Mizoroki-Heck reactions catalyzed by palladium dichloro-bis(aminophosphine) complexes under mild reaction conditions. the importance of ligand composition on the catalytic activity

Article abstract of DOI:10.1039/c3gc40493e

Dichloro-bis(aminophosphine) complexes of palladium with the general formula [(P{(NC₅H₁₀)_3-n(C₆H ₁₁)_n})₂Pd(Cl)₂] (where n = 0-2) are easily accessible, cheap and air stable, highly active and universally applicable C-C cross-coupling catalysts, which exhibit an excellent functional group tolerance. The ligand composition of amine-substituted phosphines (controlled by the number of P-N bonds) was found to effectively determine their catalytic activity in the Heck reaction, for which nanoparticles were demonstrated to be their catalytically active form. While dichloro{bis[1, 1′,1′′-(phosphinetriyl)tripiperidine]}palladium (1), the least stable complex (towards protons) within the series of [(P{(NC₅H ₁₀)_3-n(C₆H₁₁)_n}) ₂Pd(Cl)₂] (where n = 0-3), is a highly active Heck catalyst at 100 °C and, hence, a rare example of an effective and versatile Heck catalyst that efficiently operates under mild reaction conditions (100 °C or below), a significant successive drop in activity was noticed for dichloro-bis(1,1′-(cyclohexylphosphinediyl)dipiperidine)palladium (2, with n = 1), dichloro-bis(1-(dicyclohexylphosphinyl)piperidine)palladium (3, with n = 2) and dichloro-bis(tricyclohexylphosphine)palladium (4, with n = 3), of which the latter is essentially inactive (at least under the reaction conditions applied). This trend was explained by the successively increasing complex stability and its ensuing retarding effect on the (water-induced) generation of palladium nanoparticles thereof. This interpretation was experimentally confirmed (initial reductions of 1-4 into palladium(0) complexes of the type [Pd(P{(NC₅H₁₀)_3-n(C₆H ₁₁)_n})₂] (where n = 0-3) were excluded to be the reason for the activity difference observed as well as molecular (Pd ⁰/Pd^II) mechanisms were excluded to be operative) and thus demonstrates that the catalytic activity of dichloro-bis(aminophosphine) complexes of palladium can-in reactions where nanoparticles are involved-effectively be controlled by the number of P-N bonds in the ligand system.

Full text of DOI:10.1039/c3gc40493e

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Mizoroki–Heck reactions catalyzed by palladium
dichloro-bis(aminophosphine) complexes under mild
reaction conditions. The importance of ligand
composition on the catalytic activity†
Cite this: DOI: 10.1039/c3gc40493e
Miriam Oberholzera and Christian M. Frech*b
Dichloro-bis(aminophosphine) complexes of palladium with the general formula [(P{(NC5H10 3
−n(C6H11)n})2Pd(Cl)2] (where n = 0–2) are easily accessible, cheap and air stable, highly active and univer-
sally applicable C–C cross-coupling catalysts, which exhibit an excellent functional group tolerance. The
ligand composition of amine-substituted phosphines (controlled by the number of P–N bonds) was
found to effectively determine their catalytic activity in the Heck reaction, for which nanoparticles were
demonstrated to be their catalytically active form. While dichloro{bis[1,1’,1’’-(phosphinetriyl)tripiperi-
)
dine]}palladium (1), the least stable complex (towards protons) within the series of [(P{(NC5H10 3−n-
)
(C6H11)n})2Pd(Cl)2] (where n = 0–3), is a highly active Heck catalyst at 100 °C and, hence, a rare example
of an effective and versatile Heck catalyst that efficiently operates under mild reaction conditions (100 °C
or below), a significant successive drop in activity was noticed for dichloro-bis(1,1’-(cyclohexylphosphine-
diyl)dipiperidine)palladium (2, with n = 1), dichloro-bis(1-(dicyclohexylphosphinyl)piperidine)palladium
(3, with n = 2) and dichloro-bis(tricyclohexylphosphine)palladium (4, with n = 3), of which the latter is
essentially inactive (at least under the reaction conditions applied). This trend was explained by the suc-
cessively increasing complex stability and its ensuing retarding effect on the (water-induced) generation
of palladium nanoparticles thereof. This interpretation was experimentally confirmed (initial reductions
of 1–4 into palladium(0) complexes of the type [Pd(P{(NC5H10)3−n(C6H11)n})2] (where n = 0–3) were
Received 15th March 2013,
Accepted 18th April 2013
excluded to be the reason for the activity difference observed as well as molecular (Pd0/PdII) mechanisms
were excluded to be operative) and thus demonstrates that the catalytic activity of dichloro-bis(amino-
phosphine) complexes of palladium can – in reactions where nanoparticles are involved – effectively be
controlled by the number of P–N bonds in the ligand system.
DOI: 10.1039/c3gc40493e
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Introduction
The Mizoroki–Heck reaction (Scheme 1) is nowadays the most
important palladium-catalyzed C–C bond forming process for
the arylation of olefins and, thus, the method of choice for the
preparation of vinylbenzenes.1,2 Even though recent develop-
ments have considerably increased the activity of Heck cata-
a typical reaction protocol with aryl bromides
as substrates still requires catalyst loadings between 1 and
5 mol%, a reaction temperature of 140 °C (lower reaction
Scheme 1 General scheme of a Heck cross-coupling reaction between an aryl
bromide and an olefin.
lysts,2
temperatures typically lead to a dramatic drop of activity) and
reaction times of up to 24 hours for high conversions.
Moreover, in most reports only few reactions with rather
simple substrates and coupling partners are tested. In
addition, modified reaction conditions (e.g. reaction tempera-
tures, catalyst loadings, bases, solvents, and additives) are
often reported for different substrates, which strongly limit
their general application in laboratory syntheses and industrial
processes. Furthermore, many catalysts exhibit low thermal
stability and suffer from inefficiency, low functional group
tolerance and/or sensitivity towards both, air and moisture. In
aInstitute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190,
CH-8057 Zürich, Switzerland
bInstitute of Chemistry and Biological Chemistry, Zürich University of Applied
Sciences, Einsiedlerstrasse 31, CH-8820 Wädenswil, Switzerland.
