An Investigation of the Reaction of 2-Aminobenzaldehyde Derivatives with Conjugated Nitro-olefins: An Easy and Efficient Synthesis of 3-Nitro-1,2-dihydroquinolines and 3-Nitroquinolines

Article abstract of DOI:10.1021/jo030070z

2-Aryl-3-nitro-1,2-dihydroquinolines 3 were prepared from the reaction of β-nitrostyrenes 2 and 2-aminobenzaldehyde 1 in the presence of DABCO. Not only β-nitrostyrenes but other alkyl nitro olefins also can be used in this reaction as well. When DDQ or silica gel was added to a solution of 3-nitro-1,2-dihydroquinolines 3, 3-nitro-2-substituted-quinolines 4 were obtained. When 2-aminobenzaldehyde derivatives 7 and 12 were reacted with β-nitrostyrenes 2, unique rearrangement products were produced.

Full text of DOI:10.1021/jo030070z

An In vestiga tion of th e Rea ction of 2-Am in oben za ld eh yd e
Der iva tives w ith Con ju ga ted Nitr o-olefin s: An Ea sy a n d Efficien t
Syn th esis of 3-Nitr o-1,2-d ih yd r oqu in olin es a n d 3-Nitr oqu in olin es
Ming-Chung Yan, Zhijay Tu, Chunchi Lin, Shengkai Ko, J ianming Hsu, and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road,
Taipei, Taiwan 116, R. O. C.
cheyaocf@scc.ntnu.edu.tw
Received February 24, 2003
2-Aryl-3-nitro-1,2-dihydroquinolines 3 were prepared from the reaction of â-nitrostyrenes 2 and
2-aminobenzaldehyde 1 in the presence of DABCO. Not only â-nitrostyrenes but other alkyl nitro
olefins also can be used in this reaction as well. When DDQ or silica gel was added to a solution of
3-nitro-1,2-dihydroquinolines 3, 3-nitro-2-substituted-quinolines 4 were obtained. When 2-ami-
nobenzaldehyde derivatives 7 and 12 were reacted with â-nitrostyrenes 2, unique rearrangement
products were produced.
SCHEME 1. Con d en sa tion of Nitr o Com p ou n d s
w ith 2-Am in o Ca r bon yl Com p ou n d s
In tr od u ction
Quinolines1-5 are important and widely used hetero-
cyclic compounds in organic chemistry, and a variety of
methods for the preparation of nitroquinolines have been
reported.2 Three general methods are typically used to
prepare nitroquinolines. First, nitroquinolines can be
prepared by the nitration of quinolines.2a,g,h,j However,
several regioisomers occur during the nitration. Second,
3-nitro-2-substituted quinolines can also be prepared via
the reaction of 3-nitroquinoline N-oxide with limited
reactants.2i,f Third, a method involving a modified Fried-
lander synthesis1e involves the condensation of certain
nitro compounds with 2-amino carbonyl compounds
(Scheme 1).2b-e The preparation of 2-aryl-3-nitroquino-
lines from the condensation of 2-aminobenzaldehyde and
ω-nitroacetophenones has been reported by Baumgarten
and Saylor.2e We herein describe an easy and convenient
method for the selective preparation of 1,2-dihydro-2-
substituted 3-nitroquinolines and 2-aryl-3-nitroquinolines
(eq 1). 1,2-Dihydroquinolines are usually prepared by the
reduction3 of quinolines or by the nucleophilic attack4 of
quinolines and are useful in preparing some biologically
active quinoline derivatives.5 Our work expands the scope
of this reaction to include 1,2-dihydroquinolines.
(1) (a) Rees, C. W.; Smithen, C. E. Adv. Heterocycl. Chem. 1964, 3,
57. (b) Popp, F. D. Adv. Heterocycl. Chem. 1968, 9, 1. (c) Crawforth, C.
E.; Meth-Cohen, O.; Russell, C. A. J . Chem. Soc., Perkin Trans. 1 1972,
2807. (d) Vierhapper, F. W.; Eliel, E. L. J . Am. Chem. Soc., 1974, 96,
2256. (e) Cheng, C.; Yan, S. Org. React. 1982, 28, 37. (f) Popp, F. D.;
Uff, B. B. Heterocycles 1985, 23, 731. (g) Minisci, F.; Vismara, E.;
Fontana, F. J . Org. Chem. 1989, 54, 5224.
(2) (a) Bacharach, G.; Haut, A. H.; Caroline, L. Recl. Trav. Chim.
