[Link].

org/joc

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@[Link]
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.

Introduction SCHEME 1. Methods of Nitration

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 nitro group donor.3a,b,f,l However, nitration reactions using
Group in Organic Synthesis; John Wiley-VCH: New York, 2001. (c) Ballini,
R.; Petrini, M. ARKIVOC 2009, 195. these reagents have drawbacks such as difficulty of handling
(2) For reviews on nitration of aromatic compounds, see: (a) Olah, G. A.; and the limitation of substrates due to toxicity and extreme
Malhotra, R.; Narang, S. C. Nitration: Methods and Mechanisms; VCH reactivity. As a method for synthesis of aliphatic nitro com-
Publishers Inc.: New York, 1989. (b) Suzuki, T.; Noyori, R. Chemtracts 1997,
10, 813. pounds, nucleophilic substitution reaction of an alkyl halide
(3) For examples of nitration of alkenes, see: (a) Shechter, H.; Conrad, F.; with nitrite anion (NO2-) has been used (Scheme 1, eq 2).5
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.; Oxidation of amines and oximes also affords corresponding
Whitehouse, M. L. J. Org. Chem. 1967, 32, 2303. (d) Corey, E. J.; Estreicher, nitro compounds.6 Recently, Fors and Buchwald have re-
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.; ported palladium-catalyzed synthesis of nitroaromatics from
Cho, Y.-S.; Cook, C.-H. Chem. Lett. 1986, 1747. (g) Butts, C. P.; Calvert, J. L.; aryl chlorides, triflates, and nonaflates using sodium nitrite.7
Eberson, L.; Hartshorn, M. P.; Robinson, W. T. J. Chem. Soc., Perkin Trans. 2 On the other hand, nitrogen dioxide gas (NO2), which is a
1994, 1485. (h) Hata, E.; Yanada, T.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
1995, 68, 3629. (i) Campos, P. J.; Garcı́a, B.; Rodrı́guez, M. A. Tetrahedron Lett. free radical, is one of the simplest and most common nitra-
2000, 41, 979. (j) Stepanov, A. V.; Veselovsky, V. V. Russ. Chem. Rev. 2003, 72, tion reagents.8 Addition of nitrogen dioxide to a C-C
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.; multiple bond easily affords aliphatic nitro compounds
M€ori, M.; Marti, R. Helv. Chim. Acta 2010, 93, 90. See also refs 9 and 10. (Scheme 1, eq 3).9,10 However, this method has serious
(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. (5) (a) Kornblum, N.; Taub, B.; Ungnade, H. E. J. Am. Chem. Soc. 1954,
1993, 115, 7246. 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.
JOC Article
drawbacks such as the difficulty of handling NO2 gas and its SCHEME 2. Radical Nitro-Cyclization of 1,6-Dienes
toxicity. Therefore, the reaction using nitrogen dioxide is
used in limited cases of synthetic chemistry.
It is well-known that thermal decomposition of iron(III)
nitrate nonahydrate, Fe(NO3)3 3 9H2O, generates nitrogen
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 TABLE 1. Chloro-Nitration of Decene (3a)
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
entry NO3 Cl solvent time (h) yield (%)
nitro group by sequential steps that involved radical addi-
1 Fe(NO3)3 3 9H2O FeCl3 THF 2 77
tion of nitrogen dioxide to 1,6-dienes promoted by the 2 Fe(NO3)3 3 9H2O FeCl3 MeCN 1 84
thermal decomposition of iron(III) nitrate nonahydrate, 3 Fe(NO3)3 3 9H2O LiCl MeCN 5 71
cyclization, and trapping of the resultant terminal radicals by 4a LiNO3 FeCl3 MeCN 4 61
a halogen atom in the presence of halogen salt (Scheme 2).15 a
5 equiv of LiNO3 and 2 equiv of FeCl3 were employed.
It is expected that radical nitration of alkenes using Fe(NO3)3 3
9H2O will provide a general and practical method for the Results and Discussion
synthesis of nitro compounds from the viewpoints of safety
In our previous study, reaction conditions using several
and economy. In this paper, we present a full account of this
nitrate and chloride salts were examined, and the results indi-
work including extension to nitration reactions of various
cated that a combination of Fe(NO3)3 3 9H2O/FeCl3 in boil-
alkenes. ing THF was the best condition.15 First, we examined the
application of these reaction conditions to simple alkenes.
(6) (a) Emmons, W. D.; Pagano, A. S. J. Am. Chem. Soc. 1955, 77, 4557. Treatment of decene (3a) under similar conditions (Fe(NO3)3 3
(b) Emmons, W. D. J. Am. Chem. Soc. 1957, 79, 5528. (c) McKillop, A.; 9H2O/FeCl3 in boiling THF) gave 2-chloro-1-nitrodecane
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.; (4a) in good yield (Table 1, entry 1). We found that using
Moormann, A. E.; Beck, K. R., Jr. Tetrahedron Lett. 1988, 29, 4501. MeCN instead of THF as a solvent resulted in slight improve-
(7) Fors, B. P.; Buchwald, S. L. J. Am. Chem. Soc. 2009, 131, 12898. ment in yield with shorter reaction time (Table 1, entry 2).
(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, Using LiCl as a chlorine source and LiNO3 as a nitrate source
S.; Ishii, Y. J. Org. Chem. 2002, 67, 5663. in the presence of iron also gave nitrated compound 4a in
(9) For examples of addition of nitrogen dioxide to alkenes, see: (a) Stevens, slightly lower yields than in the case of conditions of entry 2
T. E.; Emmons, W. D. J. Am. Chem. Soc. 1958, 80, 338. (b) J€ager, V.; G€ unther, J.
Angew. Chem., Int. Ed. Engl. 1977, 16, 246. (c) Suzuki, H.; Mori, T. J. Org. Chem. (Table 1, entries 3 and 4).
1997, 62, 6498. (d) Grossi, L.; Montevecchi, P. C.; Strazzari, S. Eur. J. Org. Chem. Iron-mediated chloro-nitration of various alkenes is shown
2001, 741. (e) Grossi, L.; Montevecchi, P. C. Chem.;Eur. J. 2002, 8, 380.
(10) Radical nitration of styrene derivatives using cerium(IV) ammonium in Table 2. The nitration reactions of allylamine derivative 3b
nitrate and sodium nitrite has been reported; see: (a) Hwu, J. R.; Chen, K.-L.; and 2,2-disubstitute alkene 3c gave chloro-nitrated compounds
Ananthan, S.; Patel, H. V. Organometallics 1996, 15, 499. (b) Grenier, J.-L.; 4b and 4c, respectively, in good yields (Table 2, entries 1
Catteau, J.-P.; Cotelle, P. Synth. Commun. 1999, 29, 1201. (c) Jayakanthan,
K.; Madhusudanan, K. P.; Vankar, Y. D. Tetrahedron 2004, 60, 397. and 2). The reaction using styrene (3d) as a substrate also
(11) (a) Hill, W. D., Jr. Inorg. Chem. Acta 1986, 121, L33. (b) Wieczorek- readily proceeded to give 2-chloro-1-nitro-3-phenylethane
Ciurowa, K.; Kozak, A. J. J. Therm. Anal. Calorim. 1999, 58, 647.
(12) The synthesis of azides from hydrazines using nitrogen dioxide (4d) in good yield along with a small amount of eliminated
generated from clay-supported Fe(NO3)3 (clayfen) has been reported; see: product 4d0 . When the reaction of R-methylstyrene (3e) was
(a) Laszlo, P.; Polla, E. Tetrahedron Lett. 1984, 25, 3701. The synthesis of performed with Fe(NO3)3 3 9H2O/FeCl3 in MeCN, polymer-
β-nitrostyrenes using clayfen has been also reported: (b) Verma, R. S.;
Naicker, K. P.; Liesen, P. J. Tetrahedron Lett. 1998, 39, 3977. ization and nitration of the aromatic ring probably competed
(13) For reviews on iron-catalyzed reactions, see: (a) Iron Catalysis in to give a complex mixture. However, we soon found that
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.; using LiCl instead of FeCl3 gave the desired chloro-nitrated
Garcı́a Manche~ no, O.; Bolm, C. Chem. Soc. Rev. 2008, 37, 1108. (d) Enthaler, product 4e in moderate yield along with a small amount of
S.; Junge, K.; Beller, M. Angew. Chem., Int. Ed. 2008, 47, 3317. (e) Sherry,
B. D.; F€ urstner, A. Acc. Chem. Res. 2008, 47, 1500. (f) Correa, A.; Garcı́a
eliminated product 4e0 (Table 2, entry 5). The present reac-
Manche~ no, O.; Bolm, C. Chem. Soc. Rev. 2008, 37, 1108. (g) F€ urstner, A. tion might have milder reactivity with the use of LiCl, which
Angew. Chem., Int. Ed. 2009, 48, 1364. (h) Sarhan, A. A.; Bolm, C. Chem. is a weak Lewis base, rather than FeCl3, which is a strong
Soc. Rev. 2009, 38, 2730.
(14) For selected recent examples of iron-catalyzed reactions, see: (a) Sylvester, Lewis acid. Thus, this result shows that the scope of the pre-
K. T.; Chirik, P. J. J. Am. Chem. Soc. 2009, 131, 8772. (b) Wu, J. Y.; Moreau, B.; sent reaction allows for extension by using LiCl as a chlorine
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. source. p-Bromo-R-methylstyrene (3f) gave a chloro-nitrated
(d) Junge, K.; Wendt, B.; Shaikh, N.; Beller, M. Chem. Commun. 2010, 1769. product (4f) with a small amount of eliminated product (4f0 )
(e) Hatakeyama, T.; Hashimoto, T.; Kondo, Y.; Fujiwara, Y.; Seike, H.; Takaya, under the condition of use of FeCl3 (Table 2, entry 6). The
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- reaction of p-nitro-R-methylstyrene (3g) with Fe(NO3)3 3 9H2O/
chlorination of alkenes; see: (f) Bach, T.; Schlummer, B.; Harms, K. Chem. FeCl3 readily proceeded to give chloro-nitrated product 4g in
Commun. 2000, 287. (g) Bach, T.; Schlummer, B.; Harms, K. Chem.;Eur. J.
2001, 7, 2581. high yield (Table 2, entry 7). This high yield can be attributed
(15) Taniguchi, T.; Ishibashi, H. Org. Lett. 2010, 12, 124. to restraint of side reactions such as polymerization and nitration
J. Org. Chem. Vol. 75, No. 23, 2010 8127
JOC Article Taniguchi et al.