E-mail: christian.frech@zhaw.ch
†Electronic supplementary information (ESI)
available. See DOI:
10.1039/c3gc40493e
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addition, their (multi-step) syntheses are often time-consum- rates and yields were found for the phosphine-based catalyst
ing or difficult, require inert-atmosphere techniques and typi- 4.7a,c–e
cally are made with expensive and toxic starting materials of
Furthermore, the catalytic performance of dichloro-bis(amino-
poor stability, which clearly refers to the need for new and phosphine) complexes can (in reactions where nanoparticles
improved, cheap and easily accessible, stable but reactive and are involved) effectively be controlled by simple ligand modifi-
generally applicable but green versions of Heck catalysts with a cations: an increasing number of P–N bonds in the ligand
high functional group tolerance, which efficiently and reliably system successively eases their water-induced degradation and
operate at low catalyst loadings with general applicable reac- consequently the formation of nanoparticles from the respect-
tion protocols – preferably under mild reaction conditions.
ive complexes. Accordingly, substitution of 1,1′,1′′-(phosphine-
Dichloro-bis(aminophosphine) complexes of palladium triyl)tripiperidine from 1 by 1,1′-(cyclohexylphosphinediyl)-
(1–3, Fig. 1) are easily accessible, cheap and air stable, highly dipiperidine), 1-(dicyclohexylphosphinyl)piperidine) or tricy-
active and universally applicable C–C cross-coupling catalysts clohexylphosphine successively increases the complex stability
as well as exhibit an excellent functional group tolerance.7 The and, hence, retards the (water-induced) formation of nanopar-
reason for their excellent catalytic activity and general applica- ticles thereof. As a result, while dichloro-bis(1-(dicyclohexyl-
bility is due to the unique properties of aminophosphines: the phosphinyl)piperidine)palladium (3), the most stable
steric bulk as well as the σ-donor strength of aminophosphines aminophosphine complex (with one P–N bond in the amine-
is essentially the same when compared to their phosphine- substituted phosphine), was found to be the catalyst of choice
based analogues.7e Thus, complexes of type [(P{(NC5H10)3−n
-
in the Heck reaction performed at 140 °C (only a very poor cat-
(C6H11)n})2Pd(Cl)2] (where n = 0–3; Fig. 1) show – indepen- alytic activity was observed for the phosphine based complex
dently from the number of n – comparable levels of activity in 4),7d,e the highest catalytic activity was expected to be obtained
cross-coupling reactions where molecular mechanisms are for
dichloro{bis[1,1′,1′′-(phosphinetriyl)tripiperidine]}palla-
operative. On the other hand, the labile character of P–N dium [(P(NC5H10)3)2Pd(Cl)2] (1), the least stable (and greenest)
bonds in aminophosphine-based ligands (sensitivity towards complex within the series of [(P{(NC5H10)3−n(C6H11)n})2Pd(Cl)2]
protons; in the form of water for example) also offers the possi- (where n = 0–3; Fig. 1), when the reaction temperature was
bility to efficiently promote the formation of nanoparticles in lowered – if too fast palladium nanoparticle formation does
the respective complexes. Consequently, 1–3 (Fig. 1) and the not inhibit catalysis. Therefore, we were intrigued by the possi-
phosphine based analogue (4) were found to exhibit similar bility to efficiently and reliably promote the Heck reaction with
catalytic activities in the Negishi reaction and the hydrothiola- aryl bromides – the substrates of choice for industrial appli-
tion of alkynes, where molecular (Pd0/PdII) mechanisms were cations – in the presence of 1 at 100 °C (or even below) and,
shown to be operative.7b,f This, however, is in striking contrast hence, under much milder reaction conditions than typical in
to the Heck, Suzuki and cyanation reactions for example, the Heck reaction applied.
where palladium nanoparticles were demonstrated to be their
We report herein the catalytic performance of air-stable 1 in
catalytically active form: while the aminophosphine-based the vinylation of a wide variety of different, electronically acti-
cross-coupling catalysts 1–3 generally show excellent levels of vated, non-activated, deactivated, sterically hindered, and func-
activity in these reactions, dramatically reduced conversion tionalized aryl bromides as well as sulfur and nitrogen
containing heterocyclic aryl bromides with different olefins at
100 °C in NMP (N,N-dimethylpyrrolidone) or DMF (N,N-di-
methylformamide) and K2CO3 as solvents and base in the pres-
ence of 0.05 mol% of
a catalyst and ∼10 mol% of
tetrabutylammonium bromide, which was (in contrast to the
Heck reactions performed at 140 °C) found to be essential as
an additive for the reliable conversion of the substrates into
the cross-coupling products with 1 at 100 °C.8,9 1 was quanti-
tatively prepared by treatment of toluene suspensions of [Pd-
(Cl)2(cod)] (cod = cycloocta-1,5-diene) with two equivalents of
readily prepared 1,1′,1′′-(phosphinetriyl)tripiperidine (1,1′,1′′-
(phosphinetriyl)tripiperidine is almost quantitatively prepared
in one step by the dropwise addition of 6 equiv. of piperidine
to cooled diethyl ether solutions of PCl3 and subsequent fil-
tration) in air at 25 °C within only a few minutes (Scheme 2)
Fig. 1 The effect of the ligand composition of dichloro{bis[1,1’,1’’-(phosphine-
triyl)tripiperidine]}palladium (1), dichloro-bis(1,1’-(cyclohexylphosphinediyl)di-
piperidine)palladium (2, with n = 1) and dichloro-bis(1-(dicyclohexylphosphinyl)
piperidine)palladium (3, with n = 2) as well as their phosphine-based analogue
(4, with n = 3) on the complex stability and, hence, on the ease of (water-
induced) nanoparticle formation.
Scheme 2 Synthesis of dichloro{bis[1,1’,1’’-(phosphinetriyl)tripiperidine]}palla-
dium (1).
