Palladium complexes of bulky ortho-trifluoromethylphenyl-substituted phosphines: Unusually regioselective catalysts for the hydroxycarbonylation and alkoxycarbonylation of alkenes

Article abstract of DOI:10.1016/j.molcata.2010.06.026

The reactions of the very bulky phosphine ligands containing both tert-butyl and ortho-trifluoromethylphenyl substituents with [PdCl ₂(PhCN)₂] have been studied, in order to assess the impact of steric and electronic effects on a ligand's coordination ability. The palladium complexes of tert-butyl(ortho-trifluoromethylphenyl)methyl phosphine and tert-butyl(ortho-trifluoromethylphenyl)(n-butyl)phosphine were characterised by X-ray crystallography and shown to be good precatalysts for the hydroxy- and alkoxycarbonylation of alkenes relative to Pd complexes of tricyclohexylphosphine and triphenylphosphine. A notable feature of Pd complexes of tert-butyl(ortho-trifluoromethylphenyl)methyl phosphine is significantly enhanced regioselectivity relative to previous state-of-the-art catalysts in the hydroxycarbonylation of styrene, even if lithium chloride co-catalysts are not used. These catalysts derived from large cone angle ligands consistently give higher regioselectivity in the alkoxycarbonylation of styrene using ethanol, n-propanol, and i-propanol as nucleophiles. These Pd complexes are also active in the Suzuki coupling of activated aryl chlorides, and in both carbonylation and Suzuki reactions, tert-butyl(ortho-trifluoromethylphenyl)methyl phosphine gives more productive catalysts than its bulkier analogues.

Full text of DOI:10.1016/j.molcata.2010.06.026

Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Palladium complexes of bulky ortho-trifluoromethylphenyl-substituted
phosphines: Unusually regioselective catalysts for the hydroxycarbonylation
and alkoxycarbonylation of alkenes
Arnald Grabulosa, Jamie J.R. Frew, José A. Fuentes, Alexandra M.Z. Slawin, Matthew L. Clarke∗
School of Chemistry, University of St Andrews, EaStCHEM, St Andrews, Fife KY16 9ST, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 13 April 2010
Received in revised form 24 June 2010
Accepted 25 June 2010
Available online 1 August 2010
The reactions of the very bulky phosphine ligands containing both tert-butyl and ortho-
trifluoromethylphenyl substituents with [PdCl2(PhCN)2] have been studied, in order to assess the impact
of steric and electronic effects on a ligand’s coordination ability. The palladium complexes of tert-
butyl(ortho-trifluoromethylphenyl)methyl phosphine and tert-butyl(ortho-trifluoromethylphenyl)(n-
butyl)phosphine were characterised by X-ray crystallography and shown to be good precatalysts for
the hydroxy- and alkoxycarbonylation of alkenes relative to Pd complexes of tricyclohexylphosphine and
triphenylphosphine. A notable feature of Pd complexes of tert-butyl(ortho-trifluoromethylphenyl)methyl
phosphine is significantly enhanced regioselectivity relative to previous state-of-the-art catalysts in
the hydroxycarbonylation of styrene, even if lithium chloride co-catalysts are not used. These catalysts
derived from large cone angle ligands consistently give higher regioselectivity in the alkoxycarbonylation
of styrene using ethanol, n-propanol, and i-propanol as nucleophiles. These Pd complexes are also active
in the Suzuki coupling of activated aryl chlorides, and in both carbonylation and Suzuki reactions, tert-
butyl(ortho-trifluoromethylphenyl)methyl phosphine gives more productive catalysts than its bulkier
analogues.
Keywords:
Hydroxycarbonylation
Hydrocarbonylation
Hydroesterification
Suzuki coupling
Palladium
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
ligands, 1–5, we noted that ligand 5 failed to coordinate to
any transition metals at all. Evidently, ligands with this com-
Bulky phosphorus ligands have become increasingly important
in homogeneous catalysis and organometallic chemistry as they
often radically alter the properties of late transition metal com-
plexes. This is particularly striking in carbonylation catalysis where
bulky monophosphines give enhanced activity in hydroformyla-
tion, and where bulky diphosphines give enhanced regio- and/or
enantio-selectivity [1]. Bulky diphosphines have also given remark-
able results in alkoxycarbonylations of terminal alkenes [2]. We
have recently reported the use of Pd complexes of the new biden-
tate ligands, 1–4 as highly regioselective and active catalysts for
hydroxycarbonylation of styrene [3]. However, alkyl monophos-
phines have generally been considered as relatively poor ligands
for Pd catalysed hydroxycarbonylation based on the inactivity of
Me3P and Cy3P and the lower activity (but greater regioselectivity)
observed with ligands such as Ph2P(o-tolyl) [4] (Fig. 1).
bination of tert-butyl and ortho-trifluoromethylphenyl groups
are finely balanced between coordinating as bulky ligands and
being inert to transition metals. In order to clarify the impor-
tance of steric and electronic factors within these unusual bulky
phosphines, we elected to study some simple but previously
unstudied monophosphines that contain both very bulky ortho-
trifluoromethylphenyl groups and electron donating alkyl groups.