TABLE 2. Chloro-Nitration of Various Alkenes TABLE 3. Chloro-Nitration of Cyclic Alkenes

a
Diastereomeric 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

a
Yield was determined by 1H NMR analysis. bLiCl was employed
instead of FeCl3. cDiastereomeric 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 a
Yield was determined by 1H NMR analysis.
ring competed in the reaction of 4j.
Subsequently, chloro-nitration reactions of cyclic alkenes
were examined (Table 3). Treatment of five-, six-, seven-, (7a) and ethyl methacrylate (7b) with Fe(NO3)3 3 9H2O/FeCl3
eight-, and twelve-membered cycloalkenes 5a-e with Fe- in MeCN afforded nitrated ethyl esters 8a and 8b in moder-
(NO3)3 3 9H2O/FeCl3 in MeCN afforded the corresponding ate yield along with small amounts of eliminated products 8a0
2-chloro-1-nitro cycloalkanes 6a-e in good yields (Table 3, and 8b0 , respectively (Table 4, entries 1 and 2). The reaction
entries 1-5). On the other hand, low reactivity of norbor- of ethyl tiglate (7c) gave nitrated product 8c as a single dia-
nene (5f) was observed (Table 3, entry 6). The reaction of stereomer (Table 4, entry 3). The reaction of methacrylamide
trisubstituted cycloalkenes 5g and 5h gave chloro-nitrated 7d successfully proceeded to give 2-chloro-3-nitropropiona-
products 6g and 6h, respectively, in moderate yields (Table 3, mide 8c in good yields (Table 4, entry 4). When the reaction
entries 7 and 8). of β-carvone (9) bearing electron-rich and deficient alkene moi-
Reactions using electron-deficient alkenes as substrates eties in the molecule was carried out at a lower temperature
were also examined (Table 4). Treatment of ethyl acrylate (60 °C), selective addition of a nitro group to electron-rich
8128 J. Org. Chem. Vol. 75, No. 23, 2010
Taniguchi et al.
JOC Article
SCHEME 3. Chemoselective Chloro-Nitration of β-Carvone (9) TABLE 5. One-Pot Synthesis of Nitroalkene 4a

entry base time (h) yield (%)

