An improved and easy method for the preparation of 2,2-disubstituted 1-nitroalkenes

Article abstract of DOI:10.1021/jo001215u

Reactions of ketones 1, nitromethane 2, and catalytic amount of piperidine 3 in the presence of mercaptan 6 generate β-nitroalkyl sulfides 7-9. At 0 °C and by the use of dichloromethane as solvent, β-nitroalkyl sulfides 7-9 can be oxidized by m-chloroperoxybenzoic acid (m-CPBA) 10 to generate β-nitroalkyl sulfoxides 11-13 and undergo elimination in carbon tetrachloride solution to produce medium to high yield of 2,2-disubstituted 1-nitroalkenes 5. The irreversibility of the synthetic mechanism not only can overcome the reversibility of the Henry reaction in the synthesis of 2,2-disubstituted 1-nitroalkenes 5 but also can generate the major products "exo-nitro olefins" 5c-e when cyclic ketones 1c-e were used. Under similar conditions, medium to high yield of 5-substituted-2-nitromethyl-2-phenylthioadamantane 17 also can be prepared from the reaction of 5-substituted-2-adamantanones 15, nitromethane 2, piperidine 3, thiophenol 6a. The intermediate 17 can be oxidized by m-CPBA 10 in dichloromethane solution and then undergo elimination at room temperature or can be dissolved in solvent, coated on silica gel, and then heated at 90-100 °C to generate 5-substituted-2-nitromethyleneadamantane 16.

Full text of DOI:10.1021/jo001215u

1984
J . Org. Chem. 2001, 66, 1984-1991
An Im p r oved a n d Ea sy Meth od for th e P r ep a r a tion of
2,2-Disu bstitu ted 1-Nitr oa lk en es
Wen-Wei Lin, Yeong-J iunn J ang, Yeh Wang, J u-Tsung Liu, Shin-Ru Hu,
Lian-Yong Wang, and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road,
Taipei, Taiwan 116 R.O.C.
cheyaocf@scc.ntnu.edu.tw
Received August 9, 2000
Reactions of ketones 1, nitromethane 2, and catalytic amount of piperidine 3 in the presence of
mercaptan 6 generate â-nitroalkyl sulfides 7-9. At 0 °C and by the use of dichloromethane as
solvent, â-nitroalkyl sulfides 7-9 can be oxidized by m-chloroperoxybenzoic acid (m-CPBA) 10 to
generate â-nitroalkyl sulfoxides 11-13 and undergo elimination in carbon tetrachloride solution
to produce medium to high yield of 2,2-disubstituted 1-nitroalkenes 5. The irreversibility of the
synthetic mechanism not only can overcome the reversibility of the Henry reaction in the synthesis
of 2,2-disubstituted 1-nitroalkenes 5 but also can generate the major products “exo-nitro olefins”
5c-e when cyclic ketones 1c-e were used. Under similar conditions, medium to high yield of
5-substituted-2-nitromethyl-2-phenylthioadamantane 17 also can be prepared from the reaction
of 5-substituted-2-adamantanones 15, nitromethane 2, piperidine 3, thiophenol 6a . The intermediate
17 can be oxidized by m-CPBA 10 in dichloromethane solution and then undergo elimination at
room temperature or can be dissolved in solvent, coated on silica gel, and then heated at 90-100
°C to generate 5-substituted-2-nitromethyleneadamantane 16.
Sch em e 1
In tr od u ction
Nitro olefins are useful intermediates in organic syn-
thesis and are important structural units which can be
used as starting materials for many classes of compounds
including bioactive compounds.1 Generally, nitroalkenes
are prepared by nitro-aldol approach of the nitroalkanes
with a carbonyl compound, followed by dehydration of
the 2-nitro alcohols (Scheme 1).2 Unfortunately, the
Henry reaction is impractical for the preparation of 2,2-
disubstituted 1-nitroalkenes due to the reversibility of
the reaction when ketones are used.3 Tamura et al. have
utilized N,N-dimethylethylenediamine to drive the con-
densation of ketones with nitroalkanes, but the major
products are â,γ-unsaturated tautomers (Scheme 2).3c It
has been reported by Loubinoux and co-workers that di-
and trisubstituted R-nitroalkenes can be prepared from
the treatment of tertiary â-nitro alcohols with acetic
anhydride and followed by potassium methoxide or tert-
butoxide (Scheme 3).4 Knochel and co-workers have
Sch em e 2
Sch em e 3
(1) (a) Corey, E. J .; Estreicher, H. J . Am. Chem. Soc. 1978, 100, 6294.
(b) Seebach, D.; Colvin, E. W.; Well, T. Chimia 1979, 33, 1. (c) Barrett,
A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751. (d) Rosini, G.;
Ballini, R. Synthesis 1988, 833. (e) Several articles in Tetrahedron
Symposia-in-Print 41, Nitroalkanes and Nitroalkenes in Synthesis.
Tetrahedron 1990, 46 (21), 7313. (f) Barrett, A. G. M. Chem. Soc. Rev.
1991, 20, 95.
(2) (a) Buckley, G. D.; Scaife, C. W. J . Chem. Soc. 1947, 1471. (b)
Melton, J .; McMurry, J . E. J . Org. Chem. 1975, 40, 2138. (c) Knochel,
P.; Seebach, D. Synthesis 1982, 1017. (d) Seebach, D.; Knochel, P. Helv.
Chim. Acta 1984, 67, 261. (e) Ballini, R.; Castagnani, R.; Petrini, M.
J . Org. Chem. 1992, 57, 2160. (f) Stanetty, P.; Kremslehner, M.
Tetrahedron Lett. 1998, 39, 811.
(3) (a) Rossine, G. In Comprehensive Organic Synthesis, Part 2;
Additions to c-x p-Bonds; Trost, B. N., Fleming, I., Eds.; Pergamon
Press: Oxford, 1991; Vol. 2, p 329. (b) Matsumoto, K. Angew. Chem.,
Int. Ed. Engl. 1984, 18, 617. (c) Tamura, R.; Sato, M.; Oda, D. J . Org.
Chem. 1986, 51, 4368.
(4) Ferrand, J . C.; Schneider, R.; Gerardin, P.; Loubinoux, B. Synth.
Commun. 1996, 26, 4329.
described the preparation of 2,2-disubstituted 1-nitroalk-
enes from the addition/elimination of copper-zinc orga-
nometallic reagents to nitroalkenes substituted with
leaving groups at the â-position (Scheme 4).5 In 1981,
Sakakibara et al. have reported the synthesis of 1-ni-
troalkenes from nitroalkanes utilizing selenium chem-
istry (Scheme 5).6 It was in 1993 Denmark and Marcin
(5) (a) Retherford, C.; Knochel, P. Tetrahedron Lett. 1991, 32, 441.
(b) J ubert, C.; Knochel, P. J . Org. Chem. 1992, 57, 5425. (c) J ubert,
C.; Knochel, P. J . Org. Chem. 1992, 57, 5431.
10.1021/jo001215u CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/21/2001

Preparation of 2,2-Disubstituted 1-Nitroalkenes
J . Org. Chem., Vol. 66, No. 6, 2001 1985
Sch em e 4
Sch em e 7
Sch em e 5
Sch em e 6
had reported a synthesis of 2,2-disubstituted 1-nitroalk-
enes by combining Knochel’s and Sakakibara’s work,
involving the conjugate addition of copper-zinc reagents
to 1-nitroalkenes, followed by phenylselenation and
oxidative elimination (Scheme 6).7
It has been reported that sulfoxides and sulfones with
a â-hydrogen undergo elimination on treatment with an
alkoxide.8 Sulfoxides also undergo elimination on pyroly-
sis at about 80 °C, and the reaction is proposed to proceed
through Ei mechanism with syn elimination.9 Sulfoxides
have been used as intermediates for the conversion of
ketones, aldehydes, and carboxylic esters to their R,â-
unsaturated derivatives.10 The preparation of tert-benz-
ylthionitroalkanes from the mixture of ketones, ni-
tromethane, and benzyl mercaptan in benzene in the
presence of piperidine also has been reported.11 On the
basis of above observation,9-11 we developed an improved
method by the use of ketones 1, nitromethane 2, piperi-
dine 3, mercaptan 6, and m-chloroperoxybenzoic acid (m-
CPBA) 10, which is an amalgamation of Carroll’s and
Trost’s work, involving the nitro-aldol addition to gener-
ate the intermediate tertiary â-nitro alcohols 4, dehydra-
tion of 4 to form nitroalkenes 5 (reversible), conjugate
addition of the mercaptan 6 to 5 to yield â-nitro sulfides
7-9, oxidation of 7-9 with m-CPBA 10 to form â-nitro
sulfoxides 11-13, and finally undergo â-elimination to
obtain 2,2-disubstituted 1-nitroalkenes 5 (Scheme 7).