Pays-Bas. 1933, 413. (b) Schofield, K.; Theobald, R. S. J . Chem. Soc.
1950, 395. (c) Schofield, K.; Theobald, R. S. J . Chem. Soc. 1951, 2992.
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Baumgarten, H. E.; Saylor, J . L. J . Am. Chem. Soc. 1957, 79, 1502. (f)
Sharma, K. S.; Kumari, S.; Singh, R. P. Synthesis 1981, 316. (g)
Arnestad, Berit; Bakke, J . M.; Hegbom, I.; Ranes, E. Acta Chem. Scand.
1996, 50, 556. (h) Bakke, J . M.; Ranes, E. Synthesis 1997, 281. (i)
Nakagawa, H.; Higuchi, T.; Kikuchi, K. K.; Urano, Y.; Nagano, T.
Chem. Pharm. Bull. 1998, 46, 1656. (j) Bakke, J . M.; Ranes, E.; Riha,
J .; Svensen, H. Acta Chem. Scand. 1999, 53, 141.
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Chem. 1985, 63, 412. (b) Bubnov, Y. N.; Evchenko, S. V.; Ignatenko,
A. V. Bull. Russ. Acad. Sci. Div. Chem. Sci. 1992, 41, 2239. (c) Heier,
R. F.; Dolak, L. A.; Duncan, J . N.; Hyslop, D. K.; Lipton, M. F.; Martin,
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J . Org. Chem. 1946, 11, 741. (b) Gilman, H.; Eisch, J .; Soddy, T. S. J .
Am. Chem. Soc. 1959, 81, 4000. (c) Goldstein, S. W.; Dambek, P. J .
Synthesis 1989, 221. (d) Uno, H.; Okada, S.; Suzuki, H. Tetrahedron
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897.
(5) (a) Paris, D.; Cottin, M.; Demonchaux, P.; Augert, G.; Dupas-
sieux, P.; Lenoir, P.; Peck, M. J .; J asserand, D. J . Med. Chem. 1995,
38, 669. (b) Heier, R. F.; Dolak, L. A.; Duncan, J . N.; Hyslop, D. K.;
Lipton, M. F.; Martin, I. J .; Mauragis, M. A.; Piercey, M. F.; Nichols,
N. F.; Schreur, P. J . K. D.; Smith, M. W.; Moon, M. W. J . Med. Chem.
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10.1021/jo030070z CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/12/2004
J . Org. Chem. 2004, 69, 1565-1570
1565

Yan et al.
TABLE 1. Con d en sa tion of 2-Am in oben za ld eh yd e w ith
Ar yl Nitr o Olefin s (2a -f)
TABLE 2. Con d en sa tion of 2-Am in oben za ld eh yd e w ith
Alk yl Nitr o Olefin s (2h -k )
before addition
of DDQ
after addition
of DDQ
before addition
of DDQ
after addition
of DDQ
reflux
time (h)
reacton
time (h)
entry
2
3a (%)
4a (%)
4b (%)
entry
2
3a (%)
4a (%)
4b (%)
1
2
3
4
5
6
7
2a
2a
2b
2c
2d
2e
2f
15.5
48
18.5
15
12
45.5
16
3a (86)
3a (36)
3b (99)
3c (85)
3d (19)
3e (90)
3f (47)c
4a (tr)
4a (15)
4b (tr)
4c (9)
4d (8)
4e (9)
4f (8)
4a (67)
1
2
3
4
5
6
2h
2h
2h
2i
2i
2k
1.5c
3h (7)
4h (tr)
4h (tr)
4h (tr)
4i (tr)
4j (tr)
4k (8)
8c
3h (tr)
3h (69)
3i (94)
3j (99)
3k (78)
4b (91)
4c (95)
4d (25)
4e (96)
4f (31)
9, 3.5d
12, 4d
15, 4d
5, 2d
4h (63)
4i (85)
4j (97)
4k (82)
a
All yields were obtained from 1H NMR spectral data with a
known amount of toluene as an internal standard. b All yields were
obtained from 1H NMR spectral data with a known amount of
a
All yields were obtained from 1H NMR spectral data with a
known amount of toluene as an internal standard. b All yields were
obtained from 1H NMR spectral data with a known amount of
DMF as an internal standard. c In entry 7, 3f underwent dispro-
portionation easily to form 3-nitroquinoline and indole, and the
yield of 3-nitroquinoline before addition of DDQ was 18%.
