Distinct mechanisms for the oxidative addition of chloro-, bromo-, and iodoarenes to a bisphosphine palladium(0) complex with hindered ligands

Article abstract of DOI:10.1021/ja042959i

We report an example of a bisphosphine palladium(0) complex with hindered ligands that undergoes oxidative addition of chloro-, bromo-, and iodoarenes in high yield. Addition of PhX (X = I, Br, Cl) to [Pd(Q-phos-tol)₂] produced [Pd(Q-phos-tol)(Ph)(I)], [Pd(Q-phos-tol)(Ph)(Br)], and [Pd(Q-phos-tol)(Ph)(Cl)]₂. To study the mechanisms of the oxidative addition of the three haloarenes to [Pd(Q-phos-tol)₂], we determined the order of the reaction on the concentration of ligand and haloarene. The different haloarenes reacted through different mechanistic pathways. Addition of iodobenzene occurred by irreversible associative displacement of a phosphine. Addition of bromobenzene occurred by rate-limiting dissociation of phosphine. Addition of chlorobenzene occurred by reversible dissociation of phosphine, followed by rate-limiting oxidative addition. The mechanism of exchange of ligands from the Pd(0)L₂ was also studied. The rate constant value for dissociation of ligand calculated from ligand exchange experiments is in agreement with the value calculated through experiments on oxidative addition. Copyright

Full text of DOI:10.1021/ja042959i

Published on Web 04/26/2005
Distinct Mechanisms for the Oxidative Addition of Chloro-, Bromo-, and
Iodoarenes to a Bisphosphine Palladium(0) Complex with Hindered Ligands
Fabiola Barrios-Landeros and John F. Hartwig*
Department of Chemistry, Yale UniVersity, P.O. Box 208107, New HaVen, Connecticut 06520-8107
Received November 22, 2004; E-mail: john.hartwig@yale.edu
The oxidative addition of aryl halides is the first step in most
palladium-catalyzed coupling reactions.1 Previous mechanistic
studies of this reaction have focused on additions of iodo- and
bromoarenes.2,3 Despite the identification of catalysts for mild
couplings of chloroarenes,4 few studies of the mechanism of the
oxidative addition of these reagents have been conducted.3,5 Studies
Figure 1. Plots of kobs vs [PhI] and kobs vs [Q-phos-tol] ([PhI] ) 0.95 M)
for the oxidative addition of PhI to 2 at 30 °C in THF.
on the oxidative addition of chloroarenes to Pd(0) complexes of
hindered alkylmonophosphines, which generate highly active
catalyst for coupling processes, have not been reported, and, most
strikingly, no studies have been reported on the mechanism of the
oxidative addition of chloro-, bromo-, and iodoarenes to the same
Pd(0) complex. Without such studies, extrapolation of the data on
the additions of iodo- and bromoarenes to the additions of
chloroarenes is tenuous.
To compare the mechanisms of oxidative addition of chloro-,
bromo-, and iodoarenes, we studied the addition of these reagents
to [Pd(Q-phos-tol)2] (Scheme 1). This complex adds all three types
of haloarenes in high yields. Moreover, Q-phos6,7 generates highly
active catalysts for the arylation of amines and alkoxides,7 mal-
onates, cyanoesters, azlactones, and zinc enolates.8 We report that
the addition of iodo-, bromo-, and chloroarenes to the Pd(0)
complexes of the sterically hindered Q-phos ligands occurs by three
different mechanisms.
The oxidative addition of iodo- and bromoarenes to Pd(Q-phos)2
(1) generates [Pd(Q-phos)(Ar)(X)].9,10 Because the low solubility
of complex 1 precluded mechanistic studies, analogous Pd(0)
complexes, [Pd(Q-phos-tol)2] (2) and [Pd(Q-phos-CF3)2] (3), con-
taining p-CH3 or p-CF3 groups on the phenyl rings of the ligand
were prepared. These substituted Q-phos complexes were suf-
ficiently soluble in THF for kinetic studies.
