Regioselective palladium-catalysed coupling reactions of vinyl chlorides with carbon nucleophiles

Article abstract of DOI:10.1039/a608371d

Vinyl chlorides bearing methyl groups in the 2-position can be activated catalytically by palladium(0)-complexes of 1,4-bis(dicyclohexylphosphino)butane, the process involving vinyl-allyl isomerization via CH-activation followed by nucleophilic attack of

Full text of DOI:10.1039/a608371d

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Regioselective palladium-catalysed coupling reactions of vinyl chlorides with
carbon nucleophiles
Manfred T. Reetz,* Klaus Wanninger and Marcus Hermes
Max-Planck-Institut fu¨r Kohlenforschung, Kaiser-Wilhelm Platz 1, D-45470 Mu¨lheim/Ruhr, Germany
Vinyl chlorides bearing methyl groups in the 2-position can
be activated catalytically by palladium(0)-complexes of
1,4-bis(dicyclohexylphosphino)butane, the process involving
vinyl–allyl isomerization via CH-activation followed by
nucleophilic attack of C-nucleophiles on the intermediate
palladium–p-allyl species.
to the double bond of 1 and induces CH-activation in one of the
methyl groups, the first step in the isomerization. Methallyl
chloride may not actually be set free, since palladium can
remain coordinated to the p-allyl system, chloride being
3
expelled with intermediate formation of [Pd{h -
(CH2CMe = CH2)}(dcypb)]+.
Indeed,
upon
heating
(dcypb)PdMe2 in the presence of 1 as the sole reaction partner,
this cationic palladium–p-allyl species was identified as the
The palladium-catalysed activation of carbon–chlorine bonds in
Heck reactions of chloro-aromatics is of great industrial interest
because these substrates are much cheaper than the considerably
more reactive bromo or iodo analogues.1 One interesting
approach recently published by Milstein makes use of the
1,4-bis(diisopropylphosphino)butane bidentate ligand (dippb),
which is believed to open and reclose reversibly with respect to
palladium complexation during the catalytic cycle.2 While the
quest for higher efficiency and broader synthetic scope
continues in this area, very little is known concerning the
catalytic activation of vinyl chlorides.3 Here we report a
serendipitous finding according to which this class of com-
pounds can be induced to undergo unusual C–C bond forming
reactions with carbon nucleophiles such as sodium malo-
nates.4
2
major product by NMR spectroscopy; its BF4 salt was
synthesized by an independent route and its structure proven by
X-ray structural analysis.4 Scheme 1 shows a possible catalytic
cycle which is in accord with all of the present data, including
the observation that other ligands are less effective.
Regioselectivity and therefore the possibility of two different
products becomes relevant in the case of unsymmetrically
substituted vinyl chlorides. In order to test whether the reaction
is regioselective, substrates 5 [eqn. (2)] were subjected to the
isomerization–substitution reaction. In all cases complete
regioselectivity was observed in that CH-activation occurs
solely at the methyl groups.
Cl
In initial attempts to perform a Heck reaction of 1-chloro-
2-methylprop-1-ene 1 with styrene, we essentially used the
Milstein protocol described for chlorobenzene, except that
dippb was replaced by a geometrically and electronically
similar ligand which is more readily available, namely 1,4-bis-
(dicyclohexylphosphino)butane (dcypb). However, only 5–
20% of the Heck coupling product 1,1-dimethyl-4-phenyl-
butadiene was formed. Speculating that the problem could be
due to the formation of a catalytically non-active palladium–
p-allyl species following Heck-type C–C bond formation, we
repeated the reaction in the presence of sodium dimethylmalo-
nate 2 as a carbon nucleophile in hope of inducing a tandem
Heck5–allyl substitution process [2 mol% Pd(OAc)2, 5 mol%
dcypb, DMF, 150 °C, 18 h]. To our surprise none of the
expected tandem reaction product was observed, the major
products being 2-methylallylmalonic acid dimethyl ester 3
(55%) and its decarboxylated form 4 (20%). Since styrene is not
involved, the reaction was repeated in the absence of this olefin
at a lower temperature [2 mol% Pd(OAc)2, 5 mol% dcypb,
DMF; 120 °C, 18 h]. Again the methallylated products 3 (70%)
and 4 (12%) were formed. Other ligands are less effective, the
yields of 3/4 being lower, as in the case of PPh3 (8%/3%),
1,2-bis(diphenylphosphino)ethane (4%/5%) and 1,4-bis(diphe-
nylphosphino)butane (32%/26%). In further optimization it was
discovered that the best catalyst system is the dimethylpalla-
dium complex of the ligand (dcypb) PdMe2 (2 mol%) in the
presence of additional dcypb (3 mol%) at 120 °C, 2 h, leading
to products 3 (76%) and 4 (1.4%) eqn. (1).†
+
NaCH(CO2Me)2
1
2
(dcypb)PdMe2 (2 mol%)
dcypb (3 mol%)
120 °C, 2 h
MeO2C
CO2Me
CO2Me
+
(1)
3 (76%)
4 (1.4%)
Cy
P
Cy
1
3
Pd
P
Cy
Cy
2
+
Cy
Cy
Cy
Cy
2CyP
P
Cl
P
Pd
Pd
P
Cy
H
Cy
Cl –
A plausible mechanism involves palladium-catalysed iso-
merization of the otherwise non-reactive vinyl chloride 1 to
methallyl chloride followed by classical palladium-catalysed
allylic substitution in which the malonate participates as the
carbon nucleophile. Separate NMR experiments revealed that
the reaction is initiated by thermolytic decomposition of
(dcypb)PdMe2 with formation of (dcypb) Pd° (or its dimer).4 It
is likely that the reactive palladium(0)-catalyst then coordinates
Cy
P
Cy
Cl
2CyP
Cy
2CyP
Cy
P
Pd
Pd
H
H
Cl
Scheme 1
Chem. Commun., 1997
535

