude NMR before
purification.
d

4984
Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
Table 8. The preparation of 2,2-disubstituted-1-nitroalkenes 5m, n, and 12
from 1m–o according to Barton’s methodology
Entry
1
Reflux (h)
Product
Yield (%)a
1
2
3
4
5
1m
1m
1n
1n
1o
24
36
24
36
24
5m
5m
5n
5n
12
15b
24b
27b
9b
ð2Þ
51c
a
Isolated yield.
Some unreacted starting material was recovered and the products are
EþZ isomers.
b
c
The reaction was completed and 1o was consumed.
After using 8a (m-CPBA or m-CPBA/AcOH) or 8b (H2O2/
AcOH), the use of 8c in a one-pot synthesis was attempted
(Eq. (3)). As expected, 5 was generated and these findings
are shown in Table 7. Although the procedure for the
addition of 8c to the reaction mixture is simpler than 8a and
b, however, the experimental conditions are very critical
and difficult to control especially with respect to tempera-
ture compared to Tables 5 and 6. Sometimes, unreacted 7
was recovered and only traces of 5 were detected if the
reaction temperature was kept too low during the addition of
8c to the mixture. Usually, the temperature increased
sharply when 8c was added to the solution too rapidly and
this temperature effect always had a negative impact on the
generation of 5. A possible explanation for this is that 8c
might have reacted with 3a or b before it reacted with 7.30,31
To prove this assumption, 8c was added to the CH3CN–
ClCH2CH2Cl solution which contained base 3a or b and the
temperature of the solution increased sharply. In addition to
the above side reaction, some products such as 5h and i also
underwent isomerization, generating the endo-products 10
and 11 in the presence of base (entries 8 and 9 in Table 7)
consistent with other reports.15
be prepared from the reaction of 2-adamantanone with
nitromethane in the presence of 3b under refluxing
conditions and the mechanism for this is proposed in
Scheme 2.32
Based on this report,32–35 steric ketone 1m–o was reacted
with nitromethane 2 in the presence of 3b under reflux
according to the literature procedure (Eqs. (4)–(6)).32
Although products 5m and n were generated as expected,
the yields were low and the reaction rates were also very
slow even when the reaction time was increased from 24 to
36 h. Large amounts of unreacted ketones 1m and n were
recovered (entries 1–4 of Table 8). In the case of ketone 1o,
all the starting ketone was consumed completely, but the
only product was the endo-product 12 and exo-product 5o
was not observed (entry 5 of Table 8). These results indicate
that some exo-nitroalkenes actually can be prepared and
some products easily undergo isomerization to generate
endo-nitroalkenes in the presence of base 3b.36
ð3Þ
ð4Þ
It has been reported that 2-nitromethyleneadamantane can
Scheme 2.

Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
4985
ð5Þ
ð7Þ
ð6Þ
ð8Þ
To improve these reactions, 7m–o were first prepared from
the reaction of 1m–o, respectively, with 2, 3b, and 6a as
described above (Eqs. (7)–(9)). After the isolation of 7m–
o, oxidizing reagents 8a–c were used to oxidize 7m–o in
ClCH2CH2Cl as shown in Tables 2–4. High yields of
products 5m–o were generated, as shown in Table 9.
Table 9. The preparation of 2,2-disubstituted-1-nitroalkenes 5m–o from
rigid cyclicketones 1m–o, 2 (10 equiv.), and 6a (4 equiv.) by using
different oxidation reagents 8a-1, 8b, or 8c
Entry
1
Base
(equiv.) (equiv.)
Reflux
(h)
7
8b
5
(Yield, %)a
(Yield, %)a
1
2
3
4
5
6
7
8
9
1m (1.0) 3b (1.5)
1m (1.0) 3b (1.5)
1m (1.0) 3b (1.5)
1n (1.0) 3b (1.0)
1n (1.0) 3b (1.0)
1n (1.0) 3b (1.0)
14
14
14
8
8
8
8
8
8
7m (95)c
7m (95)c
7m (95)c
7n (97)
7n (97)
7n (97)
7o (94)
7o (94)
7o (94)
8a-1 5m (87)d
8b
8c
5m (88)d
5m (93)d
8a-1 5n (94)d
8b
8c
5n (94)d
5n (94)d
ð9Þ
1o (1.0)
1o (1.0)
1o (1.0)
3b (1.0)
3b (1.0)
3b (1.0)
8a-1 5o (95)d
8b
8c
5o (95)d
5o (95)d
After the preparation 5m–o using 7m–o, a one-pot reaction
was attempted as shown in Eq. (10). Fortunately, 5m–o
were generated when solutions of 7m–o were treated with
8a–c, respectively (Table 10). Based on these results, we
found that the use of 8a (m-CPBA or m-CPBA/AcOH) or 8b
(AcOH/H2O2) consistently produced 5 in higher yields than
that of 8c (H2O2) and these phenomena are in agreement
with Tables 5–7 and also prove that the addition of AcOH
neutralizes the base, thus increasing product yields.
a
Isolated yield.
b
8a-1:1.1 equiv. of m-CPBA in ClCH2CH2Cl at room temperature for 1 h
and then under refluxing condition for 4 h; 8b: 5 equiv. of H2O2 and
14 equiv. of AcOH in ClCH2CH2Cl at room temperature 1 h and then
under refluxiong condition for 4 h; 8c: 5 equiv. of H2O2 in ClCH2CH2Cl
at 08C and stirring for 1 h at room temperature and then under refluxing
condition for 4 h.
Two isomers were isolated.
EþZ isomers.
c
d

4986
Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
Table 10. One-pot synthesis of 2,2-disubstituted-1-nitroalkenes 5m–o
from 1m–o, 2 (10 equiv.), 3 and 6a (4 equiv.) in CH3CN and then reaction
with 8 in CH3CN and ClCH2CH2Cl solution
Table 11. The preparation of 14 and 15 from the reaction of 13, 2
(10 equiv.), 3b (1 equiv.), and 6 under refluxing conditions (13 h)
Entry
6 (equiv.)
Yield (%)a
Entry
1 3b
(equiv.) (equiv.)
