Palladium-catalyzed monoarylation of nitroalkanes

Article abstract of DOI:10.1021/jo010953v

A general protocol for the Pd-catalyzed-arylation of nitroalkanes is described. Substituted aryl bromides as well as aryl chlorides can be coupled efficiently with a variety of nitroalkanes under mild conditions to selectively yield the monoarylated products. This method tolerates a number of functional groups including ketones, esters, and olefins. Notably, the arylation of nitroalkanes can be effected chemoselectively over ketone and ester arylation.

Full text of DOI:10.1021/jo010953v

106
J . Org. Chem. 2002, 67, 106-111
P a lla d iu m -Ca ta lyzed Mon oa r yla tion of Nitr oa lk a n es
Erasmus M. Vogl† and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
sbuchwal@mit.edu
Received September 26, 2001
A general protocol for the Pd-catalyzed-arylation of nitroalkanes is described. Substituted aryl
bromides as well as aryl chlorides can be coupled efficiently with a variety of nitroalkanes under
mild conditions to selectively yield the monoarylated products. This method tolerates a number of
functional groups including ketones, esters, and olefins. Notably, the arylation of nitroalkanes can
be effected chemoselectively over ketone and ester arylation.
In tr od u ction
the biaryl ligands screened, 1 proved most effective,
although commercially available 2-di-tert-butylphosphi-
nobiphenyl generally gave satisfactory yields.5 In addi-
tion, we found that catalysts based on Pd2dba3 were more
active than catalysts based on Pd(OAc)2; presumably the
in situ reduction of the Pd(II) is inefficient under the
reaction conditions.
Several procedures for the Pd-catalyzed R-arylation of
ketones with a variety of aryl bromides, chlorides, and
triflates have recently been reported.1 These methods
have also been extended to other carbonyl substrates
including esters and amides.2 Additionally, we have
reported that catalysts based on 2-di-tert-butylphosphino-
2′-methylbiphenyl (1) and Pd(OAc)2 were particularly
efficient in the arylation of malonate esters, 1,3-dike-
tones, and in isolated cases, nitroalkanes.1e Herein, we
report in full the protocol for the arylation of nitroal-
kanes.3 This method allows for the selective monoaryla-
tion of nitroalkanes under mild conditions that tolerate
several functional groups including ethers, esters, ke-
tones, and olefins. Additionally, the arylation of nitroal-
kanes can be performed chemoselectively in the presence
of enolizable esters and ketones.4
As shown in Table 1, a variety of aryl bromides and
aryl chlorides can be efficiently coupled with nitroal-
kanes. Electron-withdrawing aryl bromides react cleanly
to furnish the desired nitroalkanes in good yield. For
example, 4-bromomethylbenzoate reacts with nitroethane
to furnished the desired product in 85% yield (entry 6).
Electronically neutral aryl bromides are also good sub-
strates for the reaction; 4-tert-butylbromobenzene is
efficiently coupled with nitroethane and nitropropane to
give the arylated products in 95 and 81% yields, respec-
tively (entries 3, 11). Although the reaction is more
practical when performed at elevated temperatures (45-
60 °C), the arylation also proceeds at room temperature,
albeit very slowly (entry 11). Aryl bromide substrates
with electron-donating groups (e.g., OMe) in the ortho
or para position of the aryl bromide are transformed in
high yield as well (entries 5, 12). Additionally, aryl
chlorides can be used with this catalyst system; electron-
withdrawing substituents on the aryl chloride allow for
an efficient transformation (entries 10, 14, 16). In addi-
tion, the reaction of m-chloroanisole with nitropropane
afforded the desired nitroalkane in 68% isolated yield
(entry 13). Double arylation of the nitroalkane was not
observed in any of the examples studied. In fact, subject-
ing phenyl nitromethane to the arylation protocol re-
sulted in no reaction. Reactions with nitromethane
yielded the desired arylated compounds; however, yields
were low and multiple products were observed.
Resu lts a n d Discu ssion
Our initial studies were performed using bromoben-
zene or 4-chlorotoluene and nitroethane as coupling
partners. After screening a variety of reaction conditions,
we found that Cs2CO3 was effective as base, although K3-
PO4 was sometimes suitable. Stronger bases such as
metal alkoxides were not as effective. It was readily
apparent that catalysts based on di-tert-butyl-substituted
phosphine ligands yielded significant amounts of prod-
ucts while the dicyclohexyl- or diphenyl-substituted
ligands did not promote nitroalkane arylation at all. Of
† Present address: Bayer AG, Central Research-Synthesis Re-
search, 51368 Leverkusen, Germany.
(1) (a) Palucki, M.; Buchwald, S. L. J . Am. Chem. Soc. 1997, 119,
11108. (b) Hamann, B. C.; Hartwig, J . F. J . Am. Chem. Soc. 1997, 119,
12382. (c) Ahman, J .; Wolfe, J . P.; Troutman, M. V.; Palucki, M.;
Buchwald, S. L. J . Am. Chem. Soc. 1998, 120, 1918. (d) Kawatsura,
M.; Hartwig, J . F. J . Am. Chem. Soc. 1999, 121, 1473. (e) Fox, J . M.;
Huang, X. H.; Chieffi, A.; Buchwald, S. L. J . Am. Chem. Soc. 2000,
122, 1360 and references therein.