The oxidative addition of PhI, PhBr, and PhCl to 2 at 30-65
°C in neat PhX produced [Pd(Q-phos-tol)(Ph)(X)] (X ) I, 4; X ) Br,
5; X ) Cl, 6) quantitatively, as determined by 31P NMR spectros-
copy (94, 53, and 82% isolated yield). Like the analogous Q-phos
complexes, Q-phos-tol complexes 4 and 5 are monomeric. How-
ever, chloride complex 6 is dimeric in the solid state (X-ray diffrac-
tion) and in C6H6 solution (Signer method). The difference between
the nuclearity of the aryl halide complexes does not affect our study
because the dimerization occurs after the oxidative addition.
Potential mechanisms of oxidative addition of ArX to 2 and the
corresponding rate expressions are shown in Scheme 1. Path A
involves, under the conditions of oxidative addition, rate-limiting
associative replacement of a phosphine ligand in 2 by PhX to
generate a haloarene complex that is either bound η1 through the
halide11 or η2 through the arene.12 This step is followed by carbon-
halogen bond cleavage in the resulting monophosphine complex
of the haloarene. The kobs for this route depends on only [ArX].
Path B is similar to path A, but the replacement of ligand by ArX
is reversible. The kobs for this route depends on [ArX] and [L].
Path C involves irreversible oxidative addition of ArX directly to
2, followed by ligand dissociation from the resulting four-coordinate
arylpalladium halide intermediate. The rate expression for this route
is identical to that for path A. Path D involves irreversible, rate-
limiting dissociation of L from 2 followed by oxidative addition to
the resulting monophosphine Pd(0) complex which might be
stabilized by coordination of solvent. The kobs for this route is
independent of [ArX] and [L]. Path E is similar to path D, except
that the dissociation of phosphine is reversible. The kobs for this
route depends on [ArX] and [L].
Studies of the oxidative addition of iodo-, bromo-, and chlo-
robenzene to palladium(0) complex 2 generate three distinct sets
of rate data. The reaction of PhI was performed at 30 °C with [PhI]
) 0.90-4.47 M and [L] ) 0-0.30 M. As illustrated in Figure 1,
the oxidative addition of PhI to 2 was first-order in [PhI] and
independent of [L]. Reactions between 30 and 60 °C showed that
∆Sq was -19.8 ( 2.0 eu. These data are consistent with reaction
of PhI with 2 by associative paths A or C.13
Scheme 1. Possible Mechanisms and Rate Expressions for the
Oxidative Addition of ArX to 2
To differentiate between reaction of PhI by paths A and C, we
studied the reductive elimination of iodoarene. If the reductive
elimination of iodoarene from 4 or a closely related compound
occurred by the reverse of path A, then the reaction would be
independent of the concentration of added ligand; however, if the
reductive elimination of iodoarene occurred by the reverse of path
C, then the reaction would be first-order in added ligand.
Complex 4 did not undergo clean reductive elimination of PhI,
even at 70 °C in the presence of 30 equiv of added Q-phos-tol, but
the related complex [Pd(PBut3)(o-tol)(I)] (7) undergoes reductive
elimination of o-tolI upon addition of PBut3 (Scheme 2).14 The rate
constants for this reductive elimination were measured by 31P NMR
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C O M M U N I C A T I O N S
Scheme 2. Possible Mechanisms for the Reductive Elimination of
ArI from 7a
Figure 2. Plots of 1/kobs vs 1/[PhCl] ([Q-phos-tol] ) 0.08 M) and 1/kobs
vs [Q-phos-tol] ([PhCl] ) 6.56 M) for the oxidative addition of PhCl to
2 at 60 °C in THF.
a Paths A′ and C′ are the reverse of paths A and C in Scheme 1.
Scheme 3. Potential Mechanisms of Ligand Exchange of 3
( 0.1) × 10-3 s-1), which appears to occur by rate-limiting
dissociation of ligand. The slope of the plot allows a calculation of
the ratio of rate constants for oxidative addition of ArCl and
reassociation of ligand to PdL (k2/k-1). Oxidative addition of PhCl
to the [Pd(Q-phos-tol)] intermediate is only 30-50 times slower
than simple coordination of Q-phos-tol to [Pd(Q-phos-tol)].
