Iron-mediated radical halo-nitration of alkenes

Article abstract of DOI:10.1021/jo101769d

Radical halo-nitration of alkenes using iron(III) nitrate nonahydrate and halogen salt has been developed. The present reaction proceeds by radical addition of nitrogen dioxide generated by thermal decomposition of iron(III) nitrate nonahydrate and subsequent trapping of the resultant radical by a halogen atom in the presence of halogen salt. Application of this method to synthesis of nitroalkenes is also described. The practicality of the present method using nontoxic and inexpensive iron reagents has been shown by the application to broad alkenes.

Full text of DOI:10.1021/jo101769d

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Iron-Mediated Radical Halo-Nitration of Alkenes
Tsuyoshi Taniguchi,* Tatsuya Fujii, and Hiroyuki Ishibashi
School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences,
Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan
tsuyoshi@p.kanazawa-u.ac.jp
Received September 9, 2010
Radical halo-nitration of alkenes using iron(III) nitrate nonahydrate and halogen salt has been
developed. The present reaction proceeds by radical addition of nitrogen dioxide generated by ther-
mal decomposition of iron(III) nitrate nonahydrate and subsequent trapping of the resultant radical
by a halogen atom in the presence of halogen salt. Application of this method to synthesis of nitro-
alkenes is also described. The practicality of the present method using nontoxic and inexpensive iron
reagents has been shown by the application to broad alkenes.
SCHEME 1. Methods of Nitration
Introduction
Nitro compounds are widely used in various fields such as
medicine, industry, and fuels. In organic synthesis, nitro com-
pounds are valuable synthetic intermediates because these com-
pounds can be easily transformed into amines and ketones.1
Classical nitration of aromatics and alkenes by electrophilic
substitution using nitronium cation (NO2þ) is well-known
(Scheme 1, eq 1).2-4 In particular, nitryl chloride (NO2Cl)
and nitrosyl chloride (NOCl) have been frequently used as a
(1) (a) Feuer, H.; Nielsen, T. Nitro compounds: Recent Advances in
Synthesis and Chemistry; VCH: New York, 1990. (b) Ono, N. The Nitro
Group in Organic Synthesis; John Wiley-VCH: New York, 2001. (c) Ballini,
R.; Petrini, M. ARKIVOC 2009, 195.
(2) For reviews on nitration of aromatic compounds, see: (a) Olah, G. A.;
Malhotra, R.; Narang, S. C. Nitration: Methods and Mechanisms; VCH
Publishers Inc.: New York, 1989. (b) Suzuki, T.; Noyori, R. Chemtracts 1997,
10, 813.
(3) For examples of nitration of alkenes, see: (a) Shechter, H.; Conrad, F.;
Daulton, A. L.; Kaplan, R. B. J. Am. Chem. Soc. 1952, 74, 3052. (b) Terada, A.;
Hassner, A. Bull. Chem. Soc. Jpn. 1967, 40, 1937. (c) Bachman, G. B.;
Whitehouse, M. L. J. Org. Chem. 1967, 32, 2303. (d) Corey, E. J.; Estreicher,
H. J. Am. Chem. Soc. 1978, 100, 6294. (e) Hayama, T.; Tomoda, S.; Takeuchi,
Y.; Nomura, Y. Tetrahedron Lett. 1982, 23, 4733. (f) Jew, S.-S.; Kim, H.-D.;
Cho, Y.-S.; Cook, C.-H. Chem. Lett. 1986, 1747. (g) Butts, C. P.; Calvert, J. L.;
Eberson, L.; Hartshorn, M. P.; Robinson, W. T. J. Chem. Soc., Perkin Trans. 2
1994, 1485. (h) Hata, E.; Yanada, T.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
1995, 68, 3629. (i)Campos,P. J.;Garcıa,B.;Rodrıguez, M.A. Tetrahedron Lett.
2000, 41, 979. (j) Stepanov, A. V.; Veselovsky, V. V. Russ. Chem. Rev. 2003, 72,
327. (k) Jovel, I.; Prateeptongkum, S.; Jackstell, R.; Vogl, N.; Weckbecker, C.;
Beller, M. Adv. Synth. Catal. 2008, 350, 2493. (l) Sprecher, H.; Pletscher, S.;
nitro group donor.3a,b,f,l However, nitration reactions using
these reagents have drawbacks such as difficulty of handling
and the limitation of substrates due to toxicity and extreme
reactivity. As a method for synthesis of aliphatic nitro com-
pounds, nucleophilic substitution reaction of an alkyl halide
with nitrite anion (NO2-) has been used (Scheme 1, eq 2).5
Oxidation of amines and oximes also affords corresponding
nitro compounds.6 Recently, Fors and Buchwald have re-
ported palladium-catalyzed synthesis of nitroaromatics from
aryl chlorides, triflates, and nonaflates using sodium nitrite.7
On the other hand, nitrogen dioxide gas (NO2), which is a
free radical, is one of the simplest and most common nitra-
tion reagents.8 Addition of nitrogen dioxide to a C-C
multiple bond easily affords aliphatic nitro compounds
(Scheme 1, eq 3).9,10 However, this method has serious
€
Mori, M.; Marti, R. Helv. Chim. Acta 2010, 93, 90. See also refs 9 and 10.
(4) Olah and co-workers have also reported a direct nitration of alkane
using nitronium tetrafluoroborate; see: Olah, G. A.; Ramaiah, P.; Rao,
C. B.; Graham, S.; Golam, R.; Trivedi, N. J.; Olah, J. A. J. Am. Chem. Soc.
1993, 115, 7246.
(5) (a) Kornblum, N.; Taub, B.; Ungnade, H. E. J. Am. Chem. Soc. 1954,
76, 3209. (b) Kornblum, N.; Powers, J. W. J. Org. Chem. 1957, 22, 455.
8126 J. Org. Chem. 2010, 75, 8126–8132
Published on Web 11/10/2010
DOI: 10.1021/jo101769d
r
2010 American Chemical Society

Taniguchi et al.
JOCArticle
drawbacks such as the difficulty of handling NO2 gas and its
toxicity. Therefore, the reaction using nitrogen dioxide is
used in limited cases of synthetic chemistry.
SCHEME 2. Radical Nitro-Cyclization of 1,6-Dienes
It is well-known that thermal decomposition of iron(III)
nitrate nonahydrate, Fe(NO3)3 9H2O, generates nitrogen
3
dioxide (NO2),11,12 but synthetic applications of this method
have never been explored. In recent years, iron compounds
have become attractive as nontoxic and inexpensive green
elements.13 Many chemists have shown interest in iron
complexes as replacements for expensive transition metal
catalysts such as palladium and rhodium for carbon-carbon
or carbon-heteroatom bond formation.14 Recently, we re-
ported iron-mediated radical nitro-cyclization of 1,6-
dienes 1 to give five-membered compounds 2 bearing a
nitro group by sequential steps that involved radical addi-
tion of nitrogen dioxide to 1,6-dienes promoted by the
thermal decomposition of iron(III) nitrate nonahydrate,
cyclization, and trapping of the resultant terminal radicals by
a halogen atom in the presence of halogen salt (Scheme 2).15
TABLE 1. Chloro-Nitration of Decene (3a)
entry
NO3
Cl
solvent
time (h)
yield (%)
1
2
Fe(NO3)3 9H2O
Fe(NO3)3 9H2O
FeCl3
FeCl3
LiCl
THF
2
1
5
4
77
84
71
61
3
3
MeCN
MeCN
MeCN
3
Fe(NO3)3 9H2O
LiNO3
3
4a
FeCl3
a5 equiv of LiNO3 and 2 equiv of FeCl3 were employed.