In this paper, we report the synthesis of these ligands, their
palladium(II) complexes and the somewhat surprising finding
that Pd complexes of (tert-butyl)methyl(ortho-trifluoromethyl-
phenyl)phosphine give improved regioselectivity relative to other
ligands when used as catalyst for hydroxy- and alkoxycarbonyla-
tions of a range of vinyl arenes.
2. Experimental
There is very sparse data available on phosphines that con-
tain both bulky ortho-trifluoromethylphenyl groups and tert-butyl
groups [5], and in the preliminary report on the bidentate
2.1. General experimental procedures and instrumentation
Routine NMR data were recorded either on a Bruker Avance 300
(1H at 300 MHz, 13C at 75 MHz, 19F at 282 MHz, 31P at 121 MHz)
or a Bruker Avance II 400 (1H at 400 MHz, 13C at 100 MHz, 19F at
376 MHz, 31P at 161 MHz). 1H and 13C spectra were referenced to
∗
Corresponding author. Tel.: +44 1334 463850; fax: +44 1334 463808.
E-mail address: mc28@st-andrews.ac.uk (M.L. Clarke).
1381-1169/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2010.06.026

A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
19
2.3. n-Butyl(t-butyl)(o-trifluoromethylphenyl)phosphine, 8
The same procedure used in the preparation of 7 was followed.
From n-Butyl(t-butyl)(o-trifluoromethylphenyl)phosphine-borane
(300 mg, 0.98 mmol) the title compound was obtained as a yellow-
ish oil. Yield: 203 mg (71%).1H NMR (300 MHz, CDCl3): ı 7.77–7.70
(m, 2H, ArH), 7.85–7.82 (m, 1H, ArH), 7.55–7.43 (m, 2H, ArH),
1.98–1.87 (m, 1H, CHH), 1.74–1.61 (m, 1H, CHH), 1.38–1.28 (m, 3H,
CH2, CHH), 1.12 (m, 1H, CHH), 1.02 (d, 9H, J = 12.1 Hz), 0.83 (t, 3H,
J = 6.9 Hz). 13C{ H}NMR (75 MHz, CDCl3): ı 133.9 (d, CH, J = 3.5 Hz),
1
Fig. 1. Bulky bidentate ligands either give highly regioselective Pd catalysts or are
too bulky to act as ligands.
130.4 (CH), 129.0 (CH), 126.3 (m, CH), 28.5 (d, CH2, J = 16.6 Hz),
27.9 (d, CH3, J = 14.3 Hz), 24.4 (d, CH2, J = 12.5 Hz), 22.3 (d, CH2,
1
J = 17.9 Hz), 13.8 (s, CH3). 31P{ H} NMR (121 MHz, CDCl3): ı −8.1 (q,
1
J = 56.0 Hz). 19F{ H}NMR (282 MHz, CDCl3): ı −55.2 (d, J = 74.8 Hz).
MS (ES+): 313 (M+Na+); HRMS calcd. for C15H23F3P, 291.1489;
found 291.1495.
external tetramethylsilane, 19F spectra were referenced to exter-
nal trichlorofluoromethane, and 31P spectra were referenced to
external phosphoric acid. Chemical shifts are expressed in parts
per million. Chemical ionisation mass spectroscopy and electron
ionisation mass spectroscopy were performed on a Micromass GCT
spectrometer. Electrospray mass spectroscopy was performed on
a Micromass LCT spectrometer. All were operated by Mrs Car-
oline Horsburgh. Infra-red spectra were recorded on a Perkin
Elmer GX-FTIR System spectrometer. Thin layer chromatogra-
phy was performed using 0.20 mm layers of silica gel supported
on plastic sheets (Macherey-Nagel, Polygram Sil G/UV254) or
using 0.20 mm layers of aluminium oxide supported on plastic
sheets (Merck Aluminium oxide F254). Preparative chromatog-
raphy was performed using Davasil silica gel 35–70 ␮m. Dry
degassed diethyl ether, petroleum ether, THF and toluene were
obtained from an Innovative Technologies Puresolve 400 solvent
still. Other solvents were bought and used as received without
further purification other than degassing by either purging with
nitrogen or repeated freeze/thaw cycles under vacuum. Organic
solutions were dried by standing over anhydrous sodium sul-
phate and evaporated either under reduced pressure on a rotary
evaporator or under reduced pressure whilst agitating manu-
ally. tert-Butyldichlorophosphine was obtained from the Aldrich
Chemical Company and used as received. All manipulations were
carried out under an atmosphere of nitrogen unless otherwise
stated.
2.4. (O-trifluoromethylphenyl)(t-butyl)methylphosphineborane,
9
It is generally possible to generate the phosphine directly in
>95% purity, but if further purification is required, a more stable
borane complex can be prepared as shown below.