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and, hence, is one of the cheapest (the ligand costs for the 1-bromo-3,5-dimethoxybenzene), were applied: 1-bromo-4-phe-
preparation of 1 with 1 g of palladium precursor is less than 1 noxybenzene and 1-(benzyloxy)-4-bromobenzene, for example,
Euro), the most convenient and the most efficient and, hence, were almost fully converted into 1-(phenoxy)-4-[(E)-2-phenyl-
greenest cross-coupling catalysts available.
ethenyl]benzene (a9) and 1-{(E)-2-[4-(benzyloxy)phenyl]-
We show that dichloro{bis[1,1′,1′′-(phosphinetriyl)tripiperi- ethenyl}-3-nitrobenzene (b2) within 1 and 8 hours, respectively.
dine]}palladium [(P(NC5H10)3)2Pd(Cl)2] (1) is – in contrast to Even 1-bromo-3,5-dimethoxybenzene was fully converted into
dichloro-bis(1,1′-(cyclohexylphosphinediyl)dipiperidine)palladium 1,3-dimethoxy-5-[(E)-2-phenylethenyl]benzene (a11) when pro-
[(P{(NC5H10)2(C6H11)})2Pd(Cl)2] (2) and dichloro-bis(1-(dicyclo- longed reaction times (24 hours) were applied. Moreover, the
hexylphosphinyl)piperidine)palladium [(P{(NC5H10)(C6H11)2})2- Heck reactions also performed well with protic substrates as
Pd(Cl)2] (3) as well as their phosphine-based analogue well as aryl bromides with methylsulfanyl groups. Exemplary
[(P(C6H11)3)2Pd(Cl)2] (4), for which a successive and dramatic reactions with 4-bromophenol, 3-bromoaniline, N-(4-bromo-2-
drop in activity was noticed – a highly efficient, reliable, and methylphenyl)acetamide and 1-bromo-4-(methylsulfanyl)-
extremely versatile Heck catalyst, which offers the possibility to benzene smoothly yielded 4-[(E)-2-phenylethenyl]phenol (a13,
efficiently convert also thermally less stable substrates into the 97% within 6 h), 3-[(E)-2-(4-methoxyphenyl)ethenyl]aniline
respective Heck products in high yields within reasonable reac- (d3, 84% within 24 h), N-{4-[(E)-2-(3-chlorophenyl)ethenyl]-2-
tion times. Moreover, the reaction protocols are uniformly methylphenyl}acetamide (c3, 99% within 9 h), and 1-(methyl-
applicable and, thus, can directly be adapted to other sub- sulfanyl)-4-[(E)-2-phenylethenyl]benzene (a18, 91% within
strates without the necessity to be changed and, thus, demon- 24 h), respectively. A reduced level of activity was generally
strate the general applicability of
1 in this process. obtained when sterically hindered aryl bromides were used as
Accordingly, 1 is commercially available as well as was success- substrates: whereas only a slight decrease in activity was
fully applied in industry. Mechanistic investigations indicate noticed when 1-bromo-2-methylbenzene was coupled with
that palladium nanoparticles are the catalytically active form styrene, a significant drop in activity was found for 2-bromo-
of 1, which provides a simple explanation for the successive 1,3,5-trimethylbenzene. Even though prolonged reaction times
(dramatic) drop in activity with decreasing n and hence from 1 were required 3-bromopyridine or 3-bromoquinoline were fully
to 4.
converted into 3-[(E)-2-phenylethenyl]pyridine (a16) and 3-[(E)-
2-phenylethenyl]quinoline (a17), respectively. Similarly, pro-
longed reaction times were required to achieve high conver-
sions with 4-ethenylpyridine (e) as a coupling partner (e1–e3).
Similar yields but higher conversion rates were generally found
when the Heck reactions were performed with electronically
Results and discussion
Catalysis
Complex 1 is a highly active, reliable, and versatile Heck cata- activated olefins, such as N,N-dimethylacrylamide (f), 4-acryl-
lyst with excellent functional group tolerance. The coupling oylmorpholine (g) and butyl acrylate (h). Moreover, the
products are typically obtained in excellent yields within only E-isomers of the respective coupling products were in all the
few hours at 100 °C, of which the E-isomer of the arylated reactions examined exclusively formed. Impressively, also
olefins is often exclusively and cleanly formed (side-products heterocyclic aromatic bromides were successfully coupled with
were not detectable). Exemplary reactions were successfully alkenes at 100 °C: for example, when ethyl 1-(6-bromopyridin-
performed with styrene (a), 1-ethenyl-3-nitrobenzene (b), 2-yl)piperidine-3-carboxylate – a 6-bromopyridine-2-amine –
1-chloro-3-ethenylbenzene (c), 1-ethenyl-4-methoxybenzene (d) was coupled with butyl acrylate (h), ethyl 1-{6-[(E)-2-(4-methoxy-
and 4-ethenylpyridine (e) (Table 1) as well as N,N-dimethylacry- phenyl)ethenyl]pyridin-2-yl}piperidine-3-carboxylate (h5) was
lamide (f), 4-acryloylmorpholine (g), and butyl acrylate (h) quantitatively formed within 12 hours. An excellent perform-
(Table 2), which demonstrate its general applicability. For ance was also noticed when sulfur-containing aryl bromides
example, when electronically activated, non-ortho-substituted were used as substrates: for example, when 2-bromothiophene,
aryl bromides, such as 1-bromo-4-nitrobenzene, 1-bromo-4- 2-bromo-5-methylthiophene, and 2,5-dibromothiophene were
fluorobenzene, 4-bromobenzophenone, and 3-bromobenzalde- coupled with N,N-dimethylacrylamide (f) or butyl acrylate (h),
hyde, were coupled with styrene and derivatives of it, smooth (2E)-N,N-dimethyl-3-(5-methylthiophen-2-yl)prop-2-enamide (f4),
C–C bond formation and exclusive, quantitative product for- (2E,2′E)-3,3′-thiene-2,5-diylbis(N,N-dimethylprop-2-enamide) (f5),
mation were achieved in almost all the reactions examined and butyl (2E)-3-thiophen-2-ylprop-2-enoate (h6) were exclu-
within 8 hours. Exclusive Caryl–Br bond activation was noticed sively and quantitatively formed within 24 hours. Impressively,
when bromochlorobenzenes were used and, thus, quantitative when 5,5′-dibromo-2,2′-bithiophene was coupled with 4-acryl-
formation of 1-chloro-3-[(E)-2-phenylethenyl]benzene (a7) was oylmorpholine (g) at 100 °C, 4,4′-{2,2′-bithiene-5,5′-diylbis-
observed when 1-bromo-3-chlorobenzene was applied. Essen- [(1E)-3-oxoprop-1-ene-1,3-diyl]}dimorpholine (g4) was quanti-
tially the same conversion rates and yields were achieved when tatively formed within 24 hours.10
electronically non-activated aryl bromides, such as 1-bromo-4-
tert-butylbenzene or 1-bromonaphthalene as well as aromatic
Catalytic performance and other advantages of 1
bromides with increased electron density on the aryl unit (e.g. Overall,
dichloro{bis[1,1′,1′′-(phosphinetriyl)tripiperidine]}-
1-bromo-4-phenoxybenzene, 1-(benzyloxy)-4-bromobenzene or palladium (1) is a highly active, efficient and one of the most
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Table 1 Heck cross-coupling reactions between aryl bromides and styrene (a) and derivatives of it (b–e), catalyzed by 1a
a Reaction conditions: 1.0 mmol aryl bromide, 1.5 mmol olefin (relative to bromide), 2.0 mmol K2CO3, 2.5 ml NMP, tetrabutylammonium
bromide (10 mol%), a catalyst (0.05 mol%) added in a solution (THF), reaction performed at 100 °C in an N2 atmosphere. The conversions and
product ratios (trans/gem/cis) are determined by GC/MS and are based on aryl bromide. Isolated yields are given in brackets. b DMF was used as a
solvent.