SCHEME 4. Radical Trap by Other Halogen Atoms 1 Et3N 1 complex mixture

2 K2CO3 0.5 15
3 LiOH 3 H2O 0.5 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 derivative 13 was examined. Treatment of 13 with Fe(NO3)3 3
yield (Scheme 3). 9H2O in the presence of LiCl in MeCN resulted in elimination
Brominated or iodinated compounds were also accessible of the sulfonyl group to give nitro compound 14 in good yield
by using appropriate radical trapping reagents. In the reac- with detection of p-toluenesulfonyl chloride 15 (Scheme 6).
tion of 1,6-diene, we found that treatment of 1,6-diene with This result provides support for the generation of radical
Fe(NO3)3 3 9H2O in the presence of carbon tetrabromide or intermediate B followed by elimination of a stable sulfonyl
lithium iodide afforded brominated or iodinated products, radical C, which abstracted a chlorine atom from the iron
respectively.15 The reaction of cyclooctene (5d) was performed complex to give p-toluenesulfonyl chloride.16,17
under similar conditions to give brominated and iodinated Finally, one-pot synthesis of useful nitroalkenes using
products 11d and 12d in moderate and good yields, respec- this iron-mediated nitration reaction was examined.18 After
tively (Scheme 4). decene (3a) had been treated with Fe(NO3)3 3 9H2O/FeCl3 in
A plausible mechanism for the chloro-nitration reaction is boiling MeCN, addition of Et3N to the reaction mixture
shown in Scheme 5. For the reaction of simple alkene 3a, afforded a complex mixture (Table 5, entry 1). However, we
addition of nitrogen dioxide (NO2), generated by thermal de- soon found that using K2CO3 instead of Et3N gave desired
composition of Fe(NO3)3 3 9H2O, onto 3a takes place to give
radical intermediate A. The radical intermediate A is then (16) Guyader, F. L.; Quiclet-Sire, B.; Seguin, S.; Zard, S. Z. J. Am. Chem.
trapped by a chlorine atom from the iron chloride complex to Soc. 1997, 119, 7410.
give 4a. Although the possibility that the formation of 4a (17) In order to obtain evidence of the radical mechanism, trans-1-phenyl-
2-vinylcyclopropane was employed as a radical clock, but the decomposition
involves oxidation of the radical intermediate A followed of substrate or product was observed in the reaction of this compound.
by addition of chloride anion to the resultant cation inter- (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
mediate as another path cannot be ruled out, the main path Amino Group Chemistry; Ricci, A., Ed.; Wiley-VCH: New York, 2008; pp
would be the direct radical trapping mechanism by a chlorine 93-148. See also ref 2 1, 3, 9, and 10.

J. Org. Chem. Vol. 75, No. 23, 2010 8129

JOC Article Taniguchi et al.

