Solvent- and catalyst-free conjugate additions of organozinc to β-nitroalkene

Article abstract of DOI:10.1055/s-2007-985588

Conjugate addition of allylzinc and benzylzinc reagents to β-nitroalkenes was carried out without solvent and catalyst at room temperature to give products in high yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-985588

2
272
LETTER
Solvent- and Catalyst-Free Conjugate Additions of Organozinc to
b-Nitroalkene
a
a,b
S
a
D
olvent-
a
nd Catal
a
yst-Free Co
n
njugate
A
dd
f
itions of
e
Organozin
n
c
to
b
-Nitroa
g
lkene Huang, Jin-Xian Wang*
Institute of Chemistry, Department of Chemistry, Northwest Normal University, 967 An Ning Road (E.), Lanzhou 730070,
P. R. of China
Fax +86(931)7768159; E-mail: wangjx@nwnu.edu.cn
b
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
Received 8 May 2007
nitroalkenes. Recently, conjugate additions of nitro-
Abstract: Conjugate addition of allylzinc and benzylzinc reagents
to b-nitroalkenes was carried out without solvent and catalyst at
room temperature to give products in high yield.
1
0
11
styrenes mediated by metallic indium, samarium and
zinc12 have been conducted without catalyst in DMF or
THF and satisfactory results were obtained. Although the
simplicity of these procedures is attractive, development
of cheaper, more efficient and environmentally benign
processes is highly desirable.
Key words: b-nitroalkenes, allylzinc, benzylzinc, conjugate addi-
tion, solvent-free
Research work on organozinc halides has been performed
in our laboratory over the past few years.13 We have in-
vestigated the conjugate addition reaction of organozinc
halides such as the conjugate addition reaction of organo-
zinc halides to enone, a,b-unsaturated esters and b-nitro-
1
,4-Conjugate addition of organometallic reagents to
Michael acceptors is one of the important methods to form
carbon–carbon bonds in organic chemistry. In recent
years, organozinc reagents have become very popular in
organic synthesis due to their tolerance to a variety of
other functional groups and mild reactivity. Conjugate
reactions using organozinc reagents have been investigat-
ed extensively. However, most of the research work has
been focused on the catalytic asymmetric 1,4-conjugate
1
2
styrenes using Cu(OAc) instead of CuCN·2LiCl and
2
nickel(II) catalyst.14 With our increasing interest in effi-
cient, economic and environmentally friendly reactions
mediated by cheaper metals, we have successfully per-
formed the solvent-free addition of allyl bromide and
3
addition of dialkylzincs. Organozinc halides are seldom
15
aldehydes and ketones mediated by zinc powder. Now
we have tried to explore the conjugate addition of allyl-
used despite their ready availability. Among the conjugate
reactions of organozinc halides reported, most of them
were carried out with stoichiometric toxic CuCN·2LiCl.2
Only a few of them are catalytic processes involving
16
zinc and benzylzinc reagents to nitroalkenes under sol-
vent-free conditions. We report herein our results of the
conjugate addition of allylzinc and benzylzinc reagents17
to nitroalkenes without solvent and catalyst (Scheme 1).
4
metal copper and palladium. On the other hand, nitro-
alkene is one of the best Michael acceptors and nitro
group, which is often entitled a ‘chemical chameleon’, can
be easily transformed into other useful functional groups
including amine, aldehyde, or acid moieties via nucleo-
philic addition reaction, reduction reaction, Meyer reac-
We first tried the reaction of allylzinc bromide with
nitrostyrenes under solvent-free conditions and obtained
satisfactory results. A variety of substituted nitrostyrenes
were examined and the results are shown in Table 1. It is
noteworthy that the reaction proceeded smoothly at room
temperature and gave products in good yields. For all the
reactions, the 1,4-addition products were obtained. It is
also evident that the product yield was higher (81%) in the
absence of solvent in comparison to that (65%) in THF
3
a,5
tion or other transformations.
Conjugate reactions of nitroalkenes with Grignard or
organolithium reagents were not efficient due to undesir-
able side reactions and very poor product yield. Howev-
er, there have been some reports on 1,4-addition reaction,
initiated by organometallics such as Grignard reagents,
alkyllithium derivatives
5
a
6,7
(
Table 1, entry 1).
6
b,8
and organoaluminium,9 to
NO2
ZnBr
ZnBr
R1
NO2
NO2
R1
solvent-free, r.t.
R
solvent-free, r.t.
R
R
Scheme 1
SYNLETT 2007, No. 14, pp 2272–2276
0
3
.0
9
.2
0
0
7
Advanced online publication: 14.08.2007
DOI: 10.1055/s-2007-985588; Art ID: W09107ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Solvent- and Catalyst-Free Conjugate Additions of Organozinc to b-Nitroalkene
2273
We also found that the nature of the substituents on the To extend the scope of this methodology, we reacted
phenyl ring of the b-nitrostyrenes had a significant effect benzylzinc bromide with nitroalkenes under the same
on the reaction yield. Electron-withdrawing groups, such conditions (Table 2). We found that although Michael ad-
as 4-NO , gave a much lower product yield even after ducts were obtained, the reaction required longer reaction
2
prolonged reaction time (Table 1, entry 8). However, times (3–5 h) and the yields were lower. It is obvious that
electron-rich heterocyclic nitroalkenes afforded the corre- benzylzinc bromide was less reactive than allylzinc bro-
sponding adducts in high yields within a short reaction mide. To improve the yield, excess benzylzinc bromide
time (Table 1, entries 9 and 10).
was used (2.5 equiv vs. 2.0 equiv for allylzinc bromide).
Table 1 Addition Reactions of Allylzinc Bromide to Nitroalkenesa
Entry
Nitroalkene
Productb
Time (h)
1
Yield (%)c
81 (65)d
NO2
NO2
1
2a
NO2
NO2
2
3
2b
2c
2
2
79
84
Cl
Cl
NO2
NO2
MeO
MeO
NO2
NO2
NO2
NO2
4
5
6
7
2d
2e
2f
2
2
2
85
86
82
83
OMe
OCH3
Cl
Cl
NO2
NO2
Cl
Cl
Cl
Cl
NO2
NO2
2g
2h
2
4
Br
Br
NO2
NO2
8
9
53
86
O2N
O2N
NO2
NO2
NO2
2i
2j
1
1
O
S
O
S
1
0
NO2
84
a
b
c
d
18
All reactions were performed with allylzinc bromide (8 mmol) and nitroalkenes (4 mmol) at r.t. under solvent-free conditions.
All products were characterized by IR, H NMR, C NMR, MS, and elemental analyses.
Isolated yield.
1
13
19
The yield in brackets was from the same reaction without removal of THF after the preparation of allylzinc bromide.
Synlett 2007, No. 14, 2272–2276 © Thieme Stuttgart · New York