Reflux
(h)
8
5 Yield
(%)b
(Oxidant)a
14
15
1
2
3
4
5
6
7
8
6a (4.0)
6b (4.0)
6c (4.0)
6d (4.0)
6e (5.0)
6f (3.5)
6g (2.5)
6g (5.0)
14a (53)
14b (–)c
14c (52)
14d (17)
14e (44)
14f (56)
14g (42)
14g (81)
15a (–)b
15b (–)b
15c (–)b
15d (–)b
15e (–)b
15f (–)b
15g (7)
1
2
3
4
5
6
7
8
1m (1.0) 1.5
1m (1.0) 1.5
1m (1.0) 1.5
1m (1.0) 1.5
1n (1.0) 1.0
1n (1.0) 1.0
1n (1.0) 1.0
1n (1.0) 1.0
1o (1.0) 1.0
1o (1.0) 1.0
1o (1.0) 1.0
1o (1.0) 1.0
14
14
14
14
8
8
8
8
8
8a-1 (m-CPBA)
5m (41)c
8a-2 (m-CPBA/AcOH)d 5m (60)c
8b (H2O2/AcOH)
8c (H2O2)
8a-1 (m-CPBA)
5m (77)c
5m (39)c,e
5n (66)c
8a-2 (m-CPBA/AcOH)d 5n (96)c
8b (H2O2/AcOH)
8c (H2O2)
8a-1 (m-CPBA)
5n (93)c
5n (20)c,e
5o (31)c
15g (5)
9
a
10
11
12
8
8
8
8a-2 (m-CPBA/AcOH)d 5o (64)c
Isolated yield.
No product 15 was detectable in the crude 1H NMR or GC–MS analysis.
No product 14 was detectable in the crude 1H NMR or GC–MS analysis.
b
c
8b (H2O2/AcOH)
8c (H2O2)
5o (97)c
5o (25)c,e
Volume ratio of CH3CN–ClCH2CH2Cl¼3:4.
a
8a: 4 equiv. of m-CPBA; 8b: 21 equiv. of AcOH and 13 equiv. of H2O2;
8c: 13 equiv. of H2O2.
Isolated yield.
The generation of 14 and 15 provides indirect evidence to
support the hypothesis that intermediate 5p is formed during
the reaction. A possible mechanism for the formation of
product 14 is shown in Scheme 3, which proceeds through
the intermolecular 1,4-addition of 1 equiv. of 6 to one of the
nitroalkene groups in 5p to form nitronate A and then
nitronate A undergoes an intramolecular 1,4-addition to the
second nitroalkene group to generate B and finally accepts a
proton to generate 14. The generation of 15g in a similar
manner is proposed in Scheme 4. The mechanism involves
the intermolecular 1,4-addition of 2 equiv. of 6g to the two
nitroalkene groups of 5p at the same time to produce C,
which then accepts a proton to give 15. Compared to 15, the
yields of product 14 are much higher because only one
equiv. of mercaptan 6 is needed in the reaction. The low
yield of 15g can be explained by a steric effect between the
anion of 6 and 5p and the low probability of a simultaneous
addition of the 2 equiv. of anion 6 to substrate 5p.
b
c
d
e
EþZ isomers.
21 equiv. of AcOH were added before adding m-CPBA.
Some unreacted b-nitrosulfides 7 were recovered.
ð10Þ
Only ketones 1a–o, which contain a mono carbonyl group
were used to prepare 5a–o. It would be interesting to use a
dicarbonyl ketone as well. The preparation of compound 5p
was originally proposed from the reaction of 1,4-cyclo-
hexanedione 13 with 2, 3b, and mercaptan 6 (Eq. (11)).
However, 14a, c–g were obtained in only low to
medium (17–81%) yields and small amounts (5–7%) of
15g could be isolated when mercaptans such as 6g were
used (Table 11).
3. Conclusion
In conclusion, we report on improvements in an earlier
method for the preparation of 2,2-disubstituted-1-nitro-
alkenes by oxidizing b-nitrosulfides 7a–o with 8a
(m-CPBA or m-CPBA/AcOH), 8b (H2O2/AcOH), or 8c
(H2O2) in 1,2-dichloroethane solution efficiently. A similar
ð11Þ

Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
4987
Scheme 3.
Scheme 4.
product 5a–o also can be synthesized by using 1a–o, 2, 3,
6a, and 8 under one-pot conditions. The generation of 14
and 15 provides indirect evidence to support the formation
of intermediate 5p during the reaction.
4.3. Typical experimental procedures for the
preparation of the b-nitrosulfides 7a–o from the
reaction of ketones 1a–o, nitromethane 2, and benzyl
mercaptan 6a in the presence of piperidine 3a or
ethylenediamine 3b as base in different solvents
(Tables 1 and 9)
4. Experimental
In a 100 ml round-bottomed flask were placed ethyl methyl
ketone 1b (5 mmol), nitromethane 2 (50 mmol), ethylene-
diamine 3b (5 mmol), and benzyl mercaptan 6a (20 mmol)
in 15 ml of CH3CN and the solution was refluxed for 8 h.
After cooling, the solvent was evaporated and the crude was
purified by flash column chromatography using hexane–
ethyl acetate (200:1) as the eluent to give pure 7b (95%
isolated yield). Similar procedures were used when other
ketones 1c–l were used to prepare intermediates 7c–l in
different solvents. Due to the low boiling point of 1a, 2 was
used as the limiting reagent and an excess of 1a was
continuously added to the solution during the reaction until
all the nitromethane 2 was consumed. All the experimental
data concerning the reaction, the solvents used, and the
yields of product 7a–l can be found in Table 1. When
ketones 1m–o were used, similar procedures and conditions
were used and the experimental data concerning 7m–o are
shown in Table 9.