nitroalkene 4a0 in one pot (Table 5, entry 2). Eventually, the N-(2-Chloro-3-nitropropyl)toluenesulfonamide (4b). 95% yield.
use of LiOH 3 H2O as a base significantly improved the yield Colorless crystals, mp 68.0-68.5 °C. IR (CHCl3) υ 1563, 1337,
of the product (Table 5, entry 3). As shown in Table 6, sty- 1223, 1163 cm-1; 1H NMR (400 MHz, CDCl3) δ 2.45 (3H, s),
rene (3d) and cycloalkene 5d and 5e also readily underwent 3.32-3.46 (2H, m), 4.56-4.62 (1H, m), 4.70 (1H, dd, J = 14.1,
the one-pot chloro-nitration/elimination process to give nitro- 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
alkenes 4d0 , 6d0 , and 6e0 , respectively, in good yields.
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.
Conclusions Found: C, 40.90; H, 4.34; N, 9.55.
In conclusion, we have developed an iron-mediated nitra- 2-Chloro-2-methyl-1-nitro-4-phenylbutane (4c). 56% yield.
tion reaction of alkenes to give halo-nitro compounds. In the Colorless oil. IR (CHCl3) υ 1556, 1456, 1375 cm-1; 1H NMR
present reaction, a radical mechanism was suggested by in- (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),
vestigation of nitro-cyclization of 1,6-dienes, and this reac- 7.20-7.32 (5H, m); 13C NMR (100 MHz, CDCl3) δ 28.5, 30.8,
tion was extended to halo-nitration of various alkenes. 43.6, 66.8, 84.0, 126.4, 128.4, 128.6, 140.3; HRFABMS calcd for
Furthermore, one-pot synthesis of synthetic valuable nitro- C11H15ClNO2 (Mþ þH) 228.0791, found 228.0799.
alkene using this method was shown. The present reaction 1-Chloro-2-nitro-1-phenylethane (4d) and 1-Nitro-2-pheny-
has large advantages such as the simple and safe experimen- lethene (4d0 ).25 75% (4d) and 11% (4d0 ) yields (4d and 4d0 were
tal procedure using nontoxic and inexpensive reagents. isolated as an inseparable mixture). Colorless oil. IR (CHCl3) υ
Therefore, the present reaction will provide a general and 1564, 1377, 1346 cm-1; 1H NMR (400 MHz, CDCl3, for 4d
practical method for the synthesis of nitro compounds. 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),
Experimental Section 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
General. All reactions were carried out in flame-dried glass- 4d0 ) δ 56.8, 80.7, 127.1, 129.1 (4d0 ), 129.2, 129.3 (4d0 ), 129.7, 130.0
ware under nitrogen atmosphere. All reagents were purchased (4d0 ), 132.1 (4d0 ), 135.7, 137.0 (4d0 ), 139.1(4d0 ); HRFABMS (for
commercially and used without further purification. Melting 4d) calcd for C8H9ClNO2 (Mþ þ H) 186.0322, found 186.0320.
points are uncorrected. IR spectra were recorded on a commer- HRFABMS (for 4d0 ) calcd for C8H9NO2 (Mþ þ H) 150.0555,
cial FT/IR spectrometer. 1H NMR spectra were recorded at 600, found 150.0555.
500, and 400 MHz; chemical shifts (δ) are quoted relative to 2-Chloro-1-nitro-2-phenylpropane (4e) and 1-Nitro-2-phenyl-
tetramethylsilane. 13C NMR spectra were recorded at 150, 125, propene (4e0 ).21 54% (4e) and 9% (4e0 ) yields (4e and 4e0 were
and 100 MHz with complete proton decoupling; chemical shift isolated as an inseparable mixture). Colorless oil. IR (CHCl3) υ
(δ) are quoted relative to the residual signals of chloroform. 1558, 1448, 1373, 1269 cm-1; 1H NMR (400 MHz, CDCl3, for 4e
Silica gel column chromatography was carried out on silica gel including the partial peaks of 4e0 ) δ 2.23 (3H, s), 2.64 (3H, s, for
60N. Mass spectra were recorded on a high-resolution mass 4e0 ), 4.90 (1H, d, J = 11.7 Hz), 4.93 (1H, d, J = 11.7 Hz),
spectrometer in fast atom bombardment mode (FAB). 7.26-7.45 and 7.55-7.59 (total 11H, m, for 4e and 4e0 ), (2H,
Starting Materials. Compounds 3a, 3d, 3e, 3i, 3j, 5a-h, 7a-c, m); 13C NMR (100 MHz, CDCl3, for 4e including the par-
and 9 were commercially available. Compound 3b19 was pre- tial peaks of 4e0 ) δ 18.6 (4e0 ), 29.0, 66.9, 86.0, 126.1, 128.8,
pared by N-tosylation of allylamine. Compounds 3c,20 3f,21 3g,22 128.9, 130.3 (4e0 ), 136.3 (4e0 ), 138.2 (4e0 ), 140.0, 150.0 (4e0 );
and 3h21 were prepared by Wittig reaction of corresponding HRFABMS (for 4e) calcd for C9H11ClNO2 (Mþ þ H) 200.0478,
commercially available ketones. Compound 7d23 was prepared found 200.0483. HRFABMS (for 4e0 ) calcd for C9H11NO2
by acylation of diethylamine with methacryloyl chloride. Com- (Mþ þ H) 164.0712, found 164.0711.
pound 1324 was prepared according to literature. 2-(4-Bromophenyl)-2-chloro-1-nitropropane (4f) and 2-(4-
Typical Procedure of Halo-Nitration of Alkenes. To a solution Bromophenyl)-1-nitropropene (4f0 ).21 49% (4f) and 8% (4f0 )
of 3a (74.1 mg, 0.528 mmol) and FeCl3 (256 mg, 0.792 mmol) yields (4f and 4f0 were isolated as an inseparable mixture).
in CH3CN (2.6 mL) was added Fe(NO3)3 3 9H2O (128 mg, Colorless oil. IR (CHCl3) υ 1560, 1490, 1342 cm-1; 1H NMR
0.634 mmol), and the mixture was heated at reflux for 1 h. After (500 MHz, CDCl3, for 4f including the peaks of 4f0 ) δ 2.20 (3H, s),
cooling to room temperature, the resulting suspension was diluted 2.64 (3H, d, J=1.4 Hz, for 4f0 ) 4.82 (1H, d, J=11.9 Hz), 4.93
with Et2O and filtered. After removal of solvent under reduced (1H, d, J=11.9 Hz), 7.29 (1H, d, J=1.4 Hz, for 4f0 ), 7.33 (2H,
pressure, the residue was purified by chromatography (hexane/ d-like, J=8.2 Hz, for 4f0 ), 7.43 (2H, d-like, J=8.2 Hz), 7.54 (2H,
EtOAc, 10:1) to give 4a (97.8 mg, 84%) as a colorless oil. d-like, J=8.2 Hz), 7.58 (2H, d-like, J=8.2 Hz, for 4f0 ); 13C NMR
2-Chloro-1-nitrodecane (4a). 84% yield. Colorless oil. IR (150 MHz, CDCl3, for 4f including the peaks of 4f0 ) δ 18.4 (4f0 ),
(CHCl3) υ 1562, 1379, 1225 cm-1; 1H NMR (400 MHz, 29.0, 66.2, 85.6, 123.3, 127.9, 128.3 (4f0 ), 131.8 (4f0 ), 131.9, 132.3
CDCl3 ) δ 0.89 (3H, t, J = 6.9 Hz), 1.24-1.42 (10H, br), (4f0 ), 136.4 (4f0 ), 137.1 (4f0 ), 139.1, 148.6 (4f0 ); HRFABMS
1.48-1.58 (2H, m), 1.74-1.81(2H, m), 4.50-4.55 (1H, m), (for 4f) calcd for C9H10ClO2NBr (Mþ þ H) 277.9583, found
4.58 (1H, d, J=1.8 Hz), 4.60 (1H, m); 13C NMR (150 MHz, 277.9597. HRFABMS (for 4f0 ) calcd for C9H9O2BrN (MþþH)
CDCl3) δ 14.1, 22.6, 25.8, 28.8, 29.1, 29.3, 31.8, 35.0, 56.2, 241.9817, found 241.9818.
80.5; HRFABMS calcd for C10H21ClNO2 (Mþ þ H) 222.1261, 2-Chloro-1-nitro-2-(4-nitrophenyl)propane (4g). 80% yield.
found 222.1264. 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, CDCl3) δ 2.25 (3H, s), 4.96 (1H, d, J=12.4 Hz), 5.01 (1H, d, J=
3442. 12.4 Hz) 7.76 (2H, d, J=8.9 Hz), 8.27 (2H, d, J=8.9 Hz); 13C
(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. NMR (150 MHz, CDCl3) δ 29.3, 65.6, 85.3, 123.9, 127.5, 146.8,
Chem. 2008, 73, 4295. 147.9. Anal. Calcd for C9H9ClN2O4: C, 44.19; H, 3.71; N, 11.45.
(22) Sherrill, W. M.; Kim, R.; Rubin, M. Tetrahedron 2008, 64, 8610. Found: C, 44.44; H, 3.66; N, 11.47.
(23) Kollar, L.; Consiglio, G.; Pino, P. J. Organomet. Chem. 1990, 386,
389.
(24) Knight, D. J.; Lin, P.; Russell, S. T.; Whitham, G. H. J. Chem. Soc., (25) Black, P.-J.; Gerta, C.-K.; Edwards, M. G.; Slatford, P. A.; Whittlesey,
Perkin Trans. 1 1987, 2701. M. K.; Williams, J. M. J. Org. Biomol. Chem. 2006, 4, 116.