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D. Huang, J.-X. Wang
LETTER
Similarly, when 4-NO C H -substituted nitroalkene was In conclusion, we have developed a new procedure for the
2
6
4
used as a substrate, no adducts were obtained.
conjugate addition of organozinc halides and nitroalkenes
under solvent-free and catalyst-free conditions at room
temperature. Compared with previously reported reaction
conditions, our reaction here has the following advan-
tages: milder conditions, shorter reaction times, environ-
mentally benign, and high yield.
It is noteworthy that when the reaction between benzyl-
zinc bromide and nitrostyrene was carried out in THF, no
1
,4-addition product was obtained. Instead, a small
amount of coupling product from benzyl bromide was
isolated. Therefore the solvent-free conditions were
necessary for the successful Michael addition of benzyl-
zinc bromide to alkenes. Further investigations on the use
of other organic solvents are currently being undertaken in
our laboratory.
Table 2 Addition Reactions of Benzylzinc Bromide to Nitroalkenesa
Entry
R1
Nitroalkene
Productb
Time (h)
2
Yield (%)c
66
NO2
NO2
1
H
3a
3b
3c
NO2
NO2
2
3
H
H
3
3
67
81
Cl
Cl
NO2
NO2
H3CO
MeO
NO2
NO2
NO2
NO2
4
H
3d
3
76
Cl
Cl
5
6
7
H
3e
3f
3
5
5
70
73
68
OMe
OMe
NO2
NO2
NO2
NO2
NO2
4-Cl
3-Cl
Cl
3g
Cl
NO2
8
9
3-Cl
3-Cl
2-Br
3h
3i
3
5
5
72
69
71
OMe
Cl
OMe
NO2
NO2
Cl
Cl
Cl
NO2
Br
NO2
1
0
3j
Synlett 2007, No. 14, 2272–2276 © Thieme Stuttgart · New York

