Mono-deoxygenation of nitroalkanes, nitrones, and heterocyclic N-oxides by hexamethyldisilane through 1,2-elimination: Concept of 'counterattack reagent'

Article abstract of DOI:10.1021/jo981054i

Transformation of secondary nitroalkanes to ketoximes was achieved in 40-73% yields by treatment of the corresponding nitronate anions with hexamethyldisilane. In this new mono-deoxygenation process, hexamethyldisilane acted as a 'counterattack reagent'. The conversion of nitrones to imines was also achieved in 82-88% yields by use of trimethylsilyllithium. Similarly, heterocyclic N-oxides were converted to the corresponding N-heterocycles in 73-86% yields. These deoxygenation processes presumably involve a 1,2-elimination.

Full text of DOI:10.1021/jo981054i

J . Org. Chem. 1999, 64, 2211-2218
2211
Mon o-d eoxygen a tion of Nitr oa lk a n es, Nitr on es, a n d Heter ocyclic
N-Oxid es by Hexa m eth yld isila n e th r ou gh 1,2-Elim in a tion :
Con cep t of “Cou n ter a tta ck Rea gen t”
J ih Ru Hwu,*,†,‡ Wen Nan Tseng, Himatkumar V. Patel, Fong Fuh Wong, Den-Nan Horng,
†
†
†
§
¶
¶
Ben Ruey Liaw, and Lung Ching Lin
Organosilicon and Synthesis Laboratory, Department of Chemistry, National Tsing Hua University,
Hsinchu, Taiwan 30043, Republic of China, Institute of Chemistry, Academia Sinica, Nankang,
Taipei, Taiwan 11529, Republic of China, Department of Physics and Chemistry, Chinese Military
Academy, P.O. Box 90602-6, Feng-shan, Taiwan, Republic of China, and Department of Chemistry,
National Taiwan University, Taipei, Taiwan, Republic of China
Received J une 2, 1998
Transformation of secondary nitroalkanes to ketoximes was achieved in 40-73% yields by treatment
of the corresponding nitronate anions with hexamethyldisilane. In this new mono-deoxygenation
process, hexamethyldisilane acted as a “counterattack reagent”. The conversion of nitrones to imines
was also achieved in 82-88% yields by use of trimethylsilyllithium. Similarly, heterocyclic N-oxides
were converted to the corresponding N-heterocycles in 73-86% yields. These deoxygenation
processes presumably involve a 1,2-elimination.
In tr od u ction
elimination of R-trimethylsilyl N-oxide. These findings
prompted us to investigate its utility as a general
deoxygenation agent.
Functioning as a “counterattack reagent”,1,2 hexa-
methyldisilane can be used to bring about various organic
functional group transformations. Examples include the
conversion of allylic alcohols to allyltrimethylsilanes,
conversion of hydrazines to 2-tetrazenes, polysilylation
Reduction plays an important role in nitro chemis-
13,14
try.
A limited number of reagents can partially reduce
3
nitroalkanes to give the corresponding oximes in appeal-
4
13,15
ing yields.
Herein we report on the use of hexameth-
5
of hydrazines, and oxidation of benzyl alcohols to phe-
yldisilane for facile mono-deoxygenation of nitroalkanes
to give the corresponding ketoximes under mild condi-
tions. Furthermore, we applied the same strategy involv-
ing 1,2-elimination in the deoxygenations of nitrones to
the corresponding imines and heterocyclic N-oxides to the
corresponding N-heterocycles.
6
7
nones or benzaldehyde. This concept was also applied
in a direct syntheses of ketene thioacetals and 2-tri-
methylsilyl-1,3-dithiane derivatives from 1,3-dithiane.8
In addition, hexamethyldisilane can function as a reduc-
9
10
ing agent and a source of trimethylsilyl anion as well
as halotrimethylsilanes.11
Hexamethyldisilane can deoxygenate pyridine N-oxide
Resu lts
to give pyridine in the presence of methyllithium in a
catalytic amount.12 This reaction could go through a 1,2-
A new method is illustrated in Scheme 1 for the
reduction of nitroalkanes 1a -10a to the corresponding
ketoximes. We treated secondary nitro compounds 1a -
5a with 1.1 equiv of n-BuLi in THF at 0 °C and then
with 1.1 equiv of hexamethyldisilane at room tempera-
ture for 24 h. After normal workup and purification by
column chromatography, we obtained the corresponding
ketoximes 1b-5b in 60-73% yields. By the same method,
cyclic nitroalkanes 6a -8a were converted to ketoximes
6b-8b in 40-69% yields and bicyclic nitroalkanes 9a and
0a to ketoximes 9b and 10b, respectively, in 71-72%
yields.
Different bases (such as NaH and KH) in various
solvents (including ether and HMPA-THF) can also be
used for accomplishment of the transformation shown in
Scheme 1. Nevertheless, the oxime products were often
obtained in lower yields.
†
National Tsing Hua University.
Academia Sinica; recipient of 1997 The Third World Academy of
‡
Sciences Award in Chemistry.
§
Chinese Military Academy.
National Taiwan University.
¶
(1) Hwu, J . R.; Gilbert, B. A. Tetrahedron 1989, 45, 1233.
(2) Hwu, J . R.; Tsay, S.-C. Chem. Commun. 1998, 161.
(3) Hwu, J . R.; Lin, L. C.; Liaw, B. R. J . Am. Chem. Soc. 1988, 110,
7
252.
(
(
(
(
4) Hwu, J . R.; Wang, N.; Yung, R. T. J . Org. Chem. 1989, 54, 1070.
5) Hwu, J . R.; Wang, N. Tetrahedron 1988, 44, 4181.
6) Hwu, J . R. J . Chem. Soc., Chem. Commun. 1985, 452.
7) Hwu, J . R.; Tsay, S.-C.; Wang, N.; Hakimelahi, G. H. Organo-
1
metallics 1994, 13, 2461.
8) Hwu, J . R.; Lee, T.; Gilbert, B. A. J . Chem. Soc., Perkin Trans.
1992, 3219.
9) For representative examples, see: (a) Vorbr u¨ ggen, H.; Krolik-
(
1
(
iewicz, K. Tetrahedron Lett. 1984, 25, 1259. (b) Watanabe, H.; Saito,
M.; Sutou, N.; Nagai, Y. J . Chem. Soc., Chem. Commun. 1981, 617. (c)
Tsui, F.-P.; Vogel, T. M.; Zon, G. J . Org. Chem. 1975, 40, 761.
(
10) For the generation of trimethylsilyl anions, see: (a) Hudrlik,
P. F.; Waugh, M. A.; Hudrlik, A. M. J . Organomet. Chem. 1984, 271,
9. (b) Still, W. C. J . Org. Chem. 1976, 41, 3063.
11) For representative examples, see: (a) Olah, G. A.; Gupta, B.
(13) Hudlicky, M. Reduction in Organic Chemistry; J ohn Wiley: New
York, 1984; pp 69-76.
6
(
(14) Brown, B. R. The Organic Chemistry of Aliphatic Nitrogen
Compounds; Oxford University Press: New York, 1994; pp 433-443.
(15) For representative examples, see: (a) Albanese, D.; Landini,
D.; Penso, M. Synthesis 1990, 333. (b) Barton, D. H. R.; Fernandez, I.;
Richard, C. S.; Zard, S. Z. Tetrahedron 1987, 43, 551. (c) Olah, G. A.;
Narang, S. C. Field, L. D.; Fung, A. P. J . Org. Chem. 1983, 48, 2766.
(d) Hanson, J . R. Synthesis 1974, 1.
G. B.; Malhotra, R.; Narang, S. C. J . Org. Chem. 1980, 45, 1638. (b)
Olah, G. A.; Narang, S. C.; Gupta, B. G. B.; Malhotra, R. Angew. Chem.,
Int. Ed. Engl. 1979, 18, 612. (c) Sakurai, H.; Shirahata, A.; Sasaki,
K.; Hosomi, A. Synthesis 1979, 740.
(12) (a) Hwu, J . R.; Wetzel, J . M. J . Org. Chem. 1985, 50, 400. (b)
Tsay, S.-C.; Patel, H. V.; Hwu, J . R. Synlett 1998, 939.