Resu lts a n d Discu ssion
It has been reported by Eckstein et al. that cyclohep-
tanone 1e reacts with nitromethane 2 to give 14% of
endo-nitro olefin 1-cycloheptenylnitromethane 14c after
18 days at 45-50 °C in the presence of piperidine 3 as
catalyst. This method was also improved by treating 1e
with nitromethane 2, piperidine 3, and using benzene as
solvent, and the solution was heated on a steam bath to
remove water to give about 60% of 14c.12a,b Similarly, the
preparation of 1-cyclohexenylnitromethane 14b by heat-
ing 1-nitromethyl-1-hydroxycyclohexane with piperidine
also has been reported by the same group.12c,d The
isomerization of 2-nitro-2-nonene into the mixture of
2-nitro-2-nonene and 2-nitro-3-nonene under the cataly-
sis of N,N-dimethylethylenediamine in refluxing benzene
(6) (a) Sakakibara, T.; Takai, I.; Ohara, E.; Sudoh, R. J . Chem. Soc.,
Chem. Commun. 1981, 261. (b) Sakahibara, T.; Ikuta, S.; Sudoh, R.
Synthesis 1982, 261.
(7) Denmark, S. E.; Marcin, L. R. J . Org. Chem. 1993, 58, 3850.
(8) March, J . In Advanced Organic Chemistry: Reactions, Mecha-
nisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992; p
1021
(9) (a) Kingsbury, C. A.; Cram, D. J . J . Am. Chem. Soc. 1960, 82,
1810. (b) Walling, C.; Bollyky, L. J . Org. Chem. 1964, 29, 2699. (c)
Yoshimura, T.; Tsukurimichi, E.; Iizuka, Y.; Mizuno, H.; Isaji, H.;
Shimasaki, C. Bull. Chem. Soc. J pn. 1989, 62, 1891.
(10) (a) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J . Am. Chem. Soc.
1976, 98, 4887. (b) Trost, B. M. Acc. Chem. Res. 1978, 11, 453.
(11) Carrol, F. I.; White, J . D.; Wall, M. E. J . Org. Chem. 1963, 28,
1240.
(12) (a) Eckstein, Z.; Sacha, A.; Urbanski, T. Bull. Acad. Polon. Sci.
1957, Classe III 5, 213. (b) Chem. Abstr. 1957, 51, 16318. (c) Eckstein,
Z.; Urbanki, T.; Wojnowska, H. Bull. Acad. Polon. Sci. 1957, Classe
III 5, 219. (d) Chem. Abstr. 1957, 51, 16319.

1986 J . Org. Chem., Vol. 66, No. 6, 2001
Lin et al.
Ta ble 1. Th e P r ep a r a tion of â-Nitr oa lk yl Su lfid es 7-9 fr om th e Rea ction of Keton e 1, Nitr om eth a n e 2, P ip er id in e 3, a n d
Mer ca p ta n 6
entry
1 (equiv)
2 (equiv)
3 (equiv)
6 (equiv)
time (h)a
7-9
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a (3.2)
1b (1.2)
1c (1.0)
1d (1.2)
1e (1.1)
1a (1.0)
1b (1.0)
1c (1.0)
1d (1.0)
1e (1.0)
1a (1.0)
1b (1.0)
1c (1.1)
1d (1.0)
1e (1.1)
1.0
1.0
4.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.6
0.5
0.6
0.6
6a (3.6)
6a (1.2)
6a (2.4)
6a (3.6)
6a (1.3)
6b (1.0)
6b (1.0)
6b (1.0)
6b (1.0)
6b (1.0)
6c (0.9)
6c (1.1)
6c (1.3)
6c (0.9)
6c (1.1)
60c
23
7a
7b
7c
7d
7e
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
84
95
100
84
61
60c
0.2
70
NR
0.35
0.35
0.35
0.35
0.35
0.1
0.2
0.2
0.1
0.2
12-15
12-15
12-15
12-15
12-15
8c
87-100d
87-100d
87-100d
87-100d
87-100d
77e
17
94
78
76
8c
76e
67
22f
Benzene was used as solvent with a Dean-Stark trap to remove water. Isolated yield. c The reaction was performed in solvent-free
a
b
at 80 °C. Reference 11. e Reference 16. f 55% of 14c was also isolated.
d
Ta ble 2. Th e P r ep a r a tion of
2,2-Disu bstitu ted -1-n itr oa lk en e 5 fr om â-Nitr oa lk yl
Su lfid es 7-9
for 24 h and the mechanism has been proposed in the
literature.3c According to these reports,3c,7,12-15 it seems
to be impossible to prepare 5c-e directly by the use of
cyclic ketones and nitromethane in the presence of base.
To prepare pure exo-nitroolefins, it might be possible to
trap the product exo-nitro olefins by using suitable
reagent to prevent the transformation of exo-nitro olefins
into endo-nitro olefins. On the basis of literature re-
ports,11,16,17 we added mercaptan as trapping reagent with
a Dean-Stark trap to remove water to obtain the
intermediate â-nitroalkyl sulfides 7-9. Although litera-
ture had reported that benzyl mercaptan11 or allyl
mercaptan16 can be used to prepare â-nitroalkyl sulfides,
we speculated that the choice of trapping reagent mer-
captan 6 might be critical for successful reactions with
different ketones 1. To find the most suitable mercaptan,
condensation of ketones 1 with nitromethane 2 and
different mercaptan 6 in the presence of a catalytic
amount of piperidine 3 in refluxing benzene with a
Dean-Stark trap to remove water by azeotropic distil-
lation or just performed in solvent-free condition were
studied (Scheme 1 and Table 1).
To ketones 1a -d , mercaptan 6a , 6b, and 6c all can
trap the nitroalkenes 5 to generate medium to high yield
of â-nitroalkyl sulfides 7-9. When acetone 1a was used,
the reaction was just performed in solvent-free condition
due to the low boiling point of 1a (entries 1 and 11). No
expected product 7e was observed when 1e was used to
react with 2, 3, and thiophenol 6a under similar condi-
tions (entry 5). Only 6b can trap 5e successfully to
generate high yield of 8e when 1e was used (entry 10),
and this result is also consistent with literature report.11
We are surprised to find that not only 22% of 9e but also
55% of 14c was isolated when allyl mercaptan 6c was
used. The NMR analysis of the crude mixture at different
stage also found that both 9e and 14c increased gradually
and this result indicates that some product 5e had
already been converted into 14c before it was trapped
by allyl mercaptan 6c.
CH2Cl2 time CCl4 time
yield
entry 7-9 10 (equiv)
(h)
(h)
5
(%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
7a
7b
7c
7d
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.0
1.0
1.15
1.0
1.1
1.15
1.0
0.5
1.0
1.0
1.5
1.0
0.5
0.25
0.5
1.0
0.5
0.5
1.0
0.5
1.0
6.0
3.0
2.0
1.0
4.5
2.0
3.0
2.0
2.5
5.0
4.5
1.0
5.0
2.0
5a
5b
5c
5d 100
5a 100
5b
5c
5d 100
5e
5a
5b
5c 100
5d
5e
67
78b
67
87b
97
54
82
90b
78
78
a
b
Isolated yield. E + Z isomers.
After purified by chromatography, â-nitroalkyl sulfides
7-9 were oxidized with 1.0-1.15 equiv of m-CPBA 10
in CH2Cl2 solution, and the solution was stirred for
0.25-1 h at room temperature. When the reaction was
complete, the solvent CH2Cl2 was removed by distillation
to obtain the crude product â-nitroalkyl sulfoxides 11-
13 (11a , 12a , and 13a were purified by chromatography).