LETTER
Solvent- and Catalyst-Free Conjugate Additions of Organozinc to b-Nitroalkene
2275
Table 2 Addition Reactions of Benzylzinc Bromide to Nitroalkenesa (continued)
Entry
R1
Nitroalkene
Productb
Time (h)
3
Yield (%)c
NO2
NO2
1
1
3-F
3k
70
F
NO2
1
1
2
3
H
H
NO2
3l
3
2
72
78
O
S
O
S
NO2
NO2
NO2
NO2
3m
1
1
4
5
2-Br
3-Cl
3n
3o
3
3
73
77
O
O
O
Br
NO2
NO2
O
Cl
a
b
c
18
All reactions were performed with benzylzinc bromide (10 mmol) and nitroalkenes (4 mmol) at r.t. under solvent-free conditions.
All products were characterized by IR, H NMR, C NMR, MS, and elemental analyses.
Isolated yield.
1
13
20
Acknowledgment
(4) (a) Lipshutz, B. H.; Wood, M. R.; Tirado, R. J. Am. Chem.
Soc. 1995, 11, 6126. (b) Maezaki, N.; Sawamto, H.;
This work was supported by the Natural Science Foundation of
China (Grant 20272047, 20572086), the Gansu Natural Science
Foundation of China (3ZS051-A25-001) and Key Laboratory of
Eco-Envionment-Related Polymer Material (Northwest Normal
University), Ministry of Education of China.
Yoshigami, R.; Suzuki, T.; Tanaka, T. Org. Lett. 2003, 5,
1345. (c) Yuguchi, M.; Tokuda, M.; Orito, K. Chem. Lett.
2004, 33, 674. (d) Yuguchi, M.; Tokuda, M.; Orito, K. Bull.
Chem. Soc. Jpn. 2004, 1031.
(
(
(
5) (a) Ongeri, S.; Piarulli, U.; Jackson, R. F. W.; Gennari, C.
Eur. J. Org. Chem. 2001, 803. (b) Berner, O. M.; Tedeschi,
L.; Enders, D. Eur. J. Org. Chem. 2002, 1877.
References and Notes
6) (a) Namboothiri, I. N. N.; Hassner, A. J. Organomet. Chem.
1996, 518, 69. (b) Yao, C.-F.; Kao, K.-H.; Liu, J.-T.; Chu,
(
1) (a) Perlmuter, P. In Conjugate Addition Reaction in Organic
Synthesis, In Tetrahedron Organic Chemistry Series, No. 9;
Pergamon Press: Oxford, 1992, 1. (b) Helmchen, G.;
Hoffmann, R. W.; Mulzer, J.; Schaumann, E. In
C.-M.; Wang, Y. Tetrahedron 1998, 54, 791.
7) Ashwood, M. S.; Bell, L. A.; Houghton, P. G.; Wright, S. H.
B. Synthesis 1988, 379.
(
(
8) Knochel, P.; Seebach, D. Tetrahedron Lett. 1981, 22, 3223.
9) Pecunioso, A.; Menicagli, R. J. Org. Chem. 1988, 53, 45.
Stereoselective Synthesis. Houben–Weyl, Methods of
Organic Chemistry, Vol. E21b, 4th ed.; Georg Thieme
Verlag: Stuttgart, 1995, 1041.
(
(
10) Zhang, J. M.; Zhang, Y. M. Chin. J. Chem. 2002, 20, 296.
11) Bao, W. L.; Zheng, Y. F.; Zhang, Y. M. J. Chem. Res.,
Synop. 1999, 732.
12) Kumar, H. M. S.; Reddy, B. V. S.; Reddy, P. T.; Yadav, J. S.
Tetrahedron Lett. 1999, 40, 5387.
(
(
2) (a) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117.
(b) Knochel, P.; Prea, J. A.; Jones, P. Tetrahedron 1998, 54,
(
8275.
3) (a) Duursma, A.; Minnaard, A. J.; Feringa, B. L. J. Chem.
Soc. 2003, 125, 3700. (b) Hird, A. W.; Hoveyda, A. H.
Angew. Chem. Int. Ed. 2003, 42, 1276. (c) Degrado, S. J.;
Mizutani, H.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124,
(
13) (a) Wang, J.-X.; Fu, Y.; Hu, Y. L. Angew. Chem. Int. Ed.
2002, 41, 2757. (b) Wang, J.-X.; Wang, K.; Zhao, L.; Fu, Y.;
Hu, Y. L. Adv. Synth. Catal. 2006, 348, 1262. (c) Hu, Y. L.;
Yu, J. H.; Yang, S.; Wang, J.-X. Synlett 1998, 1213.
14) (a) Hu, Y. L.; Yu, J. H.; Wang, J.-X.; Yin, Y. Q. Synth.
Commun. 1998, 28, 2793. (b) Hu, Y. L.; Yu, J. H.; Wang, J.-
X.; Yin, Y. Q. Chin. Chem. Lett. 1998, 9, 699. (c) Huang,
D. F.; Yang, Y.; Wang, J.-X.; Hu, Y. L. J. Chem. Res.,
Synop. 2002, 79.
13362. (d) Gallo, E.; Ragaini, F.; Licia, B.; Piarulli, U.
(
J. Organomet. Chem. 2004, 689, 2169. (e) Knopff, O.;
Alexakis, A. Org. Lett. 2002, 4, 3835. (f) Mampreian, D.
M.; Hoveyda, A. D. Org. Lett. 2004, 6, 2829. (g) Bräse, S.;
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M. P.; Manyem, S. Tetrahedron 2000, 56, 8033.
(
15) Wang, J.-X.; Jia, X. F.; Meng, T. J.; Xin, L. Synthesis 2005,
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(
(
16) Menicagli, R.; Samaritani, S. Tetrahedron 1996, 52, 1425.
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Synlett 2007, No. 14, 2272–2276 © Thieme Stuttgart · New York

