The importance of ligand steric effects on transmetalation

Article abstract of DOI:10.1021/om050724p

A very striking phosphine steric effect on the rate of transmetalation of phenyl zinc bromide to platinum complexes has been observed: most Pt(II) complexes of type [Pt(diphosphine)(Ph)Br] react with PhZnBr rapidly, the slowest reacting complexes being those derived from bis(dicyclohexylphosphino)ethane and bis(di-tert-butylphosphino)xylene.

Full text of DOI:10.1021/om050724p

Organometallics 2005, 24, 6475-6478
6475
The Importance of Ligand Steric Effects on
Transmetalation
Matthew L. Clarke* and Mattias Heydt
School of Chemistry, University of St. Andrews, St. Andrews, Fife, KY16 9ST, U.K.
Received August 22, 2005
Summary: A very striking phosphine steric effect on the
rate of transmetalation of phenyl zinc bromide to plati-
num complexes has been observed: most Pt(II) complexes
of type [Pt(diphosphine)(Ph)Br] react with PhZnBr
rapidly, the slowest reacting complexes being those
derived from bis(dicyclohexylphosphino)ethane and bis-
(di-tert-butylphosphino)xylene.
either electron-poor, bulky, or possessing a wide bite
angle.15-18 There is therefore a subtle balancing act
required to match up a ligand/catalyst for a given
reaction or substrate. This explains why such a large
array of phosphines have been tested in these reactions
and why so many of these have found a niche for a
specific substrate or reaction. There are still many
substrates/reactions in cross-coupling chemistry that
remain difficult.
It is often noted that transmetalation is the least
understood of the fundamental steps in cross-coupling
chemistry, and the reactions of group 10 metal halide
complexes with organoboronic acids or organozinc re-
agents are only recently beginning to receive atten-
tion.19-23 The specific case of transmetalation of tin
nucleophiles to Pd(II) and Pt(II) complexes has been the
subject of a fascinating debate over the last 15 years,24-33
and the reaction of organotins with [Pd(AsPh3)2(Ar)X]
is now beginning to be understood: changing the nature
of incoming nucleophile, solvent, temperature, ligand,
leaving group, and aryl ligand can alter both the rate
and actual reactive species taking place in the trans-
metalation reaction. The more difficult transmetalation
of silicon nucleophiles to platinum and palladium
In the last twenty years, group 10 metal-catalyzed
cross-coupling reactions have emerged as some of the
most important reactions used in organic synthesis
today.1 Mechanistic studies have guided catalyst design
and provided knowledge on the basic mechanism of
these reactions. There are generally thought to be three
key steps in cross-coupling: Oxidative addition, trans-
metalation, and reductive elimination. Mechanistic
studies on the oxidative addition step of the reaction
have shown that certain types of (generally bulky,
electron-donating) phosphines generally favor this step,2-7
and in the last 10 years the application of electron-
donating mono-,8-11 di-,2,12 and hemilabile13,14 bulky
phosphines has made the cross-coupling of aryl chlo-
rides, which oxidatively add to Pd(0) complexes reluc-
tantly, a possibility. It has been shown that the reduc-
tive elimination step is promoted by ligands that are
(15) Merwin, R. K.; Schnabel, R. C.; Koola, J. D.; Roddick, D. M.
Organometallics 1992, 11, 2972-2978.
* Corresponding author. Fax: +44 1334 463808. Tel: +44 1334
463850. E-mail: mc28@st-andrews.ac.uk.
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Cross-Coupling Reactions; Wiley: New York, 2004. (d) Roberts, S. M.;
Xiao, J. L.; Whittall, J.; Pickett, T. E. Catalysts for Fine Chemical
Synthesis: Metal Catalysed Carbon-Carbon Bond-Forming Reactions;
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10.1021/om050724p CCC: $30.25 © 2005 American Chemical Society
Publication on Web 11/10/2005