Carbon tetrachloride was added to the mixture, and the
solution was refluxed for 1-6 h to obtain the final product
5 (Table 2). Only trace of 5 were generated if the
elimination reaction was also performed in CH2Cl2
because the temperature is too low for 11-13 to undergo
elimination reaction.9
The NMR and GC analysis of the crude product
indicated only the exo-nitro olefins 5c-e were generated,
and none of endo-nitro olefins 14a -c were detected. Only
traces of 14a -c could be found after chromatography
purification, and this result indicates that 5c-e actually
isomerize to 14a -c during column purification. Com-
pared to literature report,3c we found this improved and
easy method is good enough to prepare medium to high
yields of exo-nitro olefins 5c-e. When intermediates 11-
13 undergo Ei elimination, the generation of the exo-nitro
olefins 5c-e but not the endo-nitro olefins 14a -c is due
to the thermodynamic driving force of the conjugation of
the olefin with the nitro group in the exo product.
It was in 1983 that Barton et al. had reported 2-ni-
tromethyleneadamantane 16a can be prepared from the
(13) Houben-Weyl. Methoden der Organischen Chemie, 4th ed.;
Muller, E., Ed.; Georg Thieme Verlag: Stuttgart, 1971; Vol. X, Part 1,
pp 336-338.
(14) Bear, H. H.; Urbas, L. In The Chemistry of the Nitro and Nitroso
Groups; Feuer, H., Ed.; Interscience Publishers: New York, 1970; Part
2, pp 112-115.
(15) J ones, G. Org. React. (N.Y.) 1967, 15, 204.
(16) Hassner, A.; Dehaen, W. J . Org. Chem. 1990, 55, 5505.
(17) Parham, W. E.; Ramp, F. L. J . Am. Chem. Soc. 1951, 73, 1293.

Preparation of 2,2-Disubstituted 1-Nitroalkenes
J . Org. Chem., Vol. 66, No. 6, 2001 1987
Ta ble 3. Th e P r ep a r a tion of 5-Su bstitu ted
2-Nitr om eth ylen ea d a m a n ta n e 16 Accor d in g to Ba r ton ’s
Meth od ology
amount of dichloromethane or ethyl acetate, and then
the solution was coated on silica gel. After heating the
silica gel at 90-100 °C for 1-6 h, medium to high yield
of 16 were formed (eq 4 and Table 6). From substance
17f, 95% of 16f was isolated, and the result was much
better than the former result which was described above
(eq 3).
In conclusion, we have developed an improved and easy
method for the synthesis of 2,2-disubstituted 1-nitro-
alkenes. We have demonstrated the utility of this method
to synthesize of exo-nitro olefins 5c-e as the major
products which are not easy to be prepared according to
literature procedures. Similarly, 5-substituted-2-nitro-
methyleneadamantane 16 are also can be synthesized by
this method or can be prepared by heating 17 with silica
gel at 90-100 °C. The application of these nitroalkenes
for cycloaddition has been studied and will be reported
in the future.
entry
15
16
reflux 3 h yield (%) reflux 24 h yield (%)b
1
2
3
4
5
6
15a 16a
15b 16b
15c 16c
15d 16d
15e 16e
65
84
60
62
56
74
86
89
72
83
80
79
Exp er im en ta l Section
Gen er a l. All reactions were performed in flame- or oven-
dried glassware under a positive pressure of nitrogen. Benzene
and CH2Cl2 were distilled from calcium hydride. CCl4 was
distilled from P2O5. Analytical thin-layer chromatography was
performed with E. Merck silica gel 60F glass plates and flash
chromatography by use of E. Merck silica gel 60 (230-400
mesh). MS or HRMS were measured by J EOL J MS-D300 or
J EOL J MS-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 (δ) were given
in ppm relative to TMS. Elemental analysis was performed
on a Perkin-Elmer 2400 instrument. All melting points were
determined with MEL-TEMPII apparatus and were uncor-
rected.
15f
16f
a
b
Isolated yield. NMR yield.
reaction of 2-adamantanone 15a and nitromethane 2 in
the presence of ethylenediamine as catalyst under re-
fluxing condition (eq 1).18 According to literature proce-
dures, our study found compound 16 actually can be
synthesized by this useful methodology but some of
unreacted 5-substituted 2-adamantanone 15 were always
recovered even the solution was refluxed for 24 h (Table
3).
To improve these reactions, 15 were used to react with
nitromethane 2, thiophenol 6a , and piperidine 3 in
refluxing benzene, and the system was also equipped
with a Dean-Stark trap to remove water as described
above. To obtain higher yields of 5-substituted- 2-nitrom-
ethyl-2-phenylthioadamantane 17, equal amounts of 2,
6a , and 3 were added to the solution at different stages,
and the solution was refluxed for 36-98 h. After evapo-
ration of the solvent, medium to high yields of 17 were
isolated by column chromatography (eq 2 and Table 4).
Conversion of 15a to 16a requires a significantly longer
reaction time than does the conversion of 1c to 5c,
presumably due to the greatly increased steric hindrance
of the ketone in 15a .
When 17a -e were treated with m-CPBA 10 in CH2-
Cl2 solution and were stirred for 1-2 h at room temper-
ature, high yields of 16a -e were isolated. In contrast to
the conversion of 7-9 to 5 as summarized in Table 2, a
one-pot reaction done in CH2Cl2 solution was sufficient
to convert 17 to 16 with the exception of 17f which gave
only a trace amount of 16f as shown in eq 3 and Table 5.
During the purification of the intermediate 17 by
column chromatography, we found trace of 16 always
were isolated, and this result indicated that 17 possibly
also can undergo elimination on the silica gel surface.
To prove this assumption, 17 was dissolved in a little
Ma t er ia ls. Ketones 1a -e, nitromethane 2, piperidine 3,
mercaptan 6a -c, m-chloroperoxybenzoic acid 10, and 2-ada-
mantanone 15a were purchased from Aldrich Chemical Co and
other commercially available reagents were used without
further purification. Starting material 15b,19,20a 15c,19,20 15d,19,20a
15e,19,20a,21,22 and 15f19,23 were prepared according to the
literature procedures.
Typ ica l Exp er im en ta l P r oced u r es for th e Syn th esis
of th e â-Nitr oa lk yl Su lfid es 7-9 fr om th e Rea ction of
Keton es 1, Nitr om eth a n e 2, a n d Mer ca p ta n 6 in th e
P r esen ce of P ip er id in e 3 a s Ca ta lyst a n d Ben zen e a s
Solven t (Ta ble 1). In a 100 mL round-bottomed flask fitted
with a Dean-Stark trap were placed the ethyl methyl ketone
1b (36 mmol), nitromethane 2 (30 mmol), piperidine 3 (15
mmol), and thiophenol 6a (36 mmol) in 50 mL of benzene, and
the solution was refluxed for 23 h. After the solution was
cooled, the solution was washed with ice cold dilute hydro-
chloric acid solution, washed with brine, dried over anhydrous
magnesium sulfate, filtered, and concentrated. The purification
of the mixture was carried out by flash column chromatogra-
phy by using hexanes-ethyl acetate (200:1) to obtain 95% of
7b. Not only 22% of 9e but also 55% of 14c was isolated when
ketone 1e was used to react with allyl mercaptan 6c under
similar conditions.
Typ ica l Exp er im en ta l P r oced u r es for th e Syn th esis
of th e â-Nitr oa lk yl Su lfid es 7a , 7d , a n d 9e fr om th e
Rea ction of Keton e 1a or 1d , Nitr om eth a n e 2, a n d
Mer ca p ta n 6a or 6c in th e P r esen ce of P ip er id in e 3
u n d er Solven t-F r ee Con d ition s (Ta ble 1). A stirred mix-
(18) (a) Barton, D. H. R.; Motherwell, W. B.; Zard, S. Z. Bull. Soc.
Chim. Fr. (Engl. Transl.) 1983, 2, 61. (b) Leonova, M. V.; Klimochkin,
Y. N.; Kovalev, V. V.; Moiseev, I. K. Russ. J . Org. Chem. (Engl. Transl.)
1993, 29, 11, 1921. Zh. Org. Khim. 1993, 29, 2312. (c) Klimochkin, Y.
N.; Leonova, M. V.; Moiseev, I. K. Russ. J . Org. Chem. (Engl. Transl.)
1998, 34, 494. Zh. Org. Khim. 1998, 34, 528. (d) Klimochkin, Y. N.;
Leonova, M. V.; Moiseev, I. K. Russ. J . Org. Chem. (Engl. Transl.) 1998,
34, 34. Zh. Org. Khim. 1998, 34, 46.
(19) Geluk, H. W. Synthesis 1972, 374.