1
0.1021/jo981054i CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/12/1999

2
212 J . Org. Chem., Vol. 64, No. 7, 1999
Hwu et al.
Sch em e 1
Sch em e 2
Sch em e 3
Furthermore, we treated hexamethyldisilane with me-
thyllithium in HMPA-THF at 0 °C to generate Me
3
-
SiLi.10 In situ, we allowed Me
SiLi (∼1.1 equiv) to react
3
1
6
with nitrones 11a -15a at -78 °C for 20 min and at
room temperature for 4-6 h (Scheme 2). The correspond-
ing imines 11b-15b were obtained in 82-88% yields
after normal workup and purification. Reduction of
nitrone 11a by use of a catalytic amount of trimethylsi-
lyllithium (0.10 equiv) and hexamethyldisilane (1.0 equiv)
in HMPA-THF, however, afforded the corresponding
imine 11b in poor yield. On the other hand, reaction of
3
nitrone 11a with an excess of Me SiLi (2.1 equiv) afforded
a mixture containing N-benzylaniline (17, 27%), the
dimer 1,2-dianilino-1,2-diphenylethane (18, 16%), and the
expected mono-deoxygenated product imine 11b (31%).
In studies on the use of hexamethyldisilane as a
versatile reagent in organic synthesis, we have reported
the deoxygenation of pyridine N-oxide (19a ) to pyridine
(
19b).12 To realize the generality of this deoxygenation
process, we subjected various heterocyclic N-oxides to the
same reaction conditions (see Scheme 3).
We found that deoxygenation by Me SiLi proceeded
3
smoothly for a pyridine N-oxide bearing an electron-
donating group, such as Me (i.e., 20a ) and OMe (i.e., 21a ).
Deoxygenation, however, did not occur to a pyridine
N-oxide bearing an electron-withdrawing cyano group
(i.e., 22a ).
Furthermore, we treated quinoline N-oxide (23a ) and
isoquinoline N-oxide (24a ) with Me
The corresponding quinoline (23b) and isoquinoline (24b)
3
SiLi in HMPA-THF.
were obtained in 83% and 84% yields, respectively. We
also extended the above strategy to the deoxygenation
of dipyridineN-oxide 25a . Thus reaction of 2,2′-bipyridine
N,N′-dioxide (25a ) with hexamethyldisilane (2.2 equiv)
(
16) For their preparation, see: Br u¨ ning, I.; Grashey, R.; Hauck,
H.; Huisgen, R.; Seidl, H. Organic Syntheses; Wiley: New York, 1973;
Collect. Vol. V, p 1124.
(
17) Hwu, J . R.; Tsay, S.-C. Tetrahedron 1990, 46, 7413.

Mono-deoxygenation Processes Using Hexamethyldisilane
J . Org. Chem., Vol. 64, No. 7, 1999 2213
Sch em e 4
of primary silyl nitronates by organolithium reagents to
give ketoximes. Secondary silyl nitronates, however, react
with organolithium reagents in a different manner to
2
1
afford R-alkylated oximes via a nitroso intermediate.
-
We believe that the Me
3
Si formed in situ can coun-
terattack the electrophilic carbon center in 27 to form
the adducts 28, which undergo a 1,2-syn-elimination to
give intermediates 29. This process is similar to the
Peterson olefination.22 The resultant intermediates 29,
-
in turn, can undergo counterattack by Me
3
SiO to form
3
0. Protonation of 30 by water during workup gives the
desired ketoximes. Alternatively, we cannot rule out the
-
3
possibility that Me Si formed in situ attacks the sily-
lated O-atom of silyl nitronates 27 to give 30 directly.
This newly developed mono-deoxygenation of second-
ary nitroalkanes to ketoximes can be regarded as a
“
reductive Nef reaction”.23 In the entire transformation,
hexamethyldisilane acts as a “counterattack reagent”.
Both cyclic and acyclic secondary nitroalkanes gave the
desired ketoximes in good yields under the applied
conditions. Nevertheless, attempts to convert primary
nitroalkanes to the corresponding aldoximes under the
same conditions failed. The failure of this transformation
3
could be attributed to the elimination of Me SiOH and
thus results in the formation of labile nitrile oxides.
in the presence of methyllithium (2.1 equiv) in HMPA-
THF afforded the 2,2′-bipyridine (25b) in 81% yield.
Deoxygen a tion of Nitr on es to Im in es. Nitrones can
2
4
be deoxygenated by phosphines or phosphites. Use of
lithium aluminum hydride, sodium borohydride, or Raney
nickel leads to reduction of the C-N double bond in
nitrones.24 We considered that nitrones and silyl nitro-
nates 27 possess a similar electronic structure. Thus
conditions for mono-deoxygenation of nitro compounds
could be applicable to the conversion of nitrones to imines
Discu ssion
Recently, we have reported a general procedure for the
conversion of primary nitro compounds into the corre-
3 3
sponding thiohydroxamic acids using Me SiSSiMe under
alkaline conditions.17 Analogy was extended for the
transformation of primary nitro compounds to nitriles by
(Scheme 2).
3 3
use of Me SiSSiMe
as a counterattack reagent.18 We
Nitrones react easily with alkyllithium or Grignard
have also reported the conversion of secondary nitro
compounds to ketoximes by using sulfur-containing
reagents to give 1,3-addition products.2
4,25
In the deoxy-
genation process, the first step involves the attack of
3 3 3
reagents Me SiSSiMe or MeSSiMe in the presence of
-
Me
1
3
Si on the electrophilic carbon atom in nitrones 11a -
base.17 To avoid the use of the noxious sulfur-containing
reagents, we successfully developed a new method for the
conversion of secondary nitro compounds to ketoximes,
5a (Scheme 2). Then the 1,3-addition intermediates 16
may undergo a 1,2-elimination to form imines 11b-15b.
-
3
Deoxygenation of nitrones 11a-15a generated Me SiO
in which the nontoxic reagent Me
a counterattack reagent.
3 3
SiSiMe functioned as
as a side species. It can cleave the Si-Si bond of the
-
remaining hexamethyldisilane to regenerate Me
3
Si along
Accordingly, it is possible to propa-
Halogenated silanes or disilanes can be used in the
2
0
3 3
with Me SiOSiMe .
deoxygenation of organic oxides, such as phosphine
oxides, sulfoxides, and amine oxides.19 These halogenated
gate the reaction further and result in complete conver-
sion of nitrones to imines by initiation of the deoxygen-
ation process with base in a catalytic amount. To explore
the possibility of the catalytic cycle, we carried out the
reduction of nitrone 11a with a catalytic amount of MeLi
and an equimolar amount of hexamethyldisilane at room
temperature. Isolation of the corresponding imine 11b
in a modest yield (26%) indicates the catalytic cycle is
feasible, but not efficient enough for organic synthesis.
We found that reaction of nitrone 11a with an excess
silicon-containing reagents are often corrosive and mois-
ture-sensitive. It would be advantageous to accomplish
the mono-deoxygenations of nitro compounds, nitrones,
and heterocyclic N-oxides by use of the mild and neutral
3 3
Me SiSiMe .
Deoxygen a tion of Secon d a r y Nitr oa lk a n es to Ke-
toxim es. A plausible mechanism associated with the new
method for mono-deoxygenation of nitroalkanes is de-
picted in Scheme 4. The nitronates 26, generated from a
secondary nitro compound under basic condition, attacks
hexamethyldisilane to give silyl nitronates 27 and
3
of Me SiLi afforded the desired imine 11b in only 31%
-
20
21
(21) Colvin, E. W.; Robertson, A. D.; Seebach, D.; Beck, A. K. J .
Chem. Soc., Chem. Commun. 1981, 952.
3
Me Si . Colvin et al. reported the nucleophilic attack
(
22) For reviews, see: (a) Ager, D. J . Org. React. 1990, 38, 1. (b)
(
18) Tsay, S.-C.; Gani, P.; Hwu, J . R. J . Chem. Soc., Perkin Trans.
1991, 1493.
19) Weber, W. P. Silicon Reagents for Organic Synthesis; Springer-
Verlag: New York, 1983; pp 328-336.
20) For reports on the cleavage of the Si-Si bond by alkoxide
Hudrlik, P. F.; Agwaramgbo, E. L. O. In Silicon Chemistry; Corey, E.