6476 Organometallics, Vol. 24, No. 26, 2005
Notes
Scheme 1. Comparison of Nucleophiles in
complexes has also begun to attract attention and can
be promoted by AgO, fluoride, or hydroxide salts.34-36
In the course of our catalytic experiments on the cross-
coupling of organosilicon reagents with aryl chlorides
(Hiyama coupling),37 we observed the failure of pal-
ladium complexes of the bulky, electron-rich diphos-
phine 1,2-bis(di-tert-butylphosphino)xylene (dtbpx) to
catalyze Hiyama cross-coupling. Palladium complexes
of dtbpx have all the structural features to ensure rapid
oxidative addition and reductive elimination, which
suggested a pronounced ligand effect on the (rate-
determining) transmetalation step of the catalytic
reaction, and highlighted to us the importance
of understanding more about phosphine ligand effects
on transmetalation to group 10 metal complexes in
general.
Transmetalation
The rates of the reactions between [Pt(diphosphine)-
(Ph)Br] and PhZnBr were therefore studied in more
detail. A series of six related complexes with different
diphosphine ligands were prepared. The diphosphines
were chosen according to differences in steric or elec-
tronic parameters.
The existing knowledge in this area mainly stems
from a study by Farina and co-workers that demon-
strated the beneficial effect of less electron donating
ligands such as tris-furylphosphine and triphenylarsine
on Stille coupling of aryl iodides under catalytic condi-
tions.25 However, subsequent work by the Espinet,
Amatore, and Jutand groups seems to suggest that this
is an indirect electronic effect: although two contrasting
mechanisms have been put forward, they both involve
loss of a weakly donating triphenylarsine or trifu-
rylphosphine ligand either before27 or during31 the
transmetalation process. Farinas study did not reveal
a predictable steric effect in Stille cross-coupling. The
apparent absence of data on direct ligand effects on any
transmetalation reaction prompted us to undertake the
work described here. In this paper, we report striking
ligand steric effects on the rate of transmetalation of
organozincs to platinum-diphosphine phenyl bromide
complexes. Platinum complexes were chosen because
palladium diaryl species rapidly reductively eliminate
to give unstable Pd(0) species. The rate of decomposition
of both the palladium-diaryl and the Pd(0) species will
be highly dependent on the ligand, presenting consider-
able difficulties for studying ligand effects on the
transmetalation step in isolation. We have restricted our
preliminary study of this reaction to cis-diphosphine
complexes of platinum of type [Pt(diphosphine)(Ph)Br].
Diphosphine complexes were chosen to distinguish
direct stereoelectronic effects from the formation of
complexes with different geometry or coordination
number that could occur with monophosphines.
The six complexes were reacted with 13 equiv of
PhZnBr at room temperature in CD2Cl2/THF solution
and analyzed by 31P{1H} NMR spectroscopy 18 min
later. In the case of the dppe, depe, dfppe, and dppf
complexes (derived from sterically undemanding ligands),
quantitative reactions had occurred to give [Pt(diphos-
phine)Ph2] complexes as the only phosphorus-containing
products. [Pt(dcype)(Ph)Br] only reacted to 62% conver-
sion (to [Pt(dcype)Ph2]) during this time period, and
more strikingly, [Pt(dtbpx)(Ph)Br] did not show any
product whatsoever, even after several days.
The reactions of the C2 diphosphine complexes were
then monitored over time using 31P{1H} NMR. Figure
1 shows that the complexes derived from the smaller
ligands all react at a faster rate than [Pt(dcype)(Ph)-
Br].
From this study, we can conclude that steric proper-
ties have a pronounced effect on the transmetalation of
organozincs to platinum aryl halide complexes. This
infers that the specific transmetalations discussed here
involve a tight transition state during the Pt-C bond
forming process. There does not appear to be a signifi-
cant bite angle effect, since the complex of large bite
angle ligand, dppf, did not suffer from the slow trans-
metalation observed with the dtbpx ligand. Ligand
electronic effects on the reactions studied here represent
a direct electronic effect on the halide for aryl substitu-
tion and are probably not as important as steric effects,
since platinum complexes of electron-donating depe did
not suffer from slow transmetalation in the same way
as the two bulky electron-donating ligands. However,
the beneficial effect of the fluorine substitution in the
dfppe ligand suggested by Figure 1 does appear to be
genuine, since a reaction between [Pt(dfppe)(Ph)Br] and
5 equiv of PhZnBr started at -78 °C gave 80% yield
within 30 min, but required 100 min for 80% conversion
with the analagous dppe complex.
We also note here the effect of the halide ligand in
reactions of [Pt(dppe)(Ph)X] with PhZnBr. PhZnBr and
[Pt(dppe)(Ph)Cl] react, under the conditions in Scheme
2, quantitatively to give [Pt(dppe)Ph2] within 5 min,
which is faster than reactions with [Pt(dppe)(Ph)Br].
Scheme 3 shows reaction times for a reaction conducted
at low temperature and confirms that the transmeta-
lation to the chloride complex is significantly faster.
There are several possible explanations for this reactiv-
ity difference: formation of a zincate species between
the chloride ligand and zinc reagent, reduced steric
The reactions of [Pt(dppe)(Ph)Br] with PhSi(OMe)3/
TBAF, PhB(OH)2/TBAF, or PhZnBr were studied ini-
tially. This revealed very sluggish reactions between
silicon and boron reagents that only yielded small
amounts of [Pt(dppe)Ph2] under harsh conditions. In the
case of PhB(OH)2, the low yield of [Pt(dppe)Ph2] was
accompanied by an unknown side product. In contrast,
the reaction of PhZnBr was quantitative at room tem-
perature. Thus, the direct transmetalation of the more
polar zinc reagent is actually many, many times more
facile than either organoboronic acids or organosilanes,
even when they are activated by fluoride.
(34) Mintcheva, N.; Nishihara, Y.; Tanabe, M.; Hirabayashi, K.;
Mori, A.; Osakada, K. Organometallics 2001, 20, 1243.
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(37) Clarke, M. L. Adv. Synth. Catal. 2005, 347, 303.