DMF as an internal standard. c 60 °C. The reaction solution was
d
heated at 45 °C for few hours before DABCO was added. After
the addition of DABCO, the solution was further heated at 45 °C
for another few hours.
It is interesting to note that the bulky nitro olefin 2g
is able to react with 2-aminobenzaldehyde to form 3g,
although a long reaction time in benzene is needed (reflux
44 h, eq 2) and the yield of 3g is low (10%). When the
reaction proceeded without solvent at 60 °C for 24 h, a
better yield (40%) of 3g was obtained, and the yields
(33%) of 3g decreased when a 42 h reaction was carried
out at 60 °C under similar conditions.
Resu lts a n d Discu ssion
P a r t a . Con d en sa tion of 2-Am in oben za ld eh yd e
w ith Ar yl Nitr o Olefin s. â-Nitrostyrenes 2 (1 equiv)
were reacted with 2-aminobenzaldehyde6 1 (1.5 equiv)
and DABCO (0.5 equiv) in refluxing benzene to generate
2-substituted 3-nitro-1,2-dihydroquinolines 3 in yields of
19-99% and traces (<10%) of 2-aryl-3-nitroquinolines 4
(eq 1 and Table 1). The reaction solution always turned
dark red due to the color of compound 3. When the crude
mixture was analyzed by 1H NMR, the reaction appeared
to be very clean and only DABCO, 3, and 4 were observed
in the solution, along with a trace of 1. An increased
reaction time led to an increased yield of compound 4
(entry 2,f Table 1). It is therefore necessary to control
the reaction time so as to generate only product 3.
1,2-Dihydroquinolines can be oxidized to quinolines by
using several oxidants.7 However, DDQ has not been
reported as one of these. It has been reported that DDQ
is a widely used dehydrogenation reagent, e.g., in aro-
matization reactions.8 1,2-Dihydro-2-substituted 3-ni-
troquinolines 3 can be further oxidized by DDQ to
generate 3-nitroquinolines 4. Based on this result, we
attempted to prepare 4 in a one-pot reaction of 1 and 2
in the presence of DABCO under refluxing conditions
followed by oxidation by DDQ at room temperature for
30 min. As expected, the oxidation reaction was complete
within a few minutes, and the yields of 4 were also very
high. The experimental results are shown in Table 1.
When the reaction shown in eq 1 was conducted without
DABCO, neither product 3 nor 2-aryl-4-hydroxy-3-nitro-
1,2,3,4-tetrahydroquinoline was observed.
P a r t b. Con d en sa tion of 2-Am in oben za ld eh yd e
w ith Alk yl Nitr o Olefin s. After our study of the
condensation of 2-aminobenzaldehyde with aryl nitro
olefins, we examined the condensation of 2-aminoben-
zaldehyde with alkyl nitro olefins under similar condi-
tions. When 1-nitropropene 2h , compound 1, and DABCO
were mixed in benzene at 60 °C, only 7% of compound 3
was obtained (entry 1, Table 2). It is likely that 1-nitro-
propene 2h has isomerized to the allylic nitro compound
or polymerization may have occurred in the presence of
DABCO9 under these conditions, and as a result, only a
low yield of compound 3 was observed. To avoid this
isomerization or polymerization, 1-nitropropene 2h must
react with compound 1 before DABCO is added. When
1-nitropropene 2h and compound 1 were heated at 45
°C for 9 h, followed by the addition of DABCO and
heating the solution for another 3.5 h, 69% of compound
3 was obtained as expected (entry 3, Table 2). When other
nitroalkenes that are able to isomerize to allylic nitro
compounds or polymerize were used, procedures similar
to those described above were used (entries 4-6 of Table
2). After treatment with DDQ, high yields of 2-alkyl-3-
nitroquinoline were obtained (Table 2).
(6) (a) Anderson, W. K.; Dalvie, D. K. J . Heterocycl. Chem. 1993,
30, 1533. (b) Wang, H.; Ganesan, A. Tetrahedron Lett. 1998, 39, 9097.
(7) (a) Deeming, A. J .; Rothwell, I. P. J . Chem. Soc., Dalton Trans.
1980, 1259. (b) Forrest, T. P.; Dauphinee, G. A.; Deraniyagala, S. A.
Can. J . Chem. 1985, 63, 412. (c) Tondyz, H.; Plas, H. C.; Wozniak, M.
J . Heterocycl. Chem. 1985, 22, 353. (d) Barton, J . W.; Pearson, N. D J .
