Abnormal and regioselective Wacker oxidation of 1,5-dienes

Article abstract of DOI:10.1016/S0040-4039(03)01709-X

The presence of an additional double bond can change the regioselectivity of the Wacker oxidation of a 1-alkene moiety to give the aldehyde product.

Full text of DOI:10.1016/S0040-4039(03)01709-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6955–6957
Abnormal and regioselective Wacker oxidation of 1,5-dienes
Tse-Lok Ho,* May Hua Chang and Chuo Chen
Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan, ROC
Received 13 May 2003; revised 18 June 2003; accepted 30 June 2003
Abstract—The presence of an additional double bond can change the regioselectivity of the Wacker oxidation of a 1-alkene moiety
to give the aldehyde product.
© 2003 Published by Elsevier Ltd.
The Wacker oxidation1 of 1-alkenes (except ethene)
leads selectively to methyl ketones.2 We were interested
in reversing this regioselectivity which seems to origi-
nate from palladiohydroxylation of the alkenes in the
Markovnikov sense to afford organometallic species
that subsequently undergo dehydropalladation.3 Rever-
sal of the regioselectivity has been observed in alkene
systems by means of heteroatoms4–7 which probably
coordinate with palladium intermediates. In our study
we considered p-complexation instead of the previously
known participation of n-donors. Here we report the
successful intervention in cases of certain dienes.
mediates B then underwent elimination of the [H-PdLn]
species. In normal circumstances the p-complexes of Pd
are attacked in the alternative manner, resulting in
palladiohydroxylation according to the Markovnikov
Rule. It should be noted that A has a similar structure
as that proposed for the Pd-catalyzed Cope rearrange-
ment.8 The major difference in its fate is perhaps the
crucial presence of water that tends to intercept it. On
the other hand, in the reaction of 5 a 5-exo-trig process
was involved.
Diene 8 is a structural variant of 3. The intermediate
involving both double bonds resembles necessarily a
bridged-ring system wherein the complexed double
bonds are axially oriented. We observed the formation
of an aldehyde from reaction at the methylene moiety,
albeit 9 was isolated in only 19% yield. The result was
due to partial decomposition during chromatographic
purification and also probably reflects a higher strain
and therefore less favorable reaction. Absence of oxida-
tion at the vinyl substituent may also indicate the
importance of steric factors. Interestingly, the active
Wacker oxidation catalyst is supposed to be a poly-
meric Pd-Cu-DMF complex with a Pd:Cu stoichiome-
try of 2:1, in which the two different metal centers are
linked by a chlorine atom (apical to Cu), while the Cu
center is also coordinated by four DMF molecules.9
Diene 1a was prepared from p-methylisobutyrophenone
by allylation, Grignard reaction with MeMgI and dehy-
dration (KHSO4), whereas 1b was obtained from
methyl 2,2-dimethyl-4-pentenoate, also by Grignard
reaction and dehydration. To procure 1c starting from
2,2-dimethyl-4-pentenal the Grignard reaction, PCC
oxidation and Wittig reaction sequence was employed.
When submitted to conventional Wacker oxidation
conditions (PdCl2, CuCl, O2, DMF–H2O) only the alde-
hydes 2a, 2b, and 2c were generated in 73, 99, and 75%
yields, respectively. We have not been able to detect
any methyl ketones by NMR spectroscopy.
Analogously, diene 3 also followed the same reaction
pattern, furnishing 4 in 60% yield. Contrarily, alkenol 5
gave a normal product 6 which was shown to be a
tautomeric mixture of the methyl ketone and the cyclic
lactol.
We also believed that the p-participation did not turn
into a s-bonding event. Otherwise aldehydes with a
tetrasubstituted double bond (e.g. 7) would have
appeared. This latter scenario is dominant in the Pd-
mediated Cope rearrangement.8
In our opinion, the formation of 2a, 2b, 2c, and 4 may
be due to participation of the disubstituted double
bond, such that unsymmetrical intermediates
appeared and then captured by water. The next inter-
A
In conclusion, we have observed a change in the
regioselectivity in the polar addition of 1-alkenes from
the Markovnikov sense to an anti-Markovnikov fash-
* Corresponding author. E-mail: tlho@cc.nctu.edu.tw
0040-4039/$ - see front matter © 2003 Published by Elsevier Ltd.
doi:10.1016/S0040-4039(03)01709-X

6956
T.-L. Ho et al. / Tetrahedron Letters 44 (2003) 6955–6957
ion, when another double bond is judiciously placed in
the same molecule. The through-space interaction10 of
two double bonds seems unique for such a phe-
nomenon. On the other hand, n-donors actually accen-
tuate the normal course of addition as shown in the
case of 5. A previous observation that an acrylamide
CDCl3) l 20.8 (q), 27.4 (q), 32.1 (t), 38.5 (s), 39.8 (t),
114.0 (t), 128.0 (d), 128.3 (d), 135.7 (s), 139.6 (s), 156.4
(s), 201.5 (d). HRMS m/z 216.1517 (calcd for C15H20O
216.1515).
underwent
transformation
into
the
b,b-
dimethoxypropanamide derivative11 is electronically
biased, therefore quite different from that of ours. The
unusual behavior of certain N-acylallylamines has been
attributed to the coordination of palladium atom by the
carbonyl group which led to the formation of N-
acylaminopropanals.12
Acknowledgements
We wish to thank the National Science Council, ROC,
for financial support of this research.
References
A representative example of the Wacker oxidation
folllows: Preparation of 2a: A mixture of 1a (0.42 g, 2.1
mmol), PdCl2 (0.08 g, 1.1 mmol), and CuCl (0.21 g, 2.1
mmol) in DMF (1 mL) and water (0.1 mL) was stirred
under an oxygen atmosphere for 24 h at room tempera-
ture. It was diluted with dichloromethane, washed with
water, dried over anhydrous Na2SO4, and concentrated
in a rotary evaporator. The residual oil was chro-
matographed over silica gel [eluent:hexane:AcOEt 10:1]
to afford 2a (0.33 g, 72.8%). w (CꢀO) 1725 cm−1. H
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1H), 5.01 (s, 1H), 6.86 (d, J=8.1 Hz, 2H), 6.94 (d,
J=8.1 Hz, 2H), 9.59 (br s, 1H). 13C NMR (75 MHz,
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