R., Corey, J . Y., Gaspar, P. P., Eds.; Ellis Horwood: Chichester, 1988;
pp 95-104.
1
(
(23) Pinnick, H. W. Org. React. 1990, 38, 655.
(
(24) Torssell, K. B. G. Nitrile Oxides, Nitrones and Nitronates in
Organic Synthesis; VCH: New York, 1988; pp 75-93.
(25) Breuer, E. In The Chemistry of Amino, Nitroso and Nitro
Compounds and their Derivatives; Patai, S., Ed.; J ohn Wiley: New
York, 1982; pp 459-564.
anions, see: (a) Sakurai, H.; Okada, A.; Kira, M.; Yonezawa, K.
Tetrahedron Lett. 1971, 1511. (b) Watanabe, H.; Higuchi, K.; Koba-
yashi, M.; Hara, M.; Koike, Y.; Kitahara, T.; Nagai, Y. J . Chem. Soc.,
Chem. Commun. 1977, 534.

2
214 J . Org. Chem., Vol. 64, No. 7, 1999
Hwu et al.
Sch em e 5
from 4-cyanopyridine N-oxide (22a ), which bears an
electron-withdrawing group.
Con clu sion s
New mono-deoxygenation processes were established
by use of hexamethyldisilane under basic conditions.
They were applied successfully in the reductions of
secondary nitroalkanes, nitrones, and heterocyclic N-
oxides to the corresponding ketoximes, imines, and
N-heterocycles, respectively. These mono-deoxygenation
processes may involve a 1,2-elimination of intermediates
-
containing the Si-C-N-O moiety. In the conversion
of secondary nitroalkanes to ketoximes, hexamethyldisi-
lane acted as a “counterattack reagent”. Advantages
associate with these processes include mild reaction
conditions and generation of the desired products in
appealing yields.
Exp er im en ta l Section
Gen er a l P r oced u r e. All reactions were carried out in oven-
dried glassware (120 °C) under an atmosphere of nitrogen,
unless indicated otherwise. Tetrahydrofuran (reagent grade)
from Mallinckrodt was dried by distillation from sodium and
benzophenone under an atmosphere of nitrogen. Ethyl acetate
and hexanes from Mallinckrodt Chemical Co. were dried and
yield. The unexpected byproducts include N-benzylaniline
(
17) through over-reduction and 1,2-dianilino-1,2-diphen-
2
6
ylethane (18) through dimerization. Sakurai et al.
reported that Me
-
3
Si can donate one electron to certain
organic compounds. Thus a single electron transfer from
2
distilled from CaH . Benzaldehyde, dimethyl sulfoxide (DMSO),
-
3
Me Si to the primary product imine 11b could occur to
and sodium nitrite were purchased from Merck Inc. The
following compounds and reagents were purchased from
Aldrich Chemical Co.: 2-bromobutane, 3-bromopentane, n-
butyllithium (1.6 M solution in hexanes), (()-camphor, 2,2′-
bipyridine N,N′-dioxide, 1-fluoro-4-nitrobenzene, 4-fluoro-2-
nitrotoluene, hexamethyldisilane, hexamethylphosphoric
triamide (HMPA), isoquinoline N-oxide, 4-methoxypyridine
N-oxide hydrate, methyllithium (1.4 M solution in diethyl
ether), 4-methylpyridine N-oxide, nitrocyclohexane, nitrocy-
clopentane, 4-nitrophenyl phenyl ether, 4-nitro-o-xylene, (()-
2-norboranone, 4-phenyl-2-butanone, and quinoline N-oxide
hydrate.
Analytical thin-layer chromatography (TLC) was performed
on precoated plates (silica gel 60 F-254), purchased from Merck
Inc. Mixtures of ethyl acetate and hexanes were used as
eluants. Gas chromatographic analyses were performed on a
Hewlett-Packard 5890 Series II instrument equipped with a
give the radical anion 31 (see Scheme 5). Then H-
abstraction by radical anion 31 followed by protonation
of the resultant anionic intermediate 32 affords benzyl-
amine 17. On the other hand, intermediate 31 undergoes
a Pinacol coupling27 to give bisamine 18 via the dianionic
intermediate 33. Hence it is necessary to use an equimo-
lar amount of Me SiLi, not in excess, in the mono-
3
deoxygenation of nitrones to give imines in high yields.
Deoxygen a tion of Heter ocyclic N-Oxid es to N-
Heter ocycles. Heterocyclic N-oxides can be deoxygen-
ated by many reagents, including hydrides, trivalent
phosphorus compounds, sulfur compounds, dissolved
metals, titanium trichloride, hydrogen gas, etc.2
8,29
In
general, methods are limited for the specifically reductive
cleavage of the N-oxide bond because of interference
resulting from side reactions, relatively high reaction
temperatures, and the difficulties associated with product
isolation.
2
5-m cross-linked methyl silicone gum capillary column (0.32-
mm i.d.). Nitrogen gas was used as the carrier gas, and the
flow rate was kept constant at 14.0 mL/min. The retention time
t
R
was measured under the following conditions: injector
In the course of finding solutions to this problem, we
have reported our preliminary results on the deoxygen-
ation of pyridine N-oxide to pyridine with hexamethyl-
disilane in the presence of methyllithium.1 To explore
the generality and to study the scope of this deoxygen-
ation process, we found that N-oxides of substituted
pyridines, quinoline, and isoquinoline can be deoxygen-
ated with hexamethyldisilane in the presence of meth-
yllithium. The resultant deoxygenated N-heterocycles
were obtained in good yields for almost all substrates,
including 19b -21b and 23b -25b . The only exception
was the failure on the formation of 4-cyanopyridine (22b)
temperature 260 °C, initial temperature for column 70 °C,
duration 2.00 min, increment rate 10 °C/min, and final
temperature for column 250 °C. Gas chromatography and low-
resolution mass spectral analyses were performed on a Hewlett-
Packard 5890 Series II instrument equipped with a Hewlett-
Packard 5971A mass selective detector and a capillary HP-1
column. Purification by gravity column chromatography packed
with Merck Reagents silica gel 60 (particle size 0.063-0.200
mm, 70-230 mesh ASTM) provided the desired product with
purity >99.5%. The yields reported were based on the isolated,
pure fraction from column chromatography.
2a
P r ep a r a tion of Nitr o Com p ou n d s. 1-Methyl-2-nitrocy-
clohexane (8a ), 3-nitrophenylbutane (4a ), 1-nitrophenylethane
(
2a ), and 1,7,7-trimethyl-2-nitrobicyclo[2.2.1]heptane (10a )
1
7
were prepared by the literature method. 2-Nitrobutane (1a )
and 3-nitropentane (5a ) were synthesized from the corre-
sponding alkyl bromide and sodium nitrite in DMSO. 2-Ni-
tronorborane (9a ) and 2-nitrophenylpropane (3a ) were pro-
duced by condensation of the corresponding ketones and
(
26) Sakurai, H.; Okada, A.; Umino, H.; Kira, M. J . Am. Chem. Soc.
973, 95, 955.
27) Robertson, G. M. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Pattenden, G., Eds.; Pergamon: Oxford, 1991; Vol.
, pp 563-611.
28) Katritzky, A. R.; Lagowski, J . M. Chemistry of the Heterocyclic
N-Oxides; Academic: London, 1971; pp 166-226.
29) Albini, A.; Pietra, S. Heterocyclic N-Oxides; CRC: Boca Raton,
991; pp 120-134.
1
3
0
(
3
(
(
(30) Asaro, M. F.; Nakayama, I.; Wilson, R. B., J r. J . Org. Chem.
1992, 57, 778.