4.1. General remarks
All reactions were performed in flame or oven-dried
glassware under a positive pressure of nitrogen. THF,
CH3CN, DMF, and ClCH2CH2Cl were used directly
without purification. Analytical thin layer chromatography
was performed with E. Merck silica gel 60F glass plates and
flash chromatography used E. Merck silica gel 60 (230–400
mesh). MS or HRMS were measured by JEOL JMS-D300 or
JEOL JMS-HX110 spectrometer. 1H and 13C NMR spectra
were recorded with a Varian Gemini-200. All NMR data
were obtained in CDCl3 solution and chemical shifts (d)
were given in ppm relative to TMS. Elemental analysis was
performed on a Perkin–Elmer 2400 instrument.
4.2. Materials
Ketones 1a–l, 1m, 1o, nitromethane 2, piperidine 3a,
ethylenediamine 3b, mercaptan 6a–g, m-chloroperoxy-
benzoic acid 8a, 1,4-cyclohexanedione 13 were purchased
from Aldrich Chemical Co. and other commercially available
reagents were used directly without further purification.
4.3.1. 2-Benzylthio-2-nitromethylpropane (7a).5,6 1H
NMR (200 MHz, CDCl3) 7.37–7.23 (m, 5H), 4.43 (s,
2H), 3.81 (s, 2H), 1.50 (s, 6H). 13C NMR (50 MHz, CDCl3)
137.1, 129.0, 128.8, 127.5, 85.0, 44.4, 33.5, 26.4. MS m/z

4988
Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
(relative intensity) 225 (Mþ, 0.5), 123 (4.5), 91 (100).
HRMS calcd for C11H15NO2S (Mþ) 225.0824, found
225.0822. Anal. calcd for C11H15NO2S: C, 58.64; H, 6.71;
N, 6.22. Found: C, 58.56; H, 6.83; N, 6.42.
4.3.8. 1-Benzylthio-1-nitromethylcycloheptane (7h).5,6
1H NMR (200 MHz, CDCl3) 7.39–7.19 (m, 5H), 4.47 (s,
2H), 3.74 (s, 2H), 2.09–1.38 (m, 12H). 13C NMR (50 MHz,
CDCl3) 136.9, 129.1, 128.7, 127.3, 84.5, 52.4, 36.6, 33.0,
29.6, 22.5. MS m/z (relative intensity) 279 (Mþ, 170), 233
(20), 123 (27), 91 (100). HRMS calcd for C15H21NO2S
(Mþ) 279.1293, found 279.1290.
4.3.2. 2-Benzylthio-2-nitromethylbutane (7b).5,6 1H NMR
(200 MHz, CDCl3) 7.36–7.31 (m, 5H), 4.51 (d, J¼11 Hz,
1H), 4.44 (d, J¼11 Hz, 1H), 3.77 (d, J¼12.1 Hz, 1H), 3.70
(d, J¼12.1 Hz, 1H), 1.78 (q, J¼7.2 Hz, 2H), 1.44 (s, 3H),
1.05 (t, J¼7.3 Hz, 3H). 13C NMR (50 MHz, CDCl3) 136.9,
129.0, 128.7, 127.4, 83.5, 48.6, 32.8, 30.5, 23.5, 8.2. MS m/z
(relative intensity) 239 (Mþ, 45), 193 (100), 179 (45).
HRMS calcd for C12H17NO2S (Mþ) 239.0980, found
239.0981.
4.3.9. 1-Benzylthio-1-nitromethylcyclooctane (7i). 1H
NMR (200 MHz, CDCl3) 7.32–7.19 (m, 5H), 4.44 (s,
2H), 3.67 (s, 2H), 1.78–1.52 (m, 14H). 13C NMR (50 MHz,
CDCl3) 136.6, 129.0, 128.4, 127.0, 82.6, 52.6, 32.4, 31.2,
28.5, 27.7, 24.6, 22.1. MS m/z (relative intensity) 293 (Mþ,
tr), 154 (10), 123 (24), 91 (100), 81 (36), 67 (18). HRMS
calcd for C16H23NO2S (Mþ) 293.1450, found 293.1456.
1
4.3.3. 3-Benzylthio-3-nitromethylpentane (7c). H NMR
(200 MHz, CDCl3) 7.34–7.18 (m, 5H), 4.50 (s, 2H), 3.67 (s,
2H), 1.68 (q, J¼7.4 Hz, 2H), 1.03 (t, J¼7.4 Hz, 3H). 13C
NMR (50 MHz, CDCl3) 136.7, 129.1, 128.6, 127.3, 80.1,
52.8, 32.1, 27.1, 7.6. MS m/z (relative intensity) 253 (Mþ,
2), 223 (5), 207 (5), 205 (7), 91 (100). HRMS calcd for
C14H21NO2S (Mþ) 253.1137, found 253.1128.
4.3.10. (E)-1-Benzylthio-1-nitromethyl-2-methylcyclo-
hexane (7j). The stereochemistry of this compound was
assigned based on the NOE analysis. H NMR (200 MHz,
CDCl3) 7.35–7.18 (m, 5H), 4.67 (d, J¼11.4 Hz, 1H), 4.56
(d, J¼11.4 Hz, 1H), 3.72 (s, 2H), 2.12–1.18 (m, 9H), 1.08
(d, J¼7 Hz, 3H). 13C NMR (50 MHz, CDCl3) 136.8, 129.3,
128.6, 127.2, 80.0, 52.3, 37.3, 32.2, 31.5, 29.8, 22.5, 21.8,
15.5. MS m/z (relative intensity) 279 (Mþ, 1.3), 249 (8.3),
231 (11),137 (47.8), 109 (75), 91 (100), 67 (28). HRMS
calcd for C15H21NO2S (Mþ) 279.1278, found 279.1278.
1
4.3.4. 2-Benzylthio-2-nitromethyl-4-methylpentane (7d).
1H NMR (200 MHz, CDCl3) 7.34–7.18 (m, 5H), 4.49 (d,
J¼11 Hz, 1H), 4.42 (d, J¼11 Hz, 1H), 3.77 (d, J¼12 Hz,
1H), 3.70 (d, J¼12 Hz, 1H), 1.96 (m 1H), 1.68 (dd, J¼15,
4.8 Hz, 1H), 1.58 (dd, J¼15, 4.8 Hz, 1H), 1.47 (s, 3H), 1.01
(d, J¼6.4 Hz, 3H), 0.98 (d, J¼6.2 Hz, 3H). 13C NMR
(50 MHz, CDCl3) 136.8, 129.0, 128.7, 127.4, 84.3, 48.6,
46.1, 32.9, 24.9, 24.8, 24.2, 24.1. MS m/z (relative intensity)
267 (Mþ, tr), 139 (5), 91 (100), 55 (20). HRMS calcd for
C14H21NO2S (Mþ) 267.1283, found 267.1283.
