Nickel(II)-catalyzed dialkylation of aromatic aldehydes with organozinc reagents

Article abstract of DOI:10.1246/cl.2001.174

A novel reaction of the dialkylation of arylaldehydes is provided. The reaction of substituted aromatic aldehyde with organozinc halides in the presence of catalytic amount of Ni(acac)₂ and a tertiary amine using a silylating agent to give 1-alkyl-1-arylalkanes in satisfactory yields.

Full text of DOI:10.1246/cl.2001.174

174
Chemistry Letters 2001
Nickel(II)-Catalyzed Dialkylation of Aromatic Aldehydes with Organozinc Reagents
Yulai Hu, Jin-Xian Wang,* and Wenbo Li
Institute of Chemistry, Department of Chemistry, Northwest Normal University, Lanzhou 730070, P. R. China
(Received October 24, 2000; CL-000970)
A novel reaction of the dialkylation of arylaldehydes is
obtained from substituted aromatic aldehydes with organozinc
halides in the presence of catalytic amount of Ni(acac)2 and a
tertiary amine using a silylating agent. In this paper, we have
reported the new reaction of the dialkylation of aromatic alde-
hydes by organozinc halides. The reactions are shown in
Scheme 1 and the results are summarized in Table1.
provided. The reaction of substituted aromatic aldehyde with
organozinc halides in the presence of catalytic amount of
Ni(acac)2 and a tertiary amine using a silylating agent to give 1-
alkyl-1-arylalkanes in satisfactory yields.
Organozinc reagents are versatile organometallic reagents
that have found wide applications.1 Their excellent functional
group tolerance, high chemoselectivity and excellent stereose-
lectivity in many reactions make organozincs ideal
organometallic intermediates for the construction of complex
polyfunctional molecules. Dialkylzinc compounds are stable
and poorly reactive organometallic compounds. R2Zn reagents
are generally inert toward carbonyl compounds, but methods to
promote their reaction with aldehydes are well known.1–3 We
have found very few literature reports of dialkylation of car-
bonyl compounds.4
In 1978, Mukaiyama first reported that Et2Zn could add
smoothly to benzaldehyde in the presence of aminoalcohols.5
After this report, much attention has been given to the reaction,6
especially the enantioseletive addition reaction7 of dialkylzinc
compounds with aldehydes and ketones. However, in most
cases only one of the two alkyl group is transferred, essentially
wasting 50% of the precious reagent. Alkylzinc halides RZnX,
offer alternatives, the zinc carrying only one alkyl side chain,
however, these species are less reactive and often necessitate
the use of an additional catalyst.
In 1988, Knochel8 showed that functional organozinc
iodides RZnI could be transmetallated into organozinccopper
reagents RCu(CN)ZnI with THF soluble copper salt
CuCN·2LiCl, and then coupled with acyl chlorides or conduct-
ed 1,4-addition reaction with enones. This report greatly
extended the application range of organozinc reagents in organ-
ic synthesis. Now these regeants have been successfully used
in coupling reactions with organic halides, 1,2-addition reac-
tions with aldehydes or ketones, and 1,4-addition reactions with
β-unsaturated carbonyl compound or nitro olefins.1,6,9
However, stoichiometric CuCN·2LiCl must be used in most of
their reactions. Recently, Nickel-catalyzed coupling reaction of
halides with organozinc reagents has reported.10 Addition of
alkylzinc to carbonyl compounds is one of the most reliable
method to synthesize optically active secondary alcohols.7,11 In
our previous report,12 we used Cu(OAc)2/LiCl as a copper salt
to carried out the 1,4-addition reaction with enones. Although
the method avoided the use of toxic CN– ion in the reaction, the
amount of Cu(OAc)2 used was still stoichiometric. We also
reported13 that the nitro group of 1-aryl-2-nitroethenes can be
substituted by organozinc halides under the catalysis of
Ni(acac)2 and a tertiary amine to give 1-aryl-1-alkenes in excel-
lent yields.
The organozinc reagents, obtained by the Knochels proce-
dure,8 were added into a mixture of Ni(acac)2 and a tertiary
amine at room temperature. The reactions were carried out at
–18 °C to room temperature. In the course of the reactions, the
reaction mixture became slightly brown from milky white. In
the absence of Ni(acac)2 and a tertiary amine, the reaction was
not successful. For example, no product was isolated after the
reaction of aromatic aldehyde and n-C5H11ZnI without
Ni(acac)2 and a tertiary amine or chlorotrimethylsilane.
Me3SiCl plays an important role for activation of the organo-
zinc reagent in the reaction. We have also found that this reac-
tion is sensitive to molecular structure of aldehydes and
ketones. For example, under the same conditions, the use of
aliphatic aldehydes, ketones, and aromatic ketones led several
side reactions.
We have now found that the 1-alkyl-1-arylalkanes can be
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
175
In a typical case, under nitrogen atmosphere, a mixture of
zinc (1 g , 1.5 mmol), 1,2-dibromoethane (0.2 cm3) and THF (2
cm3) in a three-neck flask was heated to 60–70 °C for 2–3 min
and then cooled to room temperature. Chlorotrimethylsiane
(0.2 cm3) was added, and the mixture was stirred at room tem-
perature for 15 min. A solution of RI (1.2 mmol) in THF (10
cm3) was then added, and the mixture was stirred for 12 h at
35–40 °C. The resulting solution of RZnI in THF was ready to
use. In another three-neck flask, Ni(acac)2 (1.2 mmol), L (2.4
mmol for A and B, 4.8 mmol for C), and THF (10 cm3) were
added and heated at 60 °C for 10 min. The solution of RZnI in
THF obtained as above was added at room temperature, and the
resulting mixture was cooled to –18 °C. A solution of aromatic
aldehyde (8 mmol) was added drop by drop and the temperature
was allowed to rise to room temperature. After stirring for 12
h, saturated NH4Cl solution (10 cm3) and Et2O (10 cm3) were
added and the mixture was stirred for 10 min. The organic
layer was separated, dried over anhydrous MgSO4 and concen-
trated. The product was isolated from the crude reaction mix-
ture by chromatography on a silica-gel column using pertrole-
um/diethyl ether as an eluent.
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In summary, compared with the similar reaction of
dialkylzincs, the reaction reported here has the following
advantages: easier availability of organozinc iodides than
dialkylzincs and higher yields of products and provides a new
method to form the products of dialkylation.
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Further investigations on the utilization of this reaction and
the mechanism are now in progreess.
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This work was supported by the National Natural Science
Foundation of China and the Northwest Normal University
Science and Technology Devolopment Foundation of China.
References and Notes
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14 Spectroscopic data for 3c: colorless liquid; H NMR (80
MHz, CDCl3 ):δ = 7.44–6.99 (m, 4H), 3.35–3.19 (m, 1H ),
1.59–0.68 (m, 22H); 13C NMR (100MHz, CDCl3): δ =
143.712, 134.646, 129.302, 127.638, 126.774, 126.595,
40.661, 36.240, 32.009, 26.927, 22.561, 14.043; IR νmax
(neat )/cm–1: 3017, 2956, 2928, 2857, 1466, 1441, 1378,
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4