versatile and convenient Heck catalysts, which allows a wide required to achieve conversions between 51 and 84%.
variety of aryl bromides, which may contain nitro, chloro, The latter catalyst, on the other hand, is the only system
fluoro or trifluoromethane groups, ketones, aldehydes, ethers, that allows the Heck reaction to be performed at room
esters, amides, amines, anilines, phenols, as well as hetero- temperature for which product yields from 64 up to 97% were
cyclic aryl bromides, such as pyridines and derivates, or thio- achieved in reaction times between 1 and 3 days in the
phenes and aryl bromides with methylsulfanyl groups, to be presence of 1 mol% (rel. to palladium) of [Pd2(dba)3] and
selectively coupled with various olefins in very high conversion 1–3 mol% of the ligand.
rates and yields at 100 °C. Thus, 1 is a rare example of a Heck
Moreover,
dichloro{bis[1,1′,1′′-(phosphinetriyl)tripiperi-
catalyst that allows this transformation to be efficiently cata- dine]}palladium (1) also compares favorably with [Pd(OAc)2],13
lyzed under mild reaction conditions. However, two other [(PCNHCP)Pd(Cl)][Cl],14 [(C6H3-2,6-(CH2PiPr2)2Pd(TFA)] (TFA =
systems, [Pd(OAc)2]/Et4NCl/Cy2NMe and [Pd2(dba)3]/P(tBu)3/ trifluoroacetate),15
[(C6H4-2-(CH2P(tBu)2)Pd(OAc)]2,16
and
Cy2NMe (dba = dibenzylideneacetone),11,12 may be mentioned, [(C6H2-3,5-(tBu)2-2-{OP(OAr)2}Pd(Cl)]2,17 even if the Heck reac-
which catalyze the Heck reaction at temperatures of ∼100 °C tions were carried out at considerably higher temperatures
(or below). Even if the former system allows the cross-coupling (140 °C) than applied for 1. On the other hand, [(C5H3N-2,6-
of aryl bromides with disubstituted derivates of alkyl acrylates (NHCMe)Pd(Br)]+ 18 and the very recently reported systems
(unsubstituted derivatives have not been tested) at reaction [(CNHCN)Pd(fppz)] (fppzH = 2-[3-(trifluoromethyl)-1H-pyrazol-
temperatures between 85 and 110 °C, high catalyst loadings 5-yl]pyridine) and trans-di(μ-aceto)bis[2-diphenylphospino-2′-
(2–4 mol%) and prolonged reaction times (16–60 hours) were methylbiphenyl]dipalladium,19,20 show
a higher level of
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Table 2 Heck cross-coupling reactions between aryl bromides and N,N-dimethylacrylamide (f), 4-acryloylmorpholine (g), and butyl acrylate (h), catalyzed by 1a
a Reaction conditions: 1.0 mmol aryl bromide, 1.5 mmol olefin (relative to bromide), 2.0 mmol K2CO3, 2.5 ml NMP, tetrabutylammonium
bromide (10 mol%), a catalyst (0.05 mol%) added in a solution (THF), reaction performed at 100 °C in an N2 atmosphere. The conversions and
product ratios (trans/gem/cis) are determined by GC/MS and are based on aryl bromide. Isolated yields are given in brackets. b DMF was used as a
solvent. c The product ratio refers to (trans–trans/trans–gem/trans–cis).
activity at 140 °C, but were inferior when the reaction temp- stable compound, shows (by far) the lowest level of activity and
erature was increased to 140 °C for 1 as well.
is in most reactions applied even inactive. For example,
Despite the high catalytic activity, efficiency and functional whereas the cross-coupling of 1-bromonaphthalene with
group tolerance of dichloro{bis[1,1′,1′′-(phosphinetriyl)tripi- styrene quantitatively yielded the coupling product with 1 after
peridine]}palladium (1), a great advantage of 1 when compared 14 hours, a dramatically reduced level of activity and, hence, a
to Heck catalysts ligated by water-insoluble ligand systems conversion of only 32% was achieved when dichloro-bis(1,1′-
includes the well-known fate of the catalyst after catalysis: (cyclohexylphosphinediyl)dipiperidine)palladium (2, with n = 1)
treatment of 1 with aqueous hydrochloric acid in air and, thus, was used as a catalyst. A further drop in activity was found for
under work-up conditions leads to a rapid and complete cata- dichloro-bis(1-(dicyclohexylphosphinyl)piperidine)palladium (3,
lyst degradation, accompanied by the formation of phospho- with n = 2), for which a conversion of 21% was found after
nates, piperidinium salts and insoluble palladium-containing 14 hours. No product formation at all was detectable when their
decomposition products, which are easily separated from the phosphine-based analogue (4) was applied. The same obser-
coupling products. This is an often ignored, but very impor- vation was made by using sterically hindered 1-bromo-2-methyl-
tant issue to be considered (from ecologic and economic benzene as a substrate. Even though complete product formation
points of view) and is of particular importance for the prepa- was also found in single cases for 4 – typically with electronically
ration of pharmaceutically relevant compounds.
activated substrates, such as ethyl 4-bromobenzoate (Fig. 2) – the
The effect of ligand composition on the catalytic performance
of 1–4
The effect of the ligand composition in nanoparticle formation
(see below) of amine-substituted phosphines and, hence, on
the catalytic activity of dichloro-bis(aminophosphine)palla-
dium complexes of palladium (1–3) and their phosphine based
analogue 4 in the Heck reaction at 100 °C – was found to be
huge. While 1, the least stable compound (towards protons)
within the series of [(P{(NC5H10)3−n(C6H11)n})2Pd(Cl)2] (where
n = 0–3) where the formation of nanoparticles is most efficient,
exhibit the highest catalytic activity in the Heck reaction at
100 °C, a dramatic successive drop in activity was noticed in
all the reactions examined when 1,1′,1′′-(phosphinetriyl)tri-
piperidine was substituted by 1,1′-(cyclohexylphosphinediyl)-
dipiperidine), 1-(dicyclohexylphosphinyl)piperidine) and tricy-
Fig. 2 Catalytic activities of 1–4 in the Heck reaction of electronically activated
ethyl 4-bromobenzoate and styrene at 100 °C in NMP in the presence of
clohexylphosphine. Thus, [(P(C6H11)3)2Pd(Cl)2] 4, the most ∼10 mol% of tetrabutylammonium bromide and 0.05 mol% of a catalyst.