2.5. From t-butyl(o-trifluoromethylphenyl)chlorophosphine
(Route A)
t-Butyl(o-trifluoromethylphenyl)chlorophosphine
(669 mg,
2.49 mmol) was dissolved in 20 mL of diethyl ether and the solu-
tion cooled to −78 ◦C. MeLi (3.25 mL of a 1.6 M solution in diethyl
ether, 5.2 mmol) was added and the mixture was allowed to warm
to room temperature overnight. The mixture was then cooled to
0 ◦C and BH3·THF (6.2 mL of a 1 M solution in THF, 6.2 mmol) was
quickly added. The mixture was warmed to room temperature and
stirred for 2 h. A few drops of water were carefully added to quench
the excess of MeLi and subsequently the mixture was subjected to
extractive work-up (water/diethyl ether). The crude material after
concentration to dryness was purified by column chromatography
(SiO2, hexane/Et2O, 80/20). The desired product was isolated as
a white microcrystalline powder with purity of around 98% after
vacuum removal of the solvents. Yield: 370 mg (57%).
2.2. (o-Trifluoromethylphenyl)(tert-butyl)methylphosphine 7
2.6. From t-butyl(o-trifluoromethylphenyl)phosphine-borane
(Route B)
(ortho-Trifluoromethyphenyl)tert-butylchlorophosphine
(0.318 g, 1.18 mmol) was dissolved in diethyl ether (10 mL)
and cooled to −78 ◦C. MeLi (1.38 mL, 2.208 mmol, 1.6 equivalents
as a 1.6 M solution in hexanes) was added slowly and the reaction
allowed to warm to room temperature gradually over 3 h. The
solvent was then removed under vacuum to near dryness and
degassed CH2Cl2 (15 mL) added. The reaction was then quenched
with degassed water (2 mL) which was then removed by syringe,
and the remaining CH2Cl2 layer dried using Na2SO4 which was
filtered off. The solvent was then removed to give the product as
an air sensitive light brown oil (165 mg, 0.665 mmol) in 56% yield.
1H NMR (300 MHz; C6D6): ı 7.6–7.8 (2 H, d, J = 15.2 Hz, ArH),
7.55 (1 H, t, app., J = 7.0 Hz, ArH), 7.47 (1 H, t, app., J = 7.8 Hz, ArH),
1.18 (3 H, d, J = 15.2 Hz, P-CH3), 1.04 (9 H, d, J = 12.3 Hz, C(CH3)3.
t-Butyl(o-trifluoromethylphenyl)phosphine-borane (496.2 mg,
2.0 mmol) were dissolved in 15 mL of THF and the solution cooled
to −78 ◦C. n-BuLi (880 ␮L of a 2.5 M solution in hexanes, 2.2 mmol)
were dissolved in 10 mL of diethyl ether and this solution added
over 1 h to the phosphine-borane solution. After the addition, the
solution was slowly warmed to 0 ◦C and cooled back to −78 ◦C.
Methyl iodide (162 ␮L, 2.6 mmol) were added and the solution was
allowed to warm to room temperature overnight. The solvents were
then removed under vacuum and the crude product was purified by
column chromatography in similar fashion to Route A and generally
gave material with purity >99%. Yield: 357 mg (68%).
1H NMR (400 MHz, CDCl3): ı 8.30 (dd, 1H, J = 14.0 Hz, 7.3 Hz),
7.85–7.83 (m, 1H), 7.66–7.58 (m, 2H), 1.80 (dd, 3H, H, J = 10.1 Hz,
2.0 Hz), 1.14 (d, 9H, H, J = 14.3 Hz), 1.80–0.10 (br, q, 3H, BH3).
1
13C{ H} NMR (75 MHz; C6D6): ı 138.2 (d, J = 39 Hz, ArC-P), 136.6 (q
1
13C{ H} NMR (101 MHz, CDCl3): ı 139.5 (d, CH, J = 16.7 Hz),
d, J = 31 Hz, J = 2 Hz, ArC-CF3), 134.5 (d, J = 4 Hz, ArCH o-P), 130.9 (s,
ArCH), 130.9 (s, ArCH), 129.5 (s, ArCH), 126.7 (dq, J = 6 Hz, J = 6 Hz,
ArCH o-CF3), 125.4 (q, J = 278 Hz, CF3), 29.8 (d, J = 15 Hz, C(CH3)),
132.0–122.0 (m, CH), 127.3 (q, CF3, J = 6.9 Hz), 30.6 (d, J = 30.7 Hz),
26.0 (d, CH3, J = 15.0 Hz), 29.6 (dd, CH3, J = 35.7 Hz, 6.7 Hz).
29.6 (d, J = 17 Hz, CH3 methyl), 27.7 (d, J = 15 Hz, CH3 tert-butyl). 19
F
1
1
31P{ H}NMR (162 MHz, CDCl3): ı +35.5 (q, J = 56.6 Hz). 19F{ H}
NMR (376 MHz, CDCl3): ı −55.9 (s). 11B NMR (128 MHz, CDCl3): ı
−36.6 (m). MS (ES+): 285 (M+Na+); HRMS calcd. for C12H19BF3NaP,
285.1167; found 285.1166.
NMR (282 MHz; C6D6): ı −54.9 (d, J = 58 Hz), 31P NMR (121 MHz;
C6D6): ı −20.0 (q, J = 58 Hz). MS CI+: m/z 249.0 ([M+H]+ requires
249.09).