Itis expectedthat radicalnitrationofalkenesusingFe(NO3)3
3
9H2O will provide a general and practical method for the
synthesis of nitro compounds from the viewpoints of safety
and economy. In this paper, we present a full account of this
work including extension to nitration reactions of various
alkenes.
Results and Discussion
In our previous study, reaction conditions using several
nitrate and chloride salts were examined, and the results indi-
cated that a combination of Fe(NO3)3 9H2O/FeCl3 in boil-
3
ing THF was the best condition.15 First, we examined the
application of these reaction conditions to simple alkenes.
Treatment of decene (3a) under similar conditions (Fe(NO3)3
9H2O/FeCl3 in boiling THF) gave 2-chloro-1-nitrodecane
(4a) in good yield (Table 1, entry 1). We found that using
MeCN instead of THF as a solvent resulted in slight improve-
ment in yield with shorter reaction time (Table 1, entry 2).
Using LiCl as a chlorine source and LiNO3 as a nitrate source
in the presence of iron also gave nitrated compound 4a in
slightly lower yields than in the case of conditions of entry 2
(Table 1, entries 3 and 4).
Iron-mediated chloro-nitration of various alkenes is shown
in Table 2. The nitration reactions of allylamine derivative 3b
and 2,2-disubstitute alkene 3c gave chloro-nitrated compounds
4b and 4c, respectively, in good yields (Table 2, entries 1
and 2). The reaction using styrene (3d) as a substrate also
readily proceeded to give 2-chloro-1-nitro-3-phenylethane
(4d) in good yield along with a small amount of eliminated
product 4d0. When the reaction of R-methylstyrene (3e) was
(6) (a) Emmons, W. D.; Pagano, A. S. J. Am. Chem. Soc. 1955, 77, 4557.
(b) Emmons, W. D. J. Am. Chem. Soc. 1957, 79, 5528. (c) McKillop, A.;
Tarbin, J. A. Tetrahedron Lett. 1983, 24, 1505. (d) Murray, R. W.; Jeyaraman,
R.; Mohan, L. Tetrahedron Lett. 1986, 27, 2335. (e) Zabrowski, D. L.;
Moormann, A. E.; Beck, K. R., Jr. Tetrahedron Lett. 1988, 29, 4501.
(7) Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 12898.
(8) (a) Mori, T.; Suzuki, H. Synlett 1995, 383. (b) Suzuki, H.; Nonoyama,
N. J. Chem. Soc., Chem. Commun. 1996, 1783. (c) Nishiwaki, Y.; Sakaguchi,
S.; Ishii, Y. J. Org. Chem. 2002, 67, 5663.
3
(9) For examples of addition of nitrogen dioxide to alkenes, see: (a) Stevens,
€
€
T. E.; Emmons, W. D. J. Am. Chem. Soc. 1958, 80, 338. (b) Jager, V.; Gunther, J.
Angew. Chem., Int. Ed. Engl. 1977, 16, 246. (c) Suzuki, H.; Mori, T. J. Org. Chem.
1997, 62, 6498. (d) Grossi, L.; Montevecchi, P. C.; Strazzari, S. Eur. J. Org. Chem.
2001, 741. (e) Grossi, L.; Montevecchi, P. C. Chem.;Eur. J. 2002, 8, 380.
(10) Radical nitration of styrene derivatives using cerium(IV) ammonium
nitrate and sodium nitrite has been reported; see: (a) Hwu, J. R.; Chen, K.-L.;
Ananthan, S.; Patel, H. V. Organometallics 1996, 15, 499. (b) Grenier, J.-L.;
Catteau, J.-P.; Cotelle, P. Synth. Commun. 1999, 29, 1201. (c) Jayakanthan,
K.; Madhusudanan, K. P.; Vankar, Y. D. Tetrahedron 2004, 60, 397.
(11) (a) Hill, W. D., Jr. Inorg. Chem. Acta 1986, 121, L33. (b) Wieczorek-
Ciurowa, K.; Kozak, A. J. J. Therm. Anal. Calorim. 1999, 58, 647.
(12) The synthesis of azides from hydrazines using nitrogen dioxide
generated from clay-supported Fe(NO3)3 (clayfen) has been reported; see:
(a) Laszlo, P.; Polla, E. Tetrahedron Lett. 1984, 25, 3701. The synthesis of
β-nitrostyrenes using clayfen has been also reported: (b) Verma, R. S.;
Naicker, K. P.; Liesen, P. J. Tetrahedron Lett. 1998, 39, 3977.
performed with Fe(NO3)3 9H2O/FeCl3 in MeCN, polymer-
3
ization and nitration of the aromatic ring probably competed
to give a complex mixture. However, we soon found that
using LiCl instead of FeCl3 gave the desired chloro-nitrated
product 4e in moderate yield along with a small amount of
eliminated product 4e0 (Table 2, entry 5). The present reac-
tion might have milder reactivity with the use of LiCl, which
is a weak Lewis base, rather than FeCl3, which is a strong
Lewis acid. Thus, this result shows that the scope of the pre-
sent reaction allows for extension by using LiCl as a chlorine
source. p-Bromo-R-methylstyrene (3f) gave a chloro-nitrated
product (4f) with a small amount of eliminated product (4f0)
under the condition of use of FeCl3 (Table 2, entry 6). The
(13) For reviews on iron-catalyzed reactions, see: (a) Iron Catalysis in
Organic Chemistry; Plietker, B., Ed.; Wiley-VCH: Weinheim, 2008. (b) Bolm,
C.; Legros, J.; Le Paih, J.; Zani, L. Chem. Rev. 2004, 104, 6217. (c) Correa, A.;
~
Garcıa Mancheno, O.; Bolm, C. Chem. Soc. Rev. 2008, 37, 1108. (d) Enthaler,
S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317. (e) Sherry,
€
B. D.; Furstner, A. Acc. Chem. Res. 2008, 47, 1500. (f) Correa, A.; Garcıa
~
€
Mancheno, O.; Bolm, C. Chem. Soc. Rev. 2008, 37, 1108. (g) Furstner, A.
Angew. Chem., Int. Ed. 2009, 48, 1364. (h) Sarhan, A. A.; Bolm, C. Chem.
Soc. Rev. 2009, 38, 2730.
(14) Forselectedrecentexamplesofiron-catalyzed reactions, see: (a) Sylvester,
K. T.; Chirik, P. J. J. Am. Chem. Soc. 2009, 131, 8772. (b) Wu, J. Y.; Moreau, B.;
Ritter, T. J. Am. Chem. Soc. 2009, 131, 12915. (c) Yoshikai, N.; Mieczkowski, A.;
Matsumoto, A.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2010, 132, 5568.
(d) Junge, K.; Wendt, B.; Shaikh, N.; Beller, M. Chem. Commun. 2010, 1769.
(e) Hatakeyama, T.; Hashimoto, T.; Kondo, Y.; Fujiwara, Y.; Seike, H.; Takaya,
H.; Tamada, Y.; Ono, T.; Nakamura, M. J. Am. Chem. Soc. 2010, 132, 10674.
Bach and co-workers have reported iron-catalyzed intermolecular radical amino-
chlorination of alkenes; see: (f) Bach, T.; Schlummer, B.; Harms, K. Chem.
Commun. 2000, 287. (g) Bach, T.; Schlummer, B.; Harms, K. Chem.;Eur. J.