Chem. Soc., Perkin Trans. 1 1987, 1541. (e) Uno, H.; Okada, S.;
Shiraishi, Y.; Shimokawa, K.; Suzuki, H. Chem. Lett. 1988, 1165. (f)
Andersen, K. E.; Lundt, B. F.; J oergensen, A. S.; Braestrup, C. Eur. J .
Med. Chem. Chim. Ther. 1996, 31, 417. (g) Damavandi, J . A.; Zolfigol,
M. A.; Karami, B. Synth. Commun. 2001, 3183.
(8) (a) Linstead, R. P.; Braude, E. A.; J ackman, L. M.; Beames, A.
N. Chem. Ind. (London) 1954, 1174. (b) Desai, N. B.; Ramanathan,
V.; Venkataraman, K. J . Sci. Ind. Res. 1956, 15 B, 279. (c) Onda, M.;
Yuasa, K.; Okada, J .; Kataoka, K.; Abe, K. Chem. Pharm. Bull. 1973,
21, 1333. (d) Sotiriou-Leventis, C.; Mao, Z.; Rawashdeh, A.-M. M. J .
Org. Chem. 2000, 65, 6017.
(9) (a) Yan, M. C.; J ang, Y. J .; Yao, C. F. Tetrahedron Lett. 2001,
42, 2717. (b) Yan, M. C.; J ang, Y. J .; Kuo, W. Y.; Tu, Z.; Shen, K. H.;
Cuo, T. S.; Ueng, C. H.; Yao, C. F. Heterocycles 2002, 57, 1033.
1566 J . Org. Chem., Vol. 69, No. 5, 2004

Synthesis of 3-Nitro-1,2-dihydroquinolines and 3-Nitroquinolines
SCHEME 2. In ter m ed ia te 5 Gen er a ted fr om th e
1,4-a d d ition of 1-n itr op r op en e (2h ) w ith
2-Am in oben za ld eh yd e (1) P r oceed s Sm ooth ly to
In ter m ed ia te 6 in th e P r esen ce of DABCO
F ollow ed by Deh yd r a tion To Give P r od u ct 3h
nucleophilic addition to generate intermediate 6 and
finally 6 undergoes dehydration to give product 3h
(Scheme 2). This assumption was verified by the isolation
of two isomers of 6 whose spectral data were all consis-
tent with the proposed structures when compound 5 was
purified by flash column chromatography. According to
the description above, there is no doubt that the conden-
sation of 2-aminobenzaldehyde with alkyl nitro olefins
were ascribed to stepwise rather than concerted reaction.
P a r t c. Use of Silica Gel a s a R ep la cem en t of
DDQ. Although the use of DDQ for the aromatization of
a variety of compounds is widely utilized, it is expensive
and the final crude is difficult to purify due to the
increased viscosity.8 Herein, an alternative method for
the aromatization of 1,2-dihydroquinolines by using silica
gel becomes significant. Silica gel is used to support
reactants and catalyze various reactions.10 During the
purification of product 3 by flash column chromatogra-
phy, it was found that small amounts of product 3 were
converted to product 4 in the presence of silica gel. On
the basis of this fact and the oxidation of 1,2-dihydro-
quinolines by oxygen,7d,e silica gel was added to the
reaction solution after the complete formation of 3, and
the solution was then heated at 110 °C for 1 h. When
1
Based on H NMR analyses of the mixture at different
stages (entry 3, Table 2), we found that 2h can be first
attacked by the amino group of 1 to gain a 1,4-addition
intermediate 5, and 5 can then be deprotoned by DABCO
to form the anion, which undergoes intramolecular
SCHEME 3
J . Org. Chem, Vol. 69, No. 5, 2004 1567

Yan et al.
SCHEME 4. Tw o P ossible Rou tes To Give th e Rea r r a n gem en t P r od u ctsa
a
The first possibility is related to the aryl rearrangement of 2-aryl-4-hydroxy-3-nitro-1,2,3,4-tetrahydroquinoline (intermediate A),
which is produced via the Michael addition of the â-nitrostyrene (path I). The other possibility is to proceed through the rearrangement
of the nitro group of intermediate B obtained from path II.
TABLE 3. Use of Silica Gel a s a Rep la cem en t for DDQ
To Gen er a te Com p ou n d 4
P a r t d . Con d en sa tion of 2-Am in oben za ld eh yd e
Der iva tives w ith Nitr o Olefin s. Steric effects fre-
quently play an important role in reactions. When
N-methyl-2-aminobenzaldehyde11 7 was used, the results
were different from eq 1 and Table 1. For example, only
49% of 8 and 6% of 9 were observed when 7 was reacted
with 2a under reflux for 5 days (Scheme 3, eq 4).