4.3.11. (Z)-1-Benzylthio-1-nitromethyl-2-methylcyclo-
hexane (7j). The stereochemistry of this compound was
1
assigned based on the NOE analysis. H NMR (200 MHz,
CDCl3) 7.36–7.21 (m, 5H), 4.89 (d, J¼10.6 Hz, 1H), 4.36
(d, J¼10.6 Hz, 1H), 3.66 (d, J¼12 Hz, 1H), 3.56 (d,
J¼12 Hz, 1H), 2.09–1.20 (m, 9H), 1.03 (d, J¼6.4 Hz,
3H). 13C NMR (50 MHz, CDCl3) 136.9, 129.0, 128.6,
127.3, 82.6, 54.1, 36.8, 32.0, 31.3, 29.9, 25.4, 21.3, 15.9. MS
m/z (relative intensity) 279 (Mþ, 1.3), 249 (8.3), 231
(11),137 (47.8), 109 (75), 91 (100), 67 (28). HRMS calcd for
C15H21NO2S (Mþ) 279.1281, found 279.1281.
1
4.3.5. 2-Benzylthio-2-nitromethylhexane (7e). H NMR
(200 MHz, CDCl3) 7.35–7.19 (m, 5H), 4.50 (d, J¼10.8 Hz,
1H), 4.43 (d, J¼10.8 Hz, 1H), 3.77 (d, J¼12.4 Hz, 1H), 3.70
(d, J¼12.4 Hz, 1H), 1.71–1.25 (m, 6H), 1.45 (s, 3H), 0.91
(t, J¼6.8 Hz, 3H). 13C NMR (50 MHz, CDCl3) 137.0,
129.0, 128.7, 127.4, 83.7, 48.2, 37.5, 32.9, 25.8, 24.0, 22.7,
13.8. MS m/z (relative intensity) 267 (Mþ, tr),139 (5), 91
(100), 55 (20). HRMS calcd for C14H21NO2S (Mþ)
267.1289, found 267.1289.
4.3.12. 2-Benzylthio-2-nitromethyl-4-phenylbutane (7k).
1H NMR (200 MHz, CDCl3) 7.36–7.12 (m, 10H), 4.53 (d,
J¼11 Hz, 1H), 4.45 (d, J¼11 Hz, 1H), 3.80 (d, J¼11.6 Hz,
1H), 3.73 (d, J¼11.6 Hz, 1H), 2.95–2.63 (m, 2H), 1.97 (d,
J¼7.8 Hz, 1H), 1.93 (d, J¼7.8 Hz, 1H), 1.50 (s, 3H). 13C
NMR (50 MHz, CDCl3) 140.1, 136.8, 129.0, 128.8, 128.5,
128.4, 127.5, 126.1, 83.4, 48.0, 39.8, 32.9, 30.2, 24.0. MS
m/z (relative intensity) 315 (Mþ, 0.5), 145 (50), 91 (100).
HRMS calcd for C18H21NO2S (Mþ) 315.1296, found
315.1297.
4.3.6. 1-Benzylthio-1-nitromethylcyclopentane (7f).5,6 1
H
NMR (200 MHz, CDCl3) 7.37–7.19 (m, 5H), 4.55 (s, 2H),
3.76 (s, 2H), 1.97–1.65 (m, 8H). 13C NMR (50 MHz,
CDCl3) 136.7, 128.8, 128.3, 126.9, 82.1, 54.9, 36.3, 33.6,
23.4. MS m/z (relative intensity) 251 (Mþ, 9), 205 (17), 203
(78), 124 (15), 123 (71), 91 (100). HRMS calcd for
C13H17NO2S (Mþ) 251.0980, found 251.0981. Anal. calcd
for C13H17NO2S: C, 62.12; H, 6.82; N, 5.58. Found: C,
62.22; H, 6.85; N, 5.82.
4.3.13. 1-Benzylthio-1-nitromethyl-1-phenylethane (7l).
1H NMR (200 MHz, CDCl3) 7.56–7.12 (m, 10H), 4.96 (d,
J¼11.8 Hz, 1H), 4.72 (d, J¼11.8 Hz, 1H), 3.54 (d,
J¼12.8 Hz, 1H), 3.47 (d, J¼12.8 Hz, 1H), 1.98 (s, 6H).
13C NMR (50 MHz, CDCl3) 140.1, 136.7, 129.0, 128.7,
127.9, 127.3, 126.6, 83.9, 50.6, 34.4, 25.1. MS m/z (relative
intensity) 287 (Mþ, 0.5), 148 (10), 118 (85), 91 (100).
HRMS calcd for C11H15NO2S (Mþ) 287.0976, found
287.0977.
4.3.7. 1-Benzylthio-1-nitromethylcyclohexane (7g).5,6 1
H
NMR (200 MHz, CDCl3) 7.35–7.16 (m, 5H), 4.46 (s, 2H),
3.65 (s, 2H), 1.85–1.12 (m, 10H). 13C NMR (50 MHz,
CDCl3) 136.8, 129.0, 128.5, 127.2, 84.5, 49.4, 33.2, 31.9,
25.1, 21.2. MS m/z (relative intensity) 265 (Mþ, 0.5), 219
(1.5), 91 (100). HRMS calcd for C14H19NO2S (Mþ)
265.1137, found 265.1138. Anal. calcd for C14H19NO2S:
C, 63.36; H, 7.22; N, 5.28. Found: C, 63.35; H, 7.48; N,
5.37.