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D. Huang, J.-X. Wang
LETTER
(18) General Procedure for the Reaction: Organozinc halides
(m, 1 H), 2.38–2.56 (m, 2 H). 13C NMR (100 MHz, CDCl ):
3
RZnX (8 mmol and 10 mmol for allyl bromide and benzyl
bromide, respectively) were prepared according to
d = 134.1, 128.8, 127.6, 127.4, 118.1, 79.8, 43.7, 37.6. EI–
+
MS: m/z = 241 [M ], 211, 104, 91, 77. Anal. Calcd for
1
7
Knochel’s procedure. The solvent (THF) was removed in
vacuo and then the nitroalkene (4 mmol) was added slowly.
The resulting reaction mixture was stirred for the duration of
the given time. After complete conversion, as indicated by
TLC, sat. NH Cl solution (10 mL) and Et O (10 mL) were
C H NO : C, 69.09; H, 6.85; N, 7.32. Found: C, 68.46; H,
1
1
13
2
6.93; N, 6.57.
(20) 1-Nitro-3-phenyl-2-(2-furyl)propane (3l): yellow oil. IR
–
1
(KBr): 3063, 3030, 2924, 2860, 1551, 1501, 1451, 1431cm .
1
H NMR (400 MHz, CDCl ): d = 7.37 (dd, J = 0.8, 2.0 Hz,
4
2
3
added and the mixture was stirred for 10 min. The organic
layer was separated and washed with sat. brine (10 mL),
1 H), 7.20–7.30 (m, 3 H), 7.06–7.08 (m, 2 H), 6.26–6.27 (m,
1 H), 6.03–6.04 (m, 1 H), 4.61 (dd, J = 8.0, 12.8 Hz, 1 H),
4.52 (dd, J = 6.4, 12.8 Hz, 1 H), 3.85–3.92 (m, 1 H), 3.11 (dd,
dried over anhyd MgSO and concentrated. The pure product
4
1
3
was obtained by column chromatography of the crude
mixture on silica gel using PE–EtOAc as eluent.
J = 7.6, 13.6 Hz, 1 H), 2.94 (dd, J = 7.6, 13.6 Hz, 1 H). C
NMR (100 MHz, CDCl ): d = 151.9, 142.2, 137.4, 129.0,
3
(
19) 1-Nitro-2-phenylpent-4-ene (2a): pale yellow oil. IR (KBr):
128.6, 127.0, 110.4, 107.5, 77.3, 39.6, 37.3. EI–MS: m/z =
–
1
1
+
3
073, 3030, 2922, 2853, 1641, 1548, 1451, 1434 cm . H
231 [M ], 184, 91, 77. Anal. Calcd for C H NO : C, 67.52;
1
3
13
3
NMR (400 MHz, CDCl ): d = 7.17–7.34 (m, 5 H), 5.60–5.70
H, 5.67; N, 6.06. Found: C, 68.16; H, 5.27; N, 5.40.
3
(
m, 1 H), 5.02–5.09 (m, 2 H), 4.51–4.64 (m, 2 H), 3.52–3.60
Synlett 2007, No. 14, 2272–2276 © Thieme Stuttgart · New York

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