20
A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
These boranes can be converted into the free phosphine
2.9. Bis((o-trifluoromethylphenyl)tert-
butylmethylphosphine)palladiumdichloride,
12
by reaction with HBF4. (ortho-Trifluoromethylphenyl)(tert-
butyl)methylphosphineborane (262 mg, 1.0 mmol) was dissolved
in 10 mL of dichloromethane and the solution cooled to −30 ◦C.
HBF4·OMe2 (0.350 mL, 2.9 mmol) was added and the mixture
was allowed to warm to room temperature overnight. 31P NMR
spectroscopy indicated the total conversion to the phosphonium
salt (d = +20 ppm). The reaction mixture was treated with 30 mL of
previously degassed saturated aqueous solution of NaHCO3 and the
organic layer was extracted with dichloromethane under argon.
The combined organic extracts were dried with sodium sulfate
and filtered. Concentration to dryness under vacuum afforded the
desired product as a yellow/brown oil. Yield: 170 mg (68%).
(ortho-Trifluoromethylphenyl)tert-butylmethylphosphine
(55 mg, 0.220 mmol) was dissolved in dry degassed CH2Cl2 (2 mL).
[PdCl2(PhCN)2] (42 mg, 0.110 mmol) was added and the mix-
ture stirred at room temperature for 24 h. The solvent was then
reduced to near dryness and diethyl ether added resulting in
a yellow precipitate, which was filtered off and washed with
further diethyl ether to yield the title compound (45 mg, 73 mmol,
67% yield). The complex is present as a mixture of the rac and
meso isomers leading to two sets of signals in the ratio 1:2.5 by
19F NMR. Recrystallisation by slow diffusion of hexane into a
CH2Cl2solution of the product yielded crystals suitable for X-ray
crystallography.
2.7. n-Butyl(t-butyl)(o-trifluoromethylphenyl)phosphine-borane,
1H NMR (400 MHz; CD2Cl2): ı 7.79 (2H, m, ArH), 7.69 (2 H, m,
ArH), 7.49 (4H, m, ArH), 1.86 (3H, t app., J = 7.4 Hz, P-CH3 major iso-
mer), 1.85 (3H, t app., J = 7.4 Hz, P-CH3 minor isomer), 1.21 (9 H, t
app., J = 7.4 Hz, C(CH3)3 minor isomer), 1.20 (9 H, t app., J = 7.4 Hz,
C(CH3)3 major isomer). 1H{19F}NMR (400 MHz; CD2Cl2): ı 7.79
(1H, m, ArH), 7.69 (1 H, m, ArH), 7.49 (2H, m, ArH), 1.86 (3H, t
app., J = 7.4 Hz, P-CH3 major isomer), 1.85 (3H, t app., J = 7.4 Hz,
P-CH3 minor isomer), 1.21 (t app., J = 7.4 Hz, C(CH3)3 minor iso-
mer), 1.20 (t app., J = 7.4 Hz, C(CH3)3 major isomer). 1H{31P} NMR
(400 MHz; CD2Cl2): ı 7.79 (1H, m, ArH), 7.69 (1 H, m, ArH), 7.49
(2H, m, ArH), 1.86 (3H, s, P-CH3 major isomer), 1.85 (3H, s, P-CH3
minor isomer), 1.21 (s, C(CH3)3 minor isomer), 1.20 (s, C(CH3)3
10
The same procedure used in the preparation of 9 (Route A) was
followed, employing n-BuLi solution in hexanes instead of MeLi.
From t-butyl(o-trifluoromethylphenyl)chlorophosphine (927 mg,
3.45 mmol) and n-BuLi (2.9 mL of a 2.5 M solution, 7.25 mmol) the
title compound was obtained after chromatography as a colourless
oil with purity ranging from 95 to 99%. Yield: 313 mg (30%).
1H NMR (400 MHz, CDCl3): ı 8.27–8.21 (m, 1H), 7.85–7.82
(m, 2H), 7.64–7.52 (m, 2H), 2.36 (m, 1H), 1.92–1.83 (m, 1H),
1.81–1.69 (m, 1H), 1.45–1.37 (m, 2H), 1.31–1.25 (m, 1H), 1.13 (d,
9H, J = 13.8 Hz), 0.90 (t, 3H, J = 7.4 Hz), 1.80–0.10 (br, q, 3H, BH3).
1
major isomer).13C{ H} NMR (101 MHz; CD2Cl2): ı 134.7 (m, ArCH),
1
13C{ H}NMR- (101 MHz, CDCl3): ı 139.9 (d, CH, J = 18.0 Hz), 131.2
132.0 (m, ArC), 129.4 (m, ArCH), 129.2 (s, ArCH), 128.9 (m, ArC),
127.5 (m, ArCH), 123.5 (q, J = 275.5 Hz, CF3), 34.6 (t app., J = 11.1 Hz,
C(CH)3 major isomer), 34.4 (t app., J = 11.1 Hz, C(CH)3, minor iso-
mer), 26.8 (m, C(CH)3), 8.2 (m, P-CH3). 19F NMR (376 MHz; CD2Cl2):
ı −52.95 (t, J = 6.9 Hz, major isomer), −53.1 (t, J = 6.9 Hz, minor iso-
mer). 31P NMR (162 MHz; CD2Cl2): ı 27.4 (m). IR (cm−1), KBr, 3200,
3500, 2900–3000, 2200, 1300. MS ES+ 697.02 (M+Na). Calcd. for
C24H23Cl2F6P2Pd, C 42.78%, H 4.79%; found: C 42.65%, H 4.74%.