1

Mono-deoxygenation Processes Using Hexamethyldisilane
J . Org. Chem., Vol. 64, No. 7, 1999 2215
hydroxylamine, followed by oxidation of the resultant ke-
toximes with peroxytrifluoroacetic acid.31
Sta n d a r d P r oced u r e 1 for th e Red u ction of Nitr oa l-
k a n es to Oxim es. To a solution of nitroalkanes (1.0 equiv)
in THF (10.0 mL) was added n-butyllithium (1.6 M in hexanes,
tane (4a , 547 mg, 3.05 mmol, 1.0 equiv), hexamethyldisilane
(491 mg, 3.35 mmol, 1.1 equiv), and n-butyllithium (1.6 M in
hexanes, 2.1 mL, 3.4 mmol, 1.1 equiv). After the reaction was
worked up, the residue was purified by column chromatogra-
phy on silica gel (15% EtOAc in hexanes as eluant). Oximes
4b (as a Z- and E-mixture, 323 mg, 1.98 mmol) were obtained
as a white solid in 65% yield: mp (recrystallized from ethanol)
1
.1 equiv) at 0 °C. After the solution was stirred at 0 °C for 10
min, hexamethyldisilane (1.1 equiv) was added and the
mixture was stirred at room temperature for 24 h. The reaction
mixture was quenched with water at 0 °C, neutralized with
85.0-86.0 °C (lit.34 mp 85-86 °C); TLC R
0.62 (30% EtOAc
, 300 MHz) δ 1.98 (s, 3
f
1
in hexanes as eluant); H NMR (CDCl
3
1
0% aqueous HCl, and extracted with ether (3 × 50 mL). The
combined organic layers were washed with saturated aqueous
NaCl, dried over MgSO (s), filtered, and concentrated under
H), 2.55-2.77 (m, 2 H), 2.87-2.92 (m, 2 H), 7.23-7.37 (m, 5
H), 8.45 (br s, 1 H); 13C NMR (CDCl
, 75 MHz) δ 13.87, 20.22,
3
4
30.81, 31.47, 32.02, 37.70, 126.12, 128.33, 128.46, 141.10,
reduced pressure. The residue was purified by column chro-
matography on silica gel to provide the desired oximes.
141.27, 157.87, 158.20; IR (KBr) 3222 (br s, OH), 1682 (m, Cd
-
1
+
N), 953 (s, N-O) cm ; MS m/z (relative intensity) 163 (M ,
1
(
Z)- a n d (E)-2-Bu ta n on e Oxim es (1b). The standard
16), 91 (100). Its spectroscopic characteristics in IR, H NMR,
procedure 1 was followed by use of 2-nitrobutane (1a , 432 mg,
and 13C NMR are consistent with those of the same compound
reported in the literature.17
4
1
.19 mmol, 1.0 equiv), hexamethyldisilane (675 mg, 4.61 mmol,
.1 equiv), and n-butyllithium (1.6 M in hexanes, 2.9 mL, 4.6
3-P en ta n on e Oxim e (5b). The standard procedure 1 was
followed by use of 3-nitropentane (5a , 541 mg, 4.62 mmol, 1.0
equiv), hexamethyldisilane (744 mg, 5.08 mmol, 1.1 equiv), and
n-butyllithium (1.6 M in hexanes, 3.2 mL, 5.1 mmol, 1.1 equiv).
After the reaction was worked up, the residue was purified
by column chromatography on silica gel (20% EtOAc in
hexanes as eluant). Oxime 5b (294 mg, 2.91 mmol) was
f
mmol, 1.1 equiv). After the reaction was worked up, the residue
was purified by column chromatography on silica gel (20%
EtOAc in hexanes as eluant). Oximes 1b (as a Z- and
E-mixture, 223 mg, 2.56 mmol) were obtained as a colorless
oil in 61% yield: TLC R
f
0.52 (30% EtOAc in hexanes as
1
eluant); H NMR (CDCl
3
, 300 MHz) δ 1.04-1.09 (m, 3 H), 1.88
1
3
(
7
1
s, 3 H), 2.18-2.45 (m, 2 H), 8.49 (br s, 1 H); C NMR (CDCl
3
,
obtained as a colorless oil in 63% yield: TLC R 0.62 (30%
5 MHz) δ 9.68, 10.71, 13.29, 19.01, 21.92, 29.00, 159.78,
EtOAc in hexanes as eluant); H NMR (CDCl , 300 MHz) δ
1
3
60.52; IR (neat) 3251 (br s, OH), 1663 (m, CdN), 935 (s, N-O)
1.02 (t, J ) 6.0 Hz, 6 H), 2.13-2.35 (m, 4 H), 9.89 (br s, 1 H);
-
1
+
13
cm ; MS m/z (relative intensity) 87 (M , 1), 42 (100). Its
C NMR (CDCl , 75 MHz) δ 9.87, 10.54, 20.67, 26.81, 163.25;
3
1
13
-1
spectroscopic characteristics in IR, H NMR, and C NMR are
consistent with those of the same compound reported in the
IR (neat) 3249 (br s, OH), 1661 (m, CdN), 935 (s, N-O) cm ;
+
MS m/z (relative intensity) 101 (M , 2), 59 (100). Its spectro-
3
2
scopic characteristics in IR, 1H NMR, and C NMR are
13
literature.
Acetop h en on e Oxim e (2b). The standard procedure 1 was
followed by use of 1-nitrophenylethane (2a , 455 mg, 3.01 mmol,
consistent with those of the same compound reported in the
literature.32
1
.0 equiv), hexamethyldisilane (485 mg, 3.31 mmol, 1.1 equiv),
Cyclop en ta n on e Oxim e (6b). The standard procedure 1
was followed by use of nitrocyclopentane (6a , 455 mg, 3.95
mmol, 1.0 equiv), hexamethyldisilane (636 mg, 4.34 mmol, 1.1
equiv), and n-butyllithium (1.6 M in hexanes, 2.7 mL, 4.3
mmol, 1.1 equiv). After the reaction was worked up, the residue
was purified by column chromatography on silica gel (25%
EtOAc in hexanes as eluant). Oxime 6b (157 mg, 1.58 mmol)
and n-butyllithium (1.6 M in hexanes, 2.1 mL, 3.4 mmol, 1.1
equiv). After the reaction was worked up, the residue was
purified by column chromatography on silica gel (15% EtOAc
in hexanes as eluant). Oxime 2b (297 mg, 2.20 mmol) was
obtained as a white solid in 73% yield: mp (recrystallized from
3
3
hexanes) 58.0-59.0 °C (lit. mp 58 °C); TLC R
f
0.67 (30%
, 300 MHz) δ
.33 (s, 3 H), 7.24-7.66 (m, 5 H), 9.19 (br s, 1 H); 13C NMR
CDCl , 75 MHz) δ 12.40, 126.03, 128.48, 129.24, 136.36,
56.02; IR (KBr) 3221 (br s, OH), 1644 (m, CdN), 1006 (s,
1
EtOAc in hexanes as eluant); H NMR (CDCl
3
was obtained as a white solid in 40% yield: mp (recrystallized
2
34
from hexanes) 57.0-58.0 °C (lit. mp 57-58.5 °C); TLC R
f
0.38
(
3
1
(
30% EtOAc in hexanes as eluant); H NMR (CDCl
δ 1.26-1.69 (m, 4 H), 2.22-2.35 (m, 4 H), 9.91 (br s, 1 H);
NMR (CDCl , 75 MHz) δ 24.22, 24.87, 26.82, 30.42, 166.80;
IR (KBr) 3218 (br s, OH), 1689 (m, CdN), 942 (s, N-O) cm
3
, 300 MHz)
1
13
C
-1
+
N-O) cm ; MS m/z (relative intensity) 135 (M , 77), 77 (100).
Its spectroscopic characteristics in IR, H NMR, and C NMR
are consistent with those of the same compound reported in
the literature.
Z)- a n d (E)-1-P h en yl-2-p r op a n on e Oxim es (3b). The
3
1
13
-1
;
+
MS m/z (relative intensity) 99 (M , 70), 55 (100). Its spectro-
1
7
scopic characteristics in IR, 1H NMR, and 13C NMR are
consistent with those of the same compound reported in the
(
standard procedure 1 was followed by use of 2-nitrophenyl-
propane (3a , 568 mg, 3.44 mmol, 1.0 equiv), hexamethyldisi-
lane (553 mg, 3.78 mmol, 1.1 equiv), and n-butyllithium (1.6
M in hexanes, 2.3 mL, 3.7 mmol, 1.1 equiv). After the reaction
was worked up, the residue was purified by column chroma-
tography on silica gel (20% EtOAc in hexanes as eluant).
Oximes 3b (as a Z- and E-mixture, 344 mg, 2.31 mmol) were
32
literature.
