Consecutive vinylic to aryl to allylic palladium migration and multiple C-H activation processes

Article abstract of DOI:10.1002/anie.200462327

(Chemical Equation Presented) "Through-space" migration of palladium between remote carbon atoms appears to take place in the generation of π-allyl-palladium complexes, which are useful intermediates in organic synthesis. The reaction of halogenated arene

Full text of DOI:10.1002/anie.200462327

Angewandte
Chemie
Palladium Migration
Consecutive Vinylic to Aryl to Allylic Palladium
À
Migration and Multiple C H Activation
Processes**
Jian Zhao, Marino Campo, and Richard C. Larock*
The rearrangement of a Pd moiety along a saturated hydro-
À
carbon chain by a sequence involving Pd H elimination and
subsequent readdition has been extensively explored and
developed into a very useful synthetic process.[1] On the other
hand, there are few reports of the “through-space” migration
of Pd between remote carbon atoms. The facile 1,4-migration
of Pd between a vinylic position and an arene[2] and between
the ortho positions of biaryl compounds[3] have recently been
reported. Aryl to benzylic[4] and alkyl to aryl Pd migrations[5]
are also known. Herein we report a novel, consecutive vinylic
À
to aryl to allylic Pd migration that involves multiple C H
bond activations, which provides a new route to p-allyl
palladium intermediates of great interest in organic syn-
thesis.[6]
The reaction of p-iodoanisole and 1-phenyl-1-propyne
with CsO2CCMe3 as the base provides a 1:1 mixture of (E)-
and (Z)-2-(4-methoxyphenyl)-3-phenyl-2-propenyl pivalate
in 20% yield (1A/B; Table 1, entry 1). Different aryl halides
and alkynes were then used in this reaction, and most
combinations give allylic esters in respectable yields. Three
isomers are usually obtained when R2 = tBu, and only two
isomers are generated when R2 = Ph. The ratio of the various
isomers is dependent on the reaction time and temperature. It
appears that longer reaction times and higher temperatures
generally favor the formation of isomer C.
Although these reactions proceed in relatively low yields,
the mechanism of this unique transformation is quite
interesting. This process appears to involve Pd migration
from a vinylic to an aryl to an allylic position and subsequent
displacement by a pivalate anion (Scheme 1). Intermediate 5,
generated by oxidative addition of the aryl halide to Pd0, adds
to the alkyne to produce the vinylic Pd intermediate 6.
À
Insertion of Pd into the neighboring C H bond forms
palladacycle 7, and subsequent reductive elimination affords
[*] J. Zhao, Prof. Dr. R. C. Larock
Department of Chemistry
Iowa State University
Ames, IA 50011 (USA)
Fax: (+1)515-294-0105
E-mail: larock@iastate.edu
Dr. M. Campo
University of Geneva
Laboratoire de Pharmacie Galꢀnique et de Biopharmacie
Section de Pharmacie
Quai Ernest-Ansermet 30, 1211 Genꢁve 4 (Switzerland)
[**] This work was supported by the National Science Foundation. We
thank Johnson Matthey, Inc. and Kawaken Fine Chemical Co. for
donations of Pd(OAc)2.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Angew. Chem. Int. Ed. 2005, 44, 1873 –1875
DOI: 10.1002/anie.200462327
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Communications
Table 1: Results of the reactions involving multiple Pd migrations.[a]
deuterium) and 4,4-dimethyl-2-pentyne were allowed to react
with Pd(OAc)2 (10 mol%), dppm (1,2-bis-
(diphenylphosphino)methane; 10 mol%), and CsO2CCMe3
(2 equiv) in DMA at 1258C (Scheme 2). The E and Z isomers
Entry
X
R1
R2
Products
Yield [%] (A:B:C)
1
2
3
4
5
I
Br
I
Br
Br
OMe
H
H
CO2Et
Cl
Ph
1A/B
20 (1:1:0)[b]
35 (1:2:7)[c]
44 (1:2:12)[c]
50 (1:2:18)[c]
42 (1:2:20)[c]
tBu
tBu
tBu
tBu
2A/B, 2C
2A/B, 2C
3A/B, 3C
4A/B, 4C
[a] All reactions were conducted on a 0.5-mmol scale for 24 h, and the
ratio of ArX to alkyne was 1:1 (sealed vial, under Ar). [b] This reaction was
run with 5 mol% Pd(OAc)2 and 5 mol% dppm at 1008C, along with
DMF (10 mL) and CsO2CCMe3 (2 equiv). [c] This reaction was run with
10 mol% Pd(OAc)2 and 10 mol% dppm at 1258C, as well as N,N-
dimethylacetamide (DMA, 5 mL) and CsO2CCMe3 (2 equiv).
Scheme 2. Proposed formation of the deuterium-labeled product.
of 4,4-dimethyl-2-phenylpent-2-enyl pivalate and 1-tert-butyl-
2-phenyl-2-propenyl pivalate (18) were obtained in a ratio of
1:2:7. Ester 18 was isolated in 20% yield and found to contain
40% deuterium in the allylic position and 95% hydrogen in
one of the two ortho positions of the phenyl moiety (GC–MS
data indicate that hydrogen is only incorporated at one of the
two ortho positions). This result, except for the relatively low
allylic deuterium content, is consistent with the proposed
mechanism. However, the deuterium content can be
increased by adding 10 equivalents of D2O to the reaction
mixture. The three products were again obtained in a similar
ratio, and the resulting ester 18 contained 55% hydrogen in
one ortho position of the arene and 75% deuterium in the
allylic position.
The loss of deuterium in the allylic position probably
arises by deuterium/hydrogen exchange through an equili-
brium between organopalladium(iv) intermediate 12 and
palladacycle 13 or direct exchange of the metal hydride/
deuteride in intermediate 12. Incorporation of deuterium in
