One-pot synthesis of trans-β-alkylstyrenes

Article abstract of DOI:10.1016/S0040-4039(01)01185-6

One-pot synthesis of (E)-alkenes 5 from the reactions of aldehyde 1 and nitromethane 2 in the acetic acid solution and then with triethylborane 4 in the biphase of diethyl ether and aqueous solution in the presence of oxygen in air was reported. Various (E)-alkenes 7 could also be prepared when different kinds of secondary or tertiary alkyl iodides 6 were used under similar conditions.

Full text of DOI:10.1016/S0040-4039(01)01185-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6147–6150
One-pot synthesis of trans-b-alkylstyrenes
Ju-Tsung Liu and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei, Taiwan 116, ROC
Received 27 April 2001; revised 1 June 2001; accepted 29 June 2001
Abstract—One-pot synthesis of (E)-alkenes 5 from the reactions of aldehyde 1 and nitromethane 2 in the acetic acid solution and
then with triethylborane 4 in the biphase of diethyl ether and aqueous solution in the presence of oxygen in air was reported.
Various (E)-alkenes 7 could also be prepared when different kinds of secondary or tertiary alkyl iodides 6 were used under similar
conditions. © 2001 Elsevier Science Ltd. All rights reserved.
Nitro olefins are useful intermediates in organic synthe-
sis and can be used as starting materials for many
classes of compounds.1 Reactions of b-nitrostyrenes
with dialkylzinc or organozinc halides,2 t-BuHgX/KI,3
organomanganese,4 trialkylgallium,5 organoborane,6
triethylaluminum or diethylaluminum chloride,7 and
Grignard reagents,8 respectively, to generate alkenes
and/or nitroalkanes or halooximes have been reported.
These results indicate that b-nitrostyrenes can react
with different organometallic reagents to generate dif-
ferent products under different conditions and workup
procedures and the reaction mechanism is proposed to
be free-radical and/or an ionic reaction.1–8
in the presence of tin hydride under mild conditions.
On the basis of literature reports, we wish to report an
easy and effective method to synthesize different (E)-
alkenes in one-pot condition by combining our previous
study6 and literature methodology.11–13 The strategy is
to react b-nitrostyrenes 3, in situ prepared from aro-
matic aldehydes 1 with nitromethane 2 in the acetic
acid solution with a catalytic amount of ammonium
acetate at 100°C for 3 hours (method A)10 or at 70°C
for overnight (method B), with triethylborane 4 in the
biphase of diethyl ether and aqueous solution in the
presence of oxygen in air as radical initiator at room
temperature for 5–10 minutes to generate 5 (Eq. (1)).
Ar
H
H
Ar
H
H
Et2O-H2O
HOAc-NH4OAc
CH3NO2
ArCHO
+
(1)
100 oC, 3 hr or
70 oC, overnight
Et
Et3B (4)
NO2
2
1
3
5
Benzaldehyde 1a (1 mmol) reacted with nitromethane 2
(1 mL) in the acetic acid solution (1 mL) with ammo-
nium acetate (0.1 mmol) at 100°C for 3 hours (method
A)10 to generate 98% of NMR (93% of isolated) yield of
(E)-b-nitrostyrene 3a. When triethylborane 4 (4 mmol
in hexane) was dropwise added into the acetic acid and
nitromethane solution in the presence of oxygen in air
as radical initiator at room temperature for 5–10 min-
utes, 21% of (E)-1-phenylbutene 5a and 76% of (E)-b-
nitrostyrene 3a (NMR yield) were observed after the
solution was quenched with water and extracted with
diethyl ether (entry 1 of Table 1). Similarly, when 10
mL of diethyl ether was added into the acetic acid and
nitromethane solution to form the homogeneous solu-
tion and then the mixture was added triethylborane,
46% of 5a and 50% of 3a were observed (entry 2 of
Table 1). We were also surprised to find that both 43%
The Knoevenagel condensation reaction of carbonyl
compounds with nitroalkanes as the methylene compo-
nent (Henry reaction) is a general and useful method
for the preparation of nitroaldols or nitroalkenes.9 It
has been reported that 35–90% of nitroalkenes may be
isolated when different aromatic aldehydes react with
the appropriate nitroalkanes in an acetic acid solution