Cycloh exa n on e Oxim e (7b). The standard procedure 1
was followed by use of nitrocyclohexane (7a , 452 mg, 3.50
mmol, 1.0 equiv), hexamethyldisilane (563 mg, 3.85 mmol, 1.1
equiv), and n-butyllithium (1.6 M in hexanes, 2.4 mL, 3.8
mmol, 1.1 equiv). After the reaction was worked up, the residue
was purified by column chromatography on silica gel (20%
EtOAc in hexanes as eluant). Oxime 7b (273 mg, 2.41 mmol)
obtained as a colorless oil in 67% yield: TLC R
f
0.55 (30%
, 300 MHz) δ
.81 (s, 3 H), 1.82 (s, 3 H), 3.75 (s, 2 H), 3.49 (s, 2 H), 7.21-
.33 (m, 5 H), 9.06 (br s, 1 H); 13C NMR (CDCl
, 75 MHz) δ
1
EtOAc in hexanes as eluant); H NMR (CDCl
3
was obtained as a white solid in 69% yield: mp (recrystallized
1
7
1
1
34
from ethanol) 89.0-90.0 °C (lit. mp 89.5-90.5 °C); TLC R
f
3
1
0
.52 (30% EtOAc in hexanes as eluant); H NMR (CDCl
3
, 300
3.19, 19.68, 34.76, 42.11, 126.45, 126.74, 128.75, 129.14,
29.99, 136.49, 136.66, 156.92, 157.64; IR (neat) 3250 (br s,
MHz) δ 1.54-1.60 (m, 6 H), 2.14-2.47 (m, 4 H), 9.91 (br s, 1
13
H); C NMR (CDCl
3
, 75 MHz) δ 24.34, 25.39, 25.63, 26.69,
-
1
OH), 1662 (s, CdN), 922 (s, N-O) cm ; MS m/z (relative
intensity) 149 (M , 70), 91 (100). Its physical properties and
spectroscopic characteristics in IR, H NMR, and C NMR are
consistent with those of an authentic sample prepared from
the corresponding ketone and hydroxylamine.
3
(
1.66, 160.37; IR (KBr) 3221 (br s, OH), 1691 (m, CdN), 942
+
-1
+
s, N-O) cm ; MS m/z (relative intensity) 113 (M , 100), 59
1 13
1
13
(
56). Its spectroscopic characteristics in IR, H NMR, and
C
NMR are consistent with those of the same compound re-
17
ported.
(
Z)- a n d (E)-4-P h en yl-2-bu ta n on e Oxim es (4b). The
(
Z)- a n d (E)-2-Meth ylcycloh exa n on e Oxim es (8b). The
standard procedure 1 was followed by use of 3-nitrophenylbu-
standard procedure 1 was followed by use of 1-methyl-2-
nitrocyclohexane (8a , 467 mg, 3.26 mmol, 1.0 equiv), hexa-
methyldisilane (525 mg, 3.59 mmol, 1.1 equiv), and n-butyl-
lithium (1.6 M in hexanes, 2.3 mL, 3.7 mmol, 1.1 equiv). After
(
31) Olah, G. A.; Ramaiah, P.; Prakash, G. K. S.; Gilardi, R. J . Org.
Chem. 1993, 58, 763.
32) Hawkes, G. E.; Herwig, K.; Roberts, J . D. J . Org. Chem. 1974,
9, 1017.
(
3
1
(33) Ohwada, T.; Yamagata, N.; Shudo, K. J . Am. Chem. Soc. 1991,
13, 1364.
(34) Barber, G. N.; Olofson, R. A. J . Org. Chem. 1978, 43, 3015.

2
216 J . Org. Chem., Vol. 64, No. 7, 1999
Hwu et al.
the reaction was worked up, the residue was purified by
column chromatography on silica gel (10% EtOAc in hexanes
as eluant). Oximes 8b (as a Z- and E-mixture, 282 mg, 2.22
mmol) were obtained as a white solid in 68% yield: mp
hydroxylamine (812 mg, 4.04 mmol, 1.0 equiv), benzaldehyde
(449 mg, 4.23 mmol, 1.05 equiv), and ethanol (3.0 mL). Nitrone
13a (992 mg, 3.63 mmol) was obtained as colorless crystals in
90% yield: mp 135.0-136.0 °C; TLC R
f
0.17 (20% EtOAc in
, 400 MHz) δ 7.05-7.22
(m, 5 H), 7.37-7.41 (m, 2 H), 7.47-7.49 (m, 3 H), 7.74-7.76
3
4
1
(
°
(
9
2
3
recrystallized from hexanes) 42.0-43.0 °C (lit. mp 41.5-43
hexanes as eluant); H NMR (CDCl
3
1
C); TLC R
CDCl , 300 MHz) δ 1.07 (d, J ) 6.0 Hz, 3 H), 1.40-3.57 (m,
H), 9.80 (br s, 1 H); 13C NMR (CDCl
f
0.75 (30% EtOAc in hexanes as eluant); H NMR
(m, 2 H), 7.89 (s, 1 H), 8.37-8.40 (m, 2 H); 13C NMR (CDCl
,
3
3
3
, 75 MHz) δ 16.13, 16.77,
100 MHz) δ 118.12, 119.33, 123.03, 124.04, 128.41, 128.77,
0.37, 23.84, 24.65, 25.95, 26.61, 26.69, 28.30, 31.57, 35.54,
129.80, 130.53, 130.62, 133.84, 143.82, 155.90, 158.51; IR
-
1
7.13, 163.06, 163.66; IR (neat) 3282 (br s, OH), 1659 (m, Cd
(neat) 1536 (m, CdN), 1064 (s, N-O) cm ; MS m/z (relative
-
1
+
+
N), 942 (s, N-O) cm ; MS m/z (relative intensity) 127 (M ,
3
and C NMR are consistent with those of the same compound
reported in the literature.
intensity) 289 (M , 18), 183 (100); HRMS calcd for C19
289.1103, found 289.1104. Anal. Calcd for C19
78.86; H, 5.23; N, 4.84. Found: C, 78.82; H, 5.25; N, 4.82.
H
15NO
2
1
4), 41 (100). Its spectroscopic characteristics in IR, H NMR,
H
15NO : C,
2
1
3
1
7
N-(3,4-Dim eth ylph en yl)-r-ph en yln itr on e (14a). The stan-
dard procedure 2 was followed by use of N-(3,4-dimethylphen-
yl)hydroxylamine (1.22 g, 8.89 mmol, 1.0 equiv), benzaldehyde
(991 mg, 9.34 mmol, 1.05 equiv), and ethanol (7.0 mL). Nitrone
14a (1.65 g, 7.32 mmol) was obtained as yellow crystals in 82%
(
Z)- a n d (E)-2-Nor bor a n on e Oxim es (9b). The standard
procedure 1 was followed by use of 2-nitronorborane (9a , 452
mg, 3.20 mmol, 1.0 equiv), hexamethyldisilane (516 mg, 3.53
mmol, 1.1 equiv), and n-butyllithium (1.6 M in hexanes, 2.2
mL, 3.5 mmol, 1.1 equiv). After the reaction was worked up,
the residue was purified by column chromatography on silica
gel (20% EtOAc in hexanes as eluant). Oximes 9b (as a Z- and
E-mixture, 289 mg, 2.31 mmol) were obtained as a white solid
in 72% yield: mp (recrystallized from hexanes) 51.0-52.0 °C
yield: mp 61.0-62.0 °C; TLC R
f
0.23 (20% EtOAc in hexanes
, 400 MHz) δ 2.32 (s, 3 H), 2.34 (s,
3 H), 7.20-7.23 (m, 1 H), 7.46-7.49 (m, 3 H), 7.58 (s, 1 H),
, 100 MHz)
1
as eluant); H NMR (CDCl
3
7.89 (s, 1 H), 8.37-8.41 (m, 2 H); 13C NMR (CDCl
3
δ 19.10, 19.46, 118.33, 122.25, 128.13, 128.62, 129.59, 130.26,
3
5
(
lit. mp 50-51.5 °C); TLC R
f
0.48 (30% EtOAc in hexanes as
, 300 MHz) δ 1.05-3.42 (m, 10 H),
.81 (br s, 1H); C NMR (CDCl , 75 MHz) δ 25.67, 26.81, 27.10,
130.50, 133.63, 137.27, 138.33, 146.55; IR (neat) 1548 (s, Cd
1
-1
+
eluant); H NMR (CDCl
3
N), 1078 (s, N-O) cm ; MS m/z (relative intensity) 225 (M ,
26), 119 (100); HRMS calcd for C15 15NO 225.1154, found
225.1146. Anal. Calcd for C15 15NO: C, 79.97; H, 6.71; N, 6.22.
1
3
9
2
1
(
(
3
H
7.51, 34.57, 35.18, 36.87, 38.02, 38.24, 38.78, 41.96, 42.15,
66.38, 167.32; IR (KBr) 3249 (br s, OH), 1690 (m, CdN), 952
s, N-O) cm ; MS m/z (relative intensity) 125 (M , 7), 79
100). Its physical properties and spectroscopic characteristics
in IR, H NMR, and C NMR are consistent with those of an
authentic sample prepared from the corresponding ketone and
hydroxylamine.