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trend observed is obvious: the higher the number of P–N
bonds in aminophosphines the more active the respective
dichloro-bis(aminophosphine)palladium complexes (under
the reaction conditions applied) are, which is opposed to the
trend found at 140 °C for 1–3.7e,21
Consequently, 1 is the catalyst of choice for Heck reactions
performed at 100 °C and 3 for reactions at 140 °C. Complex 4,
on the other hand, is, in none of the reactions examined and
the conditions applied, even competitive. This demonstrates
that the nanoparticle formation and, hence, the catalytic
activity of dichloro-bis(aminophosphine) complexes of palla-
dium can (in reactions where nanoparticles are involved) effec-
tively be controlled by the number of P–N bonds in the ligand
system and, thus, allows the catalyst activity to be adapted to
the reaction conditions applied. This unique structure–reactiv-
ity relationship of aminophosphines, their cheap and easy
accessibility is the reason for the high catalytic activity and ver-
satility of the respective dichloro-bis(aminophosphine) com-
plexes of palladium, which make them some of the most
attractive cross-coupling catalysts for organic syntheses as well
as industrial processes.
Fig. 3 Reduction of 1 (top left), 2 (top right), 3 (bottom left) and 4 (bottom
right) (0.5 mM) into palladium(0) complexes of the type [Pd(P{(NC5H10 3−n-
)
(C6H11)n})2] (where n = 0–3),22 in THF (containing n-Bu4NBF4, 0.1 M): cyclic vol-
tammetry with gold as the working and Pt as auxiliary electrodes and Ag/AgCl
as a reference electrode with a scan rate ν = 0.1 V s−1, at 22 °C. All potentials are
given versus Ag/AgCl (Fc/FcI at +500 mV).
The effect of ligand composition on the catalytic activity of
dichloro-bis(aminophosphine) complexes of palladium
The successive drop in activity of dichloro{bis[1,1′,1′′-(phosphi-
netriyl)tripiperidine]}palladium (1, with n = 0), dichloro-bis-
(1,1′-(cyclohexylphosphinediyl)dipiperidine)palladium (2, with
n = 1), dichloro-bis(1-(dicyclohexylphosphinyl)piperidine)palla-
dium (3, with n = 2) and dichloro-bis(tricyclohexylphosphine)
palladium (4, with n = 3) in the Heck reaction performed at
100 °C was explained by the successively increasing complex
stability and its ensuing retarding effect on the (water-
induced) generation of palladium nanoparticles thereof. This
interpretation gained strong experimental support by: (1) the
electrochemical reduction of 1–4 in THF,22 showing for all
complexes an identical (irreversible) reduction wave (Fig. 3),
which for the aminophosphine based systems (1–3) are located
at −1.35 V, −1.34 V and −1.31 V and for the phosphine-based
palladium(0) complexes of the type [Pd(P{(NC5H10)3−n
-
(C6H11)n})2] (where n = 0–3) – their catalytically active species in
molecular (Pd0/PdII) mechanisms – cannot be the reason for
the activity difference observed. Indeed, catalytic cycles invol-
ving complexes with Pd(0) centers were ruled out to be operat-
ive in the Heck reaction catalyzed by 1–4, as indicated by the
results obtained from the (recently developed) dibenzyl-test:23
dibenzyl formation was – in contrast to Heck reactions cata-
lyzed by palladium(0) complexes of the type [Pd(P{(NC5H10)3−n
-
(C6H11)n})2] (where n = 0–3) – not detectable by GC/MS when
reaction mixtures of aryl bromide, olefin, benzyl chloride
(∼10 mol% rel. to aryl bromide), a catalyst and a base were
thermally treated (100 °C). Moreover, dibenzyl was neither
formed in the presence of [Pd(OAc)2] as a catalyst – another
piece of evidence that nanoparticles are their catalytically
active form in the Heck reaction – at least under the reaction
conditions applied.
system [Pd(P(C6H11)3)2(Cl)2] (4) at −1.21
V and, hence,
would suggest – if from these electrochemically determined
reduction potentials an activity trend in the Heck reaction
is deducible at all and if a molecular mechanism were
operative – an opposite trend in activity than it was experi-
mentally observed and (2) the catalytic activity of bis(amino-
phosphine)palladium(0) complexes of the type [Pd-
(P{(NC5H10)3−n(C6H11)n})2] (where n = 0–3) in the Heck reaction
at 100 °C, which show the same trend in activity as it was
found to be the case for 1–4.
Mechanistic investigations
The following experimental observations strongly indicate the
For example, whereas full conversion of 1-bromonaphtha- involvement of palladium nanoparticles in the catalytic cycle
lene and styrene into 1-[(E)-2-phenylethenyl]naphthalene (a15) of the Heck reaction catalyzed by dichloro-bis(aminophos-
was achieved with both, 1 and bis[1,1′,1′′-(phosphinetriyl)tripi- phine) complexes of palladium (1–3) as well as [(P(C6H11)3)2-
peridine]palladium(0) [Pd(P(NC5H10)3)2], within 14 hours, no Pd(Cl)2] (4) and, hence, fully confirms the above results as well
product formation at all was found for their phosphine-based as their interpretation and provides a simple and the only
analogues 4 and [Pd(P(C6H11)3)2], respectively, demonstrating possible explanation for the activity difference observed in the
that the initial reduction of dichloro-bis(aminophosphine)pal- Heck reaction catalyzed by 1–4:24 (1) the steric bulk of 1,1′,1′′-
ladium(II) (1–3) and their phosphine-based analogue 4 into (phosphinetriyl)tripiperidine, 1,1′-(cyclohexylphosphinediyl)-
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dipiperidine, 1-(dicyclohexylphosphinyl)piperidine and tri- transmission electron microscope (TEM) equipped with an
cyclohexylphosphine are almost identical as well as their σ- energy dispersive X-ray (EDX) analyzer (Fig. 4).
