Novel 1,4-palladium migration in organopalladium intermediates derived from o-lodobiaryls

Article abstract of DOI:10.1021/ja027548l

A novel 1,4-palladium migration in organopalladium intermediates derived from o-iodobiaryls has been observed under modified Heck reaction conditions. This migration process can be switched "on" or "off" by simply choosing the appropriate reaction conditi

Full text of DOI:10.1021/ja027548l

Published on Web 11/09/2002
Novel 1,4-Palladium Migration in Organopalladium Intermediates Derived from
o-Iodobiaryls
Marino A. Campo and Richard C. Larock*
Department of Chemistry, Iowa State UniVersity, Ames, Iowa 50011
Received July 3, 2002
Scheme 1
The extraordinary C-C bond-forming ability of palladium places
it among the most versatile and useful metals in organic synthesis.
Organopalladium intermediates are often prepared by oxidative
addition of an organic halide or triflate to Pd(0), and subsequent
C-C bond formation normally occurs at the position originally
occupied by the halogen or triflate. Among the most important Pd-
catalyzed C-C bond-forming reactions is the Heck reaction for
Scheme 2
which there are numerous applications in the literature,1 including
a few employing o-bromobiaryls.2
To our surprise, upon studying the Pd-catalyzed olefination of
unsymmetrical o-iodobiphenyls with ethyl acrylate, we obtained,
under certain modified reaction conditions, the expected o-olefinated
biphenyl 2 along with the o′-olefinated biphenyl 3 (Scheme 1). The
observed mixture of Heck products points to the existence of
Table 1. Pd-Catalyzed Reaction of 2-Iodo-4′-methylbiphenyl (1a)
and Ethyl Acrylate (EA)a
arylpalladium intermediates in which the metal moiety is located
in each of the two different ortho positions of the unsymmetrical
biphenyl.3 This through-space relocation of the metal moiety
between the ortho positions of biaryls amounts to an overall 1,4-
palladium shift, which could possibly involve an intermediate
hydridopallada(IV)cycle generated by insertion of palladium into
a neighboring C-H bond. The novel palladium migration observed
in our o-iodobiaryl system is reminiscent of a vinylic-to-aryl
palladium rearrangement proposed by us to account for the
formation of 9-benzylidene-9H-fluorene from diphenylacetylene and
iodobenzene.4
To obtain a clear picture of how various reaction variables effect
the palladium biaryl migration, we have studied the behavior of
2-iodo-4′-methylbiphenyl (X ) Me, 1a) and ethyl acrylate under
various reaction conditions (Scheme 2, Table 1). We have found
that under the classical reaction conditions described by Jeffrey,5
the expected ethyl E-3-(4′-methylbiphen-2-yl)acrylate (X ) Me,
2a) was obtained exclusively in a quantitative yield (Table 1, entry
1). By simply diluting the reaction mixture 4-fold, we began to
observe small amounts of the migration product ethyl E-3-(4-
methylbiphen-2-yl)acrylate (X ) Me, 3a) (entry 2), and 23% of
3a was obtained under the more dilute conditions by reducing the
number of equivalents of ethyl acrylate from 4 to 1 (entry 3). After
exploring a number of organic and inorganic bases, we have
obtained nearly equal amounts of the direct olefination product 2a
and the rearranged product 3a when using CsO2CCMe3 (CsPiv) as
the base (entry 4). Furthermore, the use of phosphine ligands, such
as bis(diphenylphosphino)methane (dppm) and PPh3, in the reaction
further changed the isomer distribution to 50:50 (entries 5 and 6).
