High yield olefination of a wide scope of aryl chlorides catalyzed by the phosphinito palladium PCP pincer complex: [PdCl{C6H3(OPPr(i)2)2-2,6}]

Article abstract of DOI:10.1039/b004412l

[PdCl{C₆H₃(OPPr(i)₂)₂-2,6}] efficiently catalyzes the olefination of a broad scope of aryl chlorides; as a result of the high thermal stability of the catalyst, the coupled products are obtained in excellent and in many cases nearly quantitative yields.

Full text of DOI:10.1039/b004412l

High yield olefination of a wide scope of aryl chlorides catalyzed by the
phosphinito palladium PCP pincer complex: [PdCl{C6H3(OPPri2)2-2,6}]
David Morales-Morales, Rocío Redón, Cathleen Yung and Craig M. Jensen*
Department of Chemistry, University of Hawaii, Honolulu, Hawaii 96822, USA.
E-mail: jensen@gold.chem.hawaii.edu
Received (in Irvine, CA, USA) 30th May 2000, Accepted 12th July 2000
Published on the Web 9th August 2000
[PdCl{C6H3(OPPri2)2-2,6}] efficiently catalyzes the olefina-
tion of a broad scope of aryl chlorides; as a result of the high
thermal stability of the catalyst, the coupled products are
obtained in excellent and in many cases nearly quantitative
yields.
The formation of vinylic C–C bonds from the palladium
catalyzed coupling of aryl bromides, iodides and triflates with
alkenes (the Heck reaction) is one of the “true power tools of
contemporary organic synthesis”.1 However, the industrial
application of the reaction has been very limited owing to the
instability of the palladium catalysts and the high cost of the aryl
starting materials. Recently a great deal of progress has been
made toward overcoming these limitations.2–9 In a pioneering
study, Milstein and coworkers found that the olefination of
relatively inexpensive aryl chlorides is catalyzed by [Pd(OAc)2]
in the presence of 1,3-bis(diisopropylphosphino)propane.2
Higher turnovers and yields have recently been achieved with
activated aryl chlorides using palladacycle,3 carbene–palla-
dium4 and palladium–phosphite5 catalysts. It has also been
discovered that the activity of more traditional Heck coupling
systems is enhanced by the addition of [PPh4]Cl6 or PBut37 such
that the chloro substrates can be utilized in the reaction.
Notably, Littke and Fu found that in the presence of PBut3,
Pd2(dba)3 catalyzes the olefination of a broad scope of aryl
chlorides.7
chlorobenzene and styrene by 1 under a variety of reaction
conditions† and analyzed the product mixtures through gas
chromatography. Unlike most previously reported systems for
Heck couplings of aryl chlorides, additional cocatalyst such as
excess LiBr,3 PBut3,7 [NBu4][Br]3–5 or [PPh4]Cl,6 are not
required to achieve high catalytic activity. We found that > 99%
isolated yield of trans-stilbene is obtained when the reaction is
carried in dioxane solvent and caesium acetate is used as base.
Employing this same combination of reagents in a preparative
scale experiment, we were able to isolate the coupled product in
nearly quantitative yield. At 120 °C, a reaction time of 5 days is
required to achieve this high conversion. We found, however,
that the catalyst can withstand prolonged heating to 180 °C and
thus the request reaction time can be reduced to 24 h.
The reactivities of a variety of aryl chlorides were examined
under the optimized conditions and uniformly showed > 99%
selective for the trans configured product. The system is also
one of the few reported systems to show high reactivity with
electron-rich2,7 and sterically hindered7 aryl chlorides. The
practical utility of this catalytic system was probed by carrying
out preparative scale couplings of 4-chloroacetophenone and
4-chloroanisole with styrene. We obtained the corresponding E-
A key feature of several of these systems is the stabilization
of the active catalysts by either ligand chelation or steric
shielding of the metal center. Both of these stabilizing effects
can be realized with mixed donor polydentate ligands. This
combination has been used to good advantage in catalytic
aliphatic dehydrogenation reactions by iridium PCP pincer
complexes, [IrH2{C6H3(CH2PR2)2-2,6}]. The pincer ligand
confers high stability on the complexes at the temperatures
required for oxidative additions of aliphatic C–H bonds.10
Similarly, the palladium PCP pincer complexes, [Pd{O-
C(O)CF3}{C6H3(CH2PPri2)2-2,6}], [Pd{OC(O)CF3}{C6CH2-
1-(CH2PR2)2-2,6-(CH2)2-3,5-H-4}] (R = Pri, But) have been
found to be an extraordinarily active catalyst for the Heck
couplings with iodo- and bromo-arenes.11 However, the
phosphino pincer complexes were found to be almost inactive
with chloroarenes. Beller5 and Zapf van Leeuwen and cowork-
ers9 have recently reported cases in which the catalytic activity
of palladium complexes are remarkably enhanced upon sub-
stitution of phosphine ligands by alternative phosphorus ligands
containing electron withdrawing groups.5,9 We have found that
unlike 1,3-bis(phosphino)benzenes, 1,3-bis(phosphinito)ben-
zene, can be conveniently prepared in 95% yield from the
reaction of inexpensive precursors.12 It was therefore of interest
to examine the activity of the phosphinito palladium complex,
[PdCl{C6H3(OPPri2)2-2,6}] 1, as a catalyst for Heck couplings
of aryl chlorides. We report here that 1 is an efficient catalyst for
this reaction, giving olefinated products in excellent, and in
many cases nearly quantitative yields.
Table 1 Heck couplings of aryl chlorides with styrene using 2 as catalyst.
Experiments conducted with 0.67 mol% catalyst and 1.1 equivalents of base
in dioxane solution except where noted
The results of our studies of the catalytic activity of 1 are
presented in Table 1. In order to optimize the efficiency of the
catalytic system, we initially examined the coupling of
DOI: 10.1039/b004412l
Chem. Commun., 2000, 1619–1620
This journal is © The Royal Society of Chemistry 2000
1619