2001, 7, 2581.
reaction of p-nitro-R-methylstyrene (3g) with Fe(NO3)3 9H2O/
3
FeCl3 readily proceeded to give chloro-nitrated product 4g in
high yield (Table 2, entry 7). This high yield can be attributed
torestraintofsidereactionssuchaspolymerizationandnitration
(15) Taniguchi, T.; Ishibashi, H. Org. Lett. 2010, 12, 124.
J. Org. Chem. Vol. 75, No. 23, 2010 8127

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TABLE 2. Chloro-Nitration of Various Alkenes
TABLE 3. Chloro-Nitration of Cyclic Alkenes
aDiastereomeric ratio was determined by 1H NMR analysis (trans
isomer is major). b5e was used as a mixture of trans and cis isomers. cLiCl
was employed instead of FeCl3.
TABLE 4. Chloro-Nitration of Electron-Deficient Alkenes
aYield was determined by 1H NMR analysis. bLiCl was employed
c
instead of FeCl3. Diastereomeric ratio was determined by 1H NMR
analysis.
of the aromatic ring because of the electron-deficient effect of
the p-nitrophenyl group. On the other hand, the reaction of
electron-rich p-methoxy-R-methylstyrene (3h) gave a com-
plex mixture, even when the reaction was carried out under
the condition of use of LiCl (Table 2, entry 8). trans-β-Meth-
ylstyrene (3i) readily underwent chloro-nitration reaction to
give 3-chloro-2-nitro-3-phenylpropane (4i) in good yield
(Table 2, entry 9), whereas trans-stilbene (3j) gave 1-nitro-
1,2-diphenylethane (4j) in very low yield (Table 2, entry 10).
As in the reactions of 3e and 3h, it is assumed that side reac-
tions such as polymerization and nitration of the aromatic
ring competed in the reaction of 4j.
aYield was determined by 1H NMR analysis.
Subsequently, chloro-nitration reactions of cyclic alkenes
were examined (Table 3). Treatment of five-, six-, seven-,
eight-, and twelve-membered cycloalkenes 5a-e with Fe-
(7a) and ethyl methacrylate (7b) with Fe(NO3)3 9H2O/FeCl3
3
in MeCN afforded nitrated ethyl esters 8a and 8b in moder-
ate yield along with small amounts of eliminated products 8a0
and 8b0, respectively (Table 4, entries 1 and 2). The reaction
of ethyl tiglate (7c) gave nitrated product 8c as a single dia-
stereomer (Table 4, entry 3). The reaction of methacrylamide
7d successfully proceeded to give 2-chloro-3-nitropropiona-
mide 8c in good yields (Table 4, entry 4). When the reaction
of β-carvone (9) bearing electron-rich and deficient alkene moi-
eties in the molecule was carried out at a lower temperature
(60 °C), selective addition of a nitro group to electron-rich
(NO3)3 9H2O/FeCl3 in MeCN afforded the corresponding
3
2-chloro-1-nitro cycloalkanes 6a-e in good yields (Table 3,
entries 1-5). On the other hand, low reactivity of norbor-
nene (5f) was observed (Table 3, entry 6). The reaction of
trisubstituted cycloalkenes 5g and 5h gave chloro-nitrated
products 6g and 6h, respectively, in moderate yields (Table 3,
entries 7 and 8).
Reactions using electron-deficient alkenes as substrates
were also examined (Table 4). Treatment of ethyl acrylate
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Taniguchi et al.
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SCHEME 3. Chemoselective Chloro-Nitration of β-Carvone (9)
TABLE 5. One-Pot Synthesis of Nitroalkene 4a
entry
base
Et3N
K2CO3
LiOH H2O
3
time (h)
yield (%)
1
2
3
1
0.5
0.5
complex mixture
SCHEME 4. Radical Trap by Other Halogen Atoms
15
82
TABLE 6. One-Pot Synthesis of Several Nitroalkenes
SCHEME 5. Plausible Reaction Mechanism
SCHEME 6. Radical Nitration of Compound 13
atom because the reactions of R,β-unsaturated esters 7a-c
and amide 7d also proceeded (Table 4). In order to obtain
evidence of a radical mechanism, the reaction of allylsulfonyl
alkene occurred to give mononitrated compound 10 in good
yield (Scheme 3).
Brominated or iodinated compounds were also accessible
by using appropriate radical trapping reagents. In the reac-
tion of 1,6-diene, we found that treatment of 1,6-diene with
derivative 13 was examined. Treatment of 13 with Fe(NO3)3
3
9H2O in the presence of LiCl in MeCN resulted in elimination
of the sulfonyl group to give nitro compound 14 in good yield
with detection of p-toluenesulfonyl chloride 15 (Scheme 6).
This result provides support for the generation of radical
intermediate B followed by elimination of a stable sulfonyl
radical C, which abstracted a chlorine atom from the iron
complex to give p-toluenesulfonyl chloride.16,17
Fe(NO3)3 9H2O in the presence of carbon tetrabromide or
3
lithium iodide afforded brominated or iodinated products,
respectively.15 The reaction of cyclooctene (5d) was performed
under similar conditions to give brominated and iodinated
products 11d and 12d in moderate and good yields, respec-
tively (Scheme 4).
Finally, one-pot synthesis of useful nitroalkenes using
this iron-mediated nitration reaction was examined.18 After
decene (3a) had been treated with Fe(NO3)3 9H2O/FeCl3 in
3
A plausible mechanism for the chloro-nitration reaction is
shown in Scheme 5. For the reaction of simple alkene 3a,
addition of nitrogen dioxide (NO2), generated by thermal de-
boiling MeCN, addition of Et3N to the reaction mixture
afforded a complex mixture (Table 5, entry 1). However, we
soon found that using K2CO3 instead of Et3N gave desired
composition of Fe(NO3)3 9H2O, onto 3a takes place to give
3
radical intermediate A. The radical intermediate A is then
trapped by a chlorine atom from the iron chloride complex to
give 4a. Although the possibility that the formation of 4a
involves oxidation of the radical intermediate A followed
by addition of chloride anion to the resultant cation inter-
mediate as another path cannot be ruled out, the main path
would be the direct radical trapping mechanism by a chlorine
(16) Guyader, F. L.; Quiclet-Sire, B.; Seguin, S.; Zard, S. Z. J. Am. Chem.
Soc. 1997, 119, 7410.
(17) In order to obtain evidence of the radical mechanism, trans-1-phenyl-
2-vinylcyclopropane was employed as a radical clock, but the decomposition
of substrate or product was observed in the reaction of this compound.
(18) For reviews on nitroalkenes, see: (a) Barret, A. G. M.; Graboski,
G. G. Chem. Rev. 1986, 86, 751. (b) Ballini, R.; Marcantoni, E.; Petrini, M. In
Amino Group Chemistry; Ricci, A., Ed.; Wiley-VCH: New York, 2008; pp
93-148. See also ref 2 1, 3, 9, and 10.
J. Org. Chem. Vol. 75, No. 23, 2010 8129

Taniguchi et al.
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nitroalkene 4a0 in one pot (Table 5, entry 2). Eventually, the
use of LiOH H2O as a base significantly improved the yield
of the product (Table 5, entry 3). As shown in Table 6, sty-
rene (3d) and cycloalkene 5d and 5e also readily underwent
the one-pot chloro-nitration/elimination process to give nitro-
alkenes 4d0, 6d0, and 6e0, respectively, in good yields.
N-(2-Chloro-3-nitropropyl)toluenesulfonamide (4b). 95% yield.
