The decisive role of ligand metathesis in Au/Pd bimetallic catalysis

Article abstract of DOI:10.1039/c3cc43133a

AuClL¹/PdCl₂L²₂ cocatalyzed coupling of Ar¹X and Ar²SnBu₃ is feasible for bulky Ar¹, provided that at least one ligand on Pd is not strongly coordinating. This can be

Full text of DOI:10.1039/c3cc43133a

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The decisive role of ligand metathesis in Au/Pd
bimetallic catalysis†
Cite this: Chem. Commun., 2013,
49, 7246
Juan delPozo, Juan A. Casares* and Pablo Espinet*
Received 27th April 2013,
Accepted 11th June 2013
DOI: 10.1039/c3cc43133a
www.rsc.org/chemcomm
AuClL1/PdCl2L2 cocatalyzed coupling of Ar1X and Ar2SnBu3 is
Having established the basic framework of the mechanism of
2
feasible for bulky Ar1, provided that at least one ligand on Pd is not the Au-cocatalyzed Stille process, it is now possible to address the
strongly coordinating. This can be achieved in situ by Au/Pd ligand effect of changing the ancillary ligands (a typical strategy used in
exchange if L1 is weakly coordinating. When the exchange is slow, synthesis optimization) from a mechanistic point of view. This study
independent preparation of appropriate catalysts is recommended.
uncovers aspects such as the thermodynamic preference of each
metal for different ligands, the kinetics of ligand scrambling, and
Bimetallic catalysis is providing new powerful alternatives to the the importance of the several mechanistic steps in the process using
classic catalytic processes with only one transition metal as catalyst.1 three representative ancillary ligands, PPh3, AsPh3, and IDM (IDM =
Many bimetallic processes are based on Au/Pd cocatalysis.2 In recent 1,3-dimethyl-imidazol-2-ylidene), and their combinations by pairs.
work we uncovered the ability of AsPh3 gold complexes to cocatalyze
As in our previous work,3 our study model is the coupling of
Stille reactions involving bulky aryls. The gold co-catalyst circum- p-CF3C6H4I (1) with the sterically demanding nucleophile
vents the formation of an overcrowded high energy Sn/Pd transition MesSnBu3 (2, Bu = n-butyl), catalyzed with [PdCl2L1L2 ] and [AuClL3]
2
state that prevents or severely slows down the classic Stille reaction, (L1, L2, or L3 = AsPh3, PPh3, or IDM). This coupling works only in the
by forming less hindered Au intermediates which, eventually, presence of gold co-catalysts. AsPh3 and LiCl were added in all of the
transmetalate the bulky aryl group to Pd (Scheme 1) through less mechanistic tests, in order to keep the reaction conditions constant.
hindered Sn/Au and Au/Pd transition states.3 In that experimental The experimental kinetic conditions were Pd : Au : Cl : Asadded
=
and DFT mechanistic study, AsPh3 was utilized as a ligand for the 1 : 1 : saturated : 2, where Pd and Au stand for the Pd and Au catalyst
two metals, in order to skip possible observational complications used, with the corresponding ligand in each case (Scheme 2).
arising from scrambling of the ancillary ligands.4 The reaction also
The initial catalytic tests using combinations of metal complexes
worked with PPh3, but much more slowly due to the fact that with different ligands revealed that in the final mixture the complexes
transmetalations on Pd are slower for phosphine than for arsine did not always correspond to the initial ones. Sometimes ligand
complexes.5 Transfer under cocatalytic conditions of PPh3 from Au rearrangement occurred during the catalytic process, and the scram-
to Pd (by HRMS) and from Pd(PPh3)4 to Au to form catalytically less bling rate could be fast or slow. This scrambling had to be studied
active [(PPh3)2Au]+ (by NMR) has been observed before but it has separately, stoichiometrically, in order to understand the catalytic
never been studied comprehensively or carefully.1f
performance. The ligand exchange processes observed stoichio-
metrically are shown in Scheme 3 (see Table 1 for ligand labels).
For instance, the stoichiometric reaction between [PdCl2(IDM)2]
(6) and [AuCl(AsPh3)] (12) (Scheme 3a) leads to [AuCl(IDM)] (10)
and the mixed palladium complex [PdCl2(IDM)(AsPh3)] (9). Thus,
Pd transfers half of the IDM ligand available in exchange for
AsPh3. However, starting from [PdCl2(AsPh3)2] (8) and [AuCl(IDM)]
Scheme 1 Au/Pd co-catalyzed Stille reaction.