Similarly, only 40% of 10 and traces of 11 were observed
when 2c was used (Scheme 3, eq 5). We also got the
similar results when compound 1211 was used (Scheme
3, eqs 6 and 7). Although the more reactive â-nitrostyrene
2l was used, the reaction time was still lengthy and the
yield of 13 was low (Scheme 3, eq 6). In eqs 5 and 6, an
increase in refluxing time failed to improve the product
yield.
The elimination products 9 and 11 were produced from
intermediate A in Scheme 4, which was obtained by a
Michael addition of nitrostyrene. There are two possible
ways (Scheme 4) to produce the rearrangement products
8, 10, 13, and 15. The first possibility is related to the
aryl rearrangement of 2-aryl-4-hydroxy-3-nitro-1,2,3,4-
tetrahydroquinoline (intermediate A in Scheme 4) which
is produced via the Michael addition (path I of Scheme
4) of â-nitrostyrene. The second possibility is to proceed
through the rearrangement of the nitro group of inter-
mediate B in Scheme 4 which is produced from path II.
To determine the mechanism of the formation of the
rearrangement product, 13C-labeled and deuterium-
labeled nitrostyrenes 2m , 2n , and 2o were reacted with
entry
2
reflux time (h)
4a (%)
1
2
3
4
5
6
7
2a
2b
2c
2e
2h
2i
15.5
18.5
15
45.5
9, 3.5b
12, 4b
15, 4b
4a (85)
4b (75)
4c (99)
4e (94)
4h (63)
4i (80)
4j (85)
2j
a
All yields were obtained from 1H NMR spectral data with a
b
known amount of toluene as an internal standard. The reaction
solution was heated at 45 °C for a few hours before DABCO was
added. After the addition of DABCO, the solution was further
heated at 45 °C for another few hours.
the solution was heated at 110 °C, the benzene evapo-
rated. The silica gel was then washed with CH2Cl2, and
upon evaporation of the solvent, product 4 was obtained
(eq 3 and Table 3). It is obvious that the treatment with
silica gel is a better method than the use of DDQ in the
purification and the yields of 3-nitroquinolines 4 in both
treatments were only slightly different.
(11) Methyl iodide and potassium carbonate were added to the
methyl anthranilate THF solution. After 3 days at room temperature,
the solution was quenched and N-methyl methylanthranilate was
isolated by flash chromatography. The procedures of ref 6a to give
N-methyl-2-aminobenzaldehyde were then followed. A similar proce-
dure was used to obtain N-benzyl-2-aminobenzaldehyde, where benzyl
bromide replaced methyl iodide.
(10) (a) Hudlicky, M. J . Org. Chem. 1974, 39, 3460. (b) Lindley, S.
M.; Flowers, G. C.; Leffler, J . E. J . Org. Chem. 1985, 50, 607. (c) Kropp,
P. J .; Breton, G. W.; Craig, S. L.; Crawford, S. D.; Durland, W. F., J r.;
J ones, J . E., III; Raleigh, J . S. J . Org. Chem. 1995, 60, 4146 and papers
cited. (d) Lin, W. W.; J ang, Y. J .; Wang, Y.; Liu, J . T.; Hu, S. R.; Wang,
L. Y.; Yao, C. F. J . Org. Chem. 2001, 66, 1984.
(12) (a) Buckley, G. D.; Scaife, C. W. J . Chem. Soc. 1947, 1471. (b)
Carroll, F. I.; White, J . D.; Wall, M. E. J . Org. Chem. 1963, 28, 1236.
1568 J . Org. Chem., Vol. 69, No. 5, 2004

Synthesis of 3-Nitro-1,2-dihydroquinolines and 3-Nitroquinolines
SCHEME 5
12, respectively (Scheme 5, eqs 8-10). From eq 8 using
2m , product 17 was produced in a reaction where the
amino group of 12 attacked the â carbon (path II in
Scheme 4) but not the R carbon (path I of Scheme 4) of
â-nitrostyrene 2m to form intermediate B (Scheme 44).