It is important to note at this point that by manipulating the reaction
conditions, we can switch the palladium migration “on” or “off”
in this biphenyl system. Thus, our optimal migration conditions
for activating palladium migration are those described in entry 5
mol ratio
entry
EA equiv
conditions
time (d)
2a : 3ab
% yield
c
1
2
3
4
5
6
4
4
1
1
1
1
TBAC, NaHCO3
TBAC, NaHCO3
TBAC, NaHCO3
CsPiv
1.0
1.0
1.0
1.5
1.5
1.5
100:0
95:5
77:23
54:46
50:50
50:50
100
100
92
93
88
5% dppm, CsPiv
10% PPh3, CsPiv
87
a Reaction was run using 0.25 mmol of the iodobiaryl, ethyl acrylate
(EA), 2 equiv of an appropriate base, and 1 equiv of n-Bu4NCl (TBAC)
where indicated in 4 mL of DMF at 100 °C unless otherwise indicated.
b Mol ratio was determined by 1H NMR spectroscopic analysis. c 1 mL of
DMF.
of Table 1, and the conditions to prevent this process are those
described in entry 1.
An obvious question to answer is whether under our standard
reaction conditions 2-iodo-4-methylbiphenyl (X ) Me, 4a) and
ethyl acrylate would generate the same distribution of isomers 2a
and 3a as previously obtained from 1a and ethyl acrylate. Indeed,
substrate 4a generated a 49:51 mixture of isomers 2a and 3a in an
86% yield under our optimized migration conditions (Scheme 2).
This interesting result seems to indicate that under our reaction
conditions, the arylpalladium intermediates generated from either
1a or 4a undergo apparent equilibration prior to olefin-trapping to
generate essentially identical mixtures of 2a and 3a. Furthermore,
under the conditions described by Jeffrey and illustrated in entry 1
of Table 1, 2-iodo-4-methylbiphenyl (4a) undergoes the usual Heck
reaction with ethyl acrylate to produce exclusively 3a in 93% yield
(Scheme 2).
The palladium-catalyzed reaction of methoxy-substituted iodobi-
phenyls with ethyl acrylate gave nearly identical results to those
obtained with their methyl-substituted counterparts. Again, we can
switch “off” the palladium migration by running the reaction under
Jeffrey’s conditions. Thus, under the reaction conditions described
in entry 1 of Table 1, 2-iodo-4′-methoxybiphenyl (X ) OMe, 1b)
* To whom correspondence should be addressed. E-mail: larock@iastate.edu.
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10.1021/ja027548l CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
Scheme 4
generates exclusively ethyl E-3-(4-methoxybiphen-2-yl)acrylate (X
) OMe, 2b) in a quantitative yield, and 2-iodo-4′-methoxybiphenyl
(X ) OMe, 4b) produces exclusively ethyl E-3-(4-methoxybiphen-
2-yl)acrylate (X ) OMe, 3b) in 99% yield. Furthermore, we can
switch “on” the palladium migration by running the reaction under
our standard migration conditions in which case 1b produces a 52:
48 mixture of isomers 2b and 3b, respectively, in a 93% yield.
Similarly, substrate 4b produced a 48:52 mixture of 2b and 3b,
respectively, in 92% yield (Scheme 2). These results validate the
idea that our reaction conditions promote palladium migration
between the o-positions of these biphenyls. What is perhaps a bit
surprising is that there does not seem to be any pronounced
electronic effect of a Me or OMe group in these migrations.
Currently, we are investigating this reaction using substituted
biphenyls bearing electron-withdrawing groups.
A more marked effect on the product distribution was observed
in the reaction of 2-iodo-3-phenylbenzofuran (5) and ethyl acrylate,
which under our standard migration conditions gives exclusively
ethyl E-3-(3-phenylbenzofuran-2-yl)acrylate (6) in 85% yield
(Scheme 3). This unexpected result showing no apparent 1,4-Pd
shift suggested one of two things in this biaryl system. Either
palladium has a strong preference for the more electron-rich
2-position of the benzofuran moiety, or the two possible arylpal-
ladium intermediates generated by palladium migration have
different reactivities toward the olefin. In either case, olefination
occurs on the 2-position of the benzofuran moiety exclusively.
When 3-(2-iodophenyl)benzofuran (7) was allowed to react with
ethyl acrylate under our standard migration conditions, 6 was
produced in a 78% yield alongside only ∼5% of isomer 8 (Scheme
3), clearly indicating a preference for palladium migration from
the phenyl to the benzofuran ring. Furthermore, ethyl E-3-[2-
(benzofuran-3-yl)phenyl]acrylate (8) was obtained exclusively in
a 75% yield from 7 when using the reaction conditions described
by Jeffrey at 80 °C for 1 d.