4.3.14. 2-Benzylthio-2-nitromethyl-bicyclo[2.2.1]hep-
1
tane (7m—major product). H NMR (200 MHz, CDCl3)
7.32–7.20 (m, 5H), 4.69 (d, J¼12.2 Hz, 1H), 4.63 (d,

Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
4989
J¼12.2 Hz, 1H), 3.83 (d, J¼11.6 Hz, 1H), 3.75 (d,
J¼11.6 Hz, 1H), 2.49–1.13 (m, 10H). 13C NMR
(50 MHz, CDCl3) 136.9, 129.2, 128.6, 127.2, 80.5, 54.3,
45.2, 43.7, 37.9, 37.1, 33.7, 28.4, 24.7. MS m/z (relative
intensity) 277 (Mþ, 0.5), 107 (15), 91 (100). HRMS calcd
for C15H19NO2S (Mþ) 277.1131, found 277.1130.
135.2, 24.1, 19.9. MS m/z (relative intensity) 101 (Mþ, 10),
84 (100), 67 (2). HRMS calcd for C4H8NO2 (Mþ) 102.0555,
found 102.0560.
4.4.2. (E)-2-Methyl-1-nitrobutene (5b).5,6 1H NMR
(200 MHz, CDCl3) 6.98–6.96 (m, 1H), 2.31–2.18 (m,
2H), 2.26–2.24 (m, 3H), 1.14 (t, J¼7.6 Hz, 3H) 13C NMR
(50 MHz, CDCl3) 154.8, 134.8, 31.2, 18.5, 11.6. MS m/z
(relative intensity) 115 (Mþ, 16), 98 (100), 81 (14), 72 (19).
HRMS calcd for C5H9NO2 (Mþ) 115.0633, found 115.0633.
4.3.15. 2-Benzylthio-2-nitromethyl-bicyclo[2.2.1]hep-
1
tane (7m—minor product). H NMR (200 MHz, CDCl3)
7.37–7.23 (m, 5H), 4.64 (d, J¼11.4 Hz, 1H), 4.51 (d,
J¼11.4 Hz, 1H), 3.80 (d, J¼11.4 Hz, 1H), 3.69 (d,
J¼11.4 Hz, 1H), 2.39–1.17 (m, 10H). 13C NMR
(50 MHz, CDCl3) 136.8, 129.1, 128.6, 127.3, 82.0, 55.1,
44.2, 43.4, 37.5, 37.2, 34.6, 28.0, 25.9. MS m/z (relative
intensity) 277 (Mþ, 0.5), 107 (15), 91 (100). HRMS calcd
for C15H19NO2S (Mþ) 277.1131, found 277.1132.
4.4.3. (Z)-2-Methyl-1-nitrobutene (5b).5,6 1H NMR
(200 MHz, CDCl3) 6.92–6.88 (m, 1H), 2.63 (q, J¼7.6 Hz,
2H), 2.23 (t, J¼10.6 Hz, 3H), 1.93 (d, J¼1.2 Hz, 3H). 13C
NMR (50 MHz, CDCl3) 155.1, 134.3, 26.0, 21.4, 11.4. MS
m/z (relative intensity) 115 (Mþ, 16), 98 (100), 81 (14), 72
(19). HRMS calcd for C5H9NO2 (Mþ) 115.0633, found
115.0633.
4.3.16. 3-Benzylthio-3-nitromethyl-tricyclo[2.2.1.02,6]-
1
heptane (7n). H NMR (200 MHz, CDCl3) 7.37–7.17 (m,
5H), 4.55 (s, 2H), 3.82 (s, 2H), 2.33–1.29 (m, 8H). 13C
NMR (50 MHz, CDCl3) 137.5, 129.0, 128.5, 127.1, 79.3,
59.0, 37.4, 34.1, 32.3, 30.9, 19.1, 12.2, 12.0. MS m/z
(relative intensity) 275 (Mþ, 0.5), 245 (10), 136 (25), 123
(15), 106 (47), 91 (100). HRMS calcd for C15H17NO2S
(Mþ) 275.0981, found 275.0982.
4.4.4. 2-Ethyl-1-nitrobutene (5c). 1H NMR (200 MHz,
CDCl3) 6.89 (s, 1H), 2.64 (q, J¼7.6 Hz, 2H), 2.26 (qd,
J¼7.6, 1.4 Hz, 2H), 1.16 (t, J¼7.4 Hz, 3H), 1.13 (t,
J¼7.4 Hz, 3H). 13C NMR (50 MHz, CDCl3) 160.0, 134.3,
28.6, 24.9, 12.2, 11.6. Anal. calcd for C6H11NO2: C, 55.80;
H, 8.58; N, 10.84. Found: C, 55.61; H, 8.78; N, 10.46.
4.3.17. 2-Benzylthio-2-nitromethyl-bicyclo[3.2.1]octane
(7o). There are two isomers were observed after reaction
and these two isomers are inseparable and still contain trace
of impurity even purified by HPLC. The spectral data of
4.4.5. (E)-2-Nitromethylene-4-methylpentane (5d). 1H
NMR (200 MHz, CDCl3) 6.93 (s, 1H), 2.23 (d, J¼1.2 Hz,
3H), 2.04 (d, J¼7 Hz, 2H), 1.98–1.82 (m, 1H), 0.93 (d,
J¼6.4 Hz, 6H). 13C NMR (50 MHz, CDCl3) 152.6, 135.9,
47.1, 26.2, 22.2, 18.4. MS m/z (relative intensity) 143 (Mþ,
2.5), 126 (15), 101 (20), 84 (100), 55 (52). Anal. calcd for
C7H13NO2: C, 58.72; H, 9.15; N, 9.78. Found: C, 58.47; H,
9.05; N, 10.07.
1
these two isomers are H NMR (200 MHz, CDCl3) 7.37–
7.23 (m), 4.78 (dd, J¼11.2 Hz), 4.53 (dd, J¼11.2 Hz), 3.77
(s), 3.72 (s), 2.45–2.18 (m), 2.00–1.20 (m). 13C NMR
(50 MHz, CDCl3) 137.0, 136.7, 129.3, 129.2, 128.59,
128.56, 127.24, 127.16, 82.8, 79.8, 52.9, 52.8, 41.7, 41.0,
34.22, 34.15, 34.0, 33.6, 32.5, 31.9, 29.0, 28.3, 28.1, 27.9,
27.8, 27.3, 26.5, 26.2.