Notes
Organometallics, Vol. 24, No. 26, 2005 6477
Scheme 2. [Pt(P∧P)(Ph)Br] Complexes Investigated in Reactions with PhZnBr
Table 1. 31P NMR Data for Complexes Used in
This Studya
1J P
1J P
2
complex
multiplicity
trans X trans Ar JP-P
[Pt(dppe)(Ph)Br] 2 × (d + Pt sats) 4150 Hz 1650 Hz 3 Hz
[Pt(dfppe)(Ph)Br] 2 × (d + Pt sats) 4164 Hz 1610 Hz 3 Hz
[Pt(dtbpx)(Ph)Br] 2 × (d + Pt sats) 4498 Hz 1714 Hz 17 Hz
[Pt(dppe)(Ph)2]
[Pt(dfppe)(Ph)2]
1 × (s + Pt sats) N/A
1 × (s + Pt sats) N/A
1704 Hz N/A
1630 Hz N/A
[Pt(depe)(Ph)Br] 2 × (d + Pt sats) 3974 Hz 1620 Hz unres
[Pt(depe)(Ph)2]
[Pt(dcype)(Ph)Br] 2 × (d + Pt sats) 4022 Hz 1708 Hz unres
[Pt(dcype)(Ph)2] 1754 Hz N/A
1 × (s + Pt sats) N/A
[Pt(dppf)(Ph)Br] 2 × (d + Pt sats) 4492 Hz 1666 Hz 16 Hz
[Pt(dppf)(Ph)2] 1784 Hz N/A
1 × (s + Pt sats) N/A
1 × (s + Pt sats) N/A
1726 Hz N/A
Figure 1. Rates of reaction between PhZnBr and [Pt-
(diphos)(Ph)Br].
a N/A ) not applicable, unres ) unresolved, sats ) 195Pt
satellites.
Scheme 3. Halide Effect on Reaction of PhZnBr
with [Pt(dppe)(Ph)X]
spectrometer. 1H and 13C NMR spectra were referenced
internally to deuterated solvents, which were referenced
relative to TMS (external). Electrospray ionization mass
spectra (ESI) were acquired using the VG Platform I instru-
ment. FAB analyses were run by the EPSRC national mass
spectrometry service. [Pt(dppe)(Ph)Br] and [Pt(dcype)(Ph)Br]
were prepared according to the literature.38,39
General Procedure for Synthesis of [Pt(diphos)(Ph)X].
A solution of the ligand in dichloromethane was added to a
dichloromethane solution of [Pt(COD)(Ph)(Br)]. After 1 h
stirring at room temperature the solvent was evaporated until
1 mL remained. The clean product was obtained by slowly
adding n-hexane and filtering.
demand of the chloride ligand, the greater electronega-
tivity of chloride making the Pt center more electro-
philic, or a stronger Pt-Br bond. Studies to fully
evaluate the effect of every ligand, L, Ar, and halide,
on the transmetalation on a range of different late
transition metal complexes are required in the future
to facilitate further developments in cross-coupling
chemistry.
The results reported here suggest that if the trans-
metalation of organometallics to metal(phosphine)halide
complexes is proving inefficient, less sterically demand-
ing diphosphine ligands could be used advantageously.
If one makes the (widely used) assumption that plati-
num complexes are suitable models for Pd catalysts,
then it is likely that very bulky ligands, which promote
oxidative addition and reductive elimination, could
inhibit transmetalation in cross-coupling catalysis, as
has already been observed in the Hiyama cross-coupling
reactions catalyzed by palladium complexes of the dtbpx
ligands. It is envisaged that the insights from mecha-
nistic studies on transmetalation will guide future
catalyst design for cross-coupling reactions that are
limited by inefficient transmetalation.
[Pt(dfppe)(Ph)Br]. Anal. Calcd: C 46.73, H 3.06. Found:
1
C 46.68, H 2.98. 31P{1H} NMR (CD2Cl2): δ 38.5 (d of t, J(PtP)
) 4163 Hz, 2J(PP) ) 2.3 Hz, 3J(PF) ) 3.8); 39.6 (d, 1J(PtP) ) 1609
Hz, 2J(PP) ) 2.3 Hz, 3J(PF) ) 3.8). 1H NMR (CDCl3): δ 2.2-2.6
(m, 4 H, CH2), 6.5-7.9 (m, 25 H, ArH). 19F NMR (CDCl3): δ
-110 (m). MS-FAB: 844 (M + Na), 818 (M), 745 (M - Br),
665 (M - Ph - Br) (peaks show expected isotope pattern).
1
[Pt(dppf)(Ph)Br]. 31P{1H} NMR (CDCl3): δ 14.3 (d, JPtP
2
1
2
) 1666 Hz, JPP ) 16 Hz), 16.3 (d, JPtP ) 4492 Hz, JPP) 16
Hz). 1H NMR (CDCl3): δ 3.7 (q (apparent), J ) 2 Hz, 2H), 4.1
(s, apparent, 2H), 4.5 (s, apparent), 2H), 4.8 (m, 2H), 6.5 (m,
2H), 7.0 (m, 2H), 7.1-8.1 (m, 21H). MS (FAB+): 826 (M -
Br), 749 (M - Br - Ph). Good isotope matches and no peaks
corresponding to dimeric complexes were observed. HRMS
(ES+): 826.1049; M - Br requires ) 826.1046. This compound
required several days stirring at room temperature for the
reaction to reach completion.
[Pt(dtbpx)(Ph)Br]. Anal. Calcd: C 48.3, H 6.61. Found:
C 48.0, H 6.79. 31P{1H} NMR (CD2Cl2): δ 11.4 (d, 1J(PtP) ) 1714
Hz, 2J(PP) ) 17 Hz), 16.4 (d, 1J(PtP) ) 4498 Hz, 2J(PP) ) 17 Hz).
1H NMR (CDCl3): δ 1.2 (m, br, 18H, But), 1.5 (d, JH-P ) 13
Hz, 18 H, But), 3.5 (s (apparent), br, 2H, CH2), 3.7 (s (app), br,
2H, CH2), 6.7-7.2 (m, 9H, ArH). MS-ES+ 666.3 (M - Br),
610.2 (M - Br - Ph) + Na), 588.2 (M - Br - Ph). Good isotope
matches and no peaks corresponding to dimeric complexes
Experimental Section
General Procedures. All experiments were carried out on
a vacuum-nitrogen Schlenk line using dried Schlenk glass-
ware. Dry, degassed solvents were used for reactions unless
otherwise indicated. Carbon, proton, and phosphorus NMR
spectra were recorded on a Bruker Avance 300 (automated)
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1449.