To further explore the scope of this migration process, we have
carried out the palladium-catalyzed reaction of diphenylacetylene
and 2-iodo-3-methoxybiphenyl (9) in the hope that the arylpalladium
intermediates generated by a 1,4-Pd shift could be trapped by way
of alkyne insertion-annulation chemistry described earlier by us.6
First, the reaction was carried out under the conditions described
previously by us employing 1.2 equiv of the acetylene, 5 mol %
Pd(OAc)2, 1 equiv of LiCl, and 2 equiv of NaOAc in DMF at 100
°C for 2 d, and we obtained the expected 1-methoxy-9,10-
diphenylphenanthrene (10) in 90% yield (Scheme 4, path 1). We
then switched “on” the palladium migration by allowing 9 to react
with 1.2 equiv of diphenylacetylene under our standard migration
conditions to obtain a 51:49 mixture of phenanthrenes 10 and 11,
respectively, in 87% overall yield (Scheme 4). The mechanism for
the formation of phenanthrenes 10 and 11 is described in Scheme
4. It is important to note that in these alkyne reactions the formation
of product 11 cannot arise directly from the intermediacy of a simple
bridged pallada(II)cycle,7 but instead its formation requires complete
migration of the palladium moiety from the methoxy-bearing ring
to the other aromatic ring. These interesting migration results with
alkenes and alkynes suggest that there is the exciting possibility of
trapping aryl- and other organopalladium intermediates generated
by 1,4-Pd shifts by many other synthetically useful palladium
methodologies. We are currently examining this possibility.
In conclusion, we have been able to establish a novel 1,4-
palladium shift in arylpalladium intermediates generated from
o-iodobiaryls. This migration of palladium has been established by
trapping the arylpalladium intermediates generated by this process
by way of a Heck reaction, as well as alkyne annulation methodol-
ogy. There appear to be important electronic effects dictating the
reactivity and apparent equilibrium between the palladium inter-
mediates, which is reflected in the isomer distribution of the Heck
type products. This migration process can be switched “on” and
“off” by simply choosing the appropriate reaction conditions. We
continue to explore the scope, mechanism, and synthetic utility of
this novel palladium migration chemistry.
Acknowledgment. We acknowledge useful discussions of this
work with Professor Timothy Gallagher, who has simultaneously
observed similar Pd migration chemistry.3 We thank the donors of
the Petroleum Research Fund, administered by the American
Chemical Society and the National Science Foundation, for partial
support of this research. Thanks are also extended to Johnson
Matthey, Inc., and Kawaken Fine Chemicals Co., for donating the
Pd(OAc)2 and PPh3.
Supporting Information Available: General experimental proce-
dures and spectroscopic characterization of all new products (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
(1) (a) de Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl. 1994, 33,
2379. (b) Gibson, S. E.; Middleton, R. J. Contemp. Org. Synth. 1996, 3,
447. (c) Overman, L. E. Pure Appl. Chem. 1994, 66, 1423. (d) Shibasaki,
M.; Boden, C. D. J.; Kojima, A. Tetrahedron 1997, 22, 7371. (e) Cabri,
W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
(2) (a) Diaz-Ortiz, A.; Prieto, P.; Vazquez, E. Synlett 1997, 269. (b) Heck,
R. F. Org. React. 1982, 27, 345.
(3) Minor amounts of similar migration products have recently been reported
in bromoarylpyridine systems, see: Karig, G.; Moon Maria-Teresa;
Thasana, N.; Gallagher, T. Org. Lett. 2002, 4, 3115.
(4) Larock, R. C.; Tian, Q. J. Org. Chem. 2001, 66, 7372.
(5) Jeffrey, T. J. Chem. Soc., Chem. Commun. 1984, 1287.
(6) Larock, R. C.; Doty, M. J.; Tian, Q.; Zenner, J. M. J. Org. Chem. 1997,
62, 7536.
(7) For similar pallada(II)cycle reactions with alkynes, see: Portscheller, J.
L.; Malinakova, H. C. Org. Lett. 2002, 4, 3679 and references therein.
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