8130 J. Org. Chem. Vol. 75, No. 23, 2010

Taniguchi et al.
JOC Article
1-Chloro-2-nitro-1-phenylpropane (4i). 80% yield. Colorless (minor), 94.0; HRFABMS calcd for C8H15ClNO2 (Mþ þ H)
oil. (4i was an inseparable mixture of two isomers, 53:47). IR 192.0791, found 192.0796.
(CHCl3) υ 1560, 1454, 1389, 1360 cm-1; 1H NMR (400 MHz, 1-Chloro-2-nitrocyclododecene (6e). 78% yield (as an insepar-
CDCl3, for a mixture of two isomers) δ 1.35 (3H, d, J=6.8 Hz), able mixture of two isomers, 72:28). Colorless oil. IR (CHCl3)
1.71 (3H, d, J=6.6 Hz), 4.93 (1H, dq, J=9.6, 6.9 Hz), 5.01 (1H, υ 1558, 1470, 1371 cm-1; 1H NMR (600 MHz, CDCl3, including
dq, J=7.3, 6.9 Hz), 5.22 (1H, d, J=10.3 Hz), 5.38 (1H, d, J= the partial peaks of minor isomer) δ 1.29-1.51 (15H, m),
7.6 Hz), 7.35-7.42 (10H, m); 13C NMR (150 MHz, CDCl3, for a 1.72-1.78 (1H, m), 1.82-1.87 (1H, m), 1.93-2.04 (3H, m),
mixture of two isomers) δ 15.7, 17.9, 62.3, 62.6, 87.5, 88.9, 127.4, 4.47 (1H, dt, J=14.4, 4.1 Hz), 4.57 (1H, br, minor isomer), 4.73
127.8, 128.9, 129.2, 129.4, 129.7, 135.5, 136.2; HRFABMS calcd (1H, dt, J=8.3, 2.1 Hz), 4.78 (1H, ddd, J=10.8, 6.1, 2.8 Hz); 13C
for C9H11ClNO2 (Mþ þ H) 200.0478, found 200.0479. NMR (150 MHz, CDCl3, including the partial peaks of minor
1-Chloro-1,2-diphenyl-2-nitroethane (4j). 11% yield. Colorless isomer) δ 20.0, 21.4 (minor), 21.9 (minor), 22.0, 22.3 (minor),
oil. IR (CHCl3) υ 1655, 1562, 1522, 1325, 1277 cm-1; 1H NMR 22.4, 22.6, 22.9, 23.1, 24.4, 24.5, 24.9 (br, minor), 28.4, 30.1, 59.2,
(600 MHz, CDCl3) δ 5.73 (1H, d, J=11.0 Hz), 5.87 (1H, d, J= 60.3 (br, minor), 86.8 (br, minor), 90.7; HRFABMS calcd for
11.0 Hz), 7.21-7.29 (10H, m); 13C NMR (150 MHz, CDCl3) δ C12H23ClNO2 (Mþ þ H) 248.1417, found 248.1418.
61.9, 96.7, 127.88, 127.93, 128.8, 129.0, 130.3, 135.1; HRFABMS 2-Chloro-3-nitrobicyclo[2.2.1]heptane (6f).27 35% yield (as a
calcd for C14H12ClNO2 (Mþ þ H) 262.0636, found 262.0635. separable mixture of two isomers, 72:28). Major isomer: color-
1-Chloro-2-nitrocyclopentane (6a). 71% yield (as a separable less oil. IR (CHCl3) υ 1550, 1456, 1375 cm-1; 1H NMR (400 MHz,
mixture of two isomers, 87:13). Major isomer: colorless oil. IR CDCl3) δ 1.41-1.47 (1H, m), 1.50-1.57 (2H, m), 1.75-1.82
(CHCl3) υ 1552, 1371 cm-1; 1H NMR (600 MHz, CDCl3) δ (1H, m), 1.84-1.86 (1H, m), 1.93-1.99 (1H, m), 2.60-2.64 (1H,
1.94-2.05 (3H, m), 2.25-2.30 (1H, m), 2.37-2.43 (1H, m), 2.49 m), 2.85 (1H, d, J=5.0 Hz), 4.31 (1H, dd, J=3.6, 2.3 Hz), 4.78
(1H, td, J = 14.4, 8.2 Hz), 4.72-4.75 (1H, m), 4.96 (1H, dt, (1H, br); 13C NMR (100 MHz, CDCl3) δ 21.1, 26.7, 35.5, 43.3,
J = 8.2, 3.4 Hz); 13C NMR (150 MHz, CDCl3) δ 22.3, 30.4, 44.4, 61.7, 95.4; HRFABMS calcd for C7H11ClNO2 (Mþ þ H)
35.3, 60.4, 93.0; HRFABMS calcd for C5H9ClNO2 (Mþ þ H) 176.0478, found 176.0486. Minor isomer: IR (CHCl3) υ 1558,
150.0322, found 150.0328. Minor isomer: colorless oil. IR 1458, 1375 cm-1; 1H NMR (400 MHz, CDCl3) δ 1.22-1.26 (2H,
(CHCl3) υ 1556, 1375, 1219 cm-1; 1H NMR (400 MHz, CDCl3) m), 1.48 (1H, dt, J=9.6, 1.8 Hz), 1.61-1.80 (2H, m), 2.34 (1H,
δ 1.76-1.84 (1H, m), 2.16-2.25 (4H, m), 2.53-2.65 (11H, m), dt, J=10.5, 1.8 Hz), 2.55 (1H, d, J=4.7 Hz), 2.88 (1H, d, J=
4.55 (1H, dd, J=10.5, 5.5 Hz) 4.98 (1H, td, J=7.3, 5.5 Hz); 13C NMR 3.2 Hz), 4.24 (1H, dd, J=7.3, 5.5 Hz), 4.70 (1H, dd, J=7.3, 6.0
(150 MHz, CDCl3) 20.5, 26.2, 33.6, 59.5, 88.9; HRFABMS Hz); 13C NMR (100 MHz, CDCl3) δ 25.6, 25.9, 34.7, 41.2, 45.4,
calcd for C5H9ClNO2 (Mþ þ H) 150.0322, found 150.0325. 60.4, 91.4; HRFABMS calcd for C7H11ClNO2 (Mþ þ H)
1-Chloro-2-nitrocyclohexane (6b).26 74% yield (as a separ- 176.0478, found 176.0468.
able mixture of two isomers, 72:28). Major isomer: colorless oil. 1-Chloro-1-methyl-2-nitrocyclohexane (6g). 48% yield. Col-
IR (CHCl3) υ 1562, 1453, 1374, 1225 cm-1; 1H NMR (400 MHz, orless oil. IR (CHCl3) υ 1552, 1458, 1371 cm-1; 1H NMR (600
CDCl3) δ 1.36-1.45 (2H, m), 1.64-1.75 (1H, m), 1.82-1.94 MHz, CDCl3) δ 1.48-1.55 (1H, m), 1.56-1.63 (1H, m), 1.72