(2) (a) Shaughnessy, K. H.; Hamann, B. C.; Hartwig, J . F. J . Org.
Chem. 1998, 63, 6546. (b) Moradi, W. A.; Buchwald, S. L J . Am. Chem.
Soc. 2001, 123, 7996. (c) Lee, S.; Beare, N. A.; Hartwig, J . F. J . Am.
Chem. Soc. 2001, 123, 8410.
(3) The Pd-catalyzed intramolecular R-arylation of nitroalkanes has
been reported: Muratake, H.; Nakai, H. Tetrahedron Lett. 1999, 40,
2355-2358.
(4) For other methods for the R-arylation of nitroalkanes, see: (a)
Aleksandrowicz, P.; Piotrowska, H.; Sas, W. Tetrahedron 1982, 38,
1321-1327. (b) Kozyrod, R. P.; Pinhey, J . T. Tetrahedron Lett. 1981,
22, 783-784. (c) Kornblum, N.; Taylor, H. J . J . Org. Chem. 1963, 28,
1424-1425. (d) Park, K. P.; Clapp, L. B. J . Org. Chem. 1964, 29, 2108-
2109.
The arylation of carbonyl-derived enolates has been
demonstrated to be an efficient process.1,2 Moreover, the
Heck arylation of terminal alkenes is has proven to be
one of the most powerful transformations in modern
organic synthesis.6 We queried whether coupling partners
containing enolizable ketones and esters, as well as
terminal olefins, would be suitable in the nitroalkane
arylation reaction. In the cases studied, we found that
the desired arylation R to the nitro group was observed;
no ketone arylation products were detected (Table 2,
(5) For the synthesis of these ligands, see: Tomori, H.; Fox, J . M.;
Buchwald, S. L. J . Org. Chem. 2000, 65, 5334-5341.
10.1021/jo010953v CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/13/2001

Pd-Catalyzed Monoarylation of Nitroalkanes
J . Org. Chem., Vol. 67, No. 1, 2002 107
Ta ble 1. P d -Ca ta lyzed r-Ar yla tion of Nitr oa lk a n es
a
b
Isolated yields are an average of two runs. All compounds >95% pure as determined by 1H NMR, GC, or combustion analysis.
4
equiv of nitroalkane and 2.2 equiv of base were used. c Reaction performed for 96 h. 1 equiv of nitroalkane and 1.1 equiv of base was
d
used.

108 J . Org. Chem., Vol. 67, No. 1, 2002
Ta ble 2. Ch em oselective P d -Ca ta lyzed r-Ar yla tion of Nitr oa lk a n es
Vogl and Buchwald
a
Isolated yields are an average of two runs. All compounds >95% pure as determined by 1H NMR, GC, or combustion analysis. 1 equiv
b
of nitroalkane and 1.1 equiv of base were used. 1.5 equiv of nitroalkane and 1.1 equiv of base were used.
crolabs, Inc, Norcross GA. Dimethoxyethane and dodecane
entries 1-3). This chemoselective arylation could also be
effected with an activated aryl chloride (entry 4). It
should be noted that di-tert-butylphosphino-derived ligands
such as 1 are not efficient supporting ligands for ketone
arylation.1e Olefins were also tolerated under the reaction
conditions; no Heck-type addition across the olefin was
observed, and the desired nitroalkanes were isolated in
moderate yield (entries 5, 6).
(used as internal standard) were purchased in small SureSeal
bottles from Aldrich Chemical Co. and used as received. Tris-
(dibenzylideneacetone)dipalladium was purchased from Strem
Chemical, Inc. Sodium tert-butoxide (NaOt-Bu), nitroethane,
1-nitropropane, 1-nitrohexane, and 6-nitro-1-hexene were
purchased from Aldrich Chemical Co. K3PO4 was purchased
from Fluka. Cs2CO3 was purchased from Chemetall. Moisture
sensitive bases were stored under nitrogen in a Vacuum
Atmospheres glovebox, and small samples were taken out,
stored in a desiccator on the bench, and replaced every 2
weeks. All materials were weighed in the air. 2-Di-tert-
butylphosphino-2′-methylbiphenyl (1),5 2-phenylnitroethane,7
4-nitrobutyric acid methyl ester,8 and tert-butyl-3-bromoben-
zoate9 were synthesized as described the literature. IR spectra
were obtained by placing neat samples directly on the DiComp
probe of an ASI REACTIR in situ IR instrument. Yields in
tables refer to isolated yields (average of two runs) of com-
pounds estimated to be g95% pure as determined by 1H NMR,
GC, and combustion analysis. Melting points were taken with
a MEL-TEMP apparatus. Compounds that are described more
than once in the same table were completely characterized
once. Other samples of these compounds were characterized
by comparing their 1H and 13C NMR spectra to those of the
fully characterized product, and their purity was confirmed
by GC analysis. Compounds previously described in the
Con clu sion s
In summary, we have developed a general protocol for
the Pd-catalyzed monoarylation of nitroalkanes. Using
a catalyst based on 1 and Pd2dba3, this transformation
may be carried out under mild conditions. The nitroal-
kane can be chemoselectively arylated in the presence
of enolizable ketone and ester groups, and an olefin-
substituted nitroalkane was also tolerated under the
reaction conditions.