(20) (a) Chung, W. S.; Liu, Y. D.; Wang, N. J . J . Chem. Soc., Perkin
Trans. 2 1995, 581. (b) Xie, M.; le Nobel, W. J . J . Org. Chem. 1989,
54, 3839. (c) Tabushi, I.; Aoyama, Y. J . Org. Chem. 1973, 38, 3447.
(21) Geluk, H. W.; Schlatmann, J . L. M. A. Tetrahedron 1968, 24,
5369.
(22) Klein, H.; Wiartalla, R. Synth. Commun. 1979, 9, 825.
(23) Adcock, W.; Trout, N. A. J . Org. Chem. 1991, 56, 3229.

1988 J . Org. Chem., Vol. 66, No. 6, 2001
Ta ble 4. Th e P r ep a r a tion of 17 fr om 15, Nitr om eth a n e 2, P ip er id in e 3, a n d Th iop h en ol 6a
Lin et al.
entry
15
2 (equiv)
3 (equiv)
6a (equiv)
time(h)a
17
yield(%)b
1
2
3
4
5
6
15a
15b
15c
15d
15e
15f
16
32
40
32
32
32
6
3
4
2
4
5
8
16
20
16
16
19
36
86
98
62
50
87
17a
17b
17c
17d
17e
17f
100
100
87
65
86
100
a
b
Benzene was used as solvent with a Dean-Stark trap to remove water. Isolated yield.
Ta ble 5. Th e P r ep a r a tion of 16 by Tr ea tin g 17 w ith
m -CP BA 10
evaporation of the solvent, the oily residue containing 7a was
purified by flash column chromatography by using hexanes-
ethyl acetate (200:1) to obtain 84% of 7a .
1-Nitr o-2-m eth yl-2-p h en ylth iop r op a n e (7a ): 1H NMR
(200 MHz, CDCl3) δ 7.60-7.35 (m, 5H), 4.42 (s, 2H), 1.44 (s,
6H). 13C NMR (50 MHz, CDCl3) δ 137.8, 130.0, 129.7, 129.2,
84.9, 46.5, 26.3. MS m/z (relative intensity) 211 (M+, 8), 165
(31), 110 (100). Anal. Calcd for C10H13NO2S: C, 56.84; H, 6.20;
N, 6.63. Found: C, 57.09; H, 6.29; N, 6.62.
1-Nit r o-2-m et h yl-2-p h en ylt h iob u t a n e (7b): 1H NMR
(200 MHz, CDCl3) δ 7.58∼7.27 (m, 5H), 4.50 (d, J ) 11.0 Hz,
1H), 4.40 (d, J ) 11.0 Hz, 1H), 1.70 (m, 2H), 1.34 (m, 3H),
1.14 (t, J ) 7.3 Hz, 3H). 13C NMR (50 MHz, CDCl3) δ 137.9,
129.9, 129.5, 129.2, 83.3, 50.9, 30.4, 23.6, 8.4. MS m/z (relative
intensity) 225 (M+, 7), 179 (13), 110 (100). HRMS calcd for
entry
17
time(h)
16
yield(%)a
1
2
3
4
5
6
17a
17b
17c
17d
17e
17f
1.5
1.0
1.0
1.0
1.0
2.0
16a
16b
16c
16d
16e
16f
97
96
96
100
100
tr
C
11H15N2S (M+) 225.0823, found 225.0804.
1-Nitr om eth yl-1-p h en ylth iocyclop en ta n e (7c): 1H NMR
(200 MHz, CDCl3) δ 7.62-7.54 (m, 2H), 7.44-7.32 (m, 3H),
4.49 (s, 2H), 2.10-1.66 (m, 8H). 13C NMR (50 MHz, CDCl3) δ
137.4, 130.8, 129.7, 129.2, 82.2, 58.1, 36.0, 23.5. HRMS calcd
for C12H15NO2S (M+) 237.0823, found 237.0818. Anal. Calcd
for C12H15NO2S: C, 60.73; H, 6.37; N, 5.90. Found: C, 60.59;
H, 6.49; N, 5.75.
a
Isolated yield.
Ta ble 6. Th e P r ep a r a tion of 16 by Hea tin g 17 w ith
Silica Gel a t 90-100 °C
1-Nitr om eth yl-1-p h en ylth iocycloh exa n e (7d ): 1H NMR
(200 MHz, CDCl3) δ 7.63-7.55 (m, 2H), 7.46-7.29 (m, 3H),
4.41 (s, 2H), 2.05-1.17 (m, 10H). 13C NMR (50 MHz, CDCl3) δ
137.8, 129.8, 129.5, 129.2, 84.1, 51.8, 33.1, 25.3, 21.6. MS m/z
(relative intensity) 251 (M+, 38), 205 (16), 110 (100). HRMS
calcd for C13H17 NO2S (M+) 251.0980, found 251.0984. Anal.
Calcd for C13H17NO2S: C, 62.12; H, 6.82; N, 5.58. Found: C,
62.05; H, 6.82; N, 5.70.
entry
17
time(h)
16
yield(%)a
2-Ben zylth io-2-n itr om eth ylpr opan e (8a):11 1H NMR (200
MHz, CDCl3) δ 7.37-7.23 (m, 5H), 4.43 (s, 2H), 3.81 (s, 2H),
1.50 (s, 6H). 13C NMR (50 MHz, CDCl3) δ 137.1, 129.0, 128.8,
127.5, 85.0, 44.4, 33.5, 26.4. MS m/z (relative intensity) 225
(M+, 0.5), 123 (4.5), 91 (100). HRMS calcd for C11H15NO2S (M+)
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.
2-Ben zylth io-2-n itr om eth ylbu ta n e (8b):11 1H NMR (200
MHz, CDCl3) δ 7.36-7.31 (m, 5H), 4.51 (d, J ) 11 Hz, 1H),
4.44 (d, J ) 11 Hz, 1H), 3.37 (d, J ) 12.1 Hz, 1H), 3.70 (d, J
) 12.1 Hz, 1H), 1.78 (q, J ) 7.2 Hz, 2H), 1.44 (s, 3H), 1.05 (t,
J ) 7.3 Hz, 3H). 13C NMR (50 MHz, CDCl3) δ 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) 339 (M+, 45), 193 (100), 179 (45). HRMS calcd for
1
2
3
4
5
6
17a
17b
17c
17d
17e
17f
6
1
1
1
6
1
16a
16b
16c
16d
16e
16f
89
70
87
79
67
95
a
Isolated yield.
ture of nitromethane 2 (10 mmol), piperidine 3 (3 mmol), and
thiophenol 6a (18 mmol) was treated with acetone 1a (16
mmol). Heat evolved, and the mixture was heated at 80 °C
(oil bath) for 8 h. After the solution was cooled, additional
acetone 1a (16 mmol), piperidine 3 (3 mmol), and thiophenol
6a (18 mmol) were added into the reaction mixture, and the
solution was heated for another 30 h at 80 °C. Dichloro-
methane was added, and the resulting solution was washed
with ice cold dilute hydrochloric acid solution, washed with
brine, and dried over anhydrous magnesium sulfate. After
C
12H17NO2S (M+) 239.0980, found 239.0982.
1-Ben zylth io-1-n itr om eth ylcyclopen tan e (8c):11 1H NMR
(200 MHz, CDCl3) δ 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) δ 136.7,
128.8, 128.3, 126.9, 82.1, 54.9, 36.3, 33.6, 23.4. MS m/z (relative

Preparation of 2,2-Disubstituted 1-Nitroalkenes
J . Org. Chem., Vol. 66, No. 6, 2001 1989
intensity) 251 (M+, 9), 205 (17), 203(78), 124 (15), 123 (71), 91
(100). HRMS calcd for C13H17NO2S (M+) 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.
(2-Meth yl-1-n itr o-pr opan e-2-su lfin yl)ben zen e (11a): 1H
NMR (200 MHz, CDCl3) δ 7.65-7.55 (m, 5H), 4.74 (d, J ) 11.2
Hz, 1H), 4.22 (d, J ) 11.2 Hz, 1H), 1.43 (s, 3H), 1.28 (s, 3H).
13C NMR (50 MHz, CDCl3) δ 137.9, 132.3, 129.1, 126.3, 76.4,
57.7, 19.5, 18.8. MS m/z (relative intensity) 227 (M+, tr), 125
(100). HRMS calcd for C10H13NO3S (M+) 227.0616, found
227.0614.