´
´
I. U. CINQUIMA/Quımica Inorganica, Facultad de Ciencias, Universidad de
Valladolid, 47071 Valladolid, Spain. E-mail: espinet@qi.uva.es, casares@qi.uva.es
† Electronic supplementary information (ESI) available: Experimental and synthetic
characterization details; NMR experiments and data. See DOI: 10.1039/c3cc43133a
Scheme 2 Summary of experiments.
c
7246 Chem. Commun., 2013, 49, 7246--7248
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Table 1 Pd/Au co-catalyzed cross-coupling reaction of p-CF3C6H4I (1) with
MesSnBu3 to give p-Mes-C6H4CF3 (3), with different ligands in the initial gold
and palladium cocatalysts, as shown in Scheme 2 above
Final conversiong
3 : 4 : 5 : 1 : other %
3 f (%)
Entry
L1, L2 (Pd cat.)
L3 (Au cat.)
(24 h)
ratio (hours)
1a
2IDM (6)
2PPh3 (7)
2AsPh3 (8)
2IDM (6)
IDM, AsPh3 (9)
IDM, AsPh3 (9)
2AsPh3 (8)
2PPh3 (7)
2AsPh3 (8)
IDM (10)
PPh3 (11)
AsPh3 (12)
AsPh3 (12)
IDM (10)
AsPh3 (12)
IDM (10)
AsPh3 (12)
PPh3 (11)
AsPh3 (12)
IDM (10)
AsPh3 (12)
IDM (10)
AsPh3 (12)
IDM (10)
AsPh3 (12)
IDM (10)
0
0 : 0 : 0 : 0 (48)
2a
14
84
44
66
76
78
59
43
40
37
60
71
29
26
41
28
96 : 3 : 1 : 0 (310)b
84 : 8 : 6 : 2 (24)
3a
4a
65 : 16 : 10 : 9 (72)c
89 : 7 : 0 : 4 (48)
87 : 8 : 4 : 1 (48)
90 : 10 : 0 : 0 (38)
96 : 3 : 1 : 0 (84)
5a
6a
7a
8a
9a
75 : 14 : 7 : 0 (250)b
53 : 26 : 13 : 3 : 5 (89)
81 : 15 : 0 : 0 : 4 (89)
81 : 15 : 0 : 0 : 4 (89)
86 : 12 : 0 : 0 : 2 (89)
83 : 2 : 0 : 15 : 0 (89)
52 : 5 : 0 : 40 : 0 (115)
53 : 6 : 0 : 34 : 7 (115)
39 : 2 : 0 : 34 : 1 (115)
10d
11d
12d
13d
14d
15e
16e
17e
2AsPh3 (8)
Scheme 3 Ligand scrambling processes.
IDM, AsPh3 (9)
IDM, AsPh3 (9)
2AsPh3 (8)
(10) (Scheme 3b), an equilibrium is reached by partial transfer of the
IDM ligand from Au to Pd. These equations show how delicate the
thermodynamic balance is for these systems, but also suggests that,
in the equilibrium, a Pd with two strongly coordinating ligands will
be prone to transfer one to gold if the starting Au complex has a more
weakly coordinating ligand. Monitoring of this ligand exchange
shows that it takes about 24 h at 80 1C (the temperature used in
the catalytic process) for completion of the ligand rearrangement (see
Fig. S1 in ESI†). Thus, this rearrangement is unexpectedly slow, with a
rate comparable to the catalytic process. It is worth warning that it
may be frequent that, in similar cases, the actual catalytic systems will
contain mixtures of catalytic species changing along the catalysis.
The PPh3/AsPh3 metathesis is much faster than the IDM/AsPh3
2PPh3 (7)
IDM, AsPh3 (9)
IDM, AsPh3 (9)
2AsPh3 (8)
a
NMR tubes were charged with solutions containing solvent MeCN
saturated with LiCl; temperature 80 1C; [p-CF3C6H4I] = 0.10 M; [SnRBu3] =
0.11 M; [AsPh3] = 4 Â 10À3 M. [Pd] = 2 Â 10À3 M; [Au] = 2 Â 10À3 M. The
reactions were monitored until total conversion of the initial reagent or for
the time indicated. Yields were determined by 19F NMR integration and
b
c
are average of two runs. Taken from ref. 3. Deposition of metal was
observed. No added AsPh3. No added AsPh3 and no LiCl. Percentage
of 3 formed in 24 h. Final conversion is the conversion achieved up to
the moment when the last measurement is taken (hours), and is the
d
e
f
g
difference to 100 of the percentage of unreacted 1 (e.g. 94% in entry 3).
