Orthopalladated triaryl phosphite complexes as highly active catalysts in biaryl coupling reactions

Article abstract of DOI:10.1039/a806041j

Orthopalladation of inexpensive, commercially available tris(2,4-di-tert-butylphenyl) phosphite gives a dimeric complex 3 which proves to be an extremely active catalyst in biaryl coupling reactions, giving unprecedented turnover numbers of up to 1000000 [mol product (mol Pd)^-1] and turnover frequencies of nearly 900000 [mol product (mol Pd)^-1 h^-1] in the Suzuki reaction and turnover numbers of up to 830000 in the Stille reaction.

Full text of DOI:10.1039/a806041j

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Orthopalladated triaryl phosphite complexes as highly active catalysts in biaryl
coupling reactions
David A. Albisson,a Robin B. Bedford,*a†‡ Simon E. Lawrenceb and P. Noelle Scullya
a Department of Chemistry, Trinity College Dublin, Dublin 2, Ireland
b Department of Chemistry, University College Cork, Cork, Ireland
Orthopalladation of inexpensive, commercially available
tris(2,4-di-tert-butylphenyl) phosphite gives a dimeric com-
plex 3 which proves to be an extremely active catalyst in
biaryl coupling reactions, giving unprecedented turnover
numbers of up to 1000000 [mol product (mol Pd)21] and
turnover frequencies of nearly 900000 [mol product (mol
Pd)21 h21] in the Suzuki reaction and turnover numbers of
up to 830000 in the Stille reaction.
X-ray analysis (Fig. 1).§ Compound 3 shows remarkable
stability to air and moisture—in solution it shows no sign of
decomposition after several weeks, whilst solid samples can be
kept in air for at least six months. No decomposition is observed
when 3 is heated at 130 °C in toluene for 24 h, demonstrating
that the catalyst also shows good thermal stability.
The coupling of aryl halides and phenylboronic acid
catalysed by 3 was investigated and representative results are
summarised in Table 1. With 4-bromoacetophenone as sub-
strate, extraordinarily high turnover numbers (TONs) of up to
1000000 [mol product (mol Pd)21] and turnover frequencies
(TOFs) of nearly 900 000 [mol product (mol Pd)21 h21] were
obtained at 110 °C. The previous highest activity with this
substrate was achieved with complex 1 which gave a TON of 74
000 at the higher temperature of 130 °C over 16 h.7 In the
present reaction, lowering the temperature to 70 °C leads to a
reduction in activity, but even at 20 °C high levels of activity are
observed relative to previous reports of ambient temperature
reactions.8 The reaction is strongly influenced by a change of
solvent or base, thus replacing toluene with THF at 70 °C leads
to a substantial drop in rate. Similarly, with NaOAc as the base
in DMA lower rates are observed.
With 4-bromobenzophenone as substrate high rates and
ultimate conversions are also seen. As expected, activity
decreases with increasing electron density on the aryl bromide.
For instance, when 4-bromoanisole is employed TOFs are about
two orders of magnitude lower than with 4-bromoacetophe-
none, however the ultimate TONs—up to 30 000—are, we
believe, without precedent.
The use of triaryl phosphite complexes in catalysis has recently
enjoyed a renaissance as a result of the activity they show in
hydroformylation,1 asymmetric hydrocyanation2 and enantiose-
lective alternating co-polymerisation of CO and propene.3 Our
interest lies in the synthesis and catalytic behaviour of
orthometallated triaryl phosphite complexes and the role that
the metallation plays in their activities.4 So far the exploitation
of such systems has been limited to a few catalytic re-
ductions4b,5 and only one example of catalytic C–C bond
formation.6
One particularly important class of C–C coupling reaction is
the catalytic formation of non-symmetric biaryls (Scheme 1) by
the coupling of aryl halides with either arylboronic acids (the
Suzuki reaction) or aryltin reagents (the Stille reaction). In
general, catalyst loadings in such reactions are high (1–10
mol%) which imposes financial constraints on scaling up
reactions and problems associated with catalyst removal.
Therefore the synthesis of high activity catalysts which can be
used in low concentrations is a desirable goal. Recently, Beller
and co-workers reported the use of the metallated tris(2-
[cat]
X
E
+
R
R′
R
R′
Scheme 1 Suzuki [E = B(OH)2] and Stille (E = SnR3) biaryl coupling
reactions
methylphenyl)phosphinepalladium(II) complex 1 as an efficient
catalyst for the Suzuki reaction.7 The ready ability of triaryl
phosphites to undergo analogous metallation reactions as well
as their ease of synthesis, commercial availability and very low
cost prompted us to examine the possibility of designing well-
defined orthometallated PdII–triaryl phosphite complexes capa-
ble of catalysing biaryl coupling reactions.
The reaction of bulky tris(2,4-di-tert-butylphenyl)phosphite
2 with PdCl2 gives the orthometallated dimer 3 in 96% yield.
Compound 3 has been characterised by satisfactory elemental
1
analysis, H and 31P NMR spectroscopy and by single crystal
ArO
OAr
Fig. 1 Molecular structure of 3. Thermal ellipsoids set at 50% probability.
All H-atoms omitted for clarity, as are all but the ipso-carbons of the non-
metallated aryl rings. Three But groups are disordered, only major
orientation of C7–10 shown. Selected distances (Å) and angles (°): Pd–C1
1.998(6), Pd–Cl 2.4180(16), Pd–Cla 2.4073(17), Pd-P 2.1668(17), P–O1
1.592(4), P–O2 1.585(4), P–O3 1.584(4), C1–Pd–P 80.7(2), P–Pd–Cl
100.35(6), Cl–Pd–Cla 83.92(6), Cla–Pd–C1 95.0(2), Pd–P–O1 108.3(2),
Pd–P–O2 120.4(2), Pd–P–O3 120.6(2).
P
Cl
But
Ar
O
Ar
Ac
O
Pd
P
But
2
But
O
P
Pd
3
2
But
3 Ar = 2,4-But2C6H3
1 Ar = 2-MeC6H4
2
Chem. Commun., 1998
2095