with ammonium acetate at 100°C for a few hours.10
Triethylborane11,12 and diethylzinc2a,12d–e,13 not only can
be served as one of the methods for the generation of
radical species but also can be used as an effective
radical initiator to generate different radicals by reac-
tion of triethylborane or diethylzinc with alkyl halides
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01185-6

6148
J.-T. Liu, C.-F. Yao / Tetrahedron Letters 42 (2001) 6147–6150
O
O
O
O
MeO
H
H
1b:
1e:
1c:
1f:
1a:
1d:
H
H
MeO
O
O
MeO
MeO
O
O
H
H
OMe
O
O
OMe O
MeO
MeO
H
H
1g:
1j:
H
1h:
1k:
1i:
1l:
Cl
MeO
F
OMe
OMe
O
F
O
O
H
H
H
F3C
O
H
H
H
1n:
1o:
1m:
O
S
O
O
Table 1. One-pot synthesis of trans-alkenes 5 from aromatic aldehyde 1, nitromethane 2, and triethylborane 4
Entry
Substrate
Method
Product
NMR yield (%)
Isolated yield (%)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1b
1b
1c
1d
1e
1f
1g
1h
1i
1i
1j
A
A
A
A
A
B
B
B
B
B
B
B
A
B
A
A
B
A
B
A
B
A
B
A
B
5a
5a
5a
5a
5b
5b
5c
5d
5e
5f
5g
5h
5i
5i
5j
21a
46b
43c
94
71d
90
90
88
75
78
96
87
77
76
72
76
64
96
65
82
83
70
51
51
69
–
–
–
79
–
79
81
78
66
68
85
79
65
–
62
61
–
83
–
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
1k
1k
1l
5k
5k
5l
1l
5l
1m
1m
1n
1n
1o
1o
5m
5m
5n
5n
5o
5o
–
75
51
–
–
55
a 76% of 3a.
b 50% of 3a.
c 53% of 3a.
d 26% of 1b.

J.-T. Liu, C.-F. Yao / Tetrahedron Letters 42 (2001) 6147–6150
6149
of 5a and 53% of 3a were also observed when 4 mL of
water were added into the acetic acid solution and then
to the mixture was added triethylborane and worked up
as described above (entry 3 of Table 1). This result
indicates that the free radical reaction also occurred in
the aqueous solution. On the basis of the results of
entries 1–3, we first tried to add 10 mL of diethyl ether
to form a homogenenous solution and then add 4 mL
of water to form the biphase of diethyl ether and
aqueous solution and then the triethylborane was
added dropwise, as described above. Surprisingly, only
94% of 5a and traces of unidentified products were
observed under these conditions (entry 4 of Table 1).
When the crude mixture was checked by NMR or
analyzed by GCMS, no 3a was detected in the solution.
This result indicates that 3a has reacted with
triethylborane6 completely under these conditions and
the purification of 3a is not necessary during the reac-
tion because the solvent, such as acetic acid, and the
catalyst, such as ammonium acetate, and other water
soluble compounds have dissolved in the aqueous solu-
tion and have no effect on the free radical reaction
which occurs in the diethyl ether solution. This is an
easy and effective method to prepare 5a from 1a and 2
to generate 3a and then react with 4 in a one-pot
reaction, and this method can also be applied to pre-
pare other trans-alkenes 5 just by using different kinds
of aromatic aldehydes 1.
analysis (entry 5 of Table 1). This result is also consis-
tent with the literature report that the condensation of
electron rich aromatic aldehyde with nitroalkanes
always affords low yield of nitroalkenes.14 To improve
the yield of 5b, the reaction temperature was decreased
from 100 to 70°C and the reaction time was increased
from 3 hours to overnight (method B) and then the
solution was treated with triethylborane in the biphase
of diethyl ether and an aqueous solution, as described
above. A higher yield (90%) of 5b and only a trace of
unreacted starting material 1b were observed in the
crude NMR analysis (entry 6 of Table 1). With elec-
tron-withdrawing substituted aldehyde 1l and by using
method A, 96% of 5l was generated (entry 18 of Table
1) and only 65% of 5l was observed by using method B
(entry 19 of Table 1) and these results indicate that the
electron-withdrawing group can accelerate the genera-
tion of the intermediate 3 dramatically so that only 3
hours are long enough for these reactions. With other
aromatic aldehydes 1, medium to high yields of 5 were
also observed; all the experimental data are shown in
Table 1.
