Nickel-Catalyzed Arylation of Acrolein Diethyl Acetal: A Substitute to the 1,4-Addition of Arylhalides to Acrolein

Article abstract of DOI:10.1021/ol035877s

(Equation presented) In the presence of catalytic amount of NIBr ₂ as catalyst precursor, organic halides are reductively coupled at 70°C with acrolein diethyl acetal to give (Z)- and (E)-enolethers by allylic deplacement of an alkoxy group. Subsequent hydrolysis affords β-arylated aldehydes.

Full text of DOI:10.1021/ol035877s

ORGANIC
LETTERS
2
003
Vol. 5, No. 24
701-4703
Nickel-Catalyzed Arylation of Acrolein
Diethyl Acetal: A Substitute to the
4
1,4-Addition of Arylhalides to Acrolein
S. Condon,* D. Dupr e´ , and J. Y. N e´ d e´ lec
Laboratoire d'Electrochimie, Catalyse et Synth e` se Organique, CNRS-UniVersit e´ Paris
XII-UMR 7582, 2 rue Henri Dunant, 94320 Thiais, France
condon@glVt-cnrs.fr
Received September 26, 2003
ABSTRACT
2
In the presence of catalytic amount of NiBr as catalyst precursor, organic halides are reductively coupled at 70 °C with acrolein diethyl acetal
to give (Z)- and (E)-enolethers by allylic deplacement of an alkoxy group. Subsequent hydrolysis affords â-arylated aldehydes.
We have already reported a very easy and efficient method
iron anode thus provides iron ions that interestingly cooperate
with the coupling process to improve the yield as compared
to metals. Some features of the process are worth mentioning.
The reaction is a one-operation process easily carried out in
an undivided electrochemical cell and without the need of
preparing an unstable organometallic intermediate. This
explains the high functional tolerance observed. Also, the
reaction is regiospecific and no 1,2-addition product is
formed. When applied to conjugated aldehydes, we could
have expected the occurrence of 1,2-addition as a side
reaction, as it is observed commonly in organometallic
chemistry. However, this was not observed, the main reaction
being the polymerization of the substrate. It has already been
of introduction of aryl,1,2 heteroaryl, or alkenyl groups onto
3
4
an activated olefin in a 1,4-addition manner (Scheme 1). This
Scheme 1. Nickel-Catalyzed Addition of Organic Halides
onto Electron-Deficient Olefins
5
shown that nucleophilic addition of organometallics onto
reaction is catalyzed by nickel complexes in combination
with cathodic reduction, which allows performance of the
reaction by electrolysis of the reagent mixture in the presence
of the catalyst precursor. In addition, the process is based
on the use of a sacrificial anode, which in the case of an
R,â-ethylenic acetals can avoid the peculiar behavior of R,â-
unsaturated aldehydes. The enol ether formed by S 2′
N
displacement of one alkoxy group can be hydrolyzed to form
the â-substituted aldehyde. Herein, we wish to show that
R,â-ethylenic acetals, as substrates equivalent to conjugated
aldehydes, can be used in the nickel-catalyzed electroreduc-
tive arylation of olefins, according to Scheme 2.
(
1) Condon-Gueugnot, S.; L e´ onel, E.; N e´ d e´ lec, J. Y.; P e´ richon, J. J. Org.
Chem. 1995, 60, 7684-7686.
2) Condon, S.; Dupr e´ , D.; Falgayrac, G.; N e´ d e´ lec, J. Y. Eur. J. Org.
Chem. 2002, 105-111.
3) Condon, S.; Dupr e´ , D.; Lachaise, I.; N e´ d e´ lec, J. Y. Synthesis 2002,
752-1758.
4) Condon-Gueugnot, S.; Dupr e´ , D.; N e´ d e´ lec, J. Y.; P e´ richon, J.
Synthesis 1997, 1457-1460.
(
(5) (a) Quelet, R.; D’Angelo, J. Bull. Soc. Chim. Fr. 1967, 1503-1511.
(b) Normant, J. F.; Commer c¸ on, A.; Bourgain, M.; Villieras, J. Tetrahedron
Lett. 1975, 16, 3833-3836. (c) Mioskowski, C.; Manna, S.; Falck, J. R.
Tetrahedron Lett. 1984, 25, 519-522. (d) Mangeney, P.; Alexakis, A.;
Normant, J. F. Tetrahedron Lett. 1986, 27, 3143-3146.
(
1
(
1
0.1021/ol035877s CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/04/2003