In eqs 9 and 10, product 15 was also obtained. The reason
15 in eq 9 is obtained is due to the loss of deuterium on
intermediate B (Scheme 4) during the rearrangement,
and this suggests that the rearrangement from interme-
diate B to the rearrangement product, as in 15, occurred
via intermediate C. Intermediate B lost HNO2 to form
intermediate C, and NO2- was then added to the 3-posi-
tion of intermediate C to form the rearrangement product
(Scheme 5). In eq 10, the loss of deuterium may be due
to the basic environment which permits the exchange of
the acidic deuterium on intermediate B.
through path II (Scheme 4) were obtained. However,
when a less bulky nitro olefin 2h reacted with 12, only a
Michael addition product was observed (eq 11).
It is not surprising that when the less sterically bulky
nitro olefin 2h was used instead of 2l or 2c in a reaction
with 12 (eq 11), only the Michael addition product 18
(39%) was obtained. In conclusion, the reactions in eq 6
and 7 only proceeded through path II but not path I
(Scheme 4), and products 9 and 11 prove that 1, 4-addi-
tion (path I in Scheme 4) occurred in eqs 4 and 5. A
different steric bulky group on the amino group of
2-aminobenzaldehyde derivatives, 1, 7, and 12, and
different steric bulky groups R on nitro olefins 2 caused
the reaction to proceed by a different mechanism. When
2-aminobenzaldehyde 1 was used (eq 1), only Michael
addition occurred. However, when the steric hindrance
increased, the reactions through path II occurred. The
reactions (eqs 4 and 5) proceeded through both paths I
and II (Scheme 4) when 7 containing a methyl group
attached on amino group was reacted with â-nitrosty-
renes 2a and 2c. When 12, which contains a benzyl group
attached to the amino group, was reacted with â-ni-
trostyrenes 2c and 2l (eqs 6 and 7), only the products
After purification of 8 and 10, the 1H NMR and 13C
NMR spectra were obtained using CDCl3 as the solvent.
When the NMR tubes containing compound 8 and 10
were kept at room temperature for 1 week, crystals
appeared. When the crystals were analyzed by the X-ray
crystallography, surprisingly, their structures were found
to be 19 and 20 (Figure 1). A possible mechanism is
F IGURE 1. Two surprising crystal structures 19 and 20 were
obtained, respectively, in mild acidic condition when pure 8
and 10 were kept in NMR tubes at room temperature for 1
week.
J . Org. Chem, Vol. 69, No. 5, 2004 1569

Yan et al.
SCHEME 6. P ossible Mech a n ism To F or m
P r od u cts 19 or 20a
found in the literature, although not with 2-aminoben-
zaldehydes. This study of such reactions involving nitro
olefins with 2-aminobenzaldehydes represents an inter-
esting variation in the Friedlander-type-quinoline syn-
thesis. The two-step/one-pot variant is an improvement
in that 3-nitro-1,2-dihydro quinolines can be obtained
from the first step and 3-nitroquinolines can be produced
from the second step and all the yields are reasonable to
good. In the second step (oxidation), two choices including
the use of DDQ or silica gel can be selected and silica gel
seems to be preferred to DDQ due to the ease of
purification. When N-substituted 2-aminobenzaldehydes
were used in the reactions, unique rearrangement prod-
ucts 8, 10, 13, and 15 were obtained. The rearrangement
leading to 8, 10, 13, 15, and their salts 19 and 20 are
unusual. In fact, 19 and 20 represent interesting elec-
trophiles and their preparation and use would be as
interest in future studies. Finally, this method can be
recommended for its ease of handling, the control of the
desired products, and the high yields of the products.
a
The key step is the transformation of intermediate D to
intermediate E under mild acidic conditions.
proposed for this in Scheme 6 to proceed through
intermediate D and E. Intermediate D in Scheme 6 and
intermediate C in Scheme 4 are the same. However, 19
and 20 were not found in eq 3 and 4, respectively,
possibly due to the basic reaction conditions employed
and the transformation from intermediate D to interme-
diate E (Scheme 6) would be improved in the mild acidic
condition. Intermediate D can proceed smoothly to
intermediate E (Scheme 6) in CDCl3 because it is mildly
acidic.
Ack n ow led gm en t. Financial support by the Na-
tional Science Council of the Republic of China is
gratefully acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for all compounds not described in the text. LRMS,
HRMS, and NMR spectra of representative compounds. X-ray
data for 3g, 4a ,c,i, 13 (isom er B), 15 (isom er A), 17, 19, and
20. This material is available free of charge via the Internet
at http://pubs.acs.org.
Con clu sion
In terms of scientific relevance, examples of addition/
condensation reactions involving nitro olefins can be
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1570 J . Org. Chem., Vol. 69, No. 5, 2004