the allylic position is dependant on the competition between
H/D exchange and Pd migration, and it appears that neither is
dominant in this case. This reaction was repeated in the
presence of 10 equivalents of H2O, and the three esters
obtained incorporate approximately the same ratio of allylic
deuterium as the reaction conducted in the absence of H2O. A
similar exchange of hydrogen and deuterium has been
observed in aryl norbornyl palladacycles.[7] When nondeuter-
ated bromobenzene and 4,4-dimethyl-2-pentyne were
allowed to react in the presence of 10 equivalents of D2O,
the ester 18 that was obtained had incorporated 40%
Scheme 1. Proposed mechanism of the Pd migration.
8. This results in Pd migration from a vinylic to an aryl
À
position by C H bond activation, a process we have reported
earlier.[2]
À
To initiate a second C H bond activation, the Pd moiety
apparently rotates into the vicinity of the methyl group.
À
Insertion of Pd into the neighboring C H bond affords
palladacycle 9, which undergoes reductive elimination with
transfer of the Pd moiety to the allylic position. This
unprecedented migration generates Pd intermediate 10,
which rapidly isomerizes to the corresponding p-allyl palla-
dium species 11. This unusual process provides a new route
for preparing p-allyl palladium compounds, which have
proven very versatile as intermediates in organic synthesis.[6]
The three isomeric ester products are presumed to arise by
attack of the pivalate anion on the Pd intermediate 11.
This proposed mechanism indicates that the migration of
Pd is always accompanied by a simultaneous migration of
hydrogen in the opposite direction. Thus, the observation of a
hydrogen or deuterium shift should provide convincing
evidence for the Pd migration. [D5]Bromobenzene (99%
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Angewandte
Chemie
deuterium in one of the ortho positions of the arene and 40%
deuterium in the allylic position. Although the experimental
data is consistent with the proposed mechanism, an alter-
native mechanism involving an organopalladium(ii) pallada-
cyle[8] and a Pd–p-arene complex[9] is also possible. Further
studies to better understand the mechanism of this process are
underway.
We also carried out a Pd migration reaction with the aryl
iodide 19, which would be expected to generate intermediate
8 directly [Eq. (1)]. This species might then undergo Pd
see Supporting Information), but no deuterium in the vinylic
or allylic positions. This suggests that the vinylic to aryl
migration is not a reversible process. Because no deuterium
incorporation in the methylene or allylic positions was
observed, we can also rule out reversible Pd migration from
the allylic to the aryl position.
In conclusion, we have discovered a novel consecutive
vinylic to aryl to allylic Pd migration, which affords a unique
way to generate p-allyl palladium complexes. This migration
process appears to involve an equilibrium between
organopalladium(iv) hydrides and organopalladium(ii) inter-
mediates, which undergo facile exchange with a hydrogen
source in the solution. However, we cannot rule out direct
exchange of the PdIV hydride. We are continuing to study this
process in order to better understand the mechanism and its
synthetic potential.
Received: October 16, 2004
Published online: February 14, 2005
À
Keywords: C H activation · deuterium · palladium ·
rearrangement · synthetic methods
.
migration to produce the same mixture of pivalate esters
formed by the consecutive rearrangement. Under the same
reaction conditions, we obtained the anticipated product
mixture (2A:2B:2C = 1:2:20) in 65% yield. Although the
ratio of the regioisomer 2C to 2A/B is a little higher than in
the consecutive migration process, the results are still
consistent with our proposed mechanism. We also examined
the reaction of aryl iodide 20 under the usual reaction
conditions, but at 1458C [Eq. (2)]. This reaction affords the
allylic pivalate 21 in 45% yield. Thus, it appears that the aryl
palladium intermediate corresponding to 20 is able to
undergo migration to a secondary allylic position.
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In terms of mechanism, an intermediate such as 17 could
also be generated by carbopalladation of the allene 4,4-
dimethyl-1,2-pentadiene, which might arise by isomerization
of 4,4-dimethyl-2-pentyne. However, when carried out with
[D5]bromobenzene, this process would not introduce a
hydrogen atom into the ortho position of the arene or a
deuterium atom into the allylic position of the final ester
product, unless the Pd moiety could reversibly migrate from
the allylic to the aryl to the vinylic position. Only then could
we observe a hydrogen atom in the ortho position of the arene
and a deuterium atom in the vinylic position, as well as
deuterium incorporation into the allylic position. To better
understand this process, the reaction shown in Equation (1)
was conducted in the presence of 10 equivalents of D2O. The
isolated product 2C contained 40% deuterium in one of the
ortho positions of the arene (according to GC–MS analysis,
[9] J. Campora, J. A. Lopez, P. Palma, V. Pedro, S. Edzard, C.
Ernesto, Angew. Chem. 1999, 111, 199 – 203; Angew. Chem. Int.
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