(3H, m), 2.33-2.42 (2H, m), 4.29 (1H, td, J=11.0, 4.6 Hz), 4.51 (3H, s), 1.72-1.79 (1H, m), 1.80-1.87 (1H, m), 1.95 (1H, ddd,
(1H, td, J=11.4, 4.6 Hz); 13C NMR (150 MHz, CDCl3) δ 23.4, J = 13.7, 9.6, 4.1 Hz), 2.06-2.13 (1H, m), 2.22-2.32 (2H, m),
24.8, 31.9, 34.7, 57.7, 91.5.; HRFABMS calcd for C6H11ClO2N 4.80 (1H, dd, J=8.2, 4.1 Hz); 13C NMR (150 MHz, CDCl3) δ
(Mþ þ H) 164.0478, found 164.0476. Minor isomer: colorless 21.6, 21.9, 26.2, 27.9, 40.2, 67.5, 92.4; HRFABMS calcd for
oil. IR (CHCl3) υ 1552, 1377, 1221 cm-1; 1H NMR (400 MHz, C7H13ClNO2 (Mþ þ H) 178.0635, found 178.0631.
CDCl3) δ 1.25-1.38 (1H, m), 1.54-1.60 (1H, m), 1.68-1.81 1-Chloro-1-phenyl-2-nitrocyclohexane (6h).28 65% yield. Col-
(1H, m), 1.84-1.98 (2H, m), 2.13-2.31 (3H, m), 4.47 (1H, dt, J= orless crystals, mp 85.0-85.5 °C (hexane/EtOAc). IR (CHCl3) υ
11.4, 4.1 Hz), 4.97 (1H, br); 13C NMR (150 MHz, CDCl3) δ 18.7, 1552, 1448, 1378, 1296 cm-1; 1H NMR (600 MHz, CDCl3) δ
23.3, 23.4, 32.9, 58.2, 85.4; HRFABMS calcd for C6H11ClNO2 1.64-1.76 (2H, m), 1.95-2.03 (2H, m), 2.26 (1H, dd, J=15.1,
(Mþ þ H) 164.0478, found 164.0476. 1.8 Hz), 2.41 (1H, br), 2.55-2.62 (1H, m), 3.10-3.18 (1H, m),
1-Chloro-2-nitrocycloheptane (6c). 91% yield. (as an insepar- 5.41 (1H, m), 7.31 (1H, t, J=7.6 Hz), 7.37 (2H, t, J=6.9 Hz), 7.56
able mixture of two isomers, 87:13). Colorless oil. IR (CHCl3) υ (2H, d, J=8.3 Hz); 13C NMR (150 MHz, CDCl3) δ 18.9, 20.7,
1557, 1458, 1377 cm-1; 1H NMR (600 MHz, CDCl3, including 27.1, 32.1, 69.7, 89.6, 126.0, 128.6, 128.9, 141.2. Anal. Calcd for
the partial peaks of minor isomer) δ 1.60-1.65 (4H, m), C12H14ClNO2: C, 60.13; H, 5.89; N, 5.84. Found: C, 59.77; H,
1.81-1.89 (2H, m), 1.98-2.05 (1H, m), 2.06-2.12 (1H, m), 5.72; N, 5.94.
2.15-2.20 (1H, m), 2.24-2.29 (1H, m), 2.29-2.39 (2H, m, for Ethyl 2-Chloro-3-nitropropanoate (8a)29 and Ethyl 3-Nitroa-
minor isomer), 4.58 (1H, td, J=8.9, 3.4 Hz), 4.62 (1H, dt, J= crylate (8a0 ).29,30 42% (8a) and 9% (8a0 ) yields (8a and 8a0 were
11.0, 4.1 Hz, for minor isomer), 4.69 (1H, td, J=8.9, 3.4 Hz), isolated as an inseparable mixture). Colorless oil. IR (CHCl3) υ
4.98 (1H, m, for minor isomer); 13C NMR (100 MHz, CDCl3) δ 1743, 1543, 1377, 1248 cm-1; 1H NMR (400 MHz, CDCl3, for 8a
22.2 (minor), 22.8 (minor), 23.6, 23.6, 25.9 (minor), 26.2 including the peaks of 8a0 ) δ 1.34 (3H, t, J=6.9 Hz), 1.37 (3H, t,
(minor), 27.1, 31.5, 34.1 (minor), 34.8, 60.9, 61.3 (minor), 89.7 J=6.9 Hz, for 8a0 ) 4.32 (2H, q, J=6.9 Hz), 4.33 (2H, q, J=6.9
(minor), 95.2; HRFABMS calcd for C7H13ClNO2 (Mþ þ H) Hz, for 8a0 ) 4.77 (1H, dd, J=14.2, 6.4 Hz), 4.88 (1H, t, J=6.9
178.0635, found 178.0640. Hz), 5.00 (1H, dd, J=14.2, 6.9 Hz), 7.09 (1H, d, J=13.1 Hz, for
1-Chloro-2-nitrocyclooctane (6d). 88% yield (as an insepar- 8a0 ), 7.68 (1H, d, J = 13.7 Hz, for 8a0 ); 13C NMR (150 MHz,
able mixture of two isomers, 82:18). Colorless oil. IR (CHCl3) υ CDCl3, for 8a including the peaks of 8a0 ) δ 13.8 (8a0 ), 14.0, 49.8,
1556, 1466, 1381, 1223 cm-1; 1H NMR (600 MHz, CDCl3, 62.4 (8a0 ), 63.3, 75.5, 127.7 (8a0 ), 148.9 (8a0 ), 162.6 (8a0 ), 166.2;
including the partial peaks of minor isomer) δ 1.34-1.52 (2H, HRFABMS calcd for C5H9ClNO4 (Mþ þ H) 182.0220, found
m), 1.60-1.73 (5H, m), 1.79-1.92 (2H, m), 2.05-2.19 (2H, m), 182.0218.
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= (27) Chauvet, F.; Heumann, A.; Waegell, B. J. Org. Chem. 1987, 52,
10.3, 7.6, 2.1 Hz); 13C NMR (100 MHz, CDCl3) δ 22.9 (minor), 1916.
23.3, 24.5, 24.8 (minor), 24.97 (minor), 24.99 (minor), 25.4, 26.6, (28) Arumugam, N.; Shenbagamurthi, P.; Sivasubramanian, S.; Kesavan,
27.1 (minor), 31.1, 31.3, 33.5 (minor), 60.9, 61.1 (minor), 88.3 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.
(26) Price, C. C.; Sears, C. A. J. Am. Chem. Soc. 1953, 75, 3275. (30) Addo, J. K.; Teesdale-Spittle, P.; Hoberg, J. O. Synthesis 2005, 1923.