exchange, but shows further complications. The reaction of PPh3 gives only slow reaction rates (entry 2) compared to AsPh3
[PdCl2(PPh3)2] (7) with [AuCl(AsPh3)] (12) (Scheme 3c) is complete (entry 3), which gives the fastest reaction. These results are easily
after five minutes at 80 1C,6 leading to the formation of [AuCl(PPh3)] understood in view of our recent mechanistic study:3 since the
(11) and [PdCl2(PPh3)(AsPh3)] (13) (again, Au takes one strongly transmetalation to Pd (whether associative or dissociative) implies
coordinating ligand from Pd), but 13 disproportionates in part to release of one ligand from the palladium catalyst,8 the R1 (Au-to-Pd)
[PdCl2(PPh3)2] (7) and [PdCl2(AsPh3)2] (8). While using acetonitrile as transmetalation step (Scheme 1) is rate determining when the ligand
the reaction solvent, the gold complex [AuCl(PPh3)] (12) is observed to be displaced is a strongly coordinating one. Consistently, very
by 31P NMR, but fast ligand/solvent exchange in palladium com- good donors such as IDM block efficiently the catalysis at that point;
plexes precludes the observation of the individual Pd complexes. the slightly weaker donor PPh3 produces slow transmetalation
Yet our assignment is supported by the following observations: (14% in 24 h); and the more weakly coordinating ligand AsPh3 gives
(i) evaporation of the acetonitrile and dissolution in CDCl3 (where the fastest transmetalation (84% in 24 h). Although AsPh3 is faster,
ligand–solvent exchange does not occur) allow for the observation of the highest yield after total conversion, and the highest selectivity
[PdCl2(PPh3)2] (7) and [PdCl2(PPh3)(AsPh3)] (13); (ii) the same pro- to 3, is found for PPh3, but only after 310 h (entry 3). We have shown
blem in observation by 31P NMR is found with an equimolar before that homocoupling products such as 4 are formed from
mixture of [PdCl2(PPh3)2] and [PdCl2(AsPh3)2] in acetonitrile; and undesired R1/R2 transmetalations,9 and these seem to be more
(iii) the reaction of [PdCl2(PPh3)2] (7) with [AuCl(AsPh3)] (12) in disfavoured with PPh3, as compared to AsPh3.
tetrachloroethane-d2 at 80 1C also gives [AuCl(PPh3)] (11) and a
The formation of mixed-ligand palladium complexes (Scheme 3)
mixture of [PdCl2(PPh3)(AsPh3)] (13), [PdCl2(PPh3)2] (7), and explains the catalytic activity observed for the other systems in Table 1.
[PdCl2(AsPh3)2] (8). Finally, no reaction is observed when Thus, entries 4 and 5 are closely related because the initial system in
[AuCl(PPh3)] (11) and [PdCl2(AsPh3)2] (8) are mixed in acetonitrile, entry 4 must be slowly evolving to the initial system used in entry 5 as
showing the very high preference of gold for PPh3 (Scheme 3d).
the reaction progresses. Initially, the reaction in entry 4 is inefficient
Considering the previous results, not only homogeneous but because complex 6 is blocking the process. Only when 9 starts to exist
also mixed-ligand complexes were tested as catalysts. The results of the transmetalation and coupling can complete the second catalytic
all cross-coupling catalytic experiments are gathered in Table 1. cycle, and the reaction runs at a progressively increasing rate as the
Entries 1–3 show the results of reactions with the same ligand on concentration of active 9 increases to its equilibrium value. One AsPh3
both metals.7 In each of these three entries the possible occurrence ligand in the palladium complex (as in 9) is enough to provide a
of ligand scrambling is, expectedly, kinetically irrelevant since it does kinetically active coordination site (protected with an easily leaving
not produce chemical changes in the catalysts. We find that the ligand) that allows for the Au to Pd transmetalation and subsequent
carbene ligand totally blocks the Au/Pd catalyzed coupling (entry 1). coupling reaction to occur. The slowness of the ligand metathesis has
c
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the undesired side effect observed in entry 4: since arylgold complexes since it produces a palladium complex with at least one labile ligand
are not thermally stable in solution at 80 1C, the [AuR1L] intermediates (AsPh3) and a gold complex coordinated with the best and more
initially formed by Sn/Au transmetalation do not find a palladium stabilizing ligand (IDM or PPh3). According to our previous study, the
complex suitable for transmetalation. For this reason, considerable transmetalation step from Sn to Au is much easier than the Sn to Pd
decomposition of the gold catalyst is observed during the initial transmetalation and occurs without ligand dissociation. Hence, the
period of the reaction, which reduces the overall catalytic activity of coordination of the best ligand to gold has many advantages,
the system and leads to lower yields and lower percentage of the cross- improving its stability and minimizing the formation of hydrolysis
coupling product. The problem disappears when the Pd complex used products that might occur on gold.3 On the other hand, the Au to Pd
from the beginning has one labile AsPh3 ligand (entry 5).10 Not much transmetalation to Pd is rate determining for strongly coordinating
difference is made whether Au comes with an inert or a labile (entry 6) ligands, and having one weaker, easier to displace ligand in the coordi-
ligand because the ligand on Au is not dissociated during the nation sphere of Pd strongly reduces the activation energy of this
process.11 The rate and yields in the heterocoupling compound (3) transmetalation, and increases the overall rate of the catalysis.15 The
of the catalysis can still be noticeably improved using two labile (and combination of these two conditions leads to the best catalytic systems.