Exp er im en ta l Section
Gen er a l. Reactions were carried out in a dried resealable
Schlenck tube purchased from Kontes. Flash chromatography
was performed on Silicycle ultrapure silica gel (230-400
mesh). Elemental analyses were performed by Atlantic Mi-
1
literature were characterized only by H and 13C NMR.
Gen er a l R ea ct ion P r oced u r e for t h e Ar yla t ion of
Nitr oa lk a n es. Meth od A. A dried resealable Schlenk tube
(6) For reviews on the Heck arylation, see: (a) Brase, S.; deMeijere,
A. In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J ., Eds.; Wiley-VCH: New York, 1998; pp 99-166. (b) Beletskaya,
I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009-3066.
(7) Gilbert, K. E.; Borden, W. Y. J . Org. Chem. 1979, 44, 659.
(8) Chasar, D. W. Synthesis 1982, 841.
(9) Taylor, E. C.; Ray, P. S. J . Org. Chem. 1988, 53, 35.

Pd-Catalyzed Monoarylation of Nitroalkanes
J . Org. Chem., Vol. 67, No. 1, 2002 109
containing a stir bar was charged with 1.0 mmol of the aryl
bromide or aryl chloride, the appropriate amount of Pd2(dba)3
and 2-(di-tert-butylphosphinyl)-2′-methylbiphenyl (1) as indi-
cated, and 1.2 equiv of Cs2CO3. The reaction vessel was capped
with a rubber septum, evacuated, and backfilled with argon
three times, and dimethoxyethane (5 mL) and 1.0-2.0 equiv
of the appropriate nitroalkane were added via syringe under
argon. After the mixture was stirred vigorously for 1 min at
room temperature, the Schlenk tube was sealed and placed
in a preheated oil bath at the given temperature for the time
indicated. After the reaction was complete, as judged by either
GC or TLC analysis, the reaction mixture was allowed to cool
to ambient temperature. The unpurified mixture was quenched
with a solution of sat. aqueous NH4Cl (2 mL, two times), the
aqueous phase was extracted with ether (2 mL), and the
combined organic phases were washed with brine. The solvent
was then removed, and the remaining oil was purified by flash
column chromatography.
Meth od B. A dried resealable Schlenk tube containing a
stir bar was charged with the appropriate amount of Pd2(dba)3
and 2-(di-tert-butylphosphinyl)-2′-methylbiphenyl (1) as indi-
cated and 1.2 equiv of Cs2CO3. The reaction vessel was capped
with a rubber septum, evacuated, and backfilled with argon
three times, and 1.0 mmol of the aryl bromide or aryl chloride,
dimethoxyethane (5 mL), and 1.0-2.0 equiv of the appropriate
nitroalkane were added sequentially via syringe under argon.
The mixture was stirred vigorously for 1 min at room tem-
3H), 5.80 (m, 1H), 2.01 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ:
133.9, 133.2, 133.0, 129.2, 128.5, 127.9, 127.5, 127.3, 127.0,
124.3, 86.5, 19.7 ppm; IR (neat, cm-1) ν: 3060, 2977, 2869,
1549, 1385, 1355, 1281, 1115, 824, 785, 745, 697. Anal. Calcd
for C12H11NO2: C, 71.63; H, 5.51. Found: C, 71.73; H, 5.46.
4-(1-Nitr oeth yl)m eth oxyben zen e (Ta ble 1, en tr y 5).
The reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:20) yielded the known compound11 as an oil (0.170
g, 0.94 mmol, 94%). 1H NMR (CDCl3, 300 MHz) δ: 7.41 (m,
2H), 6.92 (m, 2H), 5.58 (q, 1H, J ) 6.9 Hz), 3.82 (s, 3H), 1.88
(d, 3H, J ) 6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ: 160.8, 129.1,
127.8, 114.4, 85.9, 55.5, 19.5 ppm.
4-(1-Nitr oeth yl)ben zoic Acid Meth yl Ester (Ta ble 1,
en tr y 6 a n d en tr y 10). The reaction was carried out according
to general procedure, method A. Flash column chromatography
(toluene 100%) yielded the known compound11 as a pale yellow
oil which solidified to a crystalline solid; mp 49 °C (0.178 g,
0.85 mmol, 85%). 1H NMR (CDCl3, 300 MHz) δ: 8.08 (m, 2H),
7.54 (m, 2H), 5.67 (q, 1H, J ) 6.9 Hz), 3.94 (s, 3H), 1.93 (d,
3H, J ) 6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ: 166.5, 140.1,
131.6, 130.5, 127.7, 85.9, 52.6, 19.7 ppm.
3-(1-Nitr oeth yl)ben zoic Acid ter t-Bu tyl Ester (Ta ble 1,
en tr y 7). The reaction was carried out according to general
procedure, method B. Flash column chromatography (diethyl
ether:hexanes 1:8) yielded a colorless oil (0.206 g, 0.82 mmol,
1
82%). H NMR (CDCl3, 300 MHz) δ: 8.07-8.02 (m, 2H), 7.64
(m, 1H), 7.48 (m, 1H), 5.66 (q, 1H, J ) 6.9 Hz), 1.93 (d, 3H, J
) 6.9 Hz), 1.61 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ: 165.1,
135.8, 133.1, 131.4, 131.0, 129.2, 128.8, 85.9, 81.9, 28.4, 19.6
ppm; IR (neat, cm-1) ν: 2979, 2935, 1711, 1551, 1385, 1368,
1297, 1256, 1160, 1115, 849, 753, 731,689; Anal. Calcd for
perature, the Schlenk tube was sealed and placed in
a
preheated oil bath at the given temperature for the time
indicated. After the reaction was complete, as judged by either
GC or TLC analysis, the reaction mixture was allowed to cool
to ambient temperature. The unpurified mixture was quenched
with a solution of sat. aqueous NH4Cl (2 mL, two times), the
aqueous phase was extracted with ether (2 mL), and the
combined organic phases were washed with brine. Then the
solvent was removed, and the remaining oil was purified by
flash column chromatography.