H
Found: C, 79.95; H, 6.80; N, 6.25.
N-(5-F lu or o-2-m et h ylp h en yl)-r-p h en yln it r on e (15a ).
The standard procedure 2 was followed by use of N-(5-fluoro-
-
1
+
1
13
2
-methylphenyl)hydroxylamine (827 mg, 5.86 mmol, 1.0 equiv),
benzaldehyde (653 mg, 6.15 mmol, 1.05 equiv), and ethanol
2.0 mL). Nitrone 15a (1.22 g, 5.32 mmol) was obtained as
(
Ca m p h or Oxim e (10b). The standard procedure 1 was
followed by use of 1,7,7-trimethyl-2-nitrobicyclo[2.2.1]heptane
colorless crystals in 91% yield: mp 116.0-117.0 °C; TLC R
f
1
0.19 (20% EtOAc in hexanes as eluant); H NMR (CDCl , 300
3
MHz) δ 2.37 (s, 3 H), 7.07 (dt, J ) 8.3, 2.6 Hz, 1 H), 7.17 (dd,
J ) 8.3, 2.6 Hz, 1 H), 7.27 (dd, J ) 8.3, 7.1 Hz, 1 H), 7.48-
(10a , 603 mg, 3.29 mmol, 1.0 equiv), hexamethyldisilane (531
mg, 3.63 mmol, 1.1 equiv), and n-butyllithium (1.6 M in
hexanes, 2.3 mL, 3.7 mmol, 1.1 equiv). After the reaction was
worked up, the residue was purified by column chromatogra-
phy on silica gel (15% EtOAc in hexanes as eluant). Oxime
1
3
7.51 (m, 3 H), 7.54 (s, 1 H), 8.33-8.36 (m, 2 H); C NMR
(CDCl , 75 MHz) δ 16.13. 110.78, 116.01, 127.10, 128.38,
3
128.59, 129.89, 130.83, 132.37, 137.45, 148.56, 160.35; IR
-
1
1
0b (391 mg, 2.34 mmol) was obtained as a white solid in 71%
(neat) 1568 (m, CdN), 1055 (s, N-O) cm ; MS m/z (relative
3
6
+
yield: mp (recrystallized from ethanol) 116.0-117.0 °C (lit.
mp 116.5-117.5 °C); TLC R
intensity) 229 (M , 100), 212 (84); HRMS calcd for C H12FNO
1
4
f
0.68 (30% EtOAc in hexanes as
14
229.0903, found 229.0909. Anal. Calcd for C H12FNO: C,
73.33; H, 5.28; N, 6.11. Found: C, 73.34; H, 5.28; N, 6.16.
1
eluant); H NMR (CDCl
H), 0.97 (s, 3 H), 1.16-2.56 (m, 7 H), 9.45 (br s, 1 H); C NMR
CDCl , 75 MHz) δ 11.07, 18.49, 19.41, 27.22, 32.59, 33.04,
3.70, 48.24, 51.78, 169.67; IR (KBr) 3304 (br s, OH), 1685
3
, 300 MHz) δ 0.67 (s, 3 H), 0.88 (s, 3
1
3
Sta n d a r d P r oced u r e 3 for th e Deoxygen a tion of N,r-
Dia r yln itr on es a n d P yr id in e N-Oxid es. A solution of
hexamethyldisilane in HMPA (1.6 mL) was cooled to -78 °C
under argon, whereupon the mixture solidified. Low-halide
MeLi and THF (8.0 mL) were added slowly onto the frozen
mixture, which was then warmed to 0 °C for 5.0 min. The
resultant orange-red solution was cooled to -78 °C. A solution
of N,R-diarylnitrones or pyridine N-oxides in THF (2.0 mL)
was injected slowly into the reaction flask. The reaction
mixture was stirred at -78 °C for 20 min and at room
temperature for 4-15 h and then quenched with water. The
solution was extracted with ether (3 × 25 mL), and the
combined ether layers were washed with saturated ammonium
chloride solution (1 × 3 mL) and water (3 × 3 mL). After the
(
4
3
-
1
(
(
m, CdN), 923 (s, N-O) cm ; MS m/z (relative intensity) 167
+
1
M , 100), 124 (94). Its spectroscopic characteristics in IR, H
1
3
NMR, and C NMR are consistent with those of the same
compound reported in the literature.
1
7
Sta n d a r d P r oced u r e 2 for th e P r ep a r a tion of Su bsti-
1
6
tu ted N-Ar yl-r-p h en yln itr on es. Benzaldehyde (1.05 equiv)
was added into an ethanolic solution containing N-arylhy-
3
7
droxylamines (1.0 equiv) with stirring at 50-60 °C for 10
min. After the reaction mixture was kept at room temperature
in the dark overnight, N-aryl-R-phenylnitrones were crystal-
lized from the reaction mixture. The crystals of nitrone were
collected on a B u¨ chner funnel, washed with cold ethanol, and
ether solution was dried (MgSO ), the solvent was removed to
4
dried under reduced pressure in the presence of P
2
O
5
. Their
give the crude product. The residue was purified by column
chromatography on silica gel to provide the desired products.
structures were determined by spectroscopic methods. For
nitrones 11a and 12a , their physical properties and spectro-
N-Ben zylid en ea n ilin e (11b). Meth od 1. The standard
procedure 3 was followed by use of N,R-diphenylnitrone (11a ,
1
13
scopic characteristics in IR, H NMR, and C NMR are
consistent with those of the same compound reported in the
literature.
2
1
11 mg, 1.07 mmol, 1.0 equiv), hexamethyldisilane (172 mg,
.18 mmol, 1.1 equiv), and methyllithium (1.4 M in ether, 0.85
3
8
N-(4-P h en oxyp h en yl)-r-p h en yln itr on e (13a ). The stan-
dard procedure 2 was followed by use of N-(4-phenoxyphenyl)-
mL, 1.1 mmol, 1.1 equiv). After the reaction mixture was
stirred at room temperature for 5.0 h, it was worked up and
the residue was purified by column chromatography on silica
gel (5% EtOAc in hexanes as eluant) to give 11b (163 mg, 0.899
mmol) as a yellow solid in 84% yield: mp (recrystallized from
(
35) Hall, H. K., J r. J . Am. Chem. Soc. 1960, 82, 1209.
(36) Hutchins, R. O.; Adams, J .; Rutledge, M. C. J . Org. Chem. 1995,
6
1
1
0, 7396.
ethanol) 50.0-51.0 °C (lit.39 mp 51 °C); GC t
15.56 min; TLC
R
(37) Oxley, P. W.; Adger, B. M.; Sasse, M. J .; Forth, M. A. Org. Synth.
988, 67, 187.
(38) Suda, K.; Tsujimoto, T.; Yamauchi, M. Bull. Chem. Soc. J pn.
(39) Dictionary of Organic Compounds, 5th ed.; Buckingham, J ., Ed.;
Chapman and Hall: New York, 1982; Vol. 1, p 372.
987, 60, 3607.