In conclusion, oxidative addition of chloro-, bromo-, and
iodoarenes to sterically hindered 2 occurs through three different
mechanisms. Addition of PhI occurs by associative displacement
of a phosphine. Addition of PhBr occurs by rate-limiting dissocia-
tion of phosphine. Addition of PhCl occurs by reversible dissocia-
tion of phosphine, followed by rate-limiting oxidative addition.
Future studies will explore the generality of these findings with
palladium complexes of other hindered ligands.
spectroscopy with a 0.02 M concentration of the palladium complex
and 0.2-0.4 M concentration of added PBut3. Consistent with
reaction by the reverse of path A but not by the reverse of path C,
kobs was independent of [PBut3]. Assuming that the addition and
elimination of haloarene to the palladium complexes ligated by
PBut3 and Q-phos-tol follow the same mechanism,15 oxidative
addition of PhI to 2 would follow path A. This finding is consistent
with the low stability of four-coordinate arylpalladium halide
complexes containing these sterically demanding ligands.10
The oxidative addition of PhBr followed a path that was different
from that for oxidative addition of PhI. The rates of the oxidative
addition of PhBr were measured at 50 °C with [PhBr] between
0.96 and 6.3 M and [L] between 0 and 0.45 M. The values of kobs
were independent of the concentration of PhBr and ligand; the value
of kobs from experiments with varied [Q-phos-tol] was (6.2 ( 0.8)
× 10-4 s-1, and the value from experiments with varied [PhBr]
was (6.7 ( 0.9) × 10-4 s-1. Further, the values of kobs for reactions
of RC6H4Br (R ) 4-CF3, 4-OMe, 2-CH3) were indistinguishable
from that for reaction of PhBr, and ∆Sq (-9.8 ( 3.8 eu) was small,
albeit slightly negative.16 Among the mechanisms in Scheme 1,
these data are consistent with only path D, involving rate-limiting
dissociation of L.
If the rate constant for the oxidative addition of PhBr corresponds
to that for dissociation of ligand from [Pd(Q-phos-tol)2], then an
independent measurement of the rate constant for dissociation of
ligand from [Pd(Q-phos-tol)2] should give the same value. The rate
constant for ligand dissociation from Q-phos-CF3 complex 3 was
determined by reaction of 3 with Q-phos.17 The reaction was
conducted with a large enough excess of Q-phos (10-50 equiv)
that the equilibrium for ligand exchange lay far toward Q-phos
complex 1 (Scheme 3). This ligand substitution was dissociative,
as shown by the lack of dependence of kobs on [Q-phos]. Most
important for understanding the mechanism of oxidative addition,
the value of kobs for the exchange process in THF at 60 °C was 4.6
( 0.4 × 10-4 s-1, and the value of kobs for the oxidative addition
of bromobenzene to the same Q-phos-CF3 complex 3 at 60 °C in
THF solvent was 4.0 ( 0.2 × 10-4 s-1. Likewise, the value of
∆Sq for the exchange process (-7.4 ( 3.6 eu) was indistinguishable
from that for the oxidative addition to 2.
Acknowledgment. We thank the NIH-NIGMS (GM-58108) for
support.
Supporting Information Available: Experimental procedures and
additional kinetic data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
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(13) Because paths A and B are distinguished only by the reversibility of the
displacement of ligand by ArX, the occurrence of one pathway over the
other will depend on the concentration of added ligand.
The oxidative addition of PhCl to 2 occurred by a third
mechanism. The oxidative addition of PhCl to 2 was measured at
60 °C with [PhCl] between 0.76 and 6.8 M and [L] between 0.050
and 0.33 M. As shown by the plots in Figure 2, the rate constant
for addition of PhCl depended positively on [PhCl] and inversely
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with only path E.
The inverse of the y-intercepts of both plots (2.0 ( 0.2 and 1.7
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Q-phos-tol from 2. These values are nearly identical and match
the rate constant for oxidative addition of PhBr to 2 at 60 °C ((1.9
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(15) Unpublished studies that will be reported separately demonstrate that
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(17) Ligand exchange was studied with Q-phos-CF3 complex 6 because the
31P NMR signals of Q-phos-tol complex 2 and the parent complex 1 could
not be resolved, and 1H NMR resonances of the methyl groups of free
and coordinated Q-phos-tol could not be resolved.
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