C
13H17NO4: C, 62.14; H, 6.82. Found: C, 62.22; H, 6.97.
3-(1-Nitr oeth yl)d im eth yla m in oben zen e (Ta ble 1, en tr y
8). The reaction was carried out according to general proce-
dure, Method B. Flash column chromatography (diethyl ether:
hexanes 1:20 to 1:10) yielded a yellow oil (0.190 g, 0.98 mmol,
98%). 1H NMR (CDCl3, 300 MHz) δ: 7.29-7.23 (m, 1H), 6.80-
6.72 (m, 3H), 5.57 (q, 1H, J ) 6.9 Hz), 2.98 (s, 6H), 1.89 (d,
3H, J ) 6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ: 150.9, 136.7,
(1-Nitr oeth yl)ben zen e (Ta ble 1, en tr y 1). The reaction
was carried out according to general procedure, method B.
Flash column chromatography (diethyl ether:hexanes 1:20)
yielded the known compound10,11 as a volatile (removal of
solvent by a stream of air) colorless oil (0.136 g, 0.90 mmol,
129.8, 115.0, 113.6, 111.0, 86.9, 40.6, 19.7 ppm; IR (neat, cm-1
)
ν: 2989, 2894, 2809, 1603, 1546, 1503, 1441, 1383, 1358, 1231,
1063, 994, 961, 851, 756, 702, 691. Anal. Calcd for
1
90%). H NMR (CDCl3, 300 MHz) δ: 7.48-7.40 (m, 5H), 5.62
(q, 1H, J ) 6.9 Hz), 1.89 (d, 3H, J ) 6.9 Hz); 13C NMR (CDCl3,
75 MHz) δ: 135.7, 129.9, 129.1, 127.5, 86.3, 19.5 ppm.
C
10H14N2O2: C, 61.84; H, 7.27. Found: C, 61.94; H, 7.33.
1,4-Bis(1-n itr oeth yl)ben zen e (Ta ble 1, en tr y 9). The
reaction was carried out according to general procedure,
method A (but on a 0.5 mmol scale). 4-Dibromobenzene was
purified by column chromatography (SiO2, 100% hexanes) prior
to use. Flash column chromatography (diethyl ether:hexanes
1:4 to 1:2) yielded a crystalline solid (presumably as a mixture
of isomers); mp 63 °C (0.069 g, 0.31 mmol, 62%). 1H NMR
(CDCl3, 300 MHz) δ: 7.52 (s, 4H), 5.64 (q, 2H, J ) 6.6 Hz),
1.91 (d, 6H, J ) 6.9 Hz); 13C NMR (CDCl3, 75 MHz) δ: 137.2,
128.3, 85.8, 19.6 ppm; IR (neat, cm-1) ν: 2995, 2944, 2900,
1683, 1546, 1385, 1356, 1295, 1063, 1000, 864, 847, 697. Anal.
Calcd for C10H12N2O4: C, 53.57; H, 5.39. Found: C, 53.82; H,
5.48.
3-(1-Nit r oet h yl)et h ylb en zen e (Ta b le 1, en t r y 2). The
reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:20) yielded a colorless oil (0.170 g, 0.95 mmol, 95%).
1H NMR (CDCl3, 300 MHz) δ: 7.36-7.20 (m, 4H), 5.60 (q, 1H,
J ) 7.2 Hz), 2.67 (q, 2H, J ) 7.6 Hz), 1.89 (d, 3H, J ) 7.2 Hz),
1.25 (t, 3H, J ) 7.6 Hz); 13C NMR (CDCl3, 75 MHz) δ: 145.4,
135.8, 129.5, 129.2, 127.1, 124.8, 86.5, 28.9, 19.7, 15.6, ppm;
IR (neat, cm-1) ν: 2968, 2935, 2875, 1549, 1453, 1385, 1360,
1165, 1065, 893, 853, 807, 712, 699. Anal. Calcd for C10H13
NO2: C, 67.02; H, 7.31. Found: C, 66.85; H, 7.43.
-
4-ter t-Bu tyl-(1-n itr oeth yl)ben zen e (Ta ble 1, en tr y 3).
The reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:20) yielded the known compound11 as a colorless oil
(0.197 g, 0.95 mmol, 95%). 1H NMR (CDCl3, 300 MHz) δ: 7.41
(m, 4H), 5.61 (q, 1H, J ) 7.2 Hz), 1.89 (d, 3H, J ) 7.2 Hz),
1.32 (s, 9H); 13C NMR (CDCl3, 75 MHz) δ: 153.2, 132.8, 127.4,
126.2, 86.2, 34.9, 31.5, 19.6 ppm.