Colorless crystals, mp 68.0-68.5 °C. IR (CHCl3) υ 1563, 1337,
3
1
1223, 1163 cm-1; H NMR (400 MHz, CDCl3) δ 2.45 (3H, s),
3.32-3.46 (2H, m), 4.56-4.62 (1H, m), 4.70 (1H, dd, J=14.1,
7.5 Hz), 4.81 (1H, dd, J=13.9, 4.9 Hz), 4.96 (1H, t, J=7.1 Hz),
7.35 (2H, d, J=8.0 Hz), 7.74 (2H, d, J=8.3 Hz); 13C NMR (125
MHz, CDCl3) δ 21.5, 46.2, 54.1, 77.3, 127.0, 130.1, 136.1, 144.4.
Anal. Calcd for C10H13ClN2O4S: C, 41.03; H, 4.48; N, 9.57.
Found: C, 40.90; H, 4.34; N, 9.55.
Conclusions
2-Chloro-2-methyl-1-nitro-4-phenylbutane (4c). 56% yield.
In conclusion, we have developed an iron-mediated nitra-
tion reaction of alkenes to give halo-nitro compounds. In the
present reaction, a radical mechanism was suggested by in-
vestigation of nitro-cyclization of 1,6-dienes, and this reac-
tion was extended to halo-nitration of various alkenes.
Furthermore, one-pot synthesis of synthetic valuable nitro-
alkene using this method was shown. The present reaction
has large advantages such as the simple and safe experimen-
tal procedure using nontoxic and inexpensive reagents.
Therefore, the present reaction will provide a general and
practical method for the synthesis of nitro compounds.
1
Colorless oil. IR (CHCl3) υ 1556, 1456, 1375 cm-1; H NMR
(400 MHz, CDCl3) δ 1.80 (3H, s), 2.20 (2H, m), 2.87 (2H, td, J=
9.3, 7.3 Hz), 4.67 (1H, d, J=17.2 Hz), 4.74 (1H, d, J=17.2 Hz),
7.20-7.32 (5H, m); 13C NMR (100 MHz, CDCl3) δ 28.5, 30.8,
43.6, 66.8, 84.0, 126.4, 128.4, 128.6, 140.3; HRFABMS calcd for
C11H15ClNO2 (MþþH) 228.0791, found 228.0799.
1-Chloro-2-nitro-1-phenylethane (4d) and 1-Nitro-2-pheny-
lethene (4d0).25 75% (4d) and 11% (4d0) yields (4d and 4d0 were
isolated as an inseparable mixture). Colorless oil. IR (CHCl3) υ
1
1564, 1377, 1346 cm-1; H NMR (400 MHz, CDCl3, for 4d
including the partial peaks of 4d0) δ 4.77 (1H, dd, J=13.7, 5.5
Hz), 4.90 (1H, dd, J=13.7, 9.2 Hz), 5.56 (1H, dd, J=9.1, 5.5 Hz),
7.38-7.60 (11H, m, for 4d and 4d0), 8.00 (1H, d, J=13.7 Hz, for
4d0); 13C NMR (100 MHz, CDCl3, for 4d including the peaks of
4d0) δ 56.8, 80.7, 127.1, 129.1 (4d0), 129.2, 129.3 (4d0), 129.7, 130.0
(4d0), 132.1 (4d0), 135.7, 137.0 (4d0), 139.1(4d0); HRFABMS (for
4d) calcd for C8H9ClNO2 (Mþ þ H) 186.0322, found 186.0320.
HRFABMS (for 4d0) calcd for C8H9NO2 (Mþ þ H) 150.0555,
found 150.0555.
Experimental Section
General. All reactions were carried out in flame-dried glass-
ware under nitrogen atmosphere. All reagents were purchased
commercially and used without further purification. Melting
points are uncorrected. IR spectra were recorded on a commer-
cial FT/IR spectrometer. 1H NMR spectra were recorded at 600,
500, and 400 MHz; chemical shifts (δ) are quoted relative to
tetramethylsilane. 13C NMR spectra were recorded at 150, 125,
and 100 MHz with complete proton decoupling; chemical shift
(δ) are quoted relative to the residual signals of chloroform.
Silica gel column chromatography was carried out on silica gel
60N. Mass spectra were recorded on a high-resolution mass
spectrometer in fast atom bombardment mode (FAB).
Starting Materials. Compounds 3a, 3d, 3e, 3i, 3j, 5a-h, 7a-c,
and 9 were commercially available. Compound 3b19 was pre-
pared by N-tosylation of allylamine. Compounds 3c,20 3f,21 3g,22
and 3h21 were prepared by Wittig reaction of corresponding
commercially available ketones. Compound 7d23 was prepared
by acylation of diethylamine with methacryloyl chloride. Com-
pound 1324 was prepared according to literature.
2-Chloro-1-nitro-2-phenylpropane (4e) and 1-Nitro-2-phenyl-
propene (4e0).21 54% (4e) and 9% (4e0) yields (4e and 4e0 were
isolated as an inseparable mixture). Colorless oil. IR (CHCl3) υ
1558, 1448, 1373, 1269 cm-1; 1H NMR (400 MHz, CDCl3, for 4e
including the partial peaks of 4e0) δ 2.23 (3H, s), 2.64 (3H, s, for
4e0), 4.90 (1H, d, J = 11.7 Hz), 4.93 (1H, d, J = 11.7 Hz),
7.26-7.45 and 7.55-7.59 (total 11H, m, for 4e and 4e0), (2H,
m); 13C NMR (100 MHz, CDCl3, for 4e including the par-
tial peaks of 4e0) δ 18.6 (4e0), 29.0, 66.9, 86.0, 126.1, 128.8,
128.9, 130.3 (4e0), 136.3 (4e0), 138.2 (4e0), 140.0, 150.0 (4e0);
HRFABMS (for 4e) calcd for C9H11ClNO2 (Mþ þ H) 200.0478,
found 200.0483. HRFABMS (for 4e0) calcd for C9H11NO2
(Mþ þ H) 164.0712, found 164.0711.
2-(4-Bromophenyl)-2-chloro-1-nitropropane (4f) and 2-(4-
Bromophenyl)-1-nitropropene (4f0).21 49% (4f) and 8% (4f0)
yields (4f and 4f0 were isolated as an inseparable mixture).
Typical Procedure of Halo-Nitration of Alkenes. To a solution
of 3a (74.1 mg, 0.528 mmol) and FeCl3 (256 mg, 0.792 mmol)
in CH3CN (2.6 mL) was added Fe(NO3)3 9H2O (128 mg,
1
Colorless oil. IR (CHCl3) υ 1560, 1490, 1342 cm-1; H NMR
3
(500 MHz, CDCl3, for 4f including the peaks of 4f0) δ 2.20 (3H, s),
2.64 (3H, d, J=1.4 Hz, for 4f0) 4.82 (1H, d, J=11.9 Hz), 4.93
(1H, d, J=11.9 Hz), 7.29 (1H, d, J=1.4 Hz, for 4f0), 7.33 (2H,
d-like, J=8.2 Hz, for 4f0), 7.43 (2H, d-like, J=8.2 Hz), 7.54 (2H,
d-like, J=8.2 Hz), 7.58 (2H, d-like, J=8.2 Hz, for 4f0); 13C NMR
(150 MHz, CDCl3, for 4f including the peaks of 4f0) δ 18.4 (4f0),
29.0, 66.2, 85.6, 123.3, 127.9, 128.3 (4f0), 131.8 (4f0), 131.9, 132.3
(4f0), 136.4 (4f0), 137.1 (4f0), 139.1, 148.6 (4f0); HRFABMS
(for 4f) calcd for C9H10ClO2NBr (Mþ þ H) 277.9583, found
277.9597. HRFABMS (for 4f0) calcd for C9H9O2BrN (MþþH)
241.9817, found 241.9818.
