Pd(η3-1-PhC3H4)(η5- C5H5), an unusually effective catalyst precursor for heck-mizoroki and sonogashira cross-coupling reactions catalyzed by bis-phosphine palladium(0) compounds

Article abstract of DOI:10.1021/om301081r

The compound Pd(η³-1-PhC₃H₄) (η⁵-C₅H₅) reacts essentially quantitatively with a variety of phosphines L to form cross-coupling catalysts of the type PdL₂ and has recently been shown to be a much more effective catalyst precursor for Suzuki-Miyaura cross-coupling reactions in comparison to more commonly utilized precursors such as Pd(PPh₃)₄, Pd ₂(dba)₃, and Pd(OAc)₂, which do not effectively generate two-coordinate species PdL₂. This advantage is expected to apply also to e.g. Heck-Mizoroki and Sonogashira cross-coupling reactions, both of which are generally believed to be catalyzed by species of the type PdL ₂. Therefore, comparisons of the efficacies of catalyst systems based on Pd(η³-1-PhC₃H₄)(η⁵- C₅H₅), Pd(PPh₃)₄, Pd ₂(dba)₃, and Pd(OAc)₂ are made utilizing the conventional coupling reactions of aryl halides with methyl acrylate and styrene for Heck-Mizoroki coupling and with phenylacetylene for Sonogashira coupling. As anticipated, catalyst systems based on Pd(η³-1-PhC ₃H₄)(η⁵-C₅H₅) are found to be significantly more active.

Full text of DOI:10.1021/om301081r

Communication
pubs.acs.org/Organometallics
Pd(η3‑1-PhC3H4)(η5‑C5H5), an Unusually Effective Catalyst Precursor
for Heck−Mizoroki and Sonogashira Cross-Coupling Reactions
Catalyzed by Bis-Phosphine Palladium(0) Compounds
Andrew W. Fraser, Bryan E. Jaksic, Rhys Batcup, Christopher D. Sarsons, Michael Woolman,
and Michael C. Baird*
Department of Chemistry, Queen’s University, Kingston, Ontario K7L 3N6, Canada
S
* Supporting Information
ABSTRACT: The compound Pd(η3-1-PhC3H4)(η5-C5H5) reacts essentially quantitatively with
a variety of phosphines L to form cross-coupling catalysts of the type PdL2 and has recently been
shown to be a much more effective catalyst precursor for Suzuki−Miyaura cross-coupling
reactions in comparison to more commonly utilized precursors such as Pd(PPh3)4, Pd2(dba)3,
and Pd(OAc)2, which do not effectively generate two-coordinate species PdL2. This advantage is expected to apply also to e.g.
Heck-Mizoroki and Sonogashira cross-coupling reactions, both of which are generally believed to be catalyzed by species of the
type PdL2. Therefore, comparisons of the efficacies of catalyst systems based on Pd(η3-1-PhC3H4)(η5-C5H5), Pd(PPh3)4,
Pd2(dba)3, and Pd(OAc)2 are made utilizing the conventional coupling reactions of aryl halides with methyl acrylate and styrene
for Heck−Mizoroki coupling and with phenylacetylene for Sonogashira coupling. As anticipated, catalyst systems based on
Pd(η3-1-PhC3H4)(η5-C5H5) are found to be significantly more active.
mechanistic themes have been proposed. In addition, a variety
of cocatalysts have been utilized but their general applicability is
not always clear. Therefore, for clarity, their potential roles are
not reflected in Scheme 1.
wide variety of palladium-catalyzed carbon−carbon bond
Aforming methodologies are available through reactions
catalyzed by Pd(0) compounds believed to be of the type PdL2
(L = phosphine ligand).1 Of these, the Heck-Mizoroki (eq 1)2
and Sonogashira (eq 2)3 cross-coupling reactions are of
particular importance for the formation of C(sp2)−C(sp2)
and C(sp2)−C(sp) bonds, respectively.