4-ter t-Bu t yl-(1-n it r op r op yl)b en zen e (Ta b le 1, en t r y
11). The reaction was carried out according to general proce-
dure, method B. Flash column chromatography (diethyl ether:
hexanes 1:50) yielded a colorless oil (0.179 g, 0.81 mmol, 81%).
1H NMR (CDCl3, 300 MHz) δ: 7.42 (m, 4H), 5.37 (dd, 1H, J )
9.0 Hz, 6.3 Hz), 2.52 (m, 1H), 2.11 (m, 1H), 1.33 (s, 9H), 1.00
(t, 3H, 7.5 Hz); 13C NMR (CDCl3, 75 MHz) δ: 153.1, 131.7,
127.6, 126.1, 93.0, 34.9, 31.4, 27.4, 10.9 ppm; IR (neat, cm-1
)
2-(1-Nitr oeth yl)n a p h th a len e (Ta ble 1, en tr y 4). The
reaction was carried out according to general procedure,
method A. Vigorous stirring is important due to the reaction
heterogeneity. Additionally, 10 mL of DME were used. Flash
column chromatography (diethyl ether:hexanes 1:10) yielded
a crystalline solid; mp 51 °C (0.193 g, 0.96 mmol, 96%). 1H
NMR (CDCl3, 300 MHz) δ: 7.94-7.84 (m, 4H), 7.60-7.53 (m,
ν: 2966, 2906, 2873, 1549, 1461, 1364, 1270, 1108, 1019, 805,
672. Anal. Calcd for C13H19NO2: C, 70.56; H, 8.65. Found: C,
70.64; H, 8.78.
2-Meth oxy-(1-n itr op r op yl)ben zen e (Ta ble 1, en tr y 12).
The reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:10) yielded a colorless oil (0.185 g, 0.95 mmol, 95%).
1H NMR (CDCl3, 300 MHz) δ: 7.45 (m, 1H), 7.37 (m, 1H), 7.02
(m, 1H), 6.93 (m, 1H), 5.91 (dd, 1H, J ) 8.4 Hz, 6.6 Hz), 3.86
(s, 3H), 2.48 (m, 1H), 2.11 (m, 1H), 1.02 (d, 3H, J ) 7.2 Hz);
(10) Bose, D. S.; Vanajatha, G. Synth. Commun. 1998, 28, 4531.
(11) Baruah, A.; Kalita, B.; Barua, N. C. Synlett 2000, 1064.

110 J . Org. Chem., Vol. 67, No. 1, 2002
Vogl and Buchwald
13C NMR (CDCl3, 75 MHz) δ: 157.2, 130.9, 127.7, 123.2, 121.0,
111.0, 85.8, 55.8, 26.7, 11.0 ppm; IR (neat, cm-1) ν: 2975, 2941,
2883, 2842, 1603, 1547, 1493, 1465, 1368, 1248, 1027, 812, 753.
Anal. Calcd for C10H13NO3: C, 61.53; H, 6.71. Found: C, 61.76;
H, 6.76.
3-Meth oxy-(1-n itr op r op yl)ben zen e (Ta ble 1, en tr y 13).
The reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:8) yielded a colorless oil (0.133 g, 0.68 mmol, 68%).
1H NMR (CDCl3, 300 MHz) δ: 7.31 (t, 1H, J ) 8.1 Hz), 7.05-
6.91 (m, 3H), 5.33 (m, 1H), 3.82 (s, 3H), 2.49 (m, 1H), 2.10 (m,
1H), 0.98 (t, 3H, 7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ: 160.1,
136.0, 130.2, 120.2, 115.3, 113.5, 93.1, 55.5, 27.5, 10.8 ppm;
IR (neat, cm-1) ν: 2975, 2941, 2840, 1602, 1547, 1492, 1457,
1368, 1264, 1162, 1046, 787, 689. Anal. Calcd for C10H13NO3:
C, 61.53; H, 6.71. Found: C, 61.55; H, 6.81.
2964, 2906, 2869, 1551, 1364, 1270, 1111, 1019, 855, 745, 699.
Anal. Calcd for C18H21NO2: C, 76.30; H, 7.47. Found: C, 76.16;
H, 7.44.
1-(4-Meth oxy-p h en yl)-2-p h en yln itr oeth a n e (Ta ble 1,
en tr y 19). The reaction was carried out according to general
procedure, method B. Flash column chromatography (diethyl
ether:hexanes 1:20) yielded a crystalline solid; mp 79 °C (0.129
g, 0.50 mmol, 50%). 1H NMR (CDCl3, 300 MHz) δ: 7.45 (m,
2H), 7.30-7.15 (m, 5H), 6.93-6.90 (m, 2H), 5.66 (dd, 1H, J )
6.0 Hz, 9.3 Hz), 3.82 (s, 3H), 3.77 (dd, 1H, J ) 9.3 Hz, 14.4
Hz), 3.33 (dd, 1H, J ) 6.0 Hz, 14.4 Hz); 13C NMR (CDCl3, 75
MHz) δ: 160.9, 135.7, 129.4, 129.1, 129.0, 127.5, 126.5, 114.5,
92.3, 55.5, 40.2 ppm; IR (neat, cm-1) ν: 3012, 2904, 2834, 1609,
1546, 1513, 1455, 1366, 1254, 1177, 1028, 836, 735, 699. Anal.
