Conjugate addition of mixed diorganozinc compounds and functionalized organozinc cuprates to nitroolefins

Article abstract of DOI:10.1021/ol026557w

equation presented The copper-catalyzed conjugate addition of symmetrical and mixed diorganozinc compounds as well as functionalized diorganozinc cuprates to nitroolefins leads to synthetically versatile nitro compounds in moderate to good yields. Mixed TMSM-organozinc compounds are suitable reagents for conjugate addition, since the TMSM group is not being transferred. Ipso substitution is observed in the absence of a catalytic amount of copper(I) salt. The nitroalkene moiety in 3-nitroacrylates proved to be the predominant Michael acceptor.

Full text of DOI:10.1021/ol026557w

ORGANIC
LETTERS
2002
Vol. 4, No. 19
3289-3291
Conjugate Addition of Mixed
Diorganozinc Compounds and
Functionalized Organozinc Cuprates to
Nitroolefins
Audrius Rimkus and Norbert Sewald*
UniVersity of Bielefeld, Faculty of Chemistry, P.O. Box 10 01 31,
D-33501 Bielefeld, Germany
norbert.sewald@uni-bielefeld.de
Received July 18, 2002
ABSTRACT
The copper-catalyzed conjugate addition of symmetrical and mixed diorganozinc compounds as well as functionalized diorganozinc cuprates
to nitroolefins leads to synthetically versatile nitro compounds in moderate to good yields. Mixed TMSM-organozinc compounds are suitable
reagents for conjugate addition, since the TMSM group is not being transferred. Ipso substitution is observed in the absence of a catalytic
amount of copper(I) salt. The nitroalkene moiety in 3-nitroacrylates proved to be the predominant Michael acceptor.
The conjugate addition of organometallic compounds to R,â-
unsaturated compounds is an important method for the
construction of new carbon-carbon bonds.1 Nitroolefins
belong to the most powerful Michael acceptors.2 Nitro
compounds in general are particularly versatile intermediates
since the nitro group may be easily transformed into a wide
variety of functionalities.2,3 Nitro groups may easily be
converted into amino groups. Our interest in amino-
substituted carboxylic acids prompted us to embark on a
project dealing with the conjugate addition of functionalized
and unfunctionalized organozinc reagents to nitroolefins,4
which has also been investigated by other groups.5,6 The
ligand-accelerated addition of diethyl zinc to nitrostyrene has
been described for the first time by Alexakis et al.7 Due to
the fact that the organozinc compounds display a remarkable
functional group tolerance,8 a wide range of polyfunctional
molecules can be obtained by conjugate addition of func-
tionalized organozinc compounds to Michael acceptors.
Functionalized zinc-copper reagents have been added to a
series of simple nitroolefins.8
Here we report on the addition of symmetrical and mixed
diorganozinc compounds as well as functionalized diorga-
nozinc cuprates to aliphatic and aromatic nitroolefins. Mixed
diorganozinc reagents composed of one transferable group
R together with the nontransferable trimethylsilylmethyl
(1) For a review, see: Perlmutter, P. Conjugate Addition Reactions in
Organic Synthesis; Pergamon Press: Oxford, UK, 1992.
(2) (a) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979,
33, 1-18. (b) Barrett, A. G. M. Chem. Soc. ReV. 1991, 20, 95-127. (c)
Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002, 1877-
1894.
(3) Rosini, G.; Ballini, R. Synthesis 1988, 833-847.
(4) Wendisch, V.; Sewald, N. Tetrahedron: Asymmetry 1998, 9, 1341-
1344.
(5) Versleijen, J. P. G.; van Leusen, A. M.; Feringa, B. L. Tetrahedron
Lett. 1999, 40, 5803-5806.
(6) Alexakis, A.; Benhaim, C. Org. Lett. 2000, 2, 2579-2581.
(7) Alexakis, A.; Vastra, J.; Mangeney, P. Tetrahedron Lett. 1997, 38,
7745-7748.
(8) Knochel, P.; Singer, R. D. Chem. ReV. 1993, 93, 2117-2188 and
references therein.
10.1021/ol026557w CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/29/2002