1-Ben zylth io-1-n itr om eth ylcycloh exa n e (8d ):11 1H NMR
(200 MHz, CDCl3) δ 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) δ 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 (M+, 0.5), 219 (1.5), 91 (100). HRMS
calcd for C14H19NO2S (M+) 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.
(2-Met h yl-1-n it r op r op a n e-2-su lfin ylm et h yl)b en zen e
1
(12a ): Colorless solid and the melting point is 46-48 °C. H
NMR (200 MHz, CDCl3) δ 7.40-7.31 (m, 5H), 4.74 (d, J ) 11.4
Hz, 1H), 4.55 (d, J ) 11.4 Hz, 1H), 3.93 (d, J ) 12.8 Hz, 1H),
3.71 (d, J ) 31.2 Hz, 1H) 1.48 (s, 3H), 1.46 (s, 3H). 13C NMR
(50 MHz, CDCl3) δ 130.4, 130.1, 129.0, 128.5, 79.8, 55.9, 52.9,
19.6, 18.4. MS m/z (relative intensity) 241 (M+, 3), 129 (11),
123 (100), 91(73). HRMS calcd for C11H15NO3S (M+) 241.0773,
found 241.0778. Anal. Calcd for C11H15NO3S: C, 54.75; H, 6.27;
N, 5.80. Found: C, 54.86; H, 6.18; N, 5.68.
1-Ben zylth io-1-n itr om eth ylcycloh eptan e (8e):11 1H NMR
(200 MHz, CDCl3) δ 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) δ 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 (M+, 170), 233 (20), 123 (27), 91 (100).
HRMS calcd for C15H21NO2S (M+) 279.1293, found 279.1290.
2-Allylth io-2-m eth yl-1-n itr op r op a n e (9a ): 1H NMR (200
MHz, CDCl3) δ 5.95-5.74 (ddt, J ) 17.1, 10.0, 7.0 Hz, 1H),
5.29-5.18 (dq, J ) 17.1, 1.4 Hz, 1H), 5.18-5.10 (dq, J ) 10.0,
1.2 Hz, 1H), 4.52 (s, 2H) 3.29-3.24 (dt, J ) 6.8, 1.2 Hz, 2H),
1.48 (s, 6H). 13C NMR (50 MHz, CDCl3) δ 134.1, 117.7, 84.8,
43.9, 31.9, 26.2. MS m/z (relative intensity) 175 (M+, 6), 129
(22), 73 (100). HRMS calcd for C7H13NO2S (M+) 175.0667,
found 175.0670.
3-(2-Meth yl-1-n itr op r op a n e-2-su lfin yl)p r op en e (13a ):
1H NMR (200 MHz, CDCl3) δ 6.07-5.86 (m, 1H), 5.51 (s, 1H),
5.44 (dd, J ) 6.2, 1 Hz, 1H), 4.76 (d, J ) 11.2 Hz, 1H), 4.58 (d,
J ) 11.2 Hz, 1H), 3.377 (dd, J ) 10, 12.8 Hz, 1H), 3.376 (dd,
J ) 17.3, 12.8 Hz, 1H) 1.45 (s, 3H), 1.44 (s, 3H). 13C NMR (50
MHz, CDCl3) δ 126.5, 123.8, 79.8, 55.9, 50.8, 19.8, 18.3. MS
m/z (relative intensity) 191 (M+, tr), 73 (56), 41 (100). HRMS
calcd for C7H13NO3S (M+) 191.0616, found 191.0626.
2-Meth yl-1-n itr o-1-p r op en e (5a ): 1H NMR (200 MHz,-
CDCl3) δ 6.98 (m, 1H), 2.27 (d, J ) 1.4 Hz, 3H), 1.96 (d, J )
1.4 Hz, 3H). 13C NMR (50 MHz, CDCl3) δ 149.9, 135.2, 24.1,
19.9. MS m/z (relative intensity) 101 (M+, 10), 84 (100), 67 (2).
HRMS calcd for C4H8NO2 (M+) 102.0555, found 102.0560.
(E)-2-Meth yl-1-n itr o-1-bu ten e (5b):11 1H NMR (200 MHz,-
CDCl3) δ 6.98-6.96 (m, 1H), 2.31-2.18 (m, 2H), 2.26-2.24 (m,
3H), 1.14 (t, J ) 7.6 Hz, 3H) 13C NMR (50 MHz, CDCl3) δ
154.8, 134.8, 31.2, 18.5, 11.6. MS m/z (relative intensity) 115
(M+, 16), 98 (100), 81 (14), 72 (19). HRMS calcd for C5H9NO2
(M+) 115.0633, found 115.0635.
2-Allylth io-2-m eth yl-1-n itr obu ta n e (9b): 1H NMR (200
MHz, CDCl3) δ 5.94-5.73 (ddt, J ) 17.0, 10.7 Hz, 1H), 5.29-
5.19 (dq, J ) 17.0, 1.4 Hz, 1H), 5.16-5.08 (dq, J ) 10.0, 1.2
Hz, 1H), 4.57 (d, J ) 11.4 Hz, 1H), 4.52 (d, J ) 11.4 Hz, 1H),
3.23-3.18 (dt, J ) 7, 1.2 Hz, 2H), 1.73 (q, J ) 7 Hz, 2H), 1.42
(s, 3H), 1.05 (t, J ) 7.6 Hz, 3H). 13C NMR (50 MHz, CDCl3) δ
134.1, 117.9, 83.4, 48.3, 31.4, 30.4, 23.4, 8.1. MS m/z (relative
intensity) 189 (M+, 9), 143 (24), 87 (100). HRMS calcd for
C8H15NO2S (M+) 189.0824, found 189.0821.
1-Allylth io-1-n itr om eth ylcyclop en ta n e (9c): 1H NMR
(200 MHz, CDCl3) δ 5.96-5.75 (ddt, J ) 17.1, 9.8, 7 Hz, 1H),
5.27-5.16 (dq, J ) 17.0, 1.2 Hz, 2H), 5.14-5.10 (dq, J ) 9.9,
1.2 Hz, 1H), 4.60 (s, 2H), 3.21 (dt, J ) 7, 1.4 Hz, 2H), 1.97-
1.63 (m, 8H). 13C NMR (50 MHz, CDCl3) δ 134.1, 117.4, 82.4,
54.8, 36.4, 32.5, 23.5. MS m/z (relative intensity) 201 (M+, 60),
155 (100), 128 (40). HRMS calcd for C11H19NO2S (M+) 201.0823,
found 201.0826.
(Z)-2-Meth yl-1-n itr o-1-bu ten e (5b):11 1H NMR (200 MHz,
CDCl3) δ 6.92-6.88 (m, 1H), 2.63 (q, J ) 7.6 Hz, 2H), 2.23 (t,
J ) 10.6 Hz, 3H), 1.93 (d, J ) 1.2 Hz, 3H). 13C NMR (50 MHz,
CDCl3) δ 155.1, 134.3, 26.0, 21.4, 11.4. MS m/z (relative
intensity) 115 (M+, 16), 98 (100), 81 (14), 72 (19). HRMS calcd
for C5H9NO2 (M+) 115.0633, found 115.0635.
1
Nitr om eth ylen ecyclop en ta n e (5c): H NMR (200 MHz,
1-Allylth io-1-n itr om eth ylcycloh exa n e (9d ):16 1H NMR
(200 MHz, CDCl3) δ 5.85 (ddt, J ) 17, 9.8, 7 Hz, 1H), 5.23 (dq,
J ) 16.9, 1.4 Hz, 1H), 5.12 (dq, J ) 9.9, 1 Hz, 1H), 4.54 (s,
2H), 3.15 (dt, J ) 7, 1.4 Hz, 2H), 1.55-1.87 (m, 9H), 1.26 (m,
1H). 13C NMR (50 MHz, CDCl3) δ 134.0, 117.8, 84.7, 49.3, 33.3,
30.9, 25.2, 21.4. MS m/z (relative intensity) 215 (M+, 60), 95
(M+, 100).
CDCl3) δ 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) δ 163.7,
132.2, 33.9, 33.3, 25.9, 25.4. MS m/z (relative intensity) 127
(M+, 2), 111 (11), 81 (68), 79 (100). HRMS calcd for C6H9NO2
(M+) 127.0633, found 127.0615.