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JOC Article Taniguchi et al.

Ethyl 2-Chloro-2-methyl-3-nitropropanoate (8b) and Ethyl 27.5, 30.8, 32.7, 32.8, 96.6; HRFABMS calcd for C8H15INO2
3-Nitromethacrylate (8b0 ).3k 56% (8b) and 8% (8b0 ) yields (8b (Mþ þ H) 284.0148, found 284.0141.
and 8b0 were isolated as an inseparable mixture). Colorless oil. 4-Nitro-1-phenylbut-2-ene (14). 72% yield (as an inseparable
IR (CHCl3) υ 1751, 1566, 1383, 1213 cm-1; 1H NMR (400 MHz, mixture of two isomers, 91:9). Colorless oil. IR (CHCl3) υ 3031,
CDCl3, for 8b including the peaks of 8b0 ) δ 1.34 (3H, t, J = 1557, 1375, 1217 cm-1; 1H NMR (400 MHz, CDCl3, including
6.9 Hz), 1.36 (3H, t, J=6.9 Hz, for 8b0 ), 1.90 (3H, s), 4.33 (2H, q, the partial peaks of minor isomer) δ 3.46 (2H, d, J=6.4 Hz), 3.50
J=7.0 Hz), 4.32 (2H, q, J=6.9 Hz, for 8b0 ), 4.84 (1H, d, J=14.7 (2H, d, J=7.8 Hz, for minor isomer), 4.90 (2H, d, J=7.3 Hz),
Hz), 5.01, (1H, d, J=14.7 Hz), 7.73 (1H, q, J=1.4 Hz, for 8b0 ); 5.10 (2H, d, J=7.8 Hz, for minor isomer), 5.81 (1H, dt, J=15.6, 7.3
13
C NMR (150 MHz, CDCl3, for 8b including the peaks of 8b0 ) δ Hz), 5.88-5.91 (1H, m, for minor isomer), 6.07 (1H, dt, J=15.6,
13.7, 13.9 (8b0 ), 25.3, 61.8 (8b0 ), 62.5 (8b0 ), 63.2, 80.9, 136.8 (8b0 ), 6.4 Hz), 7.17 (2H, d, J=6.9 Hz), 7.23 (1H, t, J=5.8 Hz), 7.32 (2H, t,
143.8 (8b0 ), 143.8, 165.1 (8b0 ), 168.0; HRFABMS (for 8b) calcd J=7.3 Hz); 13C NMR (150 MHz, CDCl3, for major isomer) δ 38.6,
for C6H11ClO4N (MþþH) 197.0455, found 197.0462. HRFABMS 77.3, 119.7, 126.5, 128.59, 128.64, 138.4, 140.0; HRFABMS calcd
(for 8b0 ) calcd for C6H10NO4 (MþþH) 160.0610, found 160.0601. for C10H12NO2 (Mþ þH) 178.0868, found 178.0869.
Ethyl 2-Chloro-2-methyl-3-nitrobutanoate (8c). 64% yield. Typical Procedure for One-Pot Synthesis of Nitroalkenes. To a
Colorless oil. IR (CHCl3) υ 1751, 1556, 1456, 1392, 1298 cm-1; solution of 3a (74.1 mg, 0.528 mmol) and FeCl3 (256 mg, 0.792
1
H NMR (400 MHz, CDCl3) δ 1.31 (3H, t, J=7.3 Hz), 1.78 (3H, mmol) in CH3CN (2.6 mL) was added Fe(NO3)3 3 9H2O (128 mg,
d, J=6.9 Hz), 1.88 (3H, s), 4.29 (2H, q, J=7.3 Hz), 5.22 (1H, q, 0.634 mmol), and the mixture was heated at reflux for 1 h. LiOH 3
J=7.3 Hz); 13C NMR (100 MHz, CDCl3) δ 13.7, 14.4, 21.9, 63.0, H2O (222 mg, 5.28 mmol) was added, and the mixture was
65.7, 86.1, 168.4; HRFABMS calcd for C7H13ClNO4 (Mþ þ H) heated at reflux for 30 min. After cooling to room temperature,
210.0533, found 210.0539. the resulting suspension was diluted with Et2O and filtered.
2-Chloro-N,N-diethyl-2-methyl-3-nitropropanamide (8d). 81% After removal of solvent under reduced pressure, the residue was
yield. Colorless oil. IR (CHCl3) υ 1658, 1562, 1462, 1354 cm-1; 1H purified by chromatography (hexane/EtOAc, 10:1) to give 4a0
NMR (400 MHz, CDCl3) δ 1.15 (3H, br), 1.29 (3H, br), 2.00 (3H, (80.1 mg, 82%) as a colorless oil.
s), 3.37 (2H, br), 3.60 (1H, br), 3.80 (1H, br), 4.83 (1H, d, J=13.7 (E)-1-Nitrodecene (4a0 ).3h 82% yield. Colorless oil. IR (CH-
Hz), 4.98 (1H, d, J=13.7 Hz); 13C NMR (100 MHz, CDCl3) δ Cl3) υ 2930, 1526, 1354 cm-1; 1H NMR (400 MHz, CDCl3) δ
12.2, 13.8, 26.4, 42.2, 42.8, 63.0, 83.1, 166.7; HRFABMS calcd for 0.88 (3H, t, J=6.9 Hz), 1.26-1.37 (10H, m), 1.51 (2H, dt, J=
C8H16ClN2O3 (Mþ þ H) 223.0850, found 223.0840. 15.1, 7.6 Hz), 2.27 (2H, q, J=7.3 Hz), 6.98 (1H, dd, J=13.3,
(5R,7R)- and (5R,7S)-5-[2-Chloro-1-nitropropan-2-yl]-2-methyl- 1.4 Hz), 7.28 (1H, dt, J=13.3, 7.3 Hz); 13C NMR (150 MHz,
cyclohex-2-enone (10). 65% yield (as an inseparable mixture of CDCl3) δ 14.1, 22.6, 27.7, 28.4, 29.06, 29.08, 29.2, 31.7, 139.5,
two isomers, 50:50). Colorless oil. IR (CHCl3) υ 1674, 1556, 142.9; HRFABMS calcd for C10H20NO2 (Mþ þ H) 186.1494,
1373 cm-1; 1H NMR (600 MHz, CDCl3, for a mixture of two found 186.1501.