Mono-deoxygenation Processes Using Hexamethyldisilane
J . Org. Chem., Vol. 64, No. 7, 1999 2217
1
R
3
7
f
0.62 (20% EtOAc in hexanes as eluant); H NMR (CDCl
3
,
Hz, 1 H), 7.44-7.46 (m, 3 H), 7.86-7.90 (m, 2 H), 8.46 (s, 1
00 MHz) δ 7.20-7.26 (m, 3 H), 7.37-7.42 (m, 2 H), 7.47-
H); 13C NMR (CDCl
3
, 75 MHz) δ 19.20, 19.74, 118.01, 122.24,
.49 (m, 3 H), 7.89-7.92 (m, 2 H), 8.46 (s, 1 H); 13C NMR
128.61, 128.66, 130.19, 130.99, 134.32, 136.37, 137.19, 149.73,
(CDCl
3
, 75 MHz) δ 120.82, 125.89, 128.71, 128.77, 129.10,
159.19; IR (neat) 1627 (s, CdN), 1497 (s, CdC), 1199 (w, C-N)
-
1
+
1
(
(
31.32, 136.15, 152.02, 160.33; IR (neat) 1626 (s, CdN), 1584
cm ; MS m/z (relative intensity) 209 (M , 100), 208 (74);
-1
s, CdC), 1182 (m, C-N) cm ; MS m/z (relative intensity) 181
M , 89), 180 (100). Its spectroscopic characteristics in IR, H
NMR, and C NMR are consistent with those of the same
HRMS calcd for C15
Calcd for C15 15N: C, 86.07; H, 7.23; N, 6.70. Found: C, 86.11;
H, 7.28; N, 6.70. Its spectroscopic characteristics in IR,
H15N 209.1204, found 209.1211. Anal.
+
1
H
1
3
1
H
4
0
13
compound reported in the literature.
NMR, and C NMR are consistent with those of the same
compound reported in the literature.43
Meth od 2. The standard procedure 3 was followed by use
of N,R-diphenylnitrone (11a , 828 mg, 4.20 mmol, 1.0 equiv),
hexamethyldisilane (676 mg, 4.62 mmol, 1.1 equiv), and
methyllithium (1.4 M in ether, 0.30 mL, 0.42 mmol, 0.10
equiv). After the reaction mixture was stirred at room tem-
perature for 30 h, it was worked up and the residue was
purified to give 11b (198 mg, 1.09 mmol) in 26% yield.
N-Ben zylid en e-4-flu or oa n ilin e (12b). The standard pro-
cedure 3 was followed by use of N-(4-fluorophenyl)-R-phenylni-
trone (12a , 254 mg, 1.18 mmol, 1.0 equiv), hexamethyldisilane
N-Ben zyliden e-5-flu or o-2-m eth ylan ilin e (15b). The stan-
dard procedure 3 was followed by use of N-(5-fluoro-2-meth-
ylphenyl)-R-phenylnitrone (15a , 226 mg, 0.986 mmol, 1.0
equiv), hexamethyldisilane (159 mg, 1.09 mmol, 1.1 equiv), and
methyllithium (1.4 M in ether, 0.80 mL, 1.12 mmol, 1.1 equiv).
After the reaction mixture was stirred at room temperature
for 5.0 h, it was worked up and the residue was purified by
column chromatography on silica gel (5% EtOAc in hexanes
as eluant) to give 15b (174 mg, 0.816 mmol) as a yellow solid
in 83% yield: mp (recrystallized from ethanol) 42.0-43.0 °C;
(
191 mg, 1.30 mmol, 1.1 equiv), and methyllithium (1.4 M in
ether, 0.95 mL, 1.3 mmol, 1.1 equiv). After the reaction mixture
was stirred at room temperature for 4.0 h, it was worked up
and the residue was purified by column chromatography on
silica gel (5% EtOAc in hexanes as eluant) to give 12b (207
mg, 1.04 mmol) as a yellow solid in 88% yield: mp (recrystal-
GC t
R
16.35 min; TLC R
f
0.68 (20% EtOAc in hexanes as
1
eluant); H NMR (CDCl
3
, 300 MHz) δ 2.30 (s, 3 H), 6.67 (dd,
J ) 9.8, 2.6 Hz, 1 H), 6.82 (dt, J ) 2.6, 8.4 Hz, 1 H), 7.14 (dd,
J ) 8.1, 6.3 Hz, 1 H), 7.46-7.49 (m, 3 H), 7.90-7.93 (m, 2 H),
8.33 (s, 1 H); 13C NMR (CDCl
, 75 MHz) δ 17.05, 104.85,
3
4
1
111.80, 127.46, 128.74, 128.83, 130.98, 131.50, 136.09, 152.05,
lized from ethanol) 56.0-57.0 °C (lit. mp 56 °C); GC t
R
15.52
1
160.14, 161.64; IR (neat) 1632 (s, CdN), 1596 (s, CdC), 1496
min; TLC R
CDCl
f
0.62 (20% EtOAc in hexanes as eluant); H NMR
-1
(
7
3
, 300 MHz) δ 7.05-7.11 (m, 2 H), 7.18-7.23 (m, 2 H),
, 75 MHz) δ 115.83, 122.28, 128.71, 128.76, 131.40,
(s, CdC), 1261 (m, C-F), 1146 (m, C-N) cm ; MS m/z
(relative intensity) 213 (M , 74), 136 (100); HRMS calcd for
12
12NF 213.0954, found 213.0955. Anal. Calcd for C14H -
.47-7.51 (m, 3 H), 7.89-7.93 (m, 2 H), 8.45 (s, 1 H); 13C NMR
+
(CDCl
3
C
14
H
1
(
36.08, 148.02, 160.13, 161.24; IR (neat) 1627 (s, CdN), 1499
s, CdC), 1225 (s, C-F), 1186 (m, C-N) cm ; MS m/z (relative
intensity) 199 (M , 90), 198 (100). Its spectroscopic character-
FN: C, 78.84; H, 5.68; N, 6.57. Found: C, 78.78; H, 5.66; N,
6.60.
-1
+
N-Ben zyla n ilin e (17) a n d 1,2-Dia n ilin o-1,2-d ip h en yl-
eth a n e (18). The standard procedure 3 was followed by use
of N,R-diphenylnitrone (11a , 205 mg, 1.04 mmol, 1.0 equiv),
hexamethyldisilane (334 mg, 2.28 mmol, 2.2 equiv), and
methyllithium (1.4 M in ether, 1.6 mL, 2.2 mmol, 2.1 equiv).
After the reaction mixture was stirred at room temperature
for 4.0 h, it was worked up. The crude products were separated
by column chromatography on silica gel (8% EtOAc in hexanes
as eluant) to give pure 11b (58.4 mg, 0.322 mmol) in 31% yield,
pure 17 (51.5 mg, 0.281 mmol) in 27% yield, and 18 (60.7 mg,
1
13
istics in IR, H NMR, and C NMR are consistent with those
of the same compound reported in the literature.42
N-Ben zylid en e-4-p h en oxya n ilin e (13b). The standard
procedure 3 was followed by use of N-(4-phenoxyphenyl)-R-
phenylnitrone (13a , 201 mg, 0.735 mmol, 1.0 equiv), hexa-
methyldisilane (118 mg, 0.806 mmol, 1.1 equiv), and methyl-
lithium (1.4 M in ether, 0.60 mL, 0.84 mmol, 1.1 equiv). After
the reaction mixture was stirred at room temperature for 6.0
h, it was worked up and the residue was purified by column
chromatography on silica gel (5% EtOAc in hexanes as eluant)
to give 13b (155 mg, 0.602 mmol) as a yellow solid in 82%
0
.167 mmol) in 16% yield.
For 17: GC t 16.26 min; TLC R
hexanes as eluant); H NMR (CDCl
R
f
0.59 (20% EtOAc in
, 300 MHz) δ 4.01 (br s, 1
1
yield: mp (recrystallized from ethanol) 62.0-63.0 °C; GC t
R
3
1
H), 4.32 (s, 2 H), 6.62-7.38 (m, 10 H); IR (neat) 3405 (s, NH),
2
5.85 min; TLC R
NMR (CDCl , 300 MHz) δ 7.02-7.13 (m, 5 H), 7.21-7.37 (m,
H), 7.46-7.49 (m, 3 H), 7.89-7.92 (m, 2 H), 8.49 (s, 1 H);
f
0.59 (20% EtOAc in hexanes as eluant); H
-
1
1599 (s, CdC), 1498 (s, CdC), 1321 (m, C-N) cm ; MS m/z
3
+
4
(relative intensity) 183 (M , 71), 91 (100). Its spectroscopic
1
3
characteristics in IR,
those of the same compound reported in the literature.