Tashtoush and Sustmann reported that alkyl radicals
including 1-adamantyl radical and aryl radical can be
generated by the reduction of alkyl or aryl halides with
(ethylenediamine)chromium(II) complexes in dry
dimethylformamide.15 Bra¨se et al. also reported that the
palladium-catalyzed reaction of 1-bromoadamantane
with styrene and donor-substituted styrenes give 15–
41% of the corresponding Heck-type coupling product
With electron-donating substituted aldehyde 1b and by
using method A, not only 71% of 5b but also 26% of
unreacted 1b was also observed in the crude NMR
MeO
CHO
Et2O-H2O
H
HOAc-NH4OAc
CH3NO2
+
3b
70 oC, overnight
RI(6)/Et3B(4)
(2)
H
R
OMe
1b
2
7
Table 2. One-pot synthesis of trans-alkenes 5 from aromatic aldehyde 1, nitromethane 2, alkyl iodide 6, and triethylborane 4
O
I
I
I
6b:
6c:
6a:
6d:
6e:
Me
Me
Me
Me
Me
I
I
O
7a: R =
7d: R =
7e: R =
7b: R =
7c: R =
Me
Me
Me
Me
Me
Entry
Substrate
Method
RI
Product
NMR yield (%)
Isolated yield (%)
1
2
3
4
5
1b
1b
1b
1b
1b
B
B
B
B
B
6a
6b
6c
6d
6d
7a
7b
7c
7d
7e
88
73
70
76
84
73
65
61
65
74

6150
J.-T. Liu, C.-F. Yao / Tetrahedron Letters 42 (2001) 6147–6150
(E)-1-adamantyl-2-arylethene.16 Similarly, Yamataka
and co-workers have also reported that both (Z)- and
(E)-1-adamantyl-2-arylethene mixture can be prepared
from the Wittig reaction of substituted benzaldehydes
with (1-adamantylmethylidene)triphenylphosphorane.17
Our recent study also found that similar products can
also be prepared from the reaction of 1b with
iodoadamantane or 5-iodoadamantan-2-one and tri-
ethylaluminum in the presence of benzoyl peroxide.18
4. Namboothiri, I. N. N.; Hassner, A. J. Organomet. Chem.
1996, 518, 69.
5. Han, Y.; Huang, Y.-Z.; Zhou, C.-M. Tetrahedron Lett.
1996, 37, 3347.
6. Yao, C.-F.; Chu, C.-M.; Liu, J.-T. J. Org. Chem. 1998,
63, 719.
7. Chu, C.-M.; Liu, J.-T.; Lin, W.-W.; Yao, C.-F. J. Chem.
Soc., Perkin Trans. 1 1999, 47.
8. (a) Kohler, E. P.; Stone, J. R. J. Am. Chem. Soc. 1930,
52, 761; (b) Buckley, G. D. J. Chem. Soc. 1947, 1494; (c)
Buckley, G. D.; Ellery, E. J. J. Chem. Soc. 1947, 1497; (d)
Ashwood, M. S.; Bell, L. A.; Houghton, P. G.; Wright, S.
H. B. Synthesis 1988, 379; (e) Yao, C.-F.; Chen, W.-W.;
Lin, Y.-M. Tetrahedron Lett. 1996, 37, 6399; (f) Yao,
C.-F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.;
Chen, W.-C.; Lin, Y.-M.; Lin, W.-W.; Yan, M.-C.; Liu,
J.-Y.; Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54,
791; (g) Liu, J.-T.; Lin, W.-W.; Jang, J.-J.; Liu, J.-Y.;
Yan, M.-C.; Hung, C.; Kao, K.-H.; Wang, Y.; Yao,
C.-F. Tetrahedron 1999, 55, 7115.
9. (a) Jones, G. Organic Reactions; John Wiley: New York,
1968; Vol. 15, p. 204; (b) Luzzio, F. A. Tetrahedron 2001,
57, 915.
10. Andrew, R. G.; Raphael, R. A. Tetrahedron 1987, 43,
4803.
After observation of the literature reports, we tried to
apply this methodology to react 1b with different radi-
cals generated from alkyl iodide 6 (6–20 equivalents)
and 4 (4 equivalents), under similar conditions, to
prepare other alkenes (Eq. (2)). As expected, medium to
high yields of 7 were generated under similar proce-
dures and conditions as described above (Table 2). This
result indicates that not only the ethyl radical but also
the different secondary or tertiary radical can react with
1 to obtain different trans-alkenes 7.