0.634 mmol), and the mixture was heated at reflux for 1 h. After
cooling to room temperature, the resulting suspension was diluted
with Et2O and filtered. After removal of solvent under reduced
pressure, the residue was purified by chromatography (hexane/
EtOAc, 10:1) to give 4a (97.8 mg, 84%) as a colorless oil.
2-Chloro-1-nitrodecane (4a). 84% yield. Colorless oil. IR
(CHCl3) υ 1562, 1379, 1225 cm-1 1H NMR (400 MHz,
;
CDCl3) δ 0.89 (3H, t, J = 6.9 Hz), 1.24-1.42 (10H, br),
1.48-1.58 (2H, m), 1.74-1.81(2H, m), 4.50-4.55 (1H, m),
4.58 (1H, d, J=1.8 Hz), 4.60 (1H, m); 13C NMR (150 MHz,
CDCl3) δ 14.1, 22.6, 25.8, 28.8, 29.1, 29.3, 31.8, 35.0, 56.2,
80.5; HRFABMS calcd for C10H21ClNO2 (Mþ þ H) 222.1261,
found 222.1264.
2-Chloro-1-nitro-2-(4-nitrophenyl)propane (4g). 80% yield.
Colorless crystals, mp 68.0-68.5 °C (hexane/EtOAc). IR (CH-
Cl3) υ 1560, 1529, 1371, 1350 cm-1 1H NMR (400 MHz,
;
(19) Park, H.; Hong, Y.-L.; Kim, Y. B.; Choi, T.-L. Org. Lett. 2010, 12,
3442.
(20) Lebel, H.; Guay, D.; Paquet, V.; Huard, K. Org. Lett. 2004, 6, 3047.
(21) Fryszkowska, A.; Fisher, K.; Gardiner, J. M.; Stephens, G. M. J. Org.
Chem. 2008, 73, 4295.
(22) Sherrill, W. M.; Kim, R.; Rubin, M. Tetrahedron 2008, 64, 8610.
(23) Kollar, L.; Consiglio, G.; Pino, P. J. Organomet. Chem. 1990, 386,
389.
CDCl3) δ 2.25 (3H, s), 4.96 (1H, d, J=12.4 Hz), 5.01 (1H, d, J=
12.4 Hz) 7.76 (2H, d, J=8.9 Hz), 8.27 (2H, d, J=8.9 Hz); 13
C
NMR (150 MHz, CDCl3) δ 29.3, 65.6, 85.3, 123.9, 127.5, 146.8,
147.9. Anal. Calcd for C9H9ClN2O4: C, 44.19; H, 3.71; N, 11.45.
Found: C, 44.44; H, 3.66; N, 11.47.
(24) Knight, D. J.; Lin, P.; Russell, S. T.; Whitham, G. H. J. Chem. Soc.,
Perkin Trans. 1 1987, 2701.
(25) Black, P.-J.; Gerta, C.-K.; Edwards, M. G.; Slatford, P. A.; Whittlesey,
M. K.; Williams, J. M. J. Org. Biomol. Chem. 2006, 4, 116.
8130 J. Org. Chem. Vol. 75, No. 23, 2010

Taniguchi et al.
JOCArticle
1-Chloro-2-nitro-1-phenylpropane (4i). 80% yield. Colorless
oil. (4i was an inseparable mixture of two isomers, 53:47). IR
(minor), 94.0; HRFABMS calcd for C8H15ClNO2 (Mþ þ H)
192.0791, found 192.0796.
(CHCl3) υ 1560, 1454, 1389, 1360 cm-1; H NMR (400 MHz,
1-Chloro-2-nitrocyclododecene (6e). 78% yield (as an insepar-
able mixture of two isomers, 72:28). Colorless oil. IR (CHCl3)
υ 1558, 1470, 1371 cm-1; 1H NMR (600 MHz, CDCl3, including
the partial peaks of minor isomer) δ 1.29-1.51 (15H, m),
1.72-1.78 (1H, m), 1.82-1.87 (1H, m), 1.93-2.04 (3H, m),
4.47 (1H, dt, J=14.4, 4.1 Hz), 4.57 (1H, br, minor isomer), 4.73
1
CDCl3, for a mixture of two isomers) δ 1.35 (3H, d, J=6.8 Hz),
1.71 (3H, d, J=6.6 Hz), 4.93 (1H, dq, J=9.6, 6.9 Hz), 5.01 (1H,
dq, J=7.3, 6.9 Hz), 5.22 (1H, d, J=10.3 Hz), 5.38 (1H, d, J=
7.6 Hz), 7.35-7.42 (10H, m); 13C NMR (150 MHz, CDCl3, for a
mixture of two isomers) δ 15.7, 17.9, 62.3, 62.6, 87.5, 88.9, 127.4,
127.8, 128.9, 129.2, 129.4, 129.7, 135.5, 136.2; HRFABMS calcd
for C9H11ClNO2 (Mþ þ H) 200.0478, found 200.0479.
(1H, dt, J=8.3, 2.1 Hz), 4.78 (1H, ddd, J=10.8, 6.1, 2.8 Hz); 13
C
NMR (150 MHz, CDCl3, including the partial peaks of minor
isomer) δ 20.0, 21.4 (minor), 21.9 (minor), 22.0, 22.3 (minor),
22.4, 22.6, 22.9, 23.1, 24.4, 24.5, 24.9 (br, minor), 28.4, 30.1, 59.2,
60.3 (br, minor), 86.8 (br, minor), 90.7; HRFABMS calcd for
C12H23ClNO2 (Mþ þ H) 248.1417, found 248.1418.
1-Chloro-1,2-diphenyl-2-nitroethane (4j). 11% yield. Colorless
oil. IR (CHCl3) υ 1655, 1562, 1522, 1325, 1277 cm-1; 1H NMR
(600 MHz, CDCl3) δ 5.73 (1H, d, J=11.0 Hz), 5.87 (1H, d, J=
11.0 Hz), 7.21-7.29 (10H, m); 13C NMR (150 MHz, CDCl3) δ
61.9, 96.7, 127.88, 127.93, 128.8, 129.0, 130.3, 135.1; HRFABMS
calcd for C14H12ClNO2 (Mþ þ H) 262.0636, found 262.0635.
1-Chloro-2-nitrocyclopentane (6a). 71% yield (as a separable
mixture of two isomers, 87:13). Major isomer: colorless oil. IR
2-Chloro-3-nitrobicyclo[2.2.1]heptane (6f).27 35% yield (as a
separable mixture of two isomers, 72:28). Major isomer: color-
less oil. IR (CHCl3) υ 1550, 1456, 1375 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.41-1.47 (1H, m), 1.50-1.57 (2H, m), 1.75-1.82
(1H, m), 1.84-1.86 (1H, m), 1.93-1.99 (1H, m), 2.60-2.64 (1H,
m), 2.85 (1H, d, J=5.0 Hz), 4.31 (1H, dd, J=3.6, 2.3 Hz), 4.78
(1H, br); 13C NMR (100 MHz, CDCl3) δ 21.1, 26.7, 35.5, 43.3,
44.4, 61.7, 95.4; HRFABMS calcd for C7H11ClNO2 (Mþ þ H)
176.0478, found 176.0486. Minor isomer: IR (CHCl3) υ 1558,
1458, 1375 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.22-1.26 (2H,
m), 1.48 (1H, dt, J=9.6, 1.8 Hz), 1.61-1.80 (2H, m), 2.34 (1H,
dt, J=10.5, 1.8 Hz), 2.55 (1H, d, J=4.7 Hz), 2.88 (1H, d, J=
3.2 Hz), 4.24 (1H, dd, J=7.3, 5.5 Hz), 4.70 (1H, dd, J=7.3, 6.0
Hz); 13C NMR (100 MHz, CDCl3) δ 25.6, 25.9, 34.7, 41.2, 45.4,
60.4, 91.4; HRFABMS calcd for C7H11ClNO2 (Mþ þ H)
176.0478, found 176.0468.