4.4.6. (Z)-2-Nitromethylene-4-methylpentane (5d). 1H
NMR (200 MHz, CDCl3) 6.98 (s, 1H), 2.61 (dd, J¼7.4,
0.8 Hz, 2H), 2.03–1.90 (m, 1H), 1.91 (d, J¼1.4 Hz, 3H),
0.96 (d, J¼6.6 Hz, 6H). 13C NMR (50 MHz, CDCl3) 152.5,
135.6, 40.8, 27.4, 22.6, 18.3. MS m/z (relative intensity) 144
(Mþ, 1.5), 126 (13), 101 (22), 84 (100), 59 (42), 56 (40), 53
(22). Anal. calcd for C7H13NO2: C, 58.72; H, 9.15; N, 9.78.
Found: C, 58.50; H, 9.07; N, 10.08.
4.4. Typical experimental procedures for the synthesis of
nitroalkenes 5 from the oxidation of b-nitrosulfides 7
with 8a (m-CPBA or m-CPBA/AcOH), 8b (H2O2/AcOH),
or 8c (H2O2) in ClCH2CH2Cl solution and undergoing
elimination under refluxing conditions (Tables 2–4,
and 9)
4.4.7. (E)-2-Nitromethylenehexane (5e). 1H NMR
(200 MHz, CDCl3) 6.96 (q, J¼1.2 Hz 1H), 2.24 (d,
J¼1.4 Hz, 3H), 2.19 (t, J¼7 Hz, 2H), 1.58–1.26 (m, 4H),
0.93 (t, J¼7.2 Hz, 3H). 13C NMR (50 MHz, CDCl3) 153.6,
135.2, 37.7, 29.1, 22.1, 18.5, 13.6. MS m/z (relative
intensity) 144 (Mþ, 1.5), 126 (26), 100 (30), 84 (36), 71
(60), 55 (100). HRMS calcd for C5H9NO2 (Mþ) 143.0947,
found 143.0920.
At 08C, 1 mmol of 7a and 1.1 mmol of m-CPBA 8a-1 were
dissolved in 20 ml of ClCH2CH2Cl and stirred for few
minutes. The temperature was then increased to room
temperature and the solution was stirred for an additional
0.5 h. After the reaction was complete, as evidenced by
TLC, the solution was refluxed for 3 h, cooled, and the
solvent was evaporated. The purification of the mixture was
carried out by flash column chromatography using hexane–
ethyl acetate (400:1) to give 5a. All experimental data using
8a-1 (m-CPBA) as oxidization reagent to generate product 5
is shown in Table 2, using 8b (H2O2/AcOH) at room
temperature, in Table 3, using 8c (H2O2) at room
temperature, in Table 4. When 7m–o were used, the yields
of products 5m–o are shown in Table 9.
4.4.8. (Z)-2-Nitromethylenehexane (5e). 1H NMR
(200 MHz, CDCl3) 6.93 (s, 1H), 2.65 (t, J¼6.8 Hz, 2H),
1.92 (d, J¼1.6 Hz, 3H), 1.58–1.26 (m, 4H), 0.95 (t,
J¼6.8 Hz, 3H). 13C NMR (50 MHz, CDCl3) 13C NMR
(50 MHz, CDCl3) 153.6, 135.2, 37.7, 29.1, 22.1, 18.5, 13.6.
MS m/z (relative intensity) 144 (Mþ, 1.5), 126 (26), 100
(30), 84 (36), 71 (60), 55 (100). HRMS calcd for C5H9NO2
(Mþ) 143.0947, found 143.0922.
4.4.1. 2-Methyl-1-nitropropene (5a).5 1H NMR
(200 MHz, CDCl3) 6.98 (m, 1H), 2.27 (d, J¼1.4 Hz, 3H),
1.96 (d, J¼1.4 Hz, 3H). 13C NMR (50 MHz, CDCl3) 149.9,
4.4.9. Nitromethylenecyclopentane (5f).5 1H NMR

4990
Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
(200 MHz, CDCl3) 7.17–7.10 (m, 1H), 3.06–2.93 (m, 2H),
2.59–2.47 (m, 2H), 1.91–1.67 (m, 4H). 13C NMR (50 MHz,
CDCl3) 163.7, 132.2, 33.9, 33.3, 25.9, 25.4. MS m/z
(relative intensity) 127 (Mþ, 2), 111 (11), 81 (68), 79
(100). HRMS calcd for C6H9NO2 (Mþ) 127.0597, found
127.0615.
and still contain traces of impurity even after purification by
HPLC. The spectral data of these two isomers are 1H NMR
(200 MHz, CDCl3) 6.88 (d, J¼2.4 Hz), 6.77 (d, J¼2.0 Hz),
4.26 (s), 3.59 (dd, J¼16.4, 5.8 Hz), 2.68–1.52 (m).
4.5. Typical experimental procedures for the synthesis of
5m, n, and 18 from the reactions of ketones 1m–o,
nitromethane 2, and ethylenediamine 3b under refluxing
condition according to Barton’s methodology
(Table 8)12a
4.4.10. Nitromethylenecyclohexane (5g).5,6,14 1H NMR
(200 MHz, CDCl3) 6.94–6.89 (m, 1H), 2.89–2.83 m, 2H),
2.24–2.18 (m, 2H), 1.77–1.59 (m, 6H), 13C NMR (50 MHz,
CDCl3) 155.8, 132.4, 34.4, 28.9, 28.2, 27.3, 25.8. MS m/z
(relative intensity) 141 (Mþ, 3), 109 (15), 95 (3), 81 (100).
HRMS calcd for C7H11NO2 (Mþ) 141.0790, found
141.0788.
Ketone 1m (1 mmol), nitromethane 2 (90 mmol), and
ethylenediamine 3b (0.1 mmol) were placed in a 10 ml
round-bottomed flask and the solution refluxed for 24 h
under a nitrogen atmosphere. After the solvent was
evaporated in vacuo, the residue was further purified by
flash column chromatography using hexane–ethyl acetate
(200:1) to give pure 5m (15% isolated yield). When the
same reaction was repeated and the reaction time was
increased to 36 h, only 24% yield of 5m was found. For
substrate 1o, the only product was a 51% (isolated yield) of
12 under similar procedures and conditions. All the
experimental data are shown in Table 8.