Nitr om eth ylen ecycloh exa n e (5d ):4,11 1H NMR (200 MHz,
CDCl3) δ 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) δ 155.8,
132.4, 34.4, 28.9, 28.2, 27.3, 25.8. MS m/z (relative intensity)
1-Allylth io-1-n itr om eth ylcycloh ep ta n e (9e): 1H NMR
(200 MHz, CDCl3) δ 5.95-5.74 (ddt, J ) 17.1, 9.8, 7.0 Hz, 1H),
5.22 (dq, J ) 16.9, 1.6 Hz, 1H), 5.11 (dq, J ) 9.9, 1.2 Hz, 1H),
4.51 (s, 2H), 3.20 (dt, J ) 7, 1.2 Hz, 2H), 2.06-1.44 (m, 12H).
13C NMR (50 MHz, CDCl3) δ 134.1, 117.8, 84.6, 52.1, 36.7, 31.6,
29.5, 22.5. MS m/z (relative intensity) 229 (M+, 56), 183 (100),
156 (53). HRMS calcd for C11H19NO2S (M+) 229.1137, found
229.1138.
Typ ica l Exp er im en ta l P r oced u r es for th e Syn th esis
of Nitr oa lk en es 5 fr om th e Oxid a tion of â-Nitr oa lk yl
Su lfid es 7-9 w ith m -CP BA 10 in CH2Cl2 Solu tion a n d
F ollow ed by Elim in a tion in Reflu xin g CCl4 (Ta ble 2). At
0 °C, 8 mmol of 7d and 8 mmol m-CPBA of 10 were dissolved
in 50 mL of CH2Cl2 and stirred for few minutes at the same
temperature. The temperature was raised to room tempera-
ture, and the solution was stirred for 1.5 h. After the reaction
was complete by checking with TLC plate, CH2Cl2 was distilled
to obtain crude product 11-13 (11a , 12a , and 13a were purifed
by chromatography). To the crude mixture was then added 50
mL of CCl4, and it was refluxed for 1 h. After the solution was
cooled, the solution was washed with brine, extracted by
dichloromethane solution, dried over anhydrous magnesium
sulfate, filtered, and concentrated. The purification of the
mixture was carried out by flash column chromatography by
using hexanes-ethyl acetate (400:1) to obtain 100% of 5d .
141 (M+, 3), 109 (15), 95 (3), 81 (100). HRMS calcd for C7H11
-
NO2 (M+) 141.0790, found 141.0788.
1
Nitr om eth ylen ecycloh ep ta n e (5e): H NMR (200 MHz,
CDCl3) δ 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) δ 160.2, 134.8,
35.4, 32.1, 29.5, 28.8, 27.9, 25.5. MS m/z (relative intensity)
155 (M+, 4), 139 (64), 109 (11), 91 (100). HRMS calcd for C8H13
NO2(M+) 155.0946, found 155.0937.
-
1-Nitr om eth ylcycloh ep ten e (14c):3c 1H NMR (200 MHz,
CDCl3) δ 6.05 (t, J ) 6.2 Hz, 1H), 4.82 (s, 2H), 2.29-2.16 (m,
4H), 1.82-1.60 (m, 2H), 1.59-1.48 (m, 4H). 13C NMR (50 MHz,
CDCl3) δ 138.3, 134.4, 84.2, 31.8, 31.1, 28.4, 26.1, 26.0. MS
m/z (relative intensity) 155 (M+, tr), 109 (100), 93 (8). Anal.
Calcd for C8H13NO2: C, 61.91; H, 8.44; N, 9.03. Found: C,
62.24; H, 8.30; N, 8.72.
Typ ica l Exp er im en ta l P r oced u r es for th e Syn th esis
of Nitr oa lk en es 16a -f fr om Rea ction s of Keton e 15a -f
a n d Nitr om eth a n e 2 in th e P r esen ce of Eth ylen ed ia m in e
Accor d in g to Ba r ton ’s Meth od ology (Ta ble 3).18a Ni-
tromethane 2 (15 mL), 2-adamantanone 15a (500 mg), and
ethylenediamine (20 mg) were placed in a 25 mL round-
bottomed flask, and the solution was refluxed for 3 (or 24) h
under an nitrogen atmosphere. After the solvent was evapo-

1990 J . Org. Chem., Vol. 66, No. 6, 2001
Lin et al.
rated in vacuo, the residue was purified by flash column
chromatography by using hexanes-ethyl acetate (400:1) to
obtain 65% (or 86%) of 16a .
MHz, CDCl3) δ 7.73-7.63 (m, 2H), 7.44-7.30 (m, 3H), 4.70 (s,
2H), 2.80 (d, J ) 10.8 Hz, 2H), 2.09-1.89 (m, 6H), 1.87-1.62
(m, 6H). 13C NMR (50 MHz, CDCl3) δ 137.5, 129.5, 129.4, 128.9,
78.7, 58.6, 38.7, 33.2, 32.9, 27.4, 26.9. MS m/z (relative
intensity) 303 (M+, 7), 110 (100). HRMS calcd for C17H21NO2S
(M+) 303.1294, found 303.1292. Anal. Calcd for C17H21NO2S:
C, 67.29; H, 6.98; N, 4.62. Found: C, 66.92; H, 6.96; N, 4.65.
(Z)-2-N it r o m e t h y l-5-p h e n y l-2-p h e n y lt h io a d a m a n -
ta n e [(Z)-17b]: Colorless solid and the melting point is 171.5-
173.5 °C. 1H NMR (200 MHz, CDCl3) δ 7.75-7.65 (m, 2H),
7.49-7.30 (m, 7H), 7.28-7.18 (m, 1H), 4.76 (s, 2H), 3.02 (d, J
) 12.8 Hz, 2H), 2.25-1.72 (m, 11H). 13C NMR (50 MHz, CDCl3)
δ 149.5, 137.5, 129.5, 129.2, 129.0, 128.3, 126.0, 124.9, 78.6,
57.7, 44.1, 38.4, 35.9, 33.7, 32.4, 27.6. MS m/z (relative
intensity) 302 [(M - C6H5)+, tr], 270 [(M - C6H5S)+, tr], 218
(100). Anal. Calcd for C23H25NO2S: C, 72.79; H, 6.64; N, 3.69.
Found: C, 72.86; H, 6.68; N, 3.93.
2-Nitr om eth ylen ea d a m a n ta n e (16a ):18a Pale yellow solid
1
and the melting point is 81-82 °C (literature 78-81 °C). H
NMR (200 MHz, CDCl3) δ 6.96 (s, 1H), 4.08 (s, 1H), 2.46 (s,
1H), 2.12-1.81 (m, 12H). 13C NMR (50 MHz, CDCl3) δ 164.3,
128.7, 39.7, 38.6, 37.8, 36.1, 31.8, 27.3. MS m/z (relative
intensity) 193 (M+, 1), 77 (100). Anal. Calcd for C11H15NO2:
C, 68.37; H, 7.82; N, 7.25. Found: C, 68.09; H, 7.88; N, 7.53.
5-P h en yl-2-n itr om eth ylen ea d a m a n ta n e (16b): Colorless
solid and the melting point is 98.5-99.5 °C. 1H NMR (200
MHz, CDCl3) δ 7.40-7.15 (m, 5H), 7.00 (s, 1H), 4.23 (s, 1H),
2.63 (s, 1H), 2.32-1.86 (m, 11H). 13C NMR (50 MHz, CDCl3) δ
162.9, 148.4, 129.2, 128.4, 126.2, 124.7, 44.9, 43.8, 41.9, 39.2,
38.3, 35.9, 32.2, 28.3. MS m/z (relative intensity) 269 (M+, 4),
91 (100), 77 (25). HRMS calcd for C17H19NO2 (M+) 269.1416,
found 269.1415.
(E )-2-N it r o m e t h y l-5-p h e n y l-2-p h e n y lt h io a d a m a n -
ta n e [(E)-17b]: Colorless solid and the melting point is 99-
101 °C. 1H NMR (200 MHz, CDCl3) δ 7.77-7.70 (m, 2H), 7.44-
7.29 (m, 7H), 7.25-7.16 (m, 1H), 4.72 (s, 2H), 2.89 (d, J ) 10.6
Hz, 2H), 2.30-1.90 (m, 9H), 1.72 (d, J ) 13.2 Hz, 2H). 13C
NMR (50 MHz, CDCl3) δ 149.1, 137.6, 129.6, 129.1, 128.4,
126.2, 124.7, 78.7, 57.8, 45.0, 38.5, 35.7, 33.8, 32.2, 28.2. MS
m/z (relative intensity) 269 [(M - C6H5SH)+, 2], 91 (100).