(CHCl3) υ 1552, 1371 cm-1; H NMR (600 MHz, CDCl3) δ
1
1.94-2.05 (3H, m), 2.25-2.30 (1H, m), 2.37-2.43 (1H, m), 2.49
(1H, td, J = 14.4, 8.2 Hz), 4.72-4.75 (1H, m), 4.96 (1H, dt,
J = 8.2, 3.4 Hz); 13C NMR (150 MHz, CDCl3) δ 22.3, 30.4,
35.3, 60.4, 93.0; HRFABMS calcd for C5H9ClNO2 (Mþ þH)
150.0322, found 150.0328. Minor isomer: colorless oil. IR
(CHCl3) υ 1556, 1375, 1219 cm-1; 1H NMR (400 MHz, CDCl3)
δ 1.76-1.84 (1H, m), 2.16-2.25 (4H, m), 2.53-2.65 (11H, m),
4.55 (1H, dd, J=10.5, 5.5 Hz) 4.98 (1H, td, J=7.3, 5.5 Hz); 13CNMR
(150 MHz, CDCl3) 20.5, 26.2, 33.6, 59.5, 88.9; HRFABMS
calcd for C5H9ClNO2 (Mþ þ H) 150.0322, found 150.0325.
1-Chloro-2-nitrocyclohexane (6b).26 74% yield (as a separ-
able mixture of two isomers, 72:28). Major isomer: colorless oil.
IR (CHCl3) υ 1562, 1453, 1374, 1225 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.36-1.45 (2H, m), 1.64-1.75 (1H, m), 1.82-1.94
(3H, m), 2.33-2.42 (2H, m), 4.29 (1H, td, J=11.0, 4.6 Hz), 4.51
(1H, td, J=11.4, 4.6 Hz); 13C NMR (150 MHz, CDCl3) δ 23.4,
24.8, 31.9, 34.7, 57.7, 91.5.; HRFABMS calcd for C6H11ClO2N
(Mþ þ H) 164.0478, found 164.0476. Minor isomer: colorless
oil. IR (CHCl3) υ 1552, 1377, 1221 cm-1; 1H NMR (400 MHz,
CDCl3) δ 1.25-1.38 (1H, m), 1.54-1.60 (1H, m), 1.68-1.81
(1H, m), 1.84-1.98 (2H, m), 2.13-2.31 (3H, m), 4.47 (1H, dt, J=
11.4, 4.1 Hz), 4.97 (1H, br); 13C NMR (150 MHz, CDCl3) δ 18.7,
23.3, 23.4, 32.9, 58.2, 85.4; HRFABMS calcd for C6H11ClNO2
(Mþ þ H) 164.0478, found 164.0476.
1-Chloro-1-methyl-2-nitrocyclohexane (6g). 48% yield. Col-
orless oil. IR (CHCl3) υ 1552, 1458, 1371 cm-1; 1H NMR (600
MHz, CDCl3) δ 1.48-1.55 (1H, m), 1.56-1.63 (1H, m), 1.72
(3H, s), 1.72-1.79 (1H, m), 1.80-1.87 (1H, m), 1.95 (1H, ddd,
J=13.7, 9.6, 4.1 Hz), 2.06-2.13 (1H, m), 2.22-2.32 (2H, m),
4.80 (1H, dd, J=8.2, 4.1 Hz); 13C NMR (150 MHz, CDCl3) δ
21.6, 21.9, 26.2, 27.9, 40.2, 67.5, 92.4; HRFABMS calcd for
C7H13ClNO2 (Mþ þ H) 178.0635, found 178.0631.
1-Chloro-1-phenyl-2-nitrocyclohexane (6h).28 65% yield. Col-
orless crystals, mp 85.0-85.5 °C (hexane/EtOAc). IR (CHCl3) υ
1552, 1448, 1378, 1296 cm-1; H NMR (600 MHz, CDCl3) δ
1
1.64-1.76 (2H, m), 1.95-2.03 (2H, m), 2.26 (1H, dd, J=15.1,
1.8 Hz), 2.41 (1H, br), 2.55-2.62 (1H, m), 3.10-3.18 (1H, m),
5.41 (1H, m), 7.31 (1H, t, J=7.6 Hz), 7.37 (2H, t, J=6.9 Hz), 7.56
(2H, d, J=8.3 Hz); 13C NMR (150 MHz, CDCl3) δ 18.9, 20.7,
27.1, 32.1, 69.7, 89.6, 126.0, 128.6, 128.9, 141.2. Anal. Calcd for
C12H14ClNO2: C, 60.13; H, 5.89; N, 5.84. Found: C, 59.77; H,
5.72; N, 5.94.
1-Chloro-2-nitrocycloheptane (6c). 91% yield. (as an insepar-
able mixture of two isomers, 87:13). Colorless oil. IR (CHCl3) υ
1557, 1458, 1377 cm-1; 1H NMR (600 MHz, CDCl3, including
the partial peaks of minor isomer) δ 1.60-1.65 (4H, m),
1.81-1.89 (2H, m), 1.98-2.05 (1H, m), 2.06-2.12 (1H, m),
2.15-2.20 (1H, m), 2.24-2.29 (1H, m), 2.29-2.39 (2H, m, for
minor isomer), 4.58 (1H, td, J=8.9, 3.4 Hz), 4.62 (1H, dt, J=
11.0, 4.1 Hz, for minor isomer), 4.69 (1H, td, J=8.9, 3.4 Hz),
4.98 (1H, m, for minor isomer); 13C NMR (100 MHz, CDCl3) δ
22.2 (minor), 22.8 (minor), 23.6, 23.6, 25.9 (minor), 26.2
(minor), 27.1, 31.5, 34.1 (minor), 34.8, 60.9, 61.3 (minor), 89.7
(minor), 95.2; HRFABMS calcd for C7H13ClNO2 (Mþ þ H)
178.0635, found 178.0640.
Ethyl 2-Chloro-3-nitropropanoate (8a)29 and Ethyl 3-Nitroa-
crylate (8a0).29,30 42% (8a) and 9% (8a0) yields (8a and 8a0 were
isolated as an inseparable mixture). Colorless oil. IR (CHCl3) υ
1743, 1543, 1377, 1248 cm-1; 1H NMR (400 MHz, CDCl3, for 8a
including the peaks of 8a0) δ 1.34 (3H, t, J=6.9 Hz), 1.37 (3H, t,
J=6.9 Hz, for 8a0) 4.32 (2H, q, J=6.9 Hz), 4.33 (2H, q, J=6.9
Hz, for 8a0) 4.77 (1H, dd, J=14.2, 6.4 Hz), 4.88 (1H, t, J=6.9
Hz), 5.00 (1H, dd, J=14.2, 6.9 Hz), 7.09 (1H, d, J=13.1 Hz, for
8a0), 7.68 (1H, d, J=13.7 Hz, for 8a0); 13C NMR (150 MHz,
CDCl3, for 8a including the peaks of 8a0) δ 13.8 (8a0), 14.0, 49.8,
62.4 (8a0), 63.3, 75.5, 127.7 (8a0), 148.9 (8a0), 162.6 (8a0), 166.2;
HRFABMS calcd for C5H9ClNO4 (Mþ þ H) 182.0220, found
182.0218.