donor strength (as shown by the CO stretching frequency of
complexes of the type cis-[(PR3)(NC5H10)Mo(CO)4]).7e,25 Thus,
whereas very similar catalytic activities will be obtained for
dichloro-bis(aminophosphine)palladium complexes 1–3 and
Conclusions
[(P(C6H11)3)2Pd(Cl)2] (4) in reactions where molecular mecha- In conclusion, dichloro{bis[1,1′,1′′-(phosphinetriyl)tripiperi-
nisms are operative (as it was found to be the case in the dine]}palladium (1) is – in contrast to dichloro-bis(1,1′-(cyclo-
Negishi cross-coupling reaction and in the hydrothiolation of hexylphosphinediyl)dipiperidine)palladium (2), dichloro-bis(1-
alkynes),7b,f a significant difference in activity will be observed (dicyclohexylphosphinyl)piperidine)palladium (3) and the
in reactions where palladium nanoparticles are involved, as it phosphine-based
analogue
dichloro-bis(tricyclohexylpho-
was recently found to be the case in the Suzuki, cyanation and sphine)palladium (4) – a highly efficient Heck catalyst with an
Heck reactions (carried out at 140 °C).7a,c–e (2) The coupling excellent functional group tolerance, which reliably couples a
reactions follow for all the complexes a sigmoidal-shaped kine- wide variety of aryl bromides, which may contain nitro, chloro,
tics (Fig. 2), which is characteristic of metal-particle formation fluoro or trifluoromethane groups, nitriles, ketones, aldehydes,
and autocatalytic surface growth, which can lead to soluble ethers, esters, amides, anilines, phenols, and heterocyclic aryl
monodisperse nanoclusters or insoluble bulk metal for- bromides, such as pyridines and derivates, as well as thio-
mation.26 (3) The addition of a large excess of metallic phenes and aryl bromides containing methylsulfanyl groups
mercury to reaction mixtures of aryl bromide, olefin and cata- with various different alkenes at 100 °C in DMF or NMP and
lyst efficiently stopped catalysis at any time of its addition and K2CO3 as solvents and base in the presence of ∼10 mol% tetra-
no product formation at all was observed when few drops of butylammonium bromide and only 0.05 mol% of the catalyst.
metallic mercury were added at the beginning of the reaction. Thus, 1 is a rare example of an effective and versatile Heck
The same observations were made when poly(4-vinylpyridine) catalyst that efficiently operates under mild reaction con-
(PVPy) (2% cross-linked with divinylbenzene) was added ditions (100 °C or below) and, hence, offers the possibility to
instead.27 (4) No product formation at all was obtained when efficiently convert also thermally less stable substrates into the
0.1 equiv. (rel. to the catalyst) of CS2 was added to the reaction respective coupling products within reasonable reaction times.
mixtures. (5) Whereas only very low conversions were observed The dramatic successive drop in activity observed for com-
in the absence of tetrabutylammonium bromide (due to fast plexes of the type [(P{(NC5H10 3−n(C6H11)n})2Pd(Cl)2] (where n =
)
(visibly observable) deposition of inactive palladium black),9 0–3) when 1,1′,1′′-(phosphinetriyl)tripiperidine was substituted
excellent and highly reproducible conversion rates and by 1,1′-(cyclohexylphosphinediyl)dipiperidine), 1-(dicyclohexyl-
product yields were found in its presence (∼10 mol% rel. to phosphinyl)piperidine) and tricyclohexylphosphine was
the substrate) at 100 °C. Finally, (6) the formation of palladium explained by the successively increasing complex stability
nanoparticles could be verified by analysis of the reaction mix- (from 1 to 4) and its ensuing retarding effect on the (water-
tures of exemplary Heck cross-coupling reactions for all induced) generation of palladium nanoparticles thereof. This
dichloro-bis(aminophosphine) complexes of palladium by a interpretation was experimentally confirmed: initial reduction
of 1–4 into palladium(0) complexes of the type [Pd(P{(NC5H10)3−n
-
(C6H11)n})2] (where 0–3) was (e.g. electrochemically)
n
=
excluded to be the reason for the activity difference observed
and also molecular (Pd0/PdII) mechanisms were ruled out to
be operative (by the dibenzyl-test). On the other hand, mechan-
istic investigations strongly indicated the involvement of nano-
particles as the catalytically active form of 1–4 and
demonstrate that the catalytic activity of dichloro-bis(amino-
phosphine) complexes of palladium can – in reactions where
palladium nanoparticles are their catalytically active form –
effectively be controlled by the number of P–N bonds in the
ligand system. As a consequence, the catalyst activity can be
adapted to the reaction conditions (e.g. reaction temperature)
applied, resulting that 1 is the catalyst of choice for Heck reac-
tions performed at 100 °C and 3 for reactions at 140 °C.
Complex 4, on the other hand, was in none of the reactions
examined and reaction conditions applied even competitive
and demonstrates the unique properties of aminophosphines.
Finally, aminophosphines are cheap and easily accessible and
modular. Thus, dichloro-bis(aminophosphine) complexes of
palladium belong to some of the most attractive cross-coupling
Fig. 4 TEM image showing aggregated palladium nanoparticles (as identified
by EDX analysis) from the cross-coupling reaction of 1-bromo-4-methoxyben-
zene with styrene, catalyzed by 0.05 mol% of dichloro{bis[1,1’,1’’-(phosphine-
triyl)tripiperidine]}palladium (1) at 100 °C in DMF in the presence of ∼10 mol%
of tetrabutylammonium bromide.
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catalysts, having great potential of finding applications in
organic syntheses as well as in industrial processes.
F. E. Herkes, M. Dekker, New York, 1998, ch. 37;
(i) L. F. Tietze, G. Kettschau, U. Heuschert and
G. Nordmann, Chem.–Eur. J., 2001, 7, 368; ( j) S. Brase,
A. De Meijere and G. Dyker, et al., in Handbook of Organo-
palladium Chemistry for Organic Synthesis, ed. E. Negishi,
Wiley, New York, 2002, ch. IV, IV.1, IV1.2, IV.2.2, and IV.2.3,
pp. 1123–1315.