In conclusion, we have developed an easy and effective
method to prepare medium to high yields of (E)-alke-
nes by using aromatic aldehydes, nitromethane, alkyl
iodide RI, and triethylborane in the biphase solution of
diethyl ether and aqueous solution in one-pot condition
in the presence of oxygen in air. Further study about
the application of this methodology to synthesize other
compounds is under investigation.
11. Smadja, W. Synlett 1994, 1.
12. (a) Suzuki, A.; Nozawa, S.; Harada, M.; Itoh, M.;
Brown, H. C.; Midland, M. M. J. Am. Chem. Soc. 1971,
93, 1508; (b) Nozaki, K.; Oshima, K.; Utimoto, K. J.
Am. Chem. Soc. 1987, 109, 2547; (c) Nozaki, K.; Oshima,
K.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1041; (d)
Bertrand, M. P.; Feray, L.; Nouguier, R.; Perfetti, P. J.
Org. Chem. 1999, 64, 9189; (e) Miyabe, H.; Ushiro, C.;
Ueda, M.; Yamakawa, K.; Naito, T. J. Org. Chem. 2000,
65, 176; (f) Wu, B.; Avery, B. A.; Avery, M. A. Tetra-
hedron Lett. 2000, 41, 3797; (g) Miyabe, H.; Ueda, M.;
Naito, T. J. Org. Chem. 2000, 65, 5043; (h) Miyabe, H.;
Fujii, K.; Goto, T.; Naito, T. Org. Lett. 2000, 2, 4071; (i)
Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima,
K.; Omoto, K.; Fujimoto, H. J. Am. Chem. Soc. 2000,
122, 11041; (j) Fujita, K.; Nakamura, T.; Yorimitsu, H.;
Oshima, K. J. Am. Chem. Soc. 2001, 123, 3137.
13. Ryu, I.; Araki, F.; Minakata, S.; Komatsu, M. Tetra-
hedron Lett. 1998, 39, 6335.
14. (a) Monte, A. P.; Waldman, S. R.; Marona-Lewicka, D.;
Wainscott, D. B.; Nelson, D. L.; Sanders-Bush, E.;
Nichlos, D. E. J. Med. Chem. 1997, 40, 2997; (b)
McNulty, J.; Steere, J. A.; Wolf, S. Tetrahedron Lett.
1998, 39, 8013.
15. (a) Tashtoush, H. I.; Sustmann, R. Chem. Ber. 1992, 125,
287; (b) Tashtoush, H. I.; Sustmann, R. Chem. Ber. 1993,
126, 1759.
Acknowledgements
Financial support of this work by the National Science
Council of the Republic of China is gratefully
acknowledged.
References
1. (a) Corey, E. J.; Estreicher, H. J. Am. Chem. Soc. 1978,
100, 6294; (b) Seebach, D.; Colvin, E. W.; Weller, T.
Chimia 1979, 33, 1; (c) Barrett, A. G. M.; Graboski, G.
G. Chem. Rev. 1986, 86, 751; (d) Rosini, G.; Ballini, R.
Synthesis 1988, 833; (e) Several articles in Tetrahedron
Symposia-in-Print 41, Nitroalkanes and Nitroalkenes in
Synthesis, Tetrahedron 1990, 46, Barrett, A. G. M., Ed;
(f) Barrett, A. G. M. Chem. Soc. Rev. 1991, 20, 95.
2. (a) Seebach, D.; Schafer, H.; Schmidt, B.; Schreiber, M.
Angew. Chem., Int. Ed. Engl. 1992, 31, 1587; (b) Hu, Y.;
Yu, J.; Yang, S.; Wang, J.-X.; Yin, Y. Synlett 1998, 1213;
(c) Hu, Y.; Yu, J.; Yang, S.; Wang, J.-X.; Yin, Y. Synth.
Commun. 1999, 29, 1157.
16. Bra¨se, S.; Waegell, B.; de Meijere, A. Synthesis 1998, 148.
17. Yamataka, H.; Takatsuka, T.; Hanafusa, T. J. Org.
Chem. 1996, 61, 722.
3. Russell, G. A.; Yao, C.-F. Heteroat. Chem. 1992, 3,
209.
18. Liu, J.-Y.; Liu, J.-T.; Yao, C.-F. Tetrahedron Lett. 2001,
42, 3613.