1-Chloro-2-nitrocyclooctane (6d). 88% yield (as an insepar-
able mixture of two isomers, 82:18). Colorless oil. IR (CHCl3) υ
1556, 1466, 1381, 1223 cm-1 1H NMR (600 MHz, CDCl3,
;
including the partial peaks of minor isomer) δ 1.34-1.52 (2H,
m), 1.60-1.73 (5H, m), 1.79-1.92 (2H, m), 2.05-2.19 (2H, m),
2.26-2.32 (1H, m), 4.72 (1H, ddd, J = 10.3, 6.9, 2.7 Hz),
4.79-4.84 (1H, m, for minor isomer) 4.84-4.88 (1H, ddd, J=
10.3, 7.6, 2.1 Hz); 13C NMR (100 MHz, CDCl3) δ 22.9 (minor),
23.3, 24.5, 24.8 (minor), 24.97 (minor), 24.99 (minor), 25.4, 26.6,
27.1 (minor), 31.1, 31.3, 33.5 (minor), 60.9, 61.1 (minor), 88.3
(27) Chauvet, F.; Heumann, A.; Waegell, B. J. Org. Chem. 1987, 52,
1916.
(28) Arumugam, N.; Shenbagamurthi, P.; Sivasubramanian, S.; Kesavan,
V. Indian J. Chem. 1974, 12, 323.
(29) Shin, C.-G.; Yamaura, M.; Inui, E.; Ishida, Y.; Yoshimura, J. Bull.
Chem. Soc. Jpn. 1978, 51, 2618.
(30) Addo, J. K.; Teesdale-Spittle, P.; Hoberg, J. O. Synthesis 2005, 1923.
(26) Price, C. C.; Sears, C. A. J. Am. Chem. Soc. 1953, 75, 3275.
J. Org. Chem. Vol. 75, No. 23, 2010 8131

Taniguchi et al.
JOCArticle
Ethyl 2-Chloro-2-methyl-3-nitropropanoate (8b) and Ethyl
3-Nitromethacrylate (8b0).3k 56% (8b) and 8% (8b0) yields (8b
and 8b0 were isolated as an inseparable mixture). Colorless oil.
IR (CHCl3) υ 1751, 1566, 1383, 1213 cm-1; 1H NMR (400 MHz,
CDCl3, for 8b including the peaks of 8b0) δ 1.34 (3H, t, J =
6.9 Hz), 1.36 (3H, t, J=6.9 Hz, for 8b0), 1.90 (3H, s), 4.33 (2H, q,
J=7.0 Hz), 4.32 (2H, q, J=6.9 Hz, for 8b0), 4.84 (1H, d, J=14.7
Hz), 5.01, (1H, d, J=14.7 Hz), 7.73 (1H, q, J=1.4 Hz, for 8b0);
13C NMR (150 MHz, CDCl3, for 8b including the peaks of 8b0) δ
13.7, 13.9 (8b0), 25.3, 61.8 (8b0), 62.5 (8b0), 63.2, 80.9, 136.8 (8b0),
143.8 (8b0), 143.8, 165.1 (8b0), 168.0; HRFABMS (for 8b) calcd
for C6H11ClO4N (MþþH) 197.0455, found 197.0462. HRFABMS
(for 8b0) calcd for C6H10NO4 (MþþH) 160.0610, found 160.0601.
Ethyl 2-Chloro-2-methyl-3-nitrobutanoate (8c). 64% yield.
27.5, 30.8, 32.7, 32.8, 96.6; HRFABMS calcd for C8H15INO2
(Mþ þH) 284.0148, found 284.0141.
4-Nitro-1-phenylbut-2-ene (14). 72% yield (as an inseparable
mixture of two isomers, 91:9). Colorless oil. IR (CHCl3) υ 3031,
1557, 1375, 1217 cm-1; 1H NMR (400 MHz, CDCl3, including
the partial peaks of minor isomer) δ 3.46 (2H, d, J=6.4 Hz), 3.50
(2H, d, J=7.8 Hz, for minor isomer), 4.90 (2H, d, J=7.3 Hz),
5.10 (2H, d, J=7.8 Hz, for minor isomer), 5.81 (1H, dt, J=15.6, 7.3
Hz), 5.88-5.91 (1H, m, for minor isomer), 6.07 (1H, dt, J=15.6,
6.4 Hz), 7.17 (2H, d, J=6.9 Hz), 7.23 (1H, t, J=5.8 Hz), 7.32 (2H, t,
J=7.3 Hz); 13C NMR (150 MHz, CDCl3, for major isomer) δ 38.6,
77.3, 119.7, 126.5, 128.59, 128.64, 138.4, 140.0; HRFABMS calcd
for C10H12NO2 (MþþH) 178.0868, found 178.0869.
Typical Procedure for One-Pot Synthesis of Nitroalkenes. To a
solution of 3a (74.1 mg, 0.528 mmol) and FeCl3 (256 mg, 0.792
mmol) in CH3CN (2.6 mL) was added Fe(NO3)3 9H2O (128 mg,
Colorless oil. IR (CHCl3) υ 1751, 1556, 1456, 1392, 1298 cm-1
;
1H NMR (400 MHz, CDCl3) δ 1.31 (3H, t, J=7.3 Hz), 1.78 (3H,
d, J=6.9 Hz), 1.88 (3H, s), 4.29 (2H, q, J=7.3 Hz), 5.22 (1H, q,
J=7.3 Hz); 13C NMR (100 MHz, CDCl3) δ 13.7, 14.4, 21.9, 63.0,
65.7, 86.1, 168.4; HRFABMS calcd for C7H13ClNO4 (Mþ þ H)
210.0533, found 210.0539.
3
0.634 mmol), and the mixture was heated at reflux for 1 h. LiOH
3
H2O (222 mg, 5.28 mmol) was added, and the mixture was
heated at reflux for 30 min. After cooling to room temperature,
the resulting suspension was diluted with Et2O and filtered.
After removal of solvent under reduced pressure, the residue was
purified by chromatography (hexane/EtOAc, 10:1) to give 4a0
(80.1 mg, 82%) as a colorless oil.
2-Chloro-N,N-diethyl-2-methyl-3-nitropropanamide (8d). 81%
yield. Colorlessoil. IR(CHCl3) υ1658, 1562, 1462, 1354 cm-1; 1H
NMR (400 MHz, CDCl3) δ 1.15 (3H, br), 1.29 (3H, br), 2.00 (3H,
s), 3.37 (2H, br), 3.60 (1H, br), 3.80 (1H, br), 4.83 (1H, d, J=13.7
Hz), 4.98 (1H, d, J=13.7 Hz); 13C NMR (100 MHz, CDCl3) δ
12.2, 13.8, 26.4, 42.2, 42.8, 63.0, 83.1, 166.7; HRFABMS calcdfor
C8H16ClN2O3 (Mþ þ H) 223.0850, found 223.0840.