Experimental section
General procedure for Heck reactions
A Young Schlenk (10 mL) was charged in a N2 atmosphere with
the appropriate amounts of olefin (1.5 mmol), aryl halide
(1.0 mmol), K2CO3 (2.0 mmol), tetrabutylammonium bromide
(∼10 mol% relative to the aryl bromide), and DMF or NMP
(2.5 ml). The mixture was vigorously stirred and heated to
100 °C. Then the correct amount of a catalyst was added by a
syringe as a solution in THF (0.05 mol%, 0.1 mL of a 5 × 10−3
M solution). Samples were periodically taken from the reaction
mixture, quenched with 1 M HCl (or 1 M Na2CO3, if basic func-
tional groups were present in the substrates), extracted with
ethyl acetate, and analyzed by GC/MS. At the end of catalysis,
the reaction mixtures were allowed to cool to room tempera-
ture, quenched with 1 M HCl (or 1 M NaOH respectively), and
extracted with ethyl acetate (3 × 25 mL). The combined extracts
were dried (MgSO4) and evaporated to dryness. The crude
material was purified by flash chromatography on silica gel or
basic aluminium oxide, as necessary.
2 Various different types of palladium complexes have been
reported to promote the vinylation of aryl halides, of which
many have been shown to follow the “classical” Pd0/PdII
mechanism, as it is for example the case for [Pd(PPh3)4] or
[Pd(PPh3)2(OAc)2].3 Other systems such as [Pd(OAc)2] are
known to serve as depot forms of nanoparticles.4 In the
case of pincer-type Heck catalysts,5 however, nanoparticles
are typically considered to be their catalytically active
form even if PdII/PdIV cycles still cannot be excluded to be
operative. In contrast, theoretical and experimental
investigations recently indicated the thermal accessibility
of pincer-type PdIV complexes along the catalytic cycle.6.
3 (a) C. Amatore, E. Carre and A. Jutand, Organometallics,
1995, 14, 5605; (b) J. F. Fauvarque, F. Pflüger and
M. Troupel, J. Organomet. Chem., 1981, 208, 419.
4 G. J. de Vries, Dalton Trans., 2006, 421.
5 For
a selection of pincer-type Heck catalysts, see:
(a) M. Ohff, A. Ohff, A. M. E. van der Boom and
D. Milstein, J. Am. Chem. Soc., 1997, 119, 11687;
(b) D. Morales-Morales, R. Redon, C. Yung and
C. M. Jensen, Chem. Commun., 2000, 1619; (c) E. Peris,
J. A. Loch, J. Mata and R. H. Crabtree, Chem. Commun.,
2001, 201; (d) W. A. Herrmann, V. P. W. Böhm,
C. W. K. Gstöttmayr, M. Grosche, C.-P. Reisinger and
T. Weskamp, J. Organomet. Chem., 2001, 617, 616;
(e) D. Benito-Garagorri, V. Bocokic, K. Mereiter and
Acknowledgements
Financial support by the Zürich University of Applied
Sciences (ZHAW), the University of Zürich (UZH), as well as
the Swiss National Science Foundation (SNSF) and the
Center for Microscopy and Image Analysis at the University
of Zürich, Switzerland for TEM-EDX measurements, is
acknowledged.
K.
Kirchner,
Organometallics,
2006,
25,
3817;
(f) F. Miyazaki, K. Yamaguchi and M. Shibasaki, Tetra-
hedron Lett., 1999, 40, 7379; (g) M. R. Eberhard, Org. Lett.,
2004, 2125; (h) J. L. Bolliger, O. Blacque and C. M. Frech,
Angew. Chem., Int. Ed., 2007, 46, 6514; (i) J. L. Bolliger and
C. M. Frech, Chem.–Eur. J., 2008, 14, 7969.
6 For a computational study about the thermal accessibility
of PdII/PdIV cycles in the Heck reaction, catalyzed by
pincer-type catalysts, see: O. Blacque and C. M. Frech,
Chem.–Eur. J., 2010, 16, 1521; for the synthesis and separa-
tion of the first pincer-type PdIV complex, see: J. Vicente,
A. Arcas, F. Julia-Hernandez and D. Bautista, Chem.
Commun., 2010, 46, 7253.
7 (a) J. L. Bolliger and C. M. Frech, Chem.–Eur. J., 2010, 16,
4075; (b) J. L. Bolliger and C. M. Frech, Chem.–Eur. J., 2010,
16, 11072; (c) R. Gerber, M. Oberholzer and C. M. Frech,
Chem.–Eur. J., 2012, 18, 2978; (d) J. L. Bolliger,
M. Oberholzer and C. M. Frech, Adv. Synth. Catal., 2011,
353, 945; (e) M. Oberholzer, R. Gerber and C. M. Frech,
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C. M. Frech, Chem.–Eur. J., 2012, 18, 2978.
Notes and references
1 For reviews of the palladium-catalyzed Heck reaction, see:
(a) R. F. Heck, in Palladium Reagents in Organic Syntheses,
ed. A. R. Katritzky, O. Meth-Cohn, C. W. Rees, Academic
Press, London, 1985, p. 2; (b) R. F. Heck, Vinyl substitution
with organopalladium intermediates, in Comprehensive
Organic Synthesis, ed. B. M. Trost, I. Fleming, Pergamon,
Oxford, 1991, vol. 4; (c) J.-L. Malleron, J.-C. Fiaud and
J.-Y. Legros, in Handbook of Palladium-Catalysed Organic
Reactions, Academic Press, London, 1997; (d) M. T. Reetz,
in Transition Metal Catalysed Reactions, ed. S. G. Davies,
S.-I. Murahashi, Blackwell, Oxford, 1999; (e) J. T. Link and
L. E. Overman, in Metal-Catalyzed Cross-Coupling Reactions,
ed. F. Diederich, P. J. Stang, Wiley-VCH, New York, 1998;
ch. 6; (f) S. Bräse and A. de Meijere, in Metal-Catalyzed
Cross-Coupling Reactions, ed. F. Diederich, P. J. Stang,
Wiley, New York, 1998; ch. 3.6; (g) K. C. Nicolaou and
E. J. Sorensen, in Classics in Total Synthesis, VCH,
New York, 1996; ch. 31; (h) R. A. de Vries, P. C. Vosejpka
and M. L. Ash, in Catalysis of Organic Reactions, ed.
8 Interestingly, whereas best results were achieved with
DMF when electronically activated or non-activated aryl
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bromides were applied, NMP was the solvent of choice
when electronically deactivated and sterically hindered or
heterocyclic aryl bromides were coupled with alkenes.