(CH), 131.1 (CH), 128.0 (t, CH, J = 7.9 Hz), 125.3 (m, CF3), 31.2 (d, C,
J = 38.9 Hz), 26.6 (s, CH2), 25.4 (d, CH2), 24.5 (d, CH2, J = 19.5 Hz), 20.9
1
(dd, CH3, J = 42.4 Hz, 5.9 Hz), 13.6 (s, CH3). 31P{ H}NMR (162 MHz,
1
CDCl3): ı +43.2 (d, J = 71.9 Hz). 19F{ H}NMR (376 MHz, CDCl3): ı
−56.0 (s). 11B NMR (128 MHz, CDCl3): ı −37.4 (m).
MS (ES+): 327 (M+Na+); HRMS calcd. for C15H25BF3NaP,
327.1637; found 327.1630.
2.10. Bis[n-butyl(t-butyl)(o-
trifluoromethylphenyl)phosphine]palladiumdichloride,
2.8. tert-Butylbis(o-(trifluoromethyl)phenyl)phosphine 11
13
A
stirred solution of ortho-bromobenzotrifluoride (8.49 g,
5.26 mL, 37.7 mmol) diethyl ether (40 mL) was cooled to −78 ◦C, and
n-butyllithium (15 mL as a 2.5 M solution in hexanes, 37.7 mmol)
added slowly, after which the reaction was allowed to warm to
room temperature. The solution was then cooled to −78 ◦C and t-
butyldichlorophosphine (2.00 g as a solution in 10 mL diethyl ether,
12.57 mmol) added slowly by dropping funnel. The solution was
then allowed to warm slowly to room temperature. After 16 h the
dark green solution was washed with water. The diethyl ether layer
retained and dried with MgSO4, filtered and the solvent removed.
Recrystalisation from methanol yielded the product as air stable
white crystals (3.880 g, 10.25 mmol) in 82% yield.
The same procedure used in the preparation of 5 was followed.
From 4 (180 mg, 0.62 mmol) the title compound was obtained an
orange solid. Yield: 63 mg (28%). X-ray diffraction: crystals suitable
for X-ray diffraction were grown by slow diffusion of hexane into
a dichloromethane solution of the product at room temperature.
1H NMR (500 MHz, CD2Cl2): ı 8.16 (m, 2H, minor); 8.08 (m,
2H, major), 7.76–7.72 (m, 2H), 7.62–7.53 (m, 4H), 2.57–2.48 (m,
4H), 2.16–2.09 (m, 2H), 1.92–1.85 (m, 2H), 1.56–1.49 (m, 4H),
1.25–1.22 (m, 18H), 1.02 (t, 6H, J = 7.4 Hz, major), 0.98 (t, 6H,
1
J = 7.4 Hz, major). 13C{ H} NMR (125 MHz, CD2Cl2): ı 138.2 (CH,
minor), 137.7 (CH, major), 133.2–132.8 (m, C), 131.0–132.8 (m, C),
130.4 (d, CH, J = 3.7 Hz, minor), 130.4 (d, CH, JCP = 3.7 Hz, major),
123.4 (CH, major), 123.4 (CH, minor), 36.9–36.6 (m, C); 31.0 (s, CH2),
30.8 (s, CH2), 28.6 (s, CH3), 28.1 (s, CH3, 25.4–25.2 (m, CH2), 23.4 (m,
1H NMR (300 MHz; C6D6): ı 7.75 (2 H, d m, J = 7.5 Hz, ArH o-CF3),
7.6 (2H, ddd, J = 5.3 Hz, J = 8 Hz, ArH o-P), 7.4 (2H, td, J = 7.5 Hz, ArH),
7.32 (2H, td, J = 7.5 Hz, ArH), 1.2 (9H, d, J = 13.3, (CH3)3). 1H{31P}
NMR (300 MHz; C6D6): ı 7.75 (2 H, dm, J = 7.5 Hz, ArH o-CF3), 7.6
(2H, dd, J = 8 Hz, ArH o-P), 7.4 (2H, td, J = 7.5 Hz, ArH), 7.32 (2H,
1
CH2), 14.0 (s, CH3). 31P{ H} NMR (202 MHz, CD2Cl2): ı +39.4 (s, br).
19F{ H} NMR (470 MHz, CD2Cl2): ı −53.6 (major, br); −53.7 (minor,
1
1
td, J = 7.5 Hz, ArH), 1.2 (9 H, s, (CH3)3). 13C{ H} NMR (100 MHz;
br). MS (EI):776(M+NH4+), 722(M−Cl). Calcd. forC30H44Cl2F6P2Pd,
CDCl3): ı 136.1 (d, J = 40 Hz, ArCH), 136.0 (s, ArCH), 135.3 (m, ArC-
CF3), 130.5 (s, ArCH), 128.5 (s, ArCH), 127.2 (m, ArCH o-CF3), 124.2
(q, J = 275 Hz, CF3), 31.7 (d, J = 21 Hz, P-C(CH3)3), 29.3 (d, J = 16 Hz,
C 47.54%, H 5.85%; found: C 47.52%, H 5.76%.