HRMS calcd for C23H24S (M+) 332.1616, found 332.1591.
(Z)-5-F lu or o-2-n itr om eth yl-2-p h en ylth ioa d a m a n ta n e
[(Z)-17c]: Colorless solid and the melting point is 138-139
°C. 1H NMR (200 MHz, CDCl3) δ 7.75-7.63 (m, 2H), 7.48-
7.31 (m, 3H), 4.66 (s, 2H), 2.97 (s, 2H), 2.40-2.15 (m, 3H),
2.09-1.58 (m, 8H). 13C NMR (50 MHz, CDCl3) δ 137.4, 129.8,
129.2, 128.6, 91.5 (d, J ) 183.6 Hz), 78.3 (d, J ) 0.15 Hz),
56.5 (d, J ) 2.3 Hz), 43.5 (d, J ) 18.2 Hz), 37.7 (d, J ) 19.7
Hz), 36.4 (d, J ) 10.6 Hz), 31.5 (d, J ) 1.5 Hz), 29.8 (d, J )
9.9 Hz). MS m/z (relative intensity) 321 (M+, tr), 110 (100).
Anal. Calcd for C17H20NO2SF: C, 63.53; H, 6.27; N, 4.36.
Found: C, 63.73; H, 6.40; N, 4.22.
5-F lu or o-2-n itr om eth ylen ea d a m a n ta n e (16c): Pale yel-
low solid and the melting point is 89-91 °C. 1H NMR (200
MHz, CDCl3) δ 6.93 (s, 1H), 4.28 (s, 1H), 2.73 (s, 1H), 2.41 (s,
1H), 2.30-1.65 (m, 10H). 13C NMR (50 MHz, CDCl3) δ 158.8
(d, J ) 2.3 Hz), 130.0, 90.4 (d, J ) 185.1 Hz), 43.1 (d, J ) 19.7
Hz), 42.2 (d, J ) 19.0 Hz), 41.5 (d, J ) 18.2 Hz), 39.7 (d, J )
9.85 Hz), 38.5 (d, J ) 2.3 Hz), 37.4 (d, J ) 2.25 Hz), 33.6 (d, J
) 9.9 Hz), 30.8 (d, J ) 9.85 Hz). MS m/z (relative intensity)
211 (M+, tr), 91 (100). Anal. Calcd for C11H14NO2F: C, 62.55;
H, 6.68; N, 6.63. Found: C, 62.44; H, 6.81; N, 6.49.
5-Ch lor o-2-n itr om eth ylen ea d a m a n ta n e (16d ): Colorless
1
solid and the melting point is 74-75 °C. H NMR (200 MHz,
CDCl3) δ 6.95 (s, 1H), 4.20 (s, 1H), 2.66 (s, 1H), 2.42-1.76 (m,
11H). 13C NMR (50 MHz, CDCl3) δ 158.7, 129.7, 64.9, 47.9,
47.0, 46.0, 39.7, 37.8, 36.7, 33.9, 30.5. MS m/z (relative
intensity) 229 (tr), 227 (M+, tr), 91 (100). HRMS calcd for
C
C
C
11H13NO37Cl 212.0645, found 212.0651. HRMS calcd for
11H13NO35Cl 210.0681, found 210.0677. Anal. Calcd for
11H14NO2Cl: C, 58.03; H, 6.20; N, 6.15. Found: C, 58.23; H,
6.29; N, 6.11.
(E)-5-F lu or o-2-n itr om eth yl-2-p h en ylth ioa d a m a n ta n e
[(E)-17c]: Colorless solid and the melting point is 136-137
°C. 1H NMR (200 MHz, CDCl3) δ 7.76-7.64 (m, 2H), 7.49-
7.31 (m, 3H), 4.69 (s, 2H), 2.75 (d, J ) 12.6 Hz, 2H), 2.41 (s,
1H), 2.32-2.08 (m, 4H), 2.03-1.81 (m, 4H), 1.58 (d, J ) 13.2
Hz, 2H). 13C NMR (50 MHz, CDCl3) d 137.5, 129.8, 129.2,
129.1, 91.1 (d, J ) 184.4 Hz), 78.4, 56.6, 43.7 (d, J ) 16.7 Hz),
38.0 (d, J ) 19.0 Hz), 36.3 (d, J ) 9.85 Hz), 31.3 (d, J ) 1.5
Hz), 30.5 (d, J ) 9.85 Hz). MS m/z (relative intensity) 321 (M+,
tr), 110 (100). Anal. Calcd for C17H20NO2SF: C, 63.53; H, 6.27;
N, 4.36. Found: C, 63.77; H, 6.36; N, 4.38.
5-Br om o-2-n itr om eth ylen ea d a m a n ta n e (16e): Colorless
solid and the melting point is 69.5-70.5 °C. 1H NMR (200
MHz, CDCl3) δ 6.93 (s, 1H), 4.18 (s, 1H), 2.68-2.39 (m, 7H),
2.24 (s, 1H), 2.12-1.82 (m, 4H). 13C NMR (50 MHz, CDCl3) δ
158.7, 130.1, 60.6, 49.8, 48.8, 47.7, 40.7, 38.0, 36.9, 35.0, 31.5.
MS m/z (relative intensity) 273 (1), 271 (M+, 1), 91 (100). Anal.
Calcd for C11H14NO2Br: C, 48.55; H, 5.19; N, 5.15. Found: C,
48.52; H, 5.07; N, 4.82.
5-Iod o-2-n itr om eth ylen ea d a m a n ta n e (16f): Pale yellow
solid and the melting point is 52-54 °C. H NMR (200 MHz,
1
CDCl3) δ 6.92 (s, 1H), 4.05 (s, 1H), 3.10-2.62 (m, 6H), 2.48 (s,
1H), 2.25-1.85 (m, 5H). 13C NMR (50 MHz, CDCl3) δ 158.9,
130.2, 53.0, 52.0, 50.6, 42.4, 41.2, 37.9, 36.7, 35.7, 31.7. MS
m/z (relative intensity) 319 (M+, tr), 73 (100). Anal. Calcd for
(Z)-5-C h lo r o -2-n it r o m e t h y l-2-p h e n y lt h io a d a m a n -
ta n e [(Z)-17d ]: Colorless solid and the melting point is 137-
139 °C. 1H NMR (200 MHz, CDCl3) δ 7.76-7.66 (m, 2H), 7.49-
7.32 (m, 3H), 4.67 (s, 2H), 3.22 (d, J ) 12.4 Hz, 2H), 2.32-
1.65 (m, 11H). 13C NMR (50 MHz, CDCl3) δ 137.6, 129.8, 129.3,
128.6, 78.3, 66.4, 56.4, 48.6, 42.6, 36.4, 31.4, 30.0. MS m/z
(relative intensity) 339 (1), 337 (M+, 3), 110 (100). HRMS calcd
for C17H20NO2S35Cl (M+) 337.0903, found 337.0867. Anal. Calcd
for C17H20NO2SCl: C, 60.43; H, 5.97; N, 4.15. Found: C, 60.18;
H, 5.82; N, 4.05.
(E )-5-C h lo r o -2-n it r o m e t h y l-2-p h e n y lt h io a d a m a n -
ta n e [(E)-17d ]: Colorless solid and the melting point is 129-
131 °C. 1H NMR (200 MHz, CDCl3) δ 7.75-7.63 (m, 2H), 7.49-
7.32 (m, 3H), 4.70 (s, 2H), 2.78 (d, J ) 11.6 Hz, 2H), 2.48-
2.24 (m, 3H), 2.24-2.08 (m, 6H), 1.64 (d, J ) 13.2 Hz, 2H).
13C NMR (50 MHz, CDCl3) δ 137.5, 129.8, 129.2, 128.9, 78.3,
65.7, 56.5, 48.7, 42.9, 36.3, 31.1, 30.6. MS m/z (relative
intensity) 339 (2), 337 (M+, 6), 110 (93), 91 (100). HRMS calcd
for C17H20NO2S37Cl (M+) 339.0800, found 339.0837. HRMS
calcd for C17H20NO2S35Cl (M+) 337.0903, found 337.0883. Anal.