isomers) δ 1.77 (3H, s), 1.79 (3H, s), 1.80 (total 6H, two s), (E)-1-Nitro-2-phenylethene (4d0 ).25 66% yield. White solids,
2.47-2.62 (7H, m), 2.63-2.71 (2H, m), 2.78 (1H, d, J=15.8 Hz), mp 51.5-52.0 °C (hexane/EtOAc, lit. 58-59 °C). IR (CHCl3) υ
4.65 (1H, d, J=4.8 Hz), 4.68 (1H, d, J=4.8 Hz), 4.77 (1H, d, J= 3020, 1635, 1525, 1346, 1259 cm-1; 1H NMR (400 MHz, CDCl3)
11.7 Hz), 4.81 (1H, d, J=11.7 Hz) 6.78-6.82 (2H, m); 13C NMR δ 7.43-7.57 (6H, m), 7.59 (1H, d, J=13.7 Hz), 8.01 (1H, d, J=
(150 MHz, CDCl3, for a mixture of two isomers) δ 15.40, 15.42, 13.7 Hz); 13C NMR (150 MHz, CDCl3) δ 129.1, 129.4, 130.0,
26.3, 26.4, 26.9, 27.1, 38.8, 39.1, 42.5, 42.6, 69.2, 69.3, 82.4, 132.1, 137.1, 139.1 HRFABMS calcd for C8H8NO2 (Mþ þ H)
135.4, 135.5, 143.8, 143.9, 198.1, 198.4; HRFABMS calcd for 150.0555, found 150.0555.
C10H15ClNO3 (Mþ þ H) 232.0741, found 232.0733. (E)-1-Nitorocyclooctene (6d0 ).10a 62% yield. Colorless oil. IR
1-Bromo-2-nitrocyclooctane (11d). 56% yield (as an insepar- (CHCl3) υ 2934, 1518, 1383, 1223 cm-1; 1H NMR (400 MHz,
able mixture of two isomers, 85:15) Colorless oil. IR (CHCl3) υ CDCl3) δ 1.52 (4H, br), 1.72 (4H, br), 2.30-2.36 (2H, m), 2.75
1556, 1465, 1365 cm-1; 1H NMR (600 MHz, CDCl3, including (2H, br), 7.31 (1H, t, J=9.0 Hz); 13C NMR (100 MHz, CDCl3) δ
the partial peaks of minor isomer) δ 1.33-1.41 (1H, m), 1.43- 24.8, 25.6, 26.4, 26.6, 28.3, 29.0, 136.3, 152.3; HRFABMS calcd
1.51 (1H, m), 1.54-1.69 (2H, m), 1.72-1.92 (4H, m), 2.03-2.11 for C8H14NO2 (Mþ þ H)156.1025, found 156.1024.
(1H, m), 2.13-2.20 (2H, m), 2.24-2.33 (1H, m, for minor (E)-1-Nitorocyclododecene (6e0 ).31 56% yield. Colorless oil.
isomer), 2.34-2.42 (1H, m), 2.45-2.51 (1H, m, for minor isomer- IR (CHCl3) υ 2935, 1520, 1336, 1218 cm-1; 1H NMR (270 MHz,
), 4.73 (1H, dt, J=9.6, 2.7 Hz, for minor isomer), 4.80 (1H, ddd, CDCl3) δ 1.21-1.48 (12H, m), 1.61-1.67 (4H, m), 2.27 (2H, dd,
J=10.3, 6.9, 2.8 Hz), 4.91-4.94 (1H, m, for minor isomer), 4.98 J=15.8, 7.6 Hz), 2.66 (2H, t, J=6.6 Hz), 7.10 (1H, t, J=8.6 Hz);
(1H, ddd, J=10.7, 10.3, 2.1 Hz); 13C NMR (150 MHz, CDCl3) δ 13
C NMR (150 MHz, CDCl3) δ 21.9, 22.7, 23.2, 23.4, 24.6, 24.7,
24.48 (minor), 24.51, 24.7, 24.9 (minor), 25.0 (minor), 25.3, 26.5 24.9, 25.4, 25.7, 136.9, 152.0; HRFABMS calcd for C12H22NO2
(minor), 27.0, 27.2 (minor), 31.5, 32.1, 34.6 (minor), 52.5, 53.3 (Mþ þ H) 212.1651, found 212.1655.
(minor), 88.3 (minor), 94.6; HRFABMS calcd for C8H15BrNO2
(Mþ þ H) 236.0286, found 236.0279. Acknowledgment. This research was supported by a Grant-
1-Iodo-2-nitrocyclooctane (12d). 81% yield (as a separable in-Aid for Scientific Research from the Ministry of Education,
mixture of two isomers, 85:15). Major isomer: colorless oil. IR Culture, Sports, Science and Technology of Japan.
(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), Supporting Information Available: 1H and 13C NMR spectra
1.93-1.97 (1H, m), 2.05-2.18 (2H, m), 4.30 (1H, ddd, J=9.6, for all isolated products. This material is available free of charge via
6.2, 3.4 Hz), 5.38 (1H, dt, J=11.7, 2.2 Hz); 13C NMR (150 MHz, the Internet at [Link]
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 Note Added after ASAP Publication. Several errors in the
284.0160. Minor isomer: colorless oil. IR (CHCl3) υ 1558, 1377, Results and Discussion sections, Tables 2 and 5, and the caption
1220 cm-1; 1H NMR (600 MHz, CDCl3) δ 1.30-1.33 (1H, m), of Scheme 6 appeared in the versions that was published on
1.41-1.49 (1H, m), 1.60-1.67 (2H, m), 1.79-1.83 (4H, m), 11/10/2010. These were fixed when the paper was republished to
2.00-2.31 (1H, m), 2.10-2.20 (2H, m), 2.21-2.29 (1H, m), 4.89 the Web on 11/29/2010.
(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, (31) Ballini, R.; Palestini, C. Tetrahedron Lett. 1994, 35, 5731.

8132 J. Org. Chem. Vol. 75, No. 23, 2010