2.11. Procedure for hydroxycarbonylation
1
CH3). 19F NMR: ı −55.8 (d, J = 51.1 Hz), 31P{ H} NMR: ı −2.6 (sep,
J = 51.2 Hz), IR (cm−1), KBr, 3050, 2900–3000, 2200, 1300. MS ES+:
m/z 401.02 ([M+Na]+ requires 401.09). Anal. Calcd. for C18H17F6P:
C, 57.15; H, 4.53% found: C, 56.66; H, 4.73%.
A Biotage 2 mL microwave vial containing a stirring bar was
charged with the appropriate amounts of LiCl, para-toluenesulfonic
acid, catalyst and substrate if the latter was a solid. The vial

A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
21
Table 1
Hydroxycarbonylation of vinyl arenes.
Entrya
Substrate
Catalyst [% Pd]a
LiCl (%)
PTSA (%)
Time (h)
Conv.b
%
b:lc
Yieldd
%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
Styrene, 16
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
17
14, 1.0
15, 1.0
12, 1.0
13, 1.0
14, 0.5
15, 0.5
12, 0.5
13, 0.5
14, 1.0
12, 1.0
14, 0.5
15, 0.5
12, 0.5
13, 0.5
14, 0.5
12, 0.5
13, 0.5
14, 0.5
12, 0.5
14, 0.5
12, 0.5
20
20
20
20
5
5
5
5
0
0
0
0
0
0
5
5
5
20
20
20
20
5
5
5
5
10
10
5
5
5
5
5
5
5
6
6
6
6
6
6
6
6
24
24
16
16
16
16
24
24
24
24
24
24
24
95
32
>99
69
81
51
77
10
>99
54
>99
55
86:1
59
8
55
32
40
2
>200:1
>200:1
>200:1
76:1
>200:1
>200:1
–
8.7:1
>200:1
9.9:1
120:1
>200:1
>200:1
100:1
>200:1
>200:1
67:1
>200:1
46:1
>200:1
51
0
71
37
63
35
19
1
85
77
10
57
41
59
88
32
3
>99
>99
16
>99
85
17
17
18
18
19
19
5
5
5
5
5
5
5
5
90
>99
a
Reactions carried out at 30 bar of CO, at 80 ◦C, in 1.5 mL of degassed butanone in presence of 2.5 equivalents (with respect to styrene) of degassed water, using the
[PdCl2(L)2] precatalysts.
b
1H NMR spectroscopy of reaction mixtures before work-up does not reveal any side products, hence, conversion is calculated as acids/(acids + styrene) × 100 determined.
c
Ratio of branched/linear acid in the isolated products determined by 1H NMR integration.
d
Isolated yield of pure acids.
Indan-1-carboxylic acid: 1H NMR (400 MHz, CDCl3): ı 7.34 (d,
1H, J = 7.0 Hz), 7.15–7.10 (m, 3H), 3.98 (dd, 1H, J = 8.4 Hz, 6.1 Hz),
3.06–2.98 (m, 2H), 2.87–2.79 (m, 2H), 2.40–2.31 (m, 2H), 2.30–2.21
was sealed with a crimp cap, purged with three vacuum/argon
cycles and left under argon atmosphere. The substrate (if a liq-
uid), degassed water and degassed butanone (1.5 mL) were added
with syringe. Two needles were pierced into the vial and this was
introduced into the autoclave, which had been previously purged
with three vacuum/argon cycles. The autoclave was then purged
three times with CO, pressurised to 30 bar and immersed into an
oil bath preheated to the desired temperature. After the desired
reaction time, the autoclave was cooled down to room tempera-
ture, the pressure slowly released and opened. A small sample was
taken and analysed by 1H NMR to calculate the conversion. The
contents of the vial were then diluted with toluene and extracted
three times with saturated aqueous NaHCO3 solution. The com-
bined aqueous layers were acidified with concentrated HCl until
decidedly acidic pH according to litmus paper. This solution was
then extracted with dichloromethane and the combined organic
phases dried with MgSO4, filtered and the final solution concen-
trated to dryness under vacuum. The residue consisted in the pure
acid.
1
(m, 2H). 13C{ H} NMR (101 MHz, CDCl3): ı 180.7 (C O), 144.2 (C),
140.1 (C), 127.8 (CH), 126.6 (CH), 125.0 (CH), 124.8 (CH), 50.1 (CH),
31.8 (CH2), 28.7 (CH2). MS (ES−): 161 (M−H), HRMS calculated for
C10H9O2 161.0603; found 161.0608.
2.12. Procedure for alkoxycarbonylation
A Biotage 2 mL microwave vial containing a stirring bar was
charged with the appropriate amounts of LiCl, para-toluenesulfonic
acid and catalyst. The vial was sealed with a crimp cap, purged
with three vacuum/argon cycles and left under argon atmosphere.