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Table 1 Suzuki coupling of aryl bromides with phenylboronic acid catalysed by 3. Reaction conditions: 10 mmol aryl bromide, 15 mmol PhB(OH)2, 20 mmol
base in 30 ml solvent
TON/mol product
(mol Pd)21
Aryl bromide
Solvent
[Pd]/mol%
Base
T/°C
t/h
Conversion (%)a
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromobenzophenone
4-bromobenzophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoacetophenone
4-bromoanisole
DMA
DMA
DMA
0.1
0.1
0.1
0.1
0.0001
0.0001
0.0001
0.0001
0.1
0.1
0.1
0.1
0.001
0.001
0.001
NaOAc
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
130
130
130
110
110
110
110
110
70
70
20
110
110
110
130
18
1
15
1
1
2.25
1
15
2
2
2
66
19
98
100
87
100
33
60
100
20
95
97.5
5
660
190
980
1000
870000
1000000
330000
600000
1000
200
950
975
5000
16000
30000
toluene
toluene
toluene
toluene
toluene
toluene
THF
toluene
toluene
toluene
toluene
toluene
1
1
15
15
4-bromoanisole
4-bromoanisole
4-bromoanisole
16
30
a Determined by GC and/or 1H NMR analysis of reaction mixture samples, based on aryl bromide.
Table 2 Stille coupling of aryl bromides with PhSnBu3 catalysed by 3.
Reaction conditions: 4 mmol aryl bromide, 5 mmol PhSnBu3 in 20 ml
toluene
consequently can be used in very low concentrations. In view of
this unprecedented activity and the low cost of 2—at least two
orders of magnitude cheaper than tris(2-methylphenyl)phos-
phine—we believe that it will be the catalyst of choice in such
reactions. We are currently investigating its application to
further catalytic processes. Preliminary investigations show it to
be extremely active in the Heck arylation of alkenes, showing
TONs of up to 5.75 million for activated aryl bromides, and
these findings will be published elsewhere.
This work was supported by Forbairt and the Trinity Trust
Foundation. We thank Johnson-Matthey for the generous loan
of palladium salts and Cork University Foundation for the
purchase of an X-ray diffractometer.
TON/mol
Conversion product
Aryl bromide
[Pd]/mol% T/°C t/h (%)a
(mol Pd)21
4-bromoacetophenone 0.2
4-bromoacetophenone 0.2
4-bromoacetophenone 0.0001
100 17.5 54
120 15 100
270
500
830000
840
120 18
120 15
83
84
4-bromoanisole
0.1
a Determined by GC and/or 1H NMR analysis of reaction mixture samples,
based on aryl halide.
Notes and References
In the coupling reactions with higher catalyst concentrations
(!0.1 mol% Pd) deposition of palladium is observed in the later
stages of the reaction. Similarly, reaction of 3 with 1 equiv. of
PhB(OH)2 and K2CO3 in the absence of an aryl bromide leads
to deposition. When this reaction was repeated with 1 equiv. of
2 included, decomposition was inhibited and it was possible to
monitor the reaction by 31P NMR spectroscopy. The spectrum
