Conjugate Michael-additions with mixed diorganozincs
Philip Jones and Paul Knochel*
Fachbereich Chemie der Philipps-Universität Marburg, Hans-Meerwein-Straße,
3
5032 Marburg, Germany
Mixed diorganozincs (RZnCH SiMe ; R = alkyl, aryl)
undergo selective transfer of the R group in a 1,4-fashion
to various Michael-acceptors.
aldehyde (2d; entries 9–10) occurs smoothly providing the func-
tionalized aldehydes 2g–j in 51–91% yield. No 1,2-addition
products are observed (see Experimental section). Also, the
conjugated addition to acrylic esters like butyl acrylate pro-
duces the expected Michael-adducts 3k–l under similar reaction
conditions (Ϫ30 ЊC, 3 h) in 76–86% yield (entries 11 and 12).
The addition to acrylonitrile 2f affords the conjugated addition
product 3m in which the trimethylsilyl group has been
incorporated in the position α to the cyano group (3m: 54%;
entry 13). Finally, addition to nitroolefins like 1-nitrobutene 2g
leads to nitroalkanes such as 3n and 3o in 64–76% yield (entries
14 and 15). In no case, was transfer of the trimethylsilylmethyl
group observed.
2
3
Diorganozincs are a useful class of organometallic intermedi-
1
2
ates. They can be readily prepared via iodine–zinc exchange
3
or boron–zinc exchange and tolerate the presence of numer-
1–4
ous functional groups. In the presence of transition metal
catalysts, they react with various electrophiles leading to poly-
functional products. Recently, we have found that a polar
cosolvent like N-methylpyrrolidinone (NMP) allows the 1,4-
5
addition to proceed in the absence of any copper or transi-
tion metal catalyst. Unfortunately, only one organic group of
the diorganozinc is transferred to an organic electrophile.
However, we could show that mixed diorganozincs bearing a
trimethylsilylmethyl group (RZnCH SiMe 1) can be readily
In summary, we have shown that the mixed zinc reagents 1
undergo a conjugate addition to various Michael-acceptors.
Extension of these reactions using other chiral non-transferable
groups is underway.
2
3
6
prepared and characterized spectroscopically. It was found
that the CH SiMe group plays the role of a non-transferable
2
3
group which avoids the waste of an organic residue attached to
zinc. This proves to be especially important for the perform-
ance of asymmetric additions to aldehydes. In preliminary
Experimental
6
Standard procedure: preparation of ethyl 6-(formyl)decanoate 3j
3
experiments we have shown that the reagents 1 add to
1,2-Dibromoethane (0.2 cm ) was added dropwise to a stirred
6
3
cyclohexenone. Herein, we wish to report that mixed diorg-
mixture of zinc dust (1.57 g, 24 mmol) in THF (6 cm ) at room
anozincs of type 1 react with a variety of Michael-acceptors
leading to 1,4-adducts of type 3 in good yields (Scheme 1 and
Table 1).
temperature under argon, whilst heating with a heat gun to boil
the solvent gently. Upon complete addition the mixture was
cooled to room temperature and then trimethylsilyl chloride
3
(
0.2 cm ) was added dropwise over 5 min, again with gentle
O
FG-R
O
heating of the solvent. After complete addition, the mixture
was stirred at room temperature for a further 5 min. Ethyl 4-
iodobutanoate (1.45 g, 6 mmol) was added dropwise over 5
min, and then the reaction was heated at 50 ЊC for 3 h, and the
zinc insertion reaction monitored by GC analysis. When the
reaction was complete the reaction mixture was cooled to room
temperature and the excess zinc dust allowed to settle for 15
min. The pale grey solution was transferred to a flame dried
flask and cooled to Ϫ40 ЊC. A solution of trimethylsilylmethyl-
FG
R
ZnCH2SiMe3
i
+
X
X
FG R = Alkyl, Aryl
1
2
X = Alkyl, H, OR
3
Scheme 1 Reagents and conditions: i, Me SiBr (2 equiv.), THF, NMP,
3
Ϫ30 ЊC, 12 h
Thus, the reaction of 2-furyllithium with (trimethylsilyl-
methyl)zinc iodide in THF at Ϫ40 ЊC furnishes the mixed
Ϫ3
3
lithium (6 mmol) in pentane (1.0 mol dm
,
6.0 cm ) was added
(
trimethylsilylmethyl)(2-furyl)zinc which was allowed to react
dropwise over 3 min to the zinc iodide solution and then stirred
at Ϫ30 ЊC with hex-4-en-3-one 2a (ca. 0.7 equiv.) in the pres-
7
3
ence of trimethylsilyl bromide in NMP affording the Michael-
at Ϫ40 ЊC for one hour. NMP (1 cm ), trimethylsilyl bromide
3
3
(1.0 cm
, 8 mmol) and then 2-butylacrylaldehyde 2d (0.53 cm ,
adduct 3a as sole product in 95% yield (see entry 1 of Table 1).
Secondary zinc reagents or functionalized dialkylzincs like (4-
chlorobutyl)(trimethylsilylmethyl)zinc can also be used with
equal efficiency (see entries 2 and 3 of Table 1). In this case the
mixed zinc reagent is best prepared by adding commercially
available Me SiCH Li to 4-chlorobutylzinc iodide obtained by
4
mmol) were added to this reaction mixture at Ϫ60 ЊC. The
reaction was warmed to Ϫ30 ЊC, and stirred at this temperature
for 3 h. The reaction was poured into saturated aqueous
3
ammonium chloride (50 cm ) and worked up as usual. The resi-
due was further purified by column chromatography on silica
using 15% diethyl ether–light petroleum as eluent to give the
aldehyde 3j (0.65 g, 71%) as a colourless oil.
3
2
1
the direct insertion of zinc dust into 4-chloroiodobutane in
THF. The mixed reaction conditions involved in these Michael-
additions allow the use of reactive vinyl methyl ketone 2b which
adds various aryl and alkyl zinc reagents in 74–92% yield
Acknowledgements
(
entries 4–6). Whereas the addition of organocuprates to
unsaturated aldehydes often requires the use of highly polar
cosolvents like HMPA, the addition of the mixed zinc reagent
to unsaturated aldehydes like 2-methylbut-2-enal 2c (entries
The authors wish to thank the DFG (SFB 260 and Leibniz
program) for generous financial support, and the Royal Society
for an award (to P. J.) under the European Science Exchange
Programme.
8
7
–8) or the reactive β-unsubstituted aldehyde 2-butylacryl-
J. Chem. Soc., Perkin Trans. 1, 1997
3117