Styrene, tetraethylsilane (internal standard) and the appropriate
degassed alcohol (1.5 mL) were added with syringe. Two needles
were pierced into the vial and this was introduced into the auto-
clave, which had been previously purged with three vacuum/argon
cycles. The autoclave was then purged three times with CO, pres-
surised to 30 bar and immersed into an oil bath preheated to 80 ◦C.
After 24 h, the autoclave was cooled down to room temperature,
the pressure slowly released and opened. A small sample was taken
and analysed by 1H NMR to calculate the conversion. The contents
of the vials were vacuumed down to dryness, yielding a yellowish
gummy material, which was suspended in EtOAc/hexane (1:1) and
filtered through a small plug of SiO2. The solvents (and any styrene)
were then removed under vacuum yielding the pure desired ester.
Regioselectivities of >200:1 refer, except in the case of Table 1,
entries 17 (270:1) and 21 (370:1), refer to regioisomerically pure
products.
2-Phenylpropanoic acid: 1H NMR (400 MHz, CDCl3): ı 7.27–7.15
1
(m, 5H), 3.65 (q, 1H, J = 7.2 Hz), 1.43 (d, 3H, J = 7.2 Hz). 13C{ H} NMR
(101 MHz, CDCl3): ı 180.8 (C O), 139.8 (C), 128.7 (CH), 127.7 (CH),
127.4 (CH), 45.4 (CH), 18.1 (CH3).
MS (ES+): 173 (M+Na+); (ES−): 149 (M−H).
2-(4-tert-Butylphenyl)propanoic acid: 1HNMR(400 MHz, CDCl3):
ı 7.36 (d, 2H, J = 8.3 Hz), 7.26 (d, 2H, J = 8.3 Hz), 3.72 (q, 1H, J = 7.2 Hz),
1
1.51 (d, 3H, CH3 J = 7.2 Hz); 1.31 (s, 9H, But). 13C{ H} NMR (101 MHz,
CDCl3): ı 181.0 (C O), 150.3 (C), 136.7 (C), 127.3 (2xCH), 125.6
(2xCH), 44.9 (CH), 34.5 (C), 31.3 (3xCH3), 18.0 (CH3).
MS (ES−): 205 (M−H).
2-(6-Methoxy-2-naphthyl)propanoic acid: 1H NMR (400 MHz,
CDCl3): ı 7.71 (d, 1H, J = 2.0 Hz), 7.69 (m, 2H), 7.41 (dd, 1H, J = 8.5 Hz,
1.9 Hz), 7.14 (dd, 1H, J = 8.9 Hz, 2.6 Hz), 7.11–7.10 (m, 1H); 3.91 (s,
3H), 3.88 (q, 1H, J = 7.2 Hz), 1.59 (d, 3H, J = 7.2 Hz)
Ethyl 2-phenylpropanoate: 1H NMR (400 MHz, CDCl3):
ı
7.27–7.15 (m, 5H), 4.11–3.98 (m, 2H), 3.63 (q, 1H, J = 7.2 Hz), 1.42
1
(d, 3H, J = 7.2 Hz), 1.13 (t, 3H, J = 7.1 Hz). 13C{ H} NMR (101 MHz,
CDCl3): ı 174.6 (C O), 140.7 (C); 128.6 (CH), 127.5 (CH), 127.1 (CH),
60.7 (CH2), 45.6 (CH), 18.6 (CH3), 14.1 (CH3).
1
13C{ H} NMR: (101 MHz, CDCl3): ı 180.5 (C O), 157.7 (C), 134.9
MS (ES+): 201 (M+Na+); HRMS calculated for C11H14NaO2,
201.0891; found 201.0887
(C), 133.8 (C), 129.3 (CH), 128.9 (C), 127.3 (CH), 126.2 (CH), 126.2
(CH), 119.1 (CH), 105.6 (CH), 55.3 (CH3), 45.2 (CH), 18.1 (CH3).
MS (ES+): 253 (M+Na+); (ES−): 229 (M−H); HRMS calculated for
C14H14NaO3, 253.0841; found 253.0847.
Propyl 2-phenylpropanoate: 1H NMR (400 MHz, CDCl3):
ı
7.25–7.11 (m, 5H), 3.94 (t, 2H, J = 6.7 Hz), 3.64 (q, 1H, J = 7.2 Hz),

22
A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
1.55–1.47 (m, 2H), 1.42 (d, 3H, J = 7.2 Hz), 0.77 (t, 3H, J = 7.4 Hz).
1
13C{ H} NMR (101 MHz, CDCl3): ı 174.6 (C O), 140.7 (C), 128.6
(CH), 127.5 (CH), 127.1 (CH), 66.3 (CH2), 45.6 (CH), 21.9 (CH2), 18.5
(CH3), 10.2 (CH3). MS (ES+): 215 (M+Na+); HRMS calculated for
C12H16NaO2, 215.1048; found 215.1042.