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In summary, the relatively inexpensive, phosphinito PCP
pincer complex 1 catalyzes the high yield olefination of broad
scope of aryl chlorides. It should be noted, that while most of the
reactions reported here were expedited by heating to 180 °C,
high yields of coupled products can be obtained at longer times
at temperatures as low as 120 °C. Thus it should be possible to
apply this catalytic system to the synthesis of commercially
important, structurally complex fine chemicals containing
thermally sensitive groups.
This work was supported by the U.S. Department of Energy
Hydrogen Program.
Notes and references
† General procedure for the olefination of aryl chlorides. Under an
atmosphere of nitrogen, a solution of 0.924 mmol of aryl chloride, 1.83
mmol of olefin, 3.0 mg of 2 (0.0062 mmol) and 202 mg (0.924 mmol) of
diethylene glycol di-n-butyl ether (internal standard) in 1.0 mL of dioxane,
was introduced into a Schlenk tube containing a magnetic stir bar and
charged with 1.01 mmol of base. The tube was sealed and fully immersed
in a 180 (120) °C silicon oil bath. After 24 (120) h, the reaction mixture was
cooled to room temperature and, the organic phase analyzed by gas
chromatography (GC/FID, GC–MS). For quantitative analysis a gas
chromatograph GC HP 5980A with flame ionization detector (FID), and a
HP-1 capillary column (25.0 m) from Hewlett Packard was used.
Scheme 1 Proposed mechanism for the catalytic olefination of aryl
chlorides by [PdCl{C6H3(OPPri2)2-2,6}].
stilbenes in > 95% and 85% isolated yields respectively. To our
knowledge, these yields are the highest that have been achieved
to date for the Heck coupling of these aryl chlorides with
styrene.
In order to verify that the high catalytic activity of 1 requires
the presence of phosphinito rather than a phosphino PCP ligand,
we examined the catalytic activity of, [PdCl{C6H3(CH2PPri2)2-
2,6}] 2† under the conditions that were optimized for 1. The
chloro complex 2, like [Pd{OC(O)CF3}{C6H3(CH2PPri2)2-
2,6}],11 showed only a very low level of activity with aryl
chlorides.
1 (a) K. C Nicolaou and E. J. Sorensen, Classics in Total Synthesis, VCH,
Weinheim, 1996. Reviews: (b) R. F. Heck, Comprehensive Organic
Synthesis, eds. B. M. Trost and I. Flemming, Pergamon Press, Oxford,
1991, vol. 4, ch. 3.4, p. 833; (c) A. de Meijere and F. E. Meyer, Angew.
Chem., Int. Ed. Engl., 1994, 33, 2379; (d) W. Cabri and I. Caudiani, Acc.
Chem. Res., 1995, 28, 2; (e) T. Jeffery, Adv. Met. Org. Chem., 1996, 5,
153; (f) S. Brase and A. de Meijere, Metal Catalyzed Cross-Coupling
Reactions, eds. P. J. Stang and F. Diederich, Wiley, New York, 1998, ch.
3.
2 Y. Ben-David, M. Portnoy, M. Gozin and D. Milstein, Organometallics,
1992, 11, 1995; M. Portnoy, Y. Ben-David and D. Milstein, Organome-
tallics, 1993, 12, 4734.
3 W. A. Herrmann, C. Brossmer, K. Öfele, C. Reisinger, T. Priermeier, M.
Beller and H. Fischer, Angew. Chem., Int. Ed. Engl., 1995, 34, 1844;
W. A. Herrmann, C. Brossmer, C. Reisinger, T. H. Riermeier, K. Öfele
and M. Beller, Chem. Eur. J., 1997, 3, 1357.
4 W. A. Herrmann, M. Elison, J. Fischer, C. Köcher and G. R. J. Artus,
Angew. Chem., Int. Ed. Engl., 1995, 34, 2371.