For 18: TLC R 0.55 (20% EtOAc in hexanes as eluant); H
NMR (CDCl , 300 MHz) δ 4.54 (s, 2 H), 4.95 (s, 2 H), 6.49-
7.21 (m, 20 H); IR (neat) 3396 (s, NH), 1599 (s, CdC), 1498 (s,
1
H NMR, and MS are consistent with
C NMR (CDCl , 75 MHz) δ 118.64, 119.57, 122.25, 123.15,
28.68, 128.72, 129.72, 131.23, 136.22, 147.30, 155.49, 157.41,
59.45; IR (neat) 1624 (m, CdN), 1586 (m, CdC), 1491 (m,
CdC), 1238 (m, C-O) cm ; MS m/z (relative intensity) 273
3
4
4
1
1
1
f
-
1
3
+
(M , 100), 272 (44). Anal. Calcd for C19
H
15NO: C, 83.49; H,
.53; N, 5.12; O, 5.86. Found: C, 83.37; H, 5.54; N, 5.20; O,
.00.
N-Ben zylid en e-3,4-d im eth yla n ilin e (14b). The standard
procedure 3 was followed by use of N-(3,4-dimethylphenyl)-R-
phenylnitrone (14a , 147 mg, 0.652 mmol, 1.0 equiv), hexa-
methyldisilane (105 mg, 0.717 mmol, 1.1 equiv), and methyl-
lithium (1.4 M in ether, 0.53 mL, 0.74 mmol, 1.1 equiv). After
the reaction mixture was stirred at room temperature for 5.0
h, it was worked up and the residue was purified by column
chromatography on silica gel (5% EtOAc in hexanes as eluant)
to give 14b (115 mg, 0.549 mmol) as a yellow solid in 84%
-1
5
6
CdC), 1309 (m, C-N) cm ; MS (FAB) m/z (relative intensity)
+
365 (M + H, 12), 182 (100). Its spectroscopic characteristics
1
in IR, H NMR, and MS are consistent with those of the same
compound reported in the literature.45
P yr id in e (19b). The standard procedure 3 was followed by
use of pyridine N-oxide (19a , 191 mg, 2.01 mmol, 1.0 equiv),
hexamethyldisilane (324 mg, 2.21 mmol, 1.1 equiv), and
methyllithium (1.4 M in ether, 1.6 mL, 2.2 mmol, 1.1 equiv).
After the reaction mixture was stirred at room temperature
for 8.0 h, it was worked up and the residue was purified by
column chromatography on silica gel (1% triethylamine in
yield: mp (recrystallized from ethanol) 43.0-44.0 °C; GC t
R
1
1
8.42 min; TLC R
f
0.65 (20% EtOAc in hexanes as eluant); H
(
43) Garc ´ı a-V a´ zquez, J . A.; L o´ pez-Becerra, M.; Masaguer, J . R.
NMR (CDCl
3
, 300 MHz) δ 2.27 (s, 3 H), 2.29 (s, 3 H), 6.98 (dd,
Polyhedron 1983, 2, 1081.
(44) Katritzky, A. R.; Yao, G.; Lan, X.; Zhao, X. J . Org. Chem. 1993,
J ) 7.8, 2.2 Hz, 1 H), 7.03 (d, J ) 2.2 Hz, 1 H), 7.14 (d, J ) 7.8
5
8, 2086.
45) Katritzky, A. R.; Fan, W.-Q.; Fu, C. J . Org. Chem. 1990, 55,
3209.
(46) Its physical properties and spectroscopic characteristics in IR,
(
(
40) Ishihara, K.; Miyata, M.; Hattori, K.; Tada, T.; Yamamoto, H.
J . Am. Chem. Soc. 1994, 116, 10520.
41) Dayal, S. K.; Ehrenson, S.; Taft, R. W. J . Am. Chem. Soc. 1972,
4, 9113.
1
13
(
H NMR, and C NMR are consistent with those of authentic samples
9
available from Aldrich Chemical Co.
(47) Barlin, G. B.; Brown, D. J .; Fenn, M. D. Aust. J . Chem. 1984,
37, 2391.
(
42) Akaba, R.; Sakuragi, H.; Tokumaru, K. Bull. Chem. Soc. J pn.
1
985, 58, 1186.

2
218 J . Org. Chem., Vol. 64, No. 7, 1999
Hwu et al.
dichloromethane as eluant) to give pyridine46 (19b, 137 mg,
methyllithium (1.4 M in ether, 1.0 mL, 1.4 mmol, 1.1 equiv).
After the reaction mixture was stirred at room temperature
for 8.0 h, it was worked up and the residue was purified by
column chromatography on silica gel (1% triethylamine in
dichloromethane as eluant) to give quinoline46 (23b, 139 mg,
1.08 mmol) in 83% yield.
1
.73 mmol) in 86% yield.
-Meth ylp yr id in e (20b). The standard procedure 3 was
4
followed by use of 4-methylpyridine N-oxide (20a , 229 mg, 2.10
mmol, 1.0 equiv), hexamethyldisilane (338 mg, 2.31 mmol, 1.1
equiv), and methyllithium (1.4 M in ether, 1.7 mL, 2.4 mmol,
1
.1 equiv). After the reaction mixture was stirred at room
Isoqu in olin e (24b). The standard procedure 3 was followed
by use of isoquinoline N-oxide (24a , 218 mg, 1.50 mmol, 1.0
equiv), hexamethyldisilane (242 mg, 1.65 mmol, 1.1 equiv), and
methyllithium (1.4 M in ether, 1.2 mL, 1.7 mmol, 1.1 equiv).
After the reaction mixture was stirred at room temperature
for 10 h, it was worked up and the residue was purified by
column chromatography on silica gel (1% triethylamine in
dichloromethane as eluant) to give isoquinoline46 (24b, 163 mg,
1.26 mmol) in 84% yield.
temperature for 10 h, it was worked up and the residue was
purified by column chromatography on silica gel (1% triethyl-
amine in dichloromethane as eluant) to give 4-methylpyridine46
(
20b, 143 mg, 1.54 mmol) in 73% yield.
-Meth oxyp yr id in e (21b). The standard procedure 3 was
followed by use of 4-methoxypyridine N-oxide (21a , 187 mg,
4
1
1
.49 mmol, 1.0 equiv), hexamethyldisilane (241 mg, 1.65 mmol,
.1 equiv), and methyllithium (1.4 M in ether, 1.2 mL, 1.7
mmol, 1.1 equiv). After the reaction mixture was stirred at
room temperature for 12 h, it was worked up and the residue
was purified by column chromatography on silica gel (1%
triethylamine in dichloromethane as eluant) to give 4-meth-
2,2′-Bip yr id in e (25b). The standard procedure 3 was
followed by use of 2,2′-bipyridine N,N′-dioxide (25a , 244 mg,
1.30 mmol, 1.0 equiv), hexamethyldisilane (417 mg, 2.85 mmol,
2.2 equiv), and methyllithium (1.4 M in ether, 1.9 mL, 2.7
mmol, 2.1 equiv). After the reaction mixture was stirred at
room temperature for 15 h, it was worked up and the residue
was purified by column chromatography on silica gel (1%
triethylamine in dichloromethane as eluant) to give 2,2′-
oxypyridine (21b, 129 mg, 1.18 mmol) in 79% yield: TLC R
f
1
0
.45 (40% EtOAc in hexanes as eluant); H NMR (CDCl
3
, 400
MHz) δ 3.88 (s, 3 H), 6.87 (d, J ) 5.4 Hz, 2 H), 8.42 (d, J ) 5.4
1
3
Hz, 2 H); C NMR (CDCl
1
3
, 100 MHz) δ 55.01, 109.89, 151.10,
+
46
65.62; MS m/z (relative intensity) 109 (M , 100), 79 (44). Its
spectroscopic characteristics in IR, H NMR, and C NMR are
consistent with those of the same compound reported in the
bipyridine (25b, 164 mg, 1.05 mmol) in 81% yield.
1
13
Ack n ow led gm en t. We thank the National Science
Council of Republic of China and Academia Sinica for
financial support of this work.
4
7
literature.
Qu in olin e (23b). The standard procedure 3 was followed
by use of quinoline N-oxide (23a , 189 mg, 1.30 mmol, 1.0
equiv), hexamethyldisilane (209 mg, 1.43 mmol, 1.1 equiv), and
J O981054I