4.4.11. Nitromethylenecycloheptane (5h).5 1H NMR
(200 MHz, CDCl3) 6.99 (s, 1H), 3.00–2.92 (m, 2H),
2.42–2.35 (m, 2H), 1.85–1.50 (m, 8H). 13C NMR
(50 MHz, CDCl3) 160.2, 134.8, 35.4, 32.1, 29.5, 28.8,
27.9, 25.5. MS m/z (relative intensity) 155 (Mþ, 4), 139
(64), 109 (11), 91 (100). HRMS calcd for C8H13NO2(Mþ)
155.0946, found 155.0937.
4.4.12. Nitromethylenecyclooctane (5i). 1H NMR
(200 MHz, CDCl3) 7.04 (s, 1H), 2.82 (t, J¼6 Hz, 2H),
2.33 (t, J¼6 Hz, 2H), 1.89–1.77 (m, 4H), 1.60–1.41 (m,
6H). 13C NMR (50 MHz, CDCl3) 161.9, 134.8, 35.6, 30.0,
27.3, 27.2, 25.9, 25.5, 24.3. MS m/z (relative intensity) 169
(Mþ, tr), 149 (10), 123 (25), 81 (100), 67 (50). HRMS calcd
for C9H15NO2(Mþ) 169.1103, found 169.1095.
4.5.1. 2-Nitromethylene-bicyclo[2.2.1]heptane (5m—
major product). 1H NMR (200 MHz, CDCl3) 7.11 (t,
J¼2.2 Hz, 1H), 2.95–2.55 (m, 4H), 1.87–1.31 (m, 6H). 13C
NMR (50 MHz, CDCl3) 165.7, 129.9, 44.7, 40.1, 39.2, 35.6,
28.0, 27.2. MS m/z (relative intensity) 153 (Mþ, 1.3), 125
(25), 109 (40), 91 (70), 79 (100), 67 (90), 55 (50), 41 (73).
HRMS calcd for C8H12NO2 (Mþ) 153.0790, found
153.0782.
4.4.13. 2-Methyl-1-nitromethylenecyclohexane (5j). Two
isomers were observed after the reaction, but only the major
isomer could be isolated after column and HPLC purifi-
4.5.2. 2-Nitromethylene-bicyclo[2.2.1]heptane (5m—
minor product). 1H NMR (200 MHz, CDCl3) 6.90 (s,
1H), 4.13 (d, J¼4.2 Hz, 1H), 2.51–1.21 (m, 9H). 13C NMR
(50 MHz, CDCl3) 163.7, 130.6, 43.4, 39.3, 38.9, 35.2, 27.8,
26.8. MS m/z (relative intensity) 153 (Mþ, 1.3), 125 (25),
109 (40), 91 (70), 79 (100), 67 (90), 55 (50), 41 (73). HRMS
calcd for C8H12NO2 (Mþ) 153.0790, found 153.0765.
1
cation. The spectral data of the major isomer are H NMR
(200 MHz, CDCl3) 6.85 (s, 1H), 3.42–3.32 (m, 1H), 2.39–
2.19 (m, 2H), 1.98–1.22 (m, 6H), 1.12 (d, J¼6.6 Hz, 3H).
13C NMR (50 MHz, CDCl3) 159.1, 132.0, 38.0, 36.6, 28.3,
27.8, 24.5, 18.0. GCMS of the two isomers are m/z (relative
intensity) 155 (Mþ, tr), 138 (17), 112 (29), 97 (38), 79 (52),
67 (64), 55 (53), 43 (100), 41 (66) and m/z (relative
intensity) 155 (Mþ, tr), 138 (55), 110 (30), 97 (40), 79 (75),
67 (96), 55 (95), 43 (98), 41 (100).
4.5.3. (E)-3-Nitromethylene-tricyclo[2.2.1.02,6]heptane
(5n). The stereochemistry of this compound was assigned
1
based on NOE analysis. H NMR (200 MHz, CDCl3) 6.85
4.4.14. (E)-2-Nitromethylene-4-phenylbutane (5k). 1H
NMR (200 MHz, CDCl3) 7.36–7.12 (m, 5H), 6.90 (q,
J¼1.4 Hz, 1H), 2.87–2.79 (m, 2H), 2.53–2.45 (m, 2H),
2.29 (d, J¼1.2 Hz, 3H). 13C NMR (50 MHz, CDCl3) 152.1,
139.8, 135.7, 128.7, 128.3, 126.6, 39.7, 33.4, 18.6. MS m/z
(relative intensity) 191 (Mþ, tr), 145 (85), 117 (34), 91
(100), 41 (26). HRMS calcd for C11H13NO2(Mþ) 191.0951,
found 191.0952.
(s, 1H), 3.79 (d, J¼0.6 Hz, 1H), 1.96–1.85 (m, 4H), 1.66–
1.60 (m, 3H). 13C NMR (50 MHz, CDCl3) 165.6, 127.0,
35.1, 33.3, 19.5, 17.7. MS m/z (relative intensity) 151 (Mþ,
11), 122 (7), 103 (26), 91 (32), 77 (100). HRMS calcd for
C8H9NO2 (Mþ) 151.0638, found 151.0638.
4.5.4. (Z)-3-Nitromethylene-tricyclo[2.2.1.02,6]heptane
(5n). The stereochemistry of this compound was assigned
1
based on NOE analysis. H NMR (200 MHz, CDCl3) 7.14
4.4.15. (Z)-2-Nitromethylene-4-phenylbutane (5k). 1H
NMR (200 MHz, CDCl3) 7.36–7.18 (m, 5H), 6.97 (s,
1H), 2.99–2.78 (m, 4H), 1.89 (d, J¼1.4 Hz, 3H). 13C NMR
(50 MHz, CDCl3) 152.9, 140.5, 135.3, 128.6, 128.4, 126.4,
35.0, 33.7, 22.6. MS m/z (relative intensity) 191 (Mþ, tr),
145 (85), 117 (34), 91 (100), 41 (26). HRMS calcd for
C11H13NO2(Mþ) 191.0932, found 191.0933.