5 M. Beller and A. Zapf, Synlett., 1998, 792.
6 M. T. Reetz, G. Lohmer and R. Schwickardi, Angew. Chem., Int. Ed.,
1998, 37, 481.
7 A. F. Littke and G. C. Fu, J. Org. Chem., 1999, 64, 10.
8 K. H. Shaughnessy and J. F. Hartwig, J. Am. Chem. Soc., 1999, 121,
2123.
9 G. F. P. Van Strijdonck, M. D. K. Boele, P. C. J. Kamer, J. G. de Vries
and P. W. N. M. van Leeuwen, Eur. J. Inorg. Chem., 1999, 1073.
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Commun., 1996, 2083; M. Gupta, W. C. Kaska, R. E. Cramer and C. M.
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It has been suggested that Heck couplings catalyzed by PCP
complexes proceed through Pd(II) and Pd(IV) rather than Pd(0)
and Pd(II) intermediates.11,13 Additionally, it seems unlikely
that catalytic sequence in our system could be initiated by the
oxidative addition of aryl chlorides to 1 as the resulting
18-electron complex would not be expected to undergo further
reaction. We therefore conclude that the mechanism of the
catalytic olefination of aryl chlorides by 1 is fundamentally
different from those commonly considered for palladium
catalyzed Heck couplings1c and operates through a mechanism
like that seen in Scheme 1. Our suggestion is that the catalytic
process is initiated by the oxidative addition of a vinyl C–H
bond of the alkene reactant. This hypothesis is supported by the
recent observation that the reaction of the palladium PCP pincer
complex, with tributylstannyl furan results in the substitution of
1
the triflate by an h -vinyl ligand.14 Also the deuterium labeling
studies of the reaction of tert-butylethylene with the related PCP
pincer complex, [IrH2{C6H3-(CH2PBut2)2}-2,6] have shown
that activation of vinyl C–H bonds at the metal center occurs
rapidly at room temperature.15 The Pd(IV) intermediate result-
ing from the vinyl C–H oxidative addition would be expected to
undergo a reductive elimination of HCl. It is well established
that reductive elimination is promoted by decreasing ligand
donor strengths.16 Thus the finding that the phosphinito PCP
complex has markedly higher activity than its phosphino analog
suggests that this step is rate determining. The catalytic cycle is
completed by oxidative addition of the aryl chloride followed
by reductive elimination of the coupled product. Similar
mechanistic considerations may explain the extraordinary high
catalytic activities that Beller and Zapf5 and van Leeuwen and
coworkers9 have observed respectively for palladium phosphite
and phosphorus amidite complexes.
11 M. Ohff, A. Ohff, M. E. van der Boom and D. Milstein, J. Am. Chem.
Soc., 1997, 119, 11687.
12 D. Morales-Morales, C. Grause, K. Kasaoka, R. Redón, R. E. Cramer
and C. M. Jensen, Inorg. Chim. Acta., 2000, 300–302, 958.
13 B. L. Shaw and S. D. Perera, Chem. Commun., 1998, 1863.
14 W. A. Cotter, L. Barbour, K. L. McNamara, R. Hechter and R. J.
Lachicotte, J. Am. Chem. Soc., 1998, 120, 11016.
15 D. W. Lee, W. C. Kaska and C. M. Jensen, Organometallics, 1998, 17,
1.
16 G. O. Spessard and G. L. Miessler, Organometallic Chemistry, Prentice-
Hall, Upper Saddle River, New Jersey, 1997, p. 178.
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Chem. Commun., 2000, 1619–1620