weak) ligands on Pd, which increase the electrophilicity of the Pd
This work was supported by the Spanish MICINN (CTQ2010-
centre, and an inert (and strong) ligand on Au, which improves the 18901/BQU) and the JCyL (VA281A11-2 and VA373A11-2).
stability of the gold intermediates (entry 7). In fact IDM seems to be
the best stabilizer for gold, and the formation of the reduction product
Notes and references
5 is totally suppressed by the use of [AuCl(IDM)] (entries 5 and 7).12
´
1 Recent reviews: (a) M. H. Perez-Temprano, J. A. Casares and P. Espinet,
For entry 8 we expect, as in entry 4, ligand rearrangement (fast
in this case) to produce [AuCl(PPh3)]. Thus the gold intermediates
are fairly well stabilized and decomposition via hydrolysis is almost
absent. As shown in eqn (c) of Scheme 3, part of the palladium
catalyst remains sequestered in the kinetically slow form, which is
detrimental to the overall catalytic rate of the system. In spite of
that, this combination turns out to be as selective as entry 2, with
the best cross-coupling selectivity, and four times faster, providing
probably the most convenient catalytic system.
Chem.–Eur. J., 2012, 18, 1864–1884; (b) J. I. van der Vlugt, Eur. J. Inorg.
Chem., 2012, 363–375; (c) J. J. Hirner, Y. Shi and S. A. Blum, Acc. Chem. Res.,
2011, 44, 603–613; (d) M. Shibasaki and Y. Yamamoto, Multimetallic
Catalyst in Organic Synthesis, Wiley-VCH, Weinheim, 2004. For a variety
of types of relevant reactions see: (e) L. A. Jones, S. Sanz and M. Laguna,
Catal. Today, 2007, 122, 403–406; ( f ) Y. Shi, S. M. Peterson, W. W.
Haberaecker, III and S. A. Blum, J. Am. Chem. Soc., 2008, 130,
2168–2169; (g) Y. Shi, K. E. Roth, S. D. Ramgren and S. A. Blum, J. Am.
Chem. Soc., 2009, 131, 18022–18023; (h) T. Lauterbach, M. Livendahl,
´
A. Rosellon, P. Espinet and A. M. Echavarren, Org. Lett., 2010, 12, 3006–3009;
(i) B. Panda and T. K. Sarkar, Chem. Commun., 2010, 46, 3131–3133.
2 Ref. 1a. See also the following references which appeared after that
Somehow to our surprise the catalyst combination in entry 9 makes
a bad system, showing bad selectivity to 3. Entries 9 and 4 have in
common that noticeable reduction to metal is observed at the begin-
ning and then the catalysis yields noticeable amounts of homocoupling
and reduction products. It is not easy to understand in the case of
entry 9 but the observation of metal deposition suggests that these
combinations might be less protected against redox incompatibility,13
perhaps in minor intermediates produced by ligand dissociation.