(s, 1H), 2.84 (t, J¼5.2 Hz, 1H), 2.40 (d, J¼1 Hz, 1H), 2.03
(d, J¼5.2 Hz, 2H), 1.87–1.81 (m, 2H), 1.65–1.60 (m, 2H).
13C NMR (50 MHz, CDCl3) 165.3, 128.0, 35.6, 34.6, 20.5,
17.6. MS m/z (relative intensity) 151 (Mþ, tr), 122 (13), 104
(34), 91 (36), 77 (100). HRMS calcd for C8H9NO2 (Mþ)
151.0638, found 151.0638.
4.5.5. 2-Nitromethyl-bicyclo[3.2.1]oct-2-ene (12). 1H
NMR (200 MHz, CDCl3) 5.61 (s, 1H), 4.83 (d,
J¼13.4 Hz, 1H), 4.76 (d, J¼13.4 Hz, 1H), 2.30–2.52 (m,
4.4.16. 2-Nitromethylene-bicyclo[3.2.1]octane (5o). Two
isomers were observed after the reaction and are inseparable

Y.-J. Jang et al. / Tetrahedron 59 (2003) 4979–4992
4991
3H), 2.00–1.32 (m, 7H). 13C NMR (50 MHz, CDCl3) 136.1,
129.5, 81.4, 37.5, 36.8, 35.3, 34.9, 32.3, 30.5. MS m/z
(relative intensity) 167 (Mþ, 5), 166 (35), 136 (37), 119
(32), 107 (28), 91 (100), 79 (62), 77 (29), 67 (27).
HRMS calcd for C8H9NO2 (Mþ) 167.0946, found
167.0920.
4.6.5. 1-(2,20-Thiodiethanethio)-7-nitro-4-nitromethyl-
bicyclo[2.2.1]heptane (14f). H NMR (200 MHz, CDCl3)
1
4.73 (d, J¼12.6 Hz, 1H), 4.72 (s, 1H), 4.53 (d, J¼12.6 Hz,
1H), 2.94–2.65 (m, 8H), 2.42–1.70 (m, 9H). 13C NMR
(50 MHz, CDCl3) 92.7, 76.7, 57.3, 49.1, 36.2, 34.0, 32.4,
32.1, 31.8, 30.3, 29.0, 24.6. MS m/z (relative intensity) 352
(Mþ, 6), 91 (13), 64 (100). HRMS calcd for C12H20N2O4S3
(Mþ) 352.0572, found 352.0572.
4.6. Typical experimental procedures for the
preparation of 14 and 15g from the reaction of 1,4-
cyclohexanedione 13, nitromethane 2, and mercaptan 6
in the presence of ethylenediamine 3b as base in CH3CN
solution (Table 11)
4.6.6. 1-(Propane-1,3-dithio)-7-nitro-4-nitromethyl-bi-
cyclo[2.2.1]heptane (14g). 1H NMR (200 MHz, CDCl3)
4.72 (d, J¼12.6 Hz, 1H), 4.76 (s, 1H), 4.53 (d, J¼12.6 Hz,
1H), 2.76–2.59 (m, 6H), 1.95–1.76 (m, 8H), 1.40 (t,
J¼8 Hz, 1H). 13C NMR (50 MHz, CDCl3) 92.7, 76.8, 57.2,
49.1, 34.1, 33.0, 32.2, 32.1, 30.4, 27.0, 23.3. MS m/z
(relative intensity) 306 (Mþ, 40), 259 (37), 105 (100), 91
(99), 74 (95). HRMS calcd for C11H18N2O4S2 (Mþ)
306.0707, found 306.0708.
In a 50 ml round-bottomed flask were placed the 1,4-
cyclohexanedione 13 (5 mmol), nitromethane 2 (50 mmol),
ethylenediamine 3b (5 mmol), and benzyl mercaptan 6a
(20 mmol) in 15 ml of CH3CN and the solution refluxed for
13 h. After cooling, the solvent was evaporated and the
crude mixture was purified by flash column chromatography
using hexane–ethyl acetate (100:1) to give pure 14a (53%
isolated yield). When mercaptan 6g was used, not only the
major product 14g but also the minor product 15g was
isolated from the reaction mixture. All the experimental data
concerning the generation of 14 and 15 are shown in
Table 11.
4.6.7. 1,4-Bis(nitromethyl)-1,4-bis(propane-1,3-dithio)-
1
cyclohexane (15g). H NMR (200 MHz, CDCl3) 4.52 (s,
4H), 2.70–2.54 (m, 8H), 2.23 (s, 2H), 2.17 (s, 2H), 1.94–
1.71 (m, 8H), 1.38 (t, J¼8 Hz, 2H). 13C NMR (50 MHz,
CDCl3) 84.8, 48.0, 32.3, 28.3, 25.2, 23.4.
4.6.1. 1-Benzylthio-7-nitro-4-nitromethyl-bicyclo[2.2.1]-
heptane (14a). 1H NMR (200 MHz, CDCl3) 7.38–7.23 (m,
5H), 4.71 (d, J¼12.6 Hz, 1H), 4.63 (s, 1H), 4.51 (d,
J¼12.6 Hz, 1H), 3.91 (d, J¼12 Hz, 1H), 3.80 (d, J¼12 Hz,
1H), 2.42–1.60 (m, 8H). 13C NMR (50 MHz, CDCl3) 136.8,
128.9, 128.6, 127.4, 92.3, 76.7, 57.4, 48.9, 34.0, 33.7, 32.0,
31.9, 30.3. MS m/z (relative intensity) 322 (Mþ, 1.0), 216
(17), 107 (30), 91 (100). HRMS calcd for C15H18N2O4S
(Mþ) 322.0978, found 322.0779.
Acknowledgements
Financial support by the National Science Council of the
Republic of China is gratefully acknowledged.
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