group (TMSMZnR)9,10 are especially useful for this type of
conjugate addition, because they avoid the loss of one of
the two organic residues R.
of the ipso product. However, decreasing yields are observed
in this case (Table 1, entry 5).
Further results of the copper-catalyzed conjugate addition
of TMSMZnR to nitroolefins 3 are summarized in Table 2.
Dialkylzinc compounds or mixed diorganozinc compounds
TMSMZnR can be added to nitroolefins and other Michael
acceptors in a mixture of THF and the polar cosolvent
N-methylpyrrolidone (NMP) in the absence of any copper
or transition metal catalyst.11 Formation of the ipso-product
2 (Scheme 1) has not been observed under these conditions.
Table 2. Copper-Catalyzed Conjugate Addition to Nitroolefins
Scheme 1. Conjugate Addition versus Ipso Substitution
entry
nitroolefin
R2
yield, %
product
1
3a
3b
3b
3c
3c
3c
n-butyl
c-hexyl
n-heptyl
n-heptyl
c-hexyl
n-hexyl
72
45
72
46
69
56
4c
4d
4e
4f
4g
4h
2a
3a
4
Usually ipso-type substitution (vinylic substitution) takes
place when nitroolefins bearing an acceptor group are used
together with “soft” nucleophiles.12 However, according to
our investigations, the addition of alkyl(trimethylsilylmethyl)-
zinc reagents13 to nitrostyrene 3a in a THF/NMP mixture in
the absence of copper(I) salts leads to predominant formation
of the ipso-substituted products 5 (Table 1, entries 1 and 2).
5
6
a TMSCl was used instead of TMSBr.
The addition results show that alkyl(trimethylsilylmethyl)-
zinc reagents are suitable for the addition to functionalized
nitroolefins. Even in the case of 3-nitropropenoates 3c, the
nitroolefin moiety acts as the Michael acceptor, giving rise
to the unambiguous formation of 2-alkyl-3-nitro-propanoates
4f-h, despite 3c being a dissonant Michael acceptor (ni-
troalkene vs acrylate moiety).
Table 1. Reaction of Alkyl(trimethylsilylmethyl)zinc Reagents
with Nitrostyrene 3a; Effect of the Copper Salt
Transmetalated diorganozinc compounds RZnCu(CN)R
display a significantly higher reactivity and efficiency toward
electrophiles compared to the copper-zinc halides RZnCu-
(CN)X.14 When nitroolefins are used, useful nitro intermedi-
ates can be prepared following this methodology. The
functionalized diorganozinc compounds are easily prepared
by an iodine-zinc exchange reaction (Scheme 2).14
entry
R
Cu-salt
yield, %
1
2
3
4
c-hexyl
n-heptyl
c-hexyl
n-heptyl
n-heptyl
4a : 5
5a : 28
4b: 15
4a : 70
4b: 83
4b: 64
5b: 43
CuCl
Cu(OTf)2
Cu(OTf)2
-
-
-
5a
a Longer reaction time (24 h).
Scheme 2. Synthesis of the Functionalized Diorganozinc
Compounds
Upon addition of a catalytic amount of copper(I) salt (ca.
2-4 mol %) or copper(II) triflate, which is reduced to
copper(I) under the reaction conditions employed, exclusive
formation of the 1,4-adduct is observed in moderate to good
yields. Longer reaction time does not lead to the formation
(9) For synthesis of TMSMZnR, see: Berger, S.; Langer, F.; Lutz, C.;
Knochel, P.; Mobley, T. A.; Reddy, C. K. Angew. Chem., Int. Ed. 1997,
36, 1496-1498.
(10) TMSM group as a nontransferrable ligand: Bertz, S. H.; Eriksson,
S. H.; Miao, G.; Snyder, J. P. J. Am. Chem. Soc. 1996, 118, 10906-10907.
(11) (a) Reddy, C. K.; Davasagayaraj, A.; Knochel, P. Tetrahedron Lett.
1996, 37, 4495-4498. (b) Jones, P.; Knochel, P. J. Chem. Soc., Perkin.
Trans. 1 1997, 3117-3118. (c) Jones, P.; Reddy, C. K.; Knochel, P.
Tetrahedron 1998, 54, 1471-1490.
(12) (a) Rappoport, Z.; Gazit, A. J. Org. Chem. 1985, 50, 3184-3194.
(b) Jubert, C.; Knochel, P. J. Org. Chem. 1994, 59, 1053-1057 and literature
cited therein.
(13) Synthesized from trimethylsilylmethyllithium (TMSMLi) and the
corresponding iodide. See also footnote 4.
The organozinc cuprates 8, formed by addition of the THF-
soluble salt CuCN‚2LiCl,15 were applied in conjugate addi-
tions to nitroolefins 3 to give functionalized nitro compounds
9 in moderate to good yields (Table 3).
Diorganozinc reagents R2Zn are less readily available
compared to organozinc halides RZnX. However, they
(14) Rozema, M. J.; Sidduri, A.; Knochel, P. J. Org. Chem. 1992, 57,
1956-1958.
(15) Knochel, P.; Yeh, M. C. P.; Berk, S. C.; Talbert, J. J. Org. Chem.
1988, 53, 2390-2392.
3290
Org. Lett., Vol. 4, No. 19, 2002

Scheme 3. Conjugate Addition of Diorganozinc Compounds
Table 3. Conjugate Addition of Functionalized Diorganozinc
Compounds
entry
nitroolefin
R2
CN
CN
COOEt
yield, %
product
1
2
3
3a
3c
3c
67
66
53
9a
9b
9c
display a higher reactivity toward many electrophiles. It has
been reported earlier that a wide variety of functionalized
diorganozinc compounds can be easily prepared via boron-
zinc transmetalation.8,16 Diorganozinc compounds such as
dimyrtanylzinc 10 or bis[2-(ethoxycarbonyl)ethyl]zinc 1117
can be efficiently added to nitroolefins in a copper-catalyzed
conjugate addition reaction (Scheme 3), providing access to
more complex molecules 12 and 13.
In summary, we have shown that alkyl(trimethylsilyl)zinc
compounds (TMSMZnR) can be successfully added to
aliphatic and aromatic nitroolefins affording the correspond-
ing nitro compounds in moderate to good yields. A catalytic
amount of copper(I) salt in the reaction medium prevents
the formation of ipso-substituted product.
Synthetically versatile functionalized nitro compounds
have been synthesized by conjugate addition of functional-
ized diorganozinc cuprates (RZnCu(CN)R) and diorganozinc
compounds (R2Zn) to nitroolefins.
Acknowledgment. This project was supported by the
Fonds der Chemischen Industrie. A.R. was awarded Ph.D.
grants from Konrad Adenauer Stiftung and University of
Bielefeld, which is gratefully acknowledged.
Supporting Information Available: Full experimental
procedures, yields, and the physical and spectroscopic data
of the synthesized compounds (1H NMR, 13C NMR, MS,
IR, microanalyses). This material is available free of charge
via the Internet at http://pubs.acs.org.
(16) Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.;
Knochel, P. J. Org. Chem. 1996, 61, 8229-8243.
(17) For synthesis of 1-trimethylsilyloxy-1-ethoxycyclopropane, see:
Ru¨hlmann, K. Synthesis 1971, 5, 236-253.
OL026557W
Org. Lett., Vol. 4, No. 19, 2002
3291