Table 1. Nickel-Catalyzed Arylation of Acrolein Diethyl Acetal: An Easy Access to Enol Ethers and â-Arylated Aldehydes
a
After consumption of aryl halide, unless otherwise indicated. b Z/E ratio determined by GC are consistent with H NMR data. c All of these substances
1
d
are fully characterized by satisfactory spectral data (NMR and MS) and isolated yields are based on aryl bromide, unless otherwise indicated. Aldehydes
are directly obtained by HCl (6 N, 20 mL) hydrolysis of the electrolytic crude mixture at 20 °C. 33% of unconsumed aryl halide. At t ) 5 h only traces
of the expected product are detected. The aldehyde is obtained after deprotection of the purified enol ether in AcOH/H2O (20 mL; 3:1) refluxing solution.
e
f
g
The reaction conditions have been tuned with p-t-Bu-
aryl halide is complete after 2 equiv of electrons have been
passed. This solvent effect may indicate that the acrolein
diethyl acetal is not as much coordinated to the reduced
nickel species as R,â-unsaturated carbonyls; the required
stabilization of the reduced form of the catalyst is thus better
ensured by pyridine. The reactions were conducted at 70 °C,
in the presence of an iron or stainless steel anode (Fe/Cr/Ni,
bromobenzene and acrolein diethyl acetal as model reagents.
2
-4
We found that the 1:1 DMF/acetonitrile solvent mixture
used previously with activated olefins is not suitable here,
since the aryl halide was not transformed. On the contrary,
in DMF containing 10% of pyridine, the consumption of the
7
2/18/10) and at constant current intensity (entries 1 and 2).
Scheme 2. Syntheses of â-Arylated Aldehydes via
Electrochemical Arylation of Acrolein Diethyl Acetal Mediated
by Nickel Catalysis
The expected enol ether 3 was isolated after quenching of
the reaction mixture with 1 N HCl. Results obtained with
various aryl halides are reported in Table 1.
The isolated products are the γ-arylated-enol ethers 3,
which are regioselectively formed by allylic displacement
of one alkoxy group. No S 2 substitution product was
N
observed. Also the formation of the Z isomer is slightly
favored, the isomer ratio being constant over all the reaction.
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Org. Lett., Vol. 5, No. 24, 2003

Isolated yields of 3 are in the range of 50-60% with both
electron-withdrawing and electron-releasing groups on the
unsaturated substrate into the Ar-Ni bond; this ends with
II
the â-elimination of Ni and the ethoxy moiety, assisted by
2
+
aryl halide, though unexpectedly lower with CF
3
and CN
Fe ions.
substituents (Table 1, entries 8 and 9). The main byproduct
is the reduced form of the starting aryl compound. We found
that 3 is also formed when magnesium is used as the anode
but in lower yield (entry 5), whereas only traces of 3 were
found with zinc and aluminum (entries 3 and 4).
The aldehyde form 4 can be generated either by acid
hydrolysis (6 N HCl) of the crude mixture and then isolation
by chromatography on silica gel, or by hydrolysis of the
6
2
isolated enol ether by 3:1 AcOH/H O.
We have described in this paper a new procedure for the
arylation of acrolein diethyl acetal with the aim of obtaining
â-arylated aldehydes. The yields are only fair, but the process
makes possible the use of functionalized (ketone, ester,
nitrile) aryl bromide and thus represents an interesting
improvement over previous analogous organometallic path-
The product formation can be accounted for by the
following mechanism (Scheme 3). The reduced nickel
Scheme 3. Proposed Mechanism for the Present Catalytic
5
Reaction
ways. The Heck arylation reaction of allylic alcohols is,
7
however, a more efficient alternative.
Supporting Information Available: General procedures
for the preparation of â-arylated aldehydes and for γ-arylated
enolethers and characterization of selected compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL035877S
(6) The cleanliness of this last procedure makes further purification
unnecessary.
species, which is stabilized by both pyridine and the acrolein
acetal, first reacts with the aryl halide before inserting the
(7) (a) Melpolder, J. B.; Heck, F. J. Org. Chem 1976, 41, 265-372. (b)
Jeffery, T. Tetrahedron Lett. 1991, 32, 2121-2124.
Org. Lett., Vol. 5, No. 24, 2003
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