Calcd for C17H20NO2SCl: C, 60.43; H, 5.97; N, 4.15. Found:
C, 60.39; H, 5.93; N, 4.08.
C
11H14NO2I: C, 41.40; H, 4.42; N, 4.39. Found: C, 41.47; H,
4.27; N, 4.35.
Typ ica l Exp er im en ta l P r oced u r es for th e Syn th esis
of 5-Su bstitu ted -2-n itr om eth yl-2-p h en ylth ioa d a m a n ta n e
17 fr om Rea ction s of Keton es 15, Nitr om eth a n e 2, a n d
Th iop h en ol 6a in th e P r esen ce of P ip er id in e 3 in Re-
flu xin g Ben zen e (Ta b le 4). In a 100 mL round-bottomed
flask fitted with a Dean-Stark trap were placed the 2-ada-
mantanone 15a (2.0 mmol), nitromethane 2 (8.0 mmol),
piperidine 3 (3.0 mmol), and thiophenol 6a (4.0 mmol) in 50
mL of benzene, the solution was refluxed for 7 h, and then
additional amounts 2 (8.0 mmol), 3 (3.0 mmol), and 6a (4.0
mmol) were added to the solution. Similar procedures were
repeated, and the total amounts were as follows: nitromethane
2 (32.0 mmol), piperidine 3 (12.0 mmol), thiophenol 6a (16.0
mmol). After the solution was refluxed 36 h, the solution was
cooled and then poured into ice cold dilute hydrochloric acid
solution, washed with brine, dried over anhydrous magnesium
sulfate, filtered, and concentrated. The purification of the
mixture was carried out by flash column chromatography by
using hexanes-ethyl acetate (200:1) to obtain 100% of 17a .
2-Nitr om eth yl-2-p h en ylth ioa d a m a n ta n e (17a ): Color-
(Z)-5-Br om o-2-n itr om eth yl-2-p h en ylth ioa d a m a n ta n e
[(Z)-17e]: Colorless solid and the melting point is 117.5-119
°C. 1H NMR (200 MHz, CDCl3) δ 7.81-7.62 (m, 2H), 7.56-
7.32 (m, 3H), 4.65 (s, 2H), 3.40 (d, J ) 12.2 Hz, 2H), 2.48-
1.94 (m, 9H), 1.79 (d, J ) 13.6 Hz, 2H). 13C NMR (50 MHz,
1
less solid and the melting point is 103-105 °C. H NMR (200

Preparation of 2,2-Disubstituted 1-Nitroalkenes
J . Org. Chem., Vol. 66, No. 6, 2001 1991
CDCl3) δ 137.5, 129.8, 129.2, 128.5, 78.3, 62.9, 56.3, 50.0, 43.9,
37.0, 31.3, 30.7. MS m/z (relative intensity) 383 (2), 381 (M+,
2), 110 (100). Anal. Calcd for C17H20NO2SBr: C, 53.41; H, 5.27;
N, 3.66. Found: C, 53.64; H, 5.22; N, 3.75.
5). At 0 °C, 0.5 mmol of 17a and 0.75 mmol m-CPBA 10 were
dissolved in 50 mL of CH2Cl2 and stirred for few minutes at
the same temperature. The temperature was then raised to
room temperature, and the solution was stirred for 1.5 h. After
the reaction was complete by checking with TLC plate, the
solution was washed with brine, extracted by dichloromethane
solution, dried over anhydrous magnesium sulfate, filtered,
and concentrated. The purification of the mixture was carried
out by flash column chromatography by using hexane to obtain
97% of 17a .
Typ ica l Exp er im en ta l P r oced u r es for th e Syn th esis
of 5-Su b st it u t ed -2-n it r om et h ylen ea d a m a n t a n e 16a -f
fr om th e Rea ction of 5-Su bstitu ted -2-n itr om eth yl-2-
p h en ylth ioa d a m a n ta n e 17 w ith Silica Gel (Ta ble 6). At
room temperature, 0.5 mmol of 17a was dissolved in small
amount of methylene chloride or ethyl acetate and 3.03 g of
silica gel was added to the solution and the mixture was stirred
vigorously for few minutes at the same temperature. The
temperature was then raised to 90-100 °C and stirred for 6
h. After the reaction was complete, the mixture was washed
with ethyl acetate to obtain 89% of crude product 16a . If
necessary, 16a was purified by flash column chromatography
by using hexane as described above.
(E)-5-Br om o-2-n itr om eth yl-2-p h en ylth ioa d a m a n ta n e
[(E)-17e]: Colorless solid and the melting point is 117-118.5
°C. 1H NMR (200 MHz, CDCl3) δ 7.74-7.61 (m, 2H), 7.49-
7.31 (m, 3H), 4.71 (s, 2H), 2.82 (d, J ) 13.0 Hz, 2H), 2.61 (d,
J ) 13.6 Hz, 2H), 2.50-2.28 (m, 5H), 2.11 (s, 2H), 1.68 (d, J )
13.4 Hz, 2H). 13C NMR (50 MHz, CDCl3) δ 137.5, 129.8, 129.2,
128.8, 78.4, 61.8, 56.5, 50.2, 44.3, 37.1, 31.4, 31.1. MS m/z
(relative intensity) 383 (1), 381 (M+, 1), 110 (100). Anal. Calcd
for C17H20NO2SBr: C, 53.41; H, 5.27; N, 3.66. Found: C, 53.38;
H, 5.32; N, 3.83.
(Z)-5-Iodo-2-n itr om eth yl-2-ph en ylth ioadam an tan e [(Z)-
17f]: Colorless solid and the melting point is 134.5-135.5 °C.
1H NMR (200 MHz, CDCl3) δ 7.74-7.61 (m, 2H), 7.49-7.31
(m, 3H), 4.62 (s, 2H), 3.62 (d, J ) 12.4 Hz, 2H), 2.61 (s, 2H),
2.49 (d, J ) 12.4 Hz, 2H), 2.24-1.76 (m, 7H). 13C NMR (50
MHz, CDCl3) δ 137.4, 129.8, 129.2, 128.4, 78.3, 56.4, 53.1, 46.9,
45.3, 37.3, 31.3, 31.1. MS m/z (relative intensity) 429 (M+, tr),
110 (100). Anal. Calcd for C17H20NO2SI: C, 47.56; H, 4.70; N,
3.26. Found: C, 47.34; H, 4.54; N, 3.05.
(E)-5-Iodo-2-n itr om eth yl-2-ph en ylth ioadam an tan e [(E)-
17f]: Colorless solid and the melting point is 129.5-130.5 °C.
1H NMR (200 MHz, CDCl3) δ 7.71-7.59 (m, 2H), 7.47-7.30
(m, 3H), 4.72 (s, 2H), 3.00-2.48 (m, 8H), 2.09 (s, 1H), 1.96 (s,
2H), 1.75 (d, J ) 13.0 Hz, 2H). 13C NMR (50 MHz, CDCl3) δ
137.5, 129.8, 129.2, 128.7, 78.4, 56.6, 53.3, 47.3, 44.0, 37.5, 31.8,
31.1. MS m/z (relative intensity) 429 (M+, tr), 123 (100). Anal.
Calcd for C17H20NO2SI: C, 47.56; H, 4.70; N, 3.26. Found: C,
47.83; H, 4.52; N, 2.93.
Typ ica l Exp er im en ta l P r oced u r es for th e On e-P ot
Syn t h esis of 5-Su b st it u t ed -2-n it r om et h ylen ea d a m a n -
ta n e 16a -f fr om th e Oxid a tion of 5-Su bstitu ted -2-n i-
tr om eth yl-2-p h en ylth ioa d a m a n ta n e 17 w ith m -CP BA 10
a n d F ollow ed by Elim in a tion in CH 2Cl2 Solu tion (Ta ble
Ack n ow led gm en t. Financial support by the Na-
tional Science Council of the Republic of China (Grant
NSC 89-2113-M-003-021) is gratefully acknowledged.
The authors also thank one referee that gave us some
helpful suggestions about this paper.
Su p p or tin g In for m a tion Ava ila ble: 1H and 13C spectra
of compounds 5a -e, 7a -d , 8a -e, 9a -c, 9f, 11a , 12a , 13a ,
14c, 16a -f, 17a -f. This material is available free of charge
via Internet http://pubs.acs.org.
J O001215U