Isopropyl 2-phenylpropanoate: 1H NMR (300 MHz, CDCl3): ı
7.35–7.21 (m, 5H), 5.05–4.93 (m, 1H), 3.67 (q, 1H, J = 7.2 Hz), 1.48 (q,
1
3H, J = 7.2 Hz), 1.22 (d, 3H, J = 6.3 Hz), 1.13 (d, 3H, J = 6.3 Hz). 13C{ H}
NMR (75 MHz, CDCl3): ı 174.9 (C O), 141.5 (C), 128.9 (CH), 127.9
(CH), 127.4 (CH), 68.4 (CH), 46.2 (CH), 22.2 (CH3), 22.0 (CH3), 19.0
(CH3). MS (ES+): 215 (M+Na+).
2.13. Procedure for Suzuki–Miyaura coupling: preparation of
4-(4-fluorophenyl) acetophenone
A clean dry Schlenk tube was charged with the catalyst (0.5
mol%), 4-fluorophenylboronic acid (105 mg, 0.75 mmol) and potas-
sium triphosphate (318 mg, 1.5 mmol). The Schlenk tube was
purged and the air displaced with argon before the addition of dry
and degassed toluene (3 mL) followed by 4-chloroacetophenone
(65 ␮L, 0.5 mmol). The Schlenk tube was immersed into a preheated
oil bath at 90 ◦C. After the desired reaction time, the reaction mix-
ture was cooled down to room temperature and a small sample
taken and analysed by 1H NMR. If full conversion was achieved, the
reaction mixture was filtered through a plug of silica and the solu-
tion concentrated under vacuum to afford the desired biaryl as a
white solid. Alternatively, the reaction mixture was concentrated
in vacuo and purified by flash column chromatography.
Scheme 1. Synthesis of the new bulky monophosphines, 9–11.
−20.0 ppm. This phosphine can be prepared direct from ButPCl2 by
successive treatments with ortho-trifluoromethylphenyl lithium
and methyl lithium (without isolation of the chlorophosphine
intermediate), and can also be prepared from (tert-butyl)(ortho-
trifluoromethyl-phenyl)phosphine-borane by lithiation and
reaction with methyl iodide, followed by deprotection of the
borane,
9 in a subsequent step. (n-butyl)(tert-butyl)(ortho-
4-(4-Fluorophenyl)acetophenone: 1H NMR (400 MHz, CDCl3): ı
8.03 (d, 2H, J = 8.6 Hz), 7.64 (d, 2H, J = 8.6 Hz), 7.61–7.58 (m, 2H),
trifluoromethyl-phenyl)phosphine, 8 can be prepared from the
chloro phosphine and n-BuLi in a similar fashion, and was also
characterised further as its borane complex, 10.
7.19–7.13 (m, 2H), 2.64 (s, 3H). 13C{ H} NMR (75 MHz, CDCl3):
1
ı 198.1 (C O), 163.0 (d, C, J = 248.2 Hz), 144.7 (C), 136 (d, CH,
J = 3.3 Hz), 135.9 (C), 129.0 (CH), 128.9 (CH), 127.1 (CH), 115.9 (d, CH,
(tert-Butyl)-bis-(ortho-trifluoromethyl-phenyl)phosphine,
11 was simply prepared in high yield by adding an excess of
ortho-trifluoromethylphenyl lithium to ButPCl2. The air stable
solid product was isolated by recrystallisation from ethanol in
82% yield. This compound shows the expected septet at 2.6 ppm
1
J = 21.6 Hz), 26.7 (CH3). 19F{ H} NMR (282 MHz, CDCl3): ı −114.47.
MS (EI): 214 (M+); 199; 170; 85
Crystallographic data: X-ray diffraction studies for 12 and 13
were performed at 93 K using a Rigaku MM007/Mercury diffrac-
tometer (confocal optics Mo-K␣ radiation). Intensity data were
collected using ␻ steps accumulating area detector frames span-
ning at least a hemisphere of reciprocal space for all structures (data
were integrated using CrystalClear). All data were corrected for
Lorentz, polarisation and long-term intensity fluctuations. Absorp-
tion effects were corrected on the basis of multiple equivalent
reflections. Structures were solved by direct methods and refined
by full-matrix least-squares against F2 (SHELXTL) Hydrogen atoms
were assigned riding isotropic displacement parameters and con-
strained to idealised geometries. Tables of bond lengths and angles,
along with crystallographic experimental can be found in the
supporting information (PDF file). CCDC761532 and CCDC761533
contain the supplementary crystallographic data for compounds,
12 and 13, respectively as CIF files. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data request/cif.
(4JP–F = 51.2 Hz) in the 31P{ H} spectrum. We have not been able to
1
prepare bis(tert-butyl)(ortho-trifluoromethyl-phenyl)phosphine
by any route; surprisingly, there was no reaction between
chlorophosphine 6 and tert-butyl lithium, or any reaction between
(But)2PCl with 2-(CF3)-C6H4Li with chlorophosphines recovered
unchanged at the end of the reactions.
The cone angle of 11, using the Tollman data, [6] is 217◦ while
the cone angles of ligands 7 and 8 are 178◦ and 183◦, respec-
tively. Ligands 7 and 8 can therefore be considered as being more
bulky than Cy3P (170◦), and quite similar to the tBu3P ligand (cone
angle = 182◦), although their significantly different shape is likely
to have a significant effect on the behaviour of the transition metal
catalysts derived from them; subtle changes to bulky phosphines