after 30 min showed the mixture to be predominantly 2 and 3
but amongst other minor peaks two relatively major low field
double doublets were apparent.¶ We have tentatively assigned
these to the two isomers of [Pd(Ph){P(OC6H2-2,4-But2)-
(OC6H3-2,4-But2)2}{P(OC6H3-2,4-But2)3}] in which the P
atoms are disposed trans (major) or cis (minor). Also apparent
is a small peak at d 218.3. Such a high field shift is consistent
with the formation of a Pd0–phosphite complex. We postulate
that reductive elimination of the orthometallated phosphite aryl
and a phenyl groups occurs, yielding a catalytically active zero
valent palladium species. This is in accord with findings for the
use of 1 in the Stille reaction.9 However, a PdII/PdIV couple has
recently been suggested to be active in the Heck arylation of
alkenes catalysed by 1 and related complexes10 and at this stage
we cannot rule out a related pathway.
Encouraged by the results obtained in the Suzuki reaction we
decided to investigate the application of 3 to the Stille reaction.
Representative results for the coupling of tributylphenyltin with
aryl bromides are summarised in Table 2. With 4-bromoaceto-
phenone as substrate TONs of up to 840000 were achieved
within 18 h at 120 °C. To the best of our knowledge this is the
highest reported activity to date, comparing well with that
obtained with 1 which gives a TON of 1650 in the coupling of
4-bromoacetophenone with PhSnMe3 at the same temperature.9
The reaction is again somewhat more sluggish with 4-bromo-
anisole, but useful conversions are still obtained.
† E-mail: bedfordr@tcd.ie
‡ New address: Department of Chemistry, University of Exeter, Exeter, UK
EX4 4QD
§ Crystal data for 3: C84H124Cl2O6P2Pd2, M = 1575.47, triclinic, space
¯
group P1, Z = 1, a = 11.957(1), b = 12.911(3), c = 15.300(3) Å, a =
81.08(2), b = 69.46(1), g = 76.45(1)°, V = 2143.3(6) Å3, T = 293(2) K,
m = 0.566 mm21, the final R-factor was 0.057 for 4257 reflections with I
> 2s(I). CCDC 182/978.
¶ NMR data: dP 155.2 and 118.1 (2JPP = 29.8 Hz) (minor isomer) and 141.4
and 117.3 (2JPP = 868.4 Hz ) (major isomer).
1 K. Nozaki, N. Sakai, T. Nanno, T. Higashijima, S. Mano, T. Horiuchi
and H. Takaya, J. Am. Chem. Soc., 1997, 119, 4413 and references cited
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and D. Massi, Organometallics, 1992, 11, 3525; N. Sakai, K. Nozaki
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Chem. Commun., 1995, 2049; (b) R. B. Bedford, S. Castillon, P. A.
Chaloner, C. Claver, E. Fernandez, P. B. Hitchcock and A. Ruiz,
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In summary the complex 3 is extremely active in biaryl
coupling reactions under both Suzuki and Stille conditions and
Received in Cambridge, UK, 3rd August 1998; 8/06041J
2096
Chem. Commun., 1998