(E)-1-Nitrodecene (4a0).3h 82% yield. Colorless oil. IR (CH-
Cl3) υ 2930, 1526, 1354 cm-1; H NMR (400 MHz, CDCl3) δ
1
0.88 (3H, t, J=6.9 Hz), 1.26-1.37 (10H, m), 1.51 (2H, dt, J=
15.1, 7.6 Hz), 2.27 (2H, q, J=7.3 Hz), 6.98 (1H, dd, J=13.3,
1.4 Hz), 7.28 (1H, dt, J=13.3, 7.3 Hz); 13C NMR (150 MHz,
CDCl3) δ 14.1, 22.6, 27.7, 28.4, 29.06, 29.08, 29.2, 31.7, 139.5,
142.9; HRFABMS calcd for C10H20NO2 (Mþ þ H) 186.1494,
found 186.1501.
(5R,7R)- and (5R,7S)-5-[2-Chloro-1-nitropropan-2-yl]-2-methyl-
cyclohex-2-enone (10). 65% yield (as an inseparable mixture of
two isomers, 50:50). Colorless oil. IR (CHCl3) υ 1674, 1556,
1
1373 cm-1; H NMR (600 MHz, CDCl3, for a mixture of two
isomers) δ 1.77 (3H, s), 1.79 (3H, s), 1.80 (total 6H, two s),
2.47-2.62 (7H, m), 2.63-2.71 (2H, m), 2.78 (1H, d, J=15.8 Hz),
4.65 (1H, d, J=4.8 Hz), 4.68 (1H, d, J=4.8 Hz), 4.77 (1H, d, J=
11.7 Hz), 4.81 (1H, d, J=11.7 Hz) 6.78-6.82 (2H, m); 13C NMR
(150 MHz, CDCl3, for a mixture of two isomers) δ 15.40, 15.42,
26.3, 26.4, 26.9, 27.1, 38.8, 39.1, 42.5, 42.6, 69.2, 69.3, 82.4,
135.4, 135.5, 143.8, 143.9, 198.1, 198.4; HRFABMS calcd for
C10H15ClNO3 (Mþ þ H) 232.0741, found 232.0733.
(E)-1-Nitro-2-phenylethene (4d0).25 66% yield. White solids,
mp 51.5-52.0 °C (hexane/EtOAc, lit. 58-59 °C). IR (CHCl3) υ
3020, 1635, 1525, 1346, 1259 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.43-7.57 (6H, m), 7.59 (1H, d, J=13.7 Hz), 8.01 (1H, d, J=
13.7 Hz); 13C NMR (150 MHz, CDCl3) δ 129.1, 129.4, 130.0,
132.1, 137.1, 139.1 HRFABMS calcd for C8H8NO2 (Mþ þ H)
150.0555, found 150.0555.
(E)-1-Nitorocyclooctene (6d0).10a 62% yield. Colorless oil. IR
1
1-Bromo-2-nitrocyclooctane (11d). 56% yield (as an insepar-
able mixture of two isomers, 85:15) Colorless oil. IR (CHCl3) υ
1556, 1465, 1365 cm-1; 1H NMR (600 MHz, CDCl3, including
the partial peaks of minor isomer) δ 1.33-1.41 (1H, m), 1.43-
1.51 (1H, m), 1.54-1.69 (2H, m), 1.72-1.92 (4H, m), 2.03-2.11
(1H, m), 2.13-2.20 (2H, m), 2.24-2.33 (1H, m, for minor
isomer), 2.34-2.42 (1H, m), 2.45-2.51 (1H, m, for minor isomer-
), 4.73 (1H, dt, J=9.6, 2.7 Hz, for minor isomer), 4.80 (1H, ddd,
J=10.3, 6.9, 2.8 Hz), 4.91-4.94 (1H, m, for minor isomer), 4.98
(1H, ddd, J=10.7, 10.3, 2.1 Hz); 13C NMR (150 MHz, CDCl3) δ
24.48 (minor), 24.51, 24.7, 24.9 (minor), 25.0 (minor), 25.3, 26.5
(minor), 27.0, 27.2 (minor), 31.5, 32.1, 34.6 (minor), 52.5, 53.3
(minor), 88.3 (minor), 94.6; HRFABMS calcd for C8H15BrNO2
(Mþ þ H) 236.0286, found 236.0279.
(CHCl3) υ 2934, 1518, 1383, 1223 cm-1; H NMR (400 MHz,
CDCl3) δ 1.52 (4H, br), 1.72 (4H, br), 2.30-2.36 (2H, m), 2.75
(2H, br), 7.31 (1H, t, J=9.0 Hz); 13C NMR (100 MHz, CDCl3) δ
24.8, 25.6, 26.4, 26.6, 28.3, 29.0, 136.3, 152.3; HRFABMS calcd
for C8H14NO2 (Mþ þ H)156.1025, found 156.1024.
(E)-1-Nitorocyclododecene (6e0).31 56% yield. Colorless oil.
IR (CHCl3) υ 2935, 1520, 1336, 1218 cm-1; 1H NMR (270 MHz,
CDCl3) δ 1.21-1.48 (12H, m), 1.61-1.67 (4H, m), 2.27 (2H, dd,
J=15.8, 7.6 Hz), 2.66 (2H, t, J=6.6 Hz), 7.10 (1H, t, J=8.6 Hz);
13C NMR (150 MHz, CDCl3) δ 21.9, 22.7, 23.2, 23.4, 24.6, 24.7,
24.9, 25.4, 25.7, 136.9, 152.0; HRFABMS calcd for C12H22NO2
(Mþ þ H) 212.1651, found 212.1655.
Acknowledgment. This research was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology of Japan.
1-Iodo-2-nitrocyclooctane (12d). 81% yield (as a separable
mixture of two isomers, 85:15). Major isomer: colorless oil. IR
(CHCl3) υ 1631, 1464, 1281 cm-1; 1H NMR (600 MHz, CDCl3)
δ 1.31-1.42 (2H, m), 1.56-1.66 (2H, m), 1.76-1.90 (5H, m),
1.93-1.97 (1H, m), 2.05-2.18 (2H, m), 4.30 (1H, ddd, J=9.6,
6.2, 3.4 Hz), 5.38 (1H, dt, J=11.7, 2.2 Hz); 13C NMR (150 MHz,
CDCl3) δ 24.9, 25.0, 26.5, 26.6, 31.6, 31.9, 32.0, 90.4;
HRFABMS calcd for C8H15INO2 (Mþ þ H) 284.0148, found
284.0160. Minor isomer: colorless oil. IR (CHCl3) υ 1558, 1377,
1220 cm-1; 1H NMR (600 MHz, CDCl3) δ 1.30-1.33 (1H, m),
1.41-1.49 (1H, m), 1.60-1.67 (2H, m), 1.79-1.83 (4H, m),
2.00-2.31 (1H, m), 2.10-2.20 (2H, m), 2.21-2.29 (1H, m), 4.89
(1H, ddd, J=13.2, 6.6, 2.7 Hz), 5.04 (1H, ddd, J=10.2, 8.2,
2.1 Hz); 13C NMR (150 MHz, CDCl3) δ 24.9, 25.0, 26.7,
1
Supporting Information Available: H and 13C NMR spectra
for all isolated products. This material is available free of charge via
the Internet at http://pubs.acs.org.
Note Added after ASAP Publication. Several errors in the
Results and Discussion sections, Tables 2 and 5, and the caption
of Scheme 6 appeared in the versions that was published on
11/10/2010. These were fixed when the paper was republished to
the Web on 11/29/2010.
(31) Ballini, R.; Palestini, C. Tetrahedron Lett. 1994, 35, 5731.
8132 J. Org. Chem. Vol. 75, No. 23, 2010