9 Tetrabutylammonium bromide is known to stabilize such
nanoparticles but has a retarding effect in catalyses when
molecular mechanisms are operative. See for instance:
coupled, the far highest level of activity was observed for
dichloro-bis(1-(dicyclohexylphosphinyl)piperidine)palladium
(3) when electronically deactivated or sterically hindered
and, hence, difficult-to-couple aryl bromides were
applied.7e This was explained by the higher stabilityof 3
(towards protons) when compared to 1 (and 2). As a result,
a retarded generation of (water-induced) palladium nano-
particles will occur. Even though this can lead to prolonged
induction periods for 3 (when compared to 1) and there-
fore to (slightly) lower conversion rates when simple-to-
couple substrates are applied, the nanoparticles generated
from 3 apparently are more active than those generated
from 1 (and 2). Their retarded growth leads to a higher
number and smaller nanoparticles, which makes the ratio
between palladium on the outer rim and palladium on the
inside of the particles more favorable. This leads to a
higher concentration of leached palladium in solution –
the catalytically active species – and consequently, to a
more active system.
(a)
Advances
in
Metal–Organic
Chemistry,
ed.
L. S. Liebeskind, JAI Press, Greenwich, 1996, vol. 5, p 153;
(b) M. T. Reetz and E. Westermann, Angew. Chem., Int. Ed.,
2000, 39, 165; (c) A. Zapf and M. Beller, Chem.–Eur. J., 2001,
7, 2908.
10 Notably, the cross-coupling product of 5,5′-dibromo-2,2′-
bithiophene and 4-acryloylmorpholine – 4,4′-{2,2′-bithiene-
5,5′-diylbis[(1E)-3-oxoprop-1-ene-1,3-diyl]}dimorpholine – is
a red, THF soluble solid, which forms a yellow precipitate
in the presence of potassium bromide and, hence, under
reaction conditions. Evidence for the formation of a potass-
ium bromide adduct of 4,4′-{2,2′-bithiene-5,5′-diylbis[(1E)-
3-oxoprop-1-ene-1,3-diyl]}dimorpholine was gained by pre-
cipitation of a yellow solid upon addition of KBr to THF 22 J. Pytkowicz, S. Roland, P. Mangeney, G. Meyer and
solutions of 4,4′-{2,2′-bithiene-5,5′-diylbis[(1E)-3-oxoprop-1- A. Jutand, J. Organomet. Chem., 2003, 678, 166.
ene-1,3-diyl]}dimorpholine and by elemental analysis 23 For details about the dibenzyl-test to rule out molecular
(elemental analysis for C22H24BrKN2O4S2: calcd C, 46.89;
H, 4.29; N, 4.97; found: C, 46.76; H, 4.19; N, 4.93). Isolation
of (KBr-free) 4,4′-{2,2′-bithiene-5,5′-diylbis[(1E)-3-oxoprop-1-
ene-1,3-diyl]}dimorpholine can be achieved by filtration
over silica gel.
(Pd0/PdII) mechanisms, see: (a) J. L. Bolliger, O. Blacque
and C. M. Frech, Chem.–Eur. J., 2008, 14, 7969. See also:
(b) C. M. Frech, L. J. W. Shimon and D. Milstein, Angew.
Chem., 2005, 117, 1737; (c) C. M. Frech, G. Leitus and
D. Milstein, Organometallics, 2008, 27, 894.
11 C. Gürtler and S. L. Buchwald, Chem.–Eur. J., 1999, 5, 3107.
12 A. F. Littke and G. C. Fu, J. Am. Chem. Soc., 2001, 123, 6989.
13 A. H. M. de Vries, J. M. C. A. Mulders, J. H. M. Mommers,
H. J. W. Henderickx and J. G. de Vries, Org. Lett., 2003, 5,
3285.
24 For a comprehensive review article about the problem of
distinguishing true homogeneous catalysis from soluble or
other metal-particle heterogeneous catalysis under redu-
cing conditions see: J. A. Widegren and R. G. Finke, J. Mol.
Catal. A: Chem., 2003, 198, 317 and references therein.
14 H. M. Lee, J. Y. Zeng, C.-H. Hu and M.-T. Lee, Inorg. Chem., 25 A. L. Morris and J. T. York, J. Chem. Educ., 2009, 86, 1408.
2004, 43, 6822.
26 (a) M. A. Watzky and R. G. Finke, J. Am. Chem. Soc., 1997,
119, 10382; (b) J. A. Widegren, M. A. Bennett and
R. G. Finke, J. Am. Chem. Soc., 2003, 125, 10301.
15 M. Ohff, A. Ohff, A. M. E. van der Boom and D. Milstein,
J. Am. Chem. Soc., 1997, 119, 11687.
16 W. A. Herrmann, V. P. W. Böhm and C.-P. Reisinger, 27 PVPy is a palladium trap, which can effectively inhibit cata-
J. Organomet. Chem., 1999, 576, 23.
17 D. A. Albisson, R. B. Bedford and P. N. Scully, Tetrahedron
Lett., 1998, 39, 9793.
18 S. Gründemann, M. Albrecht, J. A. Loch, J. W. Faller and
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19 M.-H. Sie, Y.-H. Hsieh, Y.-H. Tsai, J.-R. Wu, S.-J. Chen,
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lysis when nanoparticles are the catalytically active form of
a catalyst. Nevertheless, it should be mentioned that Pd
nanoparticles immobilized on PVPy spheres also have been
applied as a catalyst in Heck reactions.28 Therefore, this
test is not definitive and does neither conclusively prove
nor rule out either catalysis by the surface of Pd nano-
particles or molecular Pd(0) species (for itself) but can
strongly support the conclusions drawn from other tests
performed. For details see: K. Yu, W. Sommer, M. Weck
and C. W. Jones, J. Catal., 2004, 226, 101 and references
therein.
20 S. Nadri, M. Joshaghan and E. Rafiee, Organometallics,
2009, 28, 6281.
21 To be more precise: whereas (in contrast to 4) excellent, but
comparable levels of activity were observed for dichloro-bis- 28 S. P. M. T. Greci, R. C. Kwong, K. Mercado,
(aminophosphine) complexes of palladium at 140 °C when
electronically activated and non-activated substrates were
G. K. S. Prakash, G. A. Olah and M. E. Thompson, Chem.
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