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MeO2C
CO2Me
R
chlorides should be possible in other types of processes using
palladium or other transition metal catalysts.
Me
R
Cl
(2)
+
2
Footnote
† Typical procedure: A dry 25 ml Schlenk tube under an argon atmosphere
is charged with 1 (0.5 ml, 5 mmol), (dcypb)PdMe2 (58 mg, 0.1 mmol),
dcypb (68 mg, 0.15 mmol), 2 (5 mmol) in DMF (5 ml) and heated to 120 °C
for 2 h. The mixture is diluted with ethyl acetate (15 ml), treated
successively with 10% HCl solution, water and NaHCO3 and NaCl
solutions and dried over MgSO4. Most of the solvent is removed and the
residue analysed by gas chromatography. 3 is purified by chromatography
(silica, pentane–Et2O 4:1).
5
6
75%
65%
a E, R = cyclo-C6H11
b Z, R = cyclo-C6H11
Finally, more highly functionalized substrates such as 7
[eqn. (3)] are also amenable to the reaction. In this case a small
O
O
CH(CO2Me)2
60%
References
(3)
1 B. Cornils and W. A. Herrmann, Applied Homogeneous Catalysis with
Organometallic Compounds, VCH, Weinheim, 1996; A. de Meijere and
F. E. Meyer, Angew. Chem., 1994, 106, 2473; Angew. Chem., Int. Ed.
Engl., 1994, 33, 2379; V. V. Grushin and H. Alpes, Chem. Rev., 1994, 94,
1047.
2 Y. Ben-David, M. Portnoy, M. Gozin and D. Milstein, Organometallics,
1992, 11, 1995.
3 R. F. Heck, Palladium Reagents in Organic Syntheses, Academic,
London, 1985; J. Tsuji, Palladium Reagents and Catalysts: Innovations
in Organic Synthesis, Wiley, Chichester, 1995.
4 K. Wanninger, Dissertation, Universita¨t Bochum, 1995.
5 Heck reactions of vinyl bromides with olefins followed by tandem
nucleophilic additions: B. A. Patel and R. F. Heck, J. Org. Chem., 1978,
43, 3898; C. S. Nylund, J. M. Klopp and S. M. Weinreb, Tetrahedron
Lett., 1994, 35, 4287.
Cl
7
8
amount of a double bond isomer was also observed (14%).
Substrates bearing groups larger than methyl do not react
analogously, probably due to steric reasons. The bulky ligands
due not tolerate additional alkyl groups in the substrate, e.g. in
the palladium–p-allyl species (Scheme 1).
In summary, vinyl chlorides having at least one methyl group
in the 2-position can be activited catalytically using palla-
dium(0)-complexes of 1,4-bis(dicyclohexylphosphino)butane.
The gross features of the mechanism involve vinyl–allyl
isomerization via CH-activation at the methyl groups followed
by classical nucleophilic attack by sodium malonate on the
intermediate cationic palladium–p-allyl species. The results
suggest that the catalytic activation of otherwise inert vinyl
Received, 13th December 1996; Com. 6/08371D
536
Chem. Commun., 1997