The best catalytic combinations were tested sparing the AsPh3
stabilizing additive (entries 10–14). Then, those still working fine
were tested without LiCl (entries 15–17). The results in Table 1
show that, for the selected reactions, the suppression of adding
AsPh3 produces an increase of homocoupling, but in the best
combination ([PdCl2(AsPh3)2] + [AuCl(IDM)]) the suppression of
added AsPh3 has no cost. In all cases the suppression of LiCl is
lethal and has a very detrimental effect on the conversion.14
In summary, although often ignored or overlooked, ligand meta-
thesis is probably a frequently operating process in homogeneous
catalysis, which can become decisive for the success of the reaction
when different metals and ligands are involved in a bimetallic
catalysis. Ligand exchange can be slow, with the consequence that
the catalytic system is changing during the reaction. Use of the most
stable ligand combination from the beginning, or preformed catalysts
with mixed ligands, is advised for these cases, thus skipping their
cumbersome or sluggish formation in solution and long preactivation
times, and prevent undesired side reactions. However, if the ligand
¨
review: (a) A. S. K. Hashmi, C. Lothschu¨tz, R. Dopp, M. Ackermann,
J. De Buck Becker, M. Rudolph, C. Scholz and F. Rominger,
Adv. Synth. Catal., 2012, 354, 133–147; (b) J. J. Hirner, K. E. Roth,
Y. Shi and S. A. Blum, Organometallics, 2012, 31, 6843–6850.
3 (a) J. delPozo, D. Carrasco, M. H. Perez-Temprano, M. Garcıa-Melchor,
R. Alvarez, J. A. Casares and P. Espinet, Angew. Chem., Int. Ed., 2013,
52, 2189–2193. For related previous studies see: (b) Y. Shi, S. D.
Ramgren and S. A. Blum, Organometallics, 2009, 28, 1275–1277;
(c) Y. Shi, S. M. Peterson, W. W. Haberaecker, III and S. A. Blum,
J. Am. Chem. Soc., 2008, 130, 2168–2169.
4 For a similar strategy to simplify a study (in that case preventing
undesired ligand exchange reactions by using a chelate ligand) see:
´
´
´
¨
A. S. K. Hashmi, C. Lothschu¨tz, R. Dopp, M. Rudolph, T. D. Ramamurthi
and F. Rominger, Angew. Chem., Int. Ed., 2009, 48, 8243–8246.
5 P. Espinet and A. M. Echavarren, Angew. Chem., Int. Ed., 2004, 43, 4704–4734.
6 [PdCl2(PPh3)2] is not soluble in acetonitrile at room temperature.
7 Entries 1 and 2 are taken from ref. 3a.
8 For a thorough discussion on the transmetalation step as an associative or
dissociative ligand substitution and the kinetic consequences, see the
following: (a) Ref. 4, Section 3; (b) A. Casado and P. Espinet, J. Am. Chem.
Soc., 1998, 120, 8978–8985; (c) A. Casado, P. Espinet and A. M. Gallego, J. Am.
Chem. Soc., 2000, 122, 11771–11782; (d) A. Nova, G. Ujaque, F. Maseras,
´
A. Lledos and P. Espinet, J. Am. Chem. Soc., 2006, 128, 14571–14578;
(e) J. A. Casares, P. Espinet and G. Salas, Chem.–Eur. J., 2002, 8, 4843–4853.
9 (a) J. A. Casares, P. Espinet, B. Fuentes and G. Salas, J. Am. Chem. Soc., 2007,
´
´
129, 3508–3509; (b) B. Fuentes, M. Garcıa-Melchor, A. Lledos, F. Maseras,
J. A. Casares, G. Ujaque and P. Espinet, Chem.–Eur. J., 2010, 16, 8596–8599.
10 [PdCl2(IDM)(AsPh3)] (9) is stable and is easily prepared, see prepara-
tion in ESI†.
11 The R1 transmetalation from Sn to linear Au occurs through a
3-coordinate transition state (see ref. 3).
12 Mesitylene is a byproduct produced by hydrolysis of the gold
intermediates [Au(Mes)L] (see ref. 3).
13 D. Weber and M. R. Gagne, Chem. Commun., 2011, 47, 5172–5174.
´
rearrangement is fast compared to the catalyzed reaction, as in 14 LiCl has an important thermodynamic effect, converting ISnBu3 to ClSnBu3.
15 Note that, in general, other steps in a cross-coupling cycle (for
entry 9, this precaution is not necessary. For the cases studied the
ligand scrambling lead to catalysts with the best s-donor ligand
instance reductive elimination) could be rate determining depending
´
on the reagents. See ref. 4 and M. H. Perez-Temprano, A. M. Gallego,
(IDM > PPh3 > AsPh3) on the gold atom, which is very convenient
J. A. Casares and P. Espinet, Organometallics, 2011, 30, 611–617.
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7248 Chem. Commun., 2013, 49, 7246--7248
This journal is The Royal Society of Chemistry 2013