Calcd for C15H15NO3: C, 70.02; H, 5.88. Found: C, 70.11; H,
5.80.
3-Meth oxyca r bon yl-(1-n itr op r op yl)ben zen e (Ta ble 1,
en tr y 14). The reaction was carried out according to general
procedure, method B. Flash column chromatography (diethyl
ether:hexanes 1:8 to 1:5) yielded a pale yellow oil (0.145 g, 0.65
4-Acetyl-(1-n itr op r op yl)ben zen e (Ta ble 2, en tr y 1). The
reaction was carried out according to general procedure,
method A. Flash column chromatography (diethyl ether:
hexanes 1:5) yielded a pale yellow oil which solidifies upon
standing; mp 39 °C (0.166 g, 0.80 mmol, 80%). 1H NMR (CDCl3,
300 MHz) δ: 7.98 (d, 2H, J ) 6.8 Hz), 7.56 (d, 2H, J ) 6.8
Hz), 5.42 (dd, 1H, J ) 8.7 Hz, 6.6 Hz), 2.61 (s, 3H), 2.51 (m,
1H), 2.12 (m, 1H), 0.99 (t, 3H, J ) 7.2 Hz); 13C NMR (CDCl3,
75 MHz) δ: 197.5, 139.1, 138.2, 129.1, 128.2, 92.6, 27.6, 26.9,
10.7 ppm; IR (neat, cm-1) ν: 2977, 2941, 2883, 1684, 1609,
1547, 1416, 1360, 1266, 959, 805. Anal. Calcd for C11H13NO3:
C, 63.76; H, 6.32. Found: C, 64.03; H, 6.40.
1
mmol, 65%). H NMR (CDCl3, 300 MHz) δ: 8.14 (s, 1H), 8.09
(d, 1H, J ) 7.5 Hz), 7.68 (d, 1H, J ) 7.8 Hz) 7.50 (t, 1H, J )
7.8 Hz), 5.43 (dd, 1H, J ) 8.4 Hz, 6.3 Hz), 3.94 (s, 3H), 2.53
(m, 1H), 2.16 (m, 1H), 1.00 (t, 3H, 7.5 Hz); 13C NMR (CDCl3,
75 MHz) δ: 166.5, 135.0, 132.3, 131.2, 131.1, 129.4, 129.2, 92.7,
52.6, 27.5, 10.8 ppm; IR (neat, cm-1) ν: 2977, 2954, 2883, 1721,
1549, 1434, 1368, 1285, 1200, 1109, 735, 691. Anal. Calcd for
C
11H13NO4: C, 59.19; H, 5.87. Found: C, 59.40; H, 5.86.
4-Meth oxyca r bon yl-(1-n itr op r op yl)ben zen e (Ta ble 1,
3-Acetyl-(1-n itr op r op yl)ben zen e (Ta ble 2, en tr y 2). The
reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:5) yielded a pale yellow oil (0.131 g, 0.63 mmol,
en tr y 15). The reaction was carried out according to general
procedure, method A. Flash column chromatography (diethyl
ether:hexanes 1:8) yielded a colorless oil (0.191 g, 0.86 mmol,
86%). 1H NMR (CDCl3, 300 MHz) δ: 8.08 (d, 2H, J ) 8.7),
7.55 (d, 2H, J ) 8.4 Hz), 5.42 (dd, 1H, J ) 9.0 Hz, 6.3 Hz),
3.93 (s, 3H), 2.53 (m, 1H), 2.15 (m, 1H), 1.00 (t, 3H, 7.5 Hz);
13C NMR (CDCl3, 75 MHz) δ: 166.5, 139.1, 131.7, 130.4, 128.0,
92.7, 52.6, 27.6, 10.8 ppm; IR (neat, cm-1) ν: 2977, 2956, 2885,
1721, 1549, 1436, 1368, 1279, 1185, 1113, 1021, 731. Anal.
Calcd for C11H13NO4: C, 59.19; H, 5.87. Found: C, 59.48; H,
5.95.
1
63%). H NMR (CDCl3, 300 MHz) δ: 8.05 (s, 1H), 8.00 (d, 1H,
J ) 7.8 Hz) 7.71 (d, 1H, J ) 7.8 Hz), 7.53 (t, 1H, J ) 7.8 Hz),
5.44 (dd, 1H, J ) 8.7 Hz, 6.3 Hz), 2.63 (s, 3H), 2.55 (m, 1H),
2.14 (m, 1H), 1.00 (t, 3H, 6.9 Hz); 13C NMR (CDCl3, 75 MHz)
δ: 197.5, 137.9, 135.2, 132.3, 129.9, 129.6, 127.8, 92.7, 27.6,
26.9, 10.8 ppm; IR (neat, cm-1) ν: 2977, 2941, 2883, 1686, 1547,
1360, 1272, 1189, 1084, 799, 764, 691; Anal. Calcd for C11H13
NO3: C, 63.76; H, 6.32. Found: C, 64.10; H, 6.38.
-
4-ter t-Bu tyl-(1-n itr oh exyl)ben zen e (Ta ble 1, en tr y 16).
The reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:100, the column was twice as long as for the other
separations, toluene:hexane 1:3 can be better if starting
material is left) yielded a colorless oil (0.242 g, 0.92 mmol,
92%). 1H NMR (CDCl3, 300 MHz) δ: 7.41 (s, 4H), 5.44 (dd,
1H, J ) 9.0 Hz, 6.3 Hz), 2.49 (m, 1H), 2.05 (m, 1H), 1.32 (s,
15H), 0.89 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ: 153.1, 131.9,
127.6, 126.1, 91.6, 34.9, 34.0, 31.4, 31.3, 26.0, 22.5, 14.1 ppm;
IR (neat, cm-1) ν: 2960, 2933, 2871, 1551, 1465, 1364, 1270,
1109, 828, 774. Anal. Calcd for C16H25NO2: C, 72.97; H, 9.57.
Found: C, 72.97; H, 9.59.
4-(Na p h th a len e-2-yl)-4-n itr obu tyr ic Acid Meth yl Ester
(Ta ble 2, en tr y 3). The reaction was carried out according to
general procedure, method A. Flash column chromatography
(diethyl ether:hexanes 1:3) yielded a viscous oil which solidified
1
upon storage; mp 37 °C (0.218 g, 0.80 mmol, 80%). H NMR
(CDCl3, 300 MHz) δ: 7.95-7.85 (m, 4H), 7.60-7.52 (m, 3H),
5.78 (m, 1H), 3.70 (s, 3H), 2.97-2.82 (m, 1H), 2.62-2.50 (m,
1H), 2.41 (m, 2H); 13C NMR (CDCl3, 75 MHz) δ: 172.5, 134.0,
133.1, 131.3, 129.4, 128.5, 128.2, 127.9, 127.4, 127.1, 124.2,
90.3, 52.2, 30.2, 29.0 ppm; IR (neat, cm-1) ν: 3058, 2954, 1735,
1549, 1511, 1437, 1360, 1200, 1177, 1129, 909, 861, 818, 749,
731. Anal. Calcd for C15H15NO4: C, 65.92; H, 5.53. Found: C,
65.98; H, 5.59.
4-(4-Meth oxy-p h en yl)-4-n itr obu tyr ic Acid Meth yl Es-
ter (Ta ble 2, en tr y 4). The reaction was carried out according
to general procedure, method B. Flash column chromatography
(diethyl ether:hexanes 1:3) yielded a yellow oil (0.179 g, 0.79
mmol, 71%). 1H NMR (CDCl3, 300 MHz) δ: 7.39 (m, 2H), 6.92
(m, 2H), 5.54 (m, 1H), 3.82 (s, 3H), 3.69 (s, 3H), 2.82-2.70 (m,
1H), 2.50-2.32 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ: 172.5,
161.0, 129.3, 126.1, 114.6, 89.7, 55.5, 52.1, 30.3, 28.9 ppm; IR
(neat, cm-1) ν: 2956, 2842, 1737, 1611, 1549, 1515, 1439, 1360,
1308, 1254, 1179, 1117, 1030, 913, 834, 733. Anal. Calcd for
2-[3-(1-n itr oh exyl)p h en yl]-[1,3]d ioxola n e (Ta ble 1, en -
tr y 17). The reaction was carried out according to general
procedure, method B. Flash column chromatography (diethyl
ether:hexanes 1:8) yielded a yellow oil (0.237 g, 0.85 mmol,
1
85%). H NMR (CDCl3, 300 MHz) δ: 7.60-7.40 (m, 4H), 5.82
(s, 1H), 5.47 (dd, 1H, J ) 9.0 Hz, 6.3 Hz), 4.17-4.03 (m, 4H),
2.50 (m, 1H), 2.05 (m, 1H), 1.33 (s, 6H), 0.88 (m, 3H); 13C NMR
(CDCl3, 75 MHz) δ: 139.0, 135.0, 129.3, 128.6, 128.2, 126.1,
103.3, 91.6, 65.6, 34.2, 31.3, 25.9, 22.5, 14.1 ppm; IR (neat,
cm-1) ν: 2958, 2931, 1549, 1364, 1165, 1079, 969, 700. Anal.
Calcd for C15H21NO4: C, 64.50; H, 7.58. Found: C, 64.59; H,
7.70.
C
12H15NO5: C, 56.91; H, 5.97. Found: C, 56.94; H, 5.90.