Unfortunately, the catalytically active PdL2 species are both
air-sensitive and highly reactive, with the result that they are
rarely used directly in practice. Instead, a majority of palladium-
catalyzed cross-coupling studies have utilized much more easily
manipulated catalyst precursors such as Pd(PPh3)4 (I),
Pd2(dba)3 (II; dba = dibenzylideneacetone), PdCl2 (III),
and/or Pd(OAc)2 (IV), the last three in the presence of added
ligand.1−3 However, as we have recently commented,4a these
precursors actually produce not the desired, oft presumed PdL2,
but rather the more sterically hindered three-coordinate Pd(0)
complexes PdL2L′, where L′ = PPh3 (I), dba (II), Cl− (III),
OAc− (IV). Furthermore, although catalytically active Pd(0)
systems can be formed by reacting III and IV with many
ArX + CH2CHAr′ → ArCHCHAr′
(1)
(2)
ArX + RC CH → RC CAr
The basic catalytic cycles are shown in Scheme 1, although
many variations, some controversial, on these general
Scheme 1
tertiary phosphines,1−4 there is little evidence in the literature
a
that reductions of the palladium(II) precursors are ever effected
either rapidly or completely with the majority of phosphines
utilized.
The question arises then, if one particular palladium-based
cross-coupling catalyst system is found to be more effective
than another, does the difference arise because one phosphine
is intrinsically superior, as seems generally thought? Conversely,
does the difference arise because one type of three-coordinate
Pd(0) species is inherently more reactive than another or,
simply, because the Pd(II) precursor used is reduced more
effectively by one phosphine than by another? These questions
Received: November 10, 2012
Published: December 24, 2012
© 2012 American Chemical Society
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Communication
seem, by and large, not to have been answered, and it follows
that a significant number of the cross-coupling studies reported
may not have made optimal use of the palladium added. The
result could be unnecessarily high reaction temperatures or
unnecessarily long reaction times and/or yields lower than
would be possible if specifically PdL2 were used. In addition, it
follows that conclusions based on comparative studies involving
different precursors may not always be valid.
We utilized PBut3, as we had previously found this ligand to
be particularly effective for Suzuki−Miyaura cross-coupling
reactions;4a in addition, the II/PBut3 catalyst system is known
to be relatively effective for Heck−Mizoroki cross-coupling
reactions.6 Shown in Figure 1 are reaction profiles for the
A simple, quantitative, unequivocal route for the synthesis of
catalysts PdL2 has therefore been desirable for some time, and
to this end we have previously advocated the use of the
compound Pd(η3-1-PhC3H4)(η5-C5H5) (V), which reacts
rapidly with a large number of phosphines L to form the
compounds PdL2 (eq 3).4 Compound V is easily synthesized
and is stable to heat and in air (even in solution for hours); it is
thus very “user friendly”.
Figure 1. Reaction profile showing the conversion to methyl
cinnamate from the cross-coupling of chlorobenzene and methyl
acrylate utilizing (a) V + 2PBut3, (b) II + 4PBut3, and (c) IV + 3PBut3.
As part of an investigation to test the hypothesis that V is
superior to the commonly used catalyst precursors I−IV in its
ability to form PdL2 and hence generate catalytically active
solutions for cross-coupling reactions, we have previously
compared V with I−IV as catalyst precursors for the Suzuki−
Miyaura cross-coupling reaction.4a We confirmed that combi-
nations of V with the representative phosphines PPh3, PCy3,
and PBut3 do indeed generate catalyst solutions which are much
more active than catalyst systems obtained using combinations
of catalyst precursors I−IV with the same phosphines. The
reason almost certainly lies in the fact that V generates
catalytically active species PdL2 quickly and quantitatively while,
in contrast, the others do not for various reasons.4
Since our initial disclosure of the merits of utilizing V for
synthesis of palladium(0) compounds,4b others have also
demonstrated its utility. Thus, Bauer et al. found V to be
useful for the high-yield synthesis of a heteroleptic
(phosphine)(NHC)Pd0 compound, Pd(PCy3)(N,N′-bis(tert-
butyl)-imidazol-2-ylidene);5a other precursors resulted in the
formation of mixtures. Similarly, Saget et al. found V to be “the
best” precursor for the synthesis of palladium(0) complexes
containing a series of new electron-rich phosphines, used as
catalysts for enantioselective C(sp3)−H functionalization.5b
Finally, and in a direct comparison, Hanthorn et al.
demonstrated that the V/XPhos catalyst system is much
more effective for a series of Buchwald−Hartwig amination
reactions than is the more conventional II/XPhos catalyst
system.5c,d
formation of methyl cinnamate using V, II, and IV, each
activated with the appropriate amount of PBut3, at 95 °C; see
the Supporting Information for experimental details.