6478 Organometallics, Vol. 24, No. 26, 2005
Notes
were observed. Long reaction times are required for this
reaction to go to completion.
Transmetalation at Room Temperature. The reaction
was carried out with 0.019 mmol of the Pt halide compound,
which was dissolved in 0.8 mL of dry DCM in a Schlenck tube.
After everything was dissolved the PhZnBr (0.5 M solution in
THF) was added (13.5 equiv, 0.500 mL) and a stopwatch
started. The reaction was syringed into a NMR tube, and the
reaction was monitored in the NMR spectrometer.
[Pt(depe)(Ph)Br]. All the syntheses of this complex gave
a second species that shows a complex NMR spectra in
solution. The exact structure of this impurity is under inves-
tigation. Addition of [Pt(COD)Ph(Br)] or more ligand changed
the relative concentrations of the two species, suggesting an
equilibrium. The impure compound gives the diphenyl com-
pound with high purity within minutes irrespective of the
relative proportions of compounds in the starting Pt(depe)-
(Ph)Br complex, also consistent with the observations above.
The results reported in Figure 1 used material that was ∼90%
pure and are corrected on this basis. In any case the results
clearly show that this ligand does not inhibit transmetalation
in the same way as the two bulky electron-donating ligands.
The identity of the diphenylplatinum species was confirmed
by comparison with NMR data from authentic samples pre-
pared by stirring the ligand with [Pt(COD)Ph2] at room
temperature. NMR data are reported in Table 1. [Pt(dppe)-
Ph2],40 [Pt(dcype)Ph2],41 and [Pt(dppf)Ph2],42 have been re-
ported previously.
Acknowledgment. The authors would like to thank
the EPSRC national mass spectrometry service, Johnson
Matthey for loan of precious metal salts, and the
ERASMUS program.
OM050724P
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