1-(4-ter t-Bu tyl-p h en yl)-2-p h en yln itr oeth a n e (Ta ble 1,
en tr y 18). The reaction was carried out according to general
procedure, method B. Flash column chromatography (diethyl
ether:hexanes 1:10; no starting material should be left prior
to purification) yielded a pale yellow oil (0.184 g, 0.65 mmol,
4-(3-Dim eth ylam in o-ph en yl)-4-n itr obu tyr ic Acid Meth -
yl Ester (Ta ble 2, en tr y 5). The reaction was carried out
according to general procedure, method B. Flash column
chromatography (diethyl ether:hexanes 1:3) yielded a yellow
1
oil (0.192 g, 0.72 mmol, 72%). H NMR (CDCl3, 300 MHz) δ:
1
65%). H NMR (CDCl3, 300 MHz) δ: 7.49-7.18 (m, 9H), 5.70
7.24 (m, 1H), 6.77-6.70 (m, 3H), 5.51 (dd, 1H, J ) 6.5 Hz, 8.6
Hz), 3.68 (s, 3H), 2.95 (s, 6H), 2.80-2.69 (m, 1H), 2.50-2.32
(m, 3H); 13C NMR (CDCl3, 75 MHz) δ: 172.6, 151.0, 135.0,
129.9, 115.2, 113.8, 111.2, 90.7, 52.1, 40.6, 30.3, 29.0 ppm; IR
(neat, cm-1) ν: 2954, 2894, 2811, 1737, 1603, 1547, 1503, 1439,
(dd, 1H, J ) 5.1 Hz, 9.9 Hz), 3.81 (dd, 1H, J ) 9.9 Hz, 14.5
Hz), 3.31 (dd, 1H, J ) 5.1 Hz, 14.5 Hz), 1.33 (s, 9H); 13C NMR
(CDCl3, 75 MHz) δ: 153.4, 135.9, 131.5, 129.1, 129.0, 127.6,
127.6, 126.2, 92.7, 40.2, 34.9, 31.4 ppm; IR (neat, cm-1) ν: 3033,

Pd-Catalyzed Monoarylation of Nitroalkanes
J . Org. Chem., Vol. 67, No. 1, 2002 111
1360, 1233, 1200, 1171, 1063, 996, 849, 764. Anal. Calcd for
ν: 2954, 1723, 1551, 1436, 1279, 1185, 1111, 917, 731; Anal.
Calcd for C14H17NO4: C, 63.86; H, 6.51. Found: C, 63.65; H,
6.53.
C
13H18N2O4: C, 58.63; H, 6.81. Found: C, 58.93; H, 6.80.
4-(4-Meth oxycar bon ylph en yl)-4-n itr obu tyr ic Acid Meth -
yl Ester (Ta ble 2, en tr y 6). The reaction was carried out
according to general procedure, method A. Flash column
chromatography (diethyl ether:hexanes 1:3) yielded a pale
yellow oil (0.187 g, 0.67 mmol, 67%). 1H NMR (CDCl3, 300
MHz) δ: 8.06 (d, 2H, J ) 8.3 Hz), 7.52 (d, 2H, J ) 8.3 Hz),
5.65 (m, 1H), 3.91 (s, 3H), 3.67 (s, 3H), 2.85-2.70 (m, 1H),
2.50-2.32 (m, 3H); 13C NMR (CDCl3, 75 MHz) δ: 172.3, 166.3,
138.5, 131.8, 130.5, 127.9, 89.6, 52.6, 52.2, 30.0, 29.0 ppm; IR
(neat, cm-1) ν: 3002, 2956, 2448, 1725, 1613, 1551, 1437, 1360,
1279, 1185, 1111, 1021, 731. Anal. Calcd for C13H15NO6: C,
55.51; H, 5.38. Found: C, 55.47; H, 5.53.
6-(4-Acetylp h en yl)-6-n itr o-1-h exen e (Ta ble 2, en tr y 8).
The reaction was carried out according to general procedure,
method B. Flash column chromatography (diethyl ether:
hexanes 1:5) yielded a pale yellow oil (0.158 g, 0.64 mmol,
1
64%). H NMR (CDCl3, 300 MHz) δ: 7.97 (d, 2H, J ) 8.1 Hz),
7.55 (d, 2H, J ) 8.4 Hz), 5.70 (m, 1H), 5.50 (dd, 1H, J ) 8.4
Hz, 6.3 Hz), 5.06-4.97 (m, 2H), 2.60 (s, 3H), 2.50 (m, 1H), 2.11
(m, 3H), 1.40 (m 2H); 13C NMR (CDCl3, 75 MHz) δ: 197.5,
139.2, 138.3, 137.3, 129.1, 128.2, 116.0, 91.0, 33.5, 33.0, 26.9,
25.3 ppm; IR (neat, cm-1) ν: 2933, 1686, 1609, 1549, 1360,
1266, 917, 834, 778. Anal. Calcd for C14H17NO3: C, 68.00; H,
6.93. Found: C, 68.16; H, 6.97.
6-(4-Meth oxyca r bon ylp h en yl)-6-n itr o-1-h exen e (Ta ble
2, en tr y 7). The reaction was carried out according to general
procedure, method A. Flash column chromatography (diethyl
ether:hexanes 1:15) yielded a colorless oil (0.176 g, 0.67 mmol,
67%, some mixed fractions had to be purified by prep. TLC
otherwise the yield is slightly lower). 1H NMR (CDCl3, 300
MHz) δ: 8.08 (d, 2H, J ) 8.4 Hz), 7.55 (d, 2H, J ) 8.1 Hz),
5.75 (m, 1H), 5.50 (dd, 1H, J ) 8.7 Hz, 6.3 Hz), 5.07-4.99 (m,
Ack n ow led gm en t. We gratefully acknowledge the
National Institutes of Health (GM 46059) for funding
as well as Merck and Pfizer for unrestricted support.
We are also grateful to Prof. H. Hugl and Bayer AG for
financial support for E.M.V. We thank Dr. Alex R. Muci
for help with this manuscript.
2H), 3.94 (s, 3H), 2.50 (m, 1H), 2.12 (m, 3H), 1.42 (m 2H); 13
NMR (CDCl3, 75 MHz) δ: 166.5, 139.1, 137.4, 131.7, 130.5,
128.0, 116.0, 91.1, 52.6, 33.5, 33.1, 25.3 ppm; IR (neat, cm-1
C
)
J O010953V