As can be seen, catalyst efficacies vary in the order V/PBut3 >
II/PBut3 ≫ IV/PBut3, as found previously for Suzuki−Miyaura
coupling by the same catalyst systems.4a We note also that the
conversion data obtained utilizing the II/PBut3 catalyst system
are in reasonable agreement, given that reaction conditions are
not precisely identical, with previous work involving the same
substrates and the II/PBut3 catalyst system.6 A complementary
cross-coupling study involving bromobenzene was carried out
in DMF at 80 °C, and again V was by far the most superior
catalyst precursor, giving ∼90% conversion within 45 min,
while catalysts based on II and IV resulted in <5% conversion.
As before, we attribute the higher activity of the V/PBut3
catalyst system to the fact that the actual catalyst, Pd(PBut3)2, is
formed in much higher yields employing V.
An analogous cross-coupling study of bromobenzene with
styrene (eq 5) to form trans-stilbene gave similar results at 80
PhBr + CH2CHPh → trans‐PhCHCHPh
(5)
°C, with V taking the reaction to near completion (96%) within
30 min while, over the same time frame, II achieved only 30%
conversion (1.5 h to reach completion). In contrast, IV
produced only trace amounts of trans-stilbene over 30 min:
10% after 24 h (see the Supporting Information, Figure S1).
Note that 1,1-diphenylethylene was at most a minor side
product (<5%) in all cases.
We have also begun an investigation of the Sonogashira
cross-coupling reaction of bromobenzene and phenylacetylene
to form diphenylacetylene (eq 6).3
As an extension of our previous work4a and to assess further
the general efficacy of V, we now report preliminary findings of
an investigation in which we compare the effectiveness of V
with those I, II, III, and/or IV for Heck−Mizoroki and
Sonogashira cross-coupling reactions (eqs 1 and 2). To begin,
we selected the representative Heck−Mizoroki cross-coupling
reaction of chlorobenzene with methyl acrylate to form trans-
methyl cinnamate (eq 4).
(6)
PhBr + PhC CH→PhC CPh
Since much of the Sonogashira cross-coupling literature
involves palladium-based catalyst systems containing PPh3,
including the precursors Pd(PPh3)4 (I) and PdCl2(PPh3)2 (i.e.,
III + 2PPh3),3 our investigation focused initially on
comparisons of the catalyst precursors I, II, preformed
PhCl + CH2CHCO2Me → trans‐PhCHCHCO2Me
(4)
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Communication
PdCl2(PPh3)2, IV, and V with II, IV, and V at 50 °C, all
activated with PPh3. The reaction profiles utilizing the various
catalyst precursors are shown in Figure 2.
ASSOCIATED CONTENT
* Supporting Information
Text and figures giving experimental procedures. This material
is available free of charge via the Internet at http://pubs.acs.
org..
■
S
AUTHOR INFORMATION
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
■
We are grateful to Johnson-Matthey for a generous loan of
PdCl2. We also acknowledge financial support from the Natural
Sciences and Engineering Research Council of Canada
(Discovery Grant to M.C.B.) and Queen’s University (R.
Samuel McLaughlin Scholarship to A.W.F.).
Figure 2. Yields of diphenylacetylene from the cross-coupling of
phenylacetylene and bromobenzene catalyzed by 1 mol % Pd catalyst
systems utilizing (a) V + 2PPh3, (b) IV + 3PPh3, (c) PdCl2(PPh3)2,
(d) I, and (e) II + 4PPh3 at 50 °C.
REFERENCES
■
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near-quantitative formation of diphenylacetylene over ∼24 h,
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effective. Sonogashira cross-couplings are often carried out in
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catalyst system was observed, as expected and consistent with
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of 1 equiv of CuI. Essentially no homocoupled product, 1,4-
diphenylbutadiyne, was formed in these reactions.
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cross-coupling reactions of various substrates with emphasis on
more challenging substrates for Suzuki−Miyaura, Heck−
Mizoroki, and Sonogashira reactions. Note that we are not
claiming to have discovered the optimal catalyst for these cross-
coupling reactions, only an excellent procedure for generating
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wishes to employ. We are also investigating carbon−
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Our results clearly confirm our hypothesis that combinations
of V with tertiary phosphines can generate catalyst solutions for
Heck−Mizoroki and Sonogashira cross-coupling reactions
which are much more active than analogous catalysts systems
obtained using catalyst precursors I−IV. The results are
consistent with previous findings for Suzuki−Miyaura cross-
coupling reactions, and again the reason almost certainly lies in
the fact that V generates catalytically active species PdL2 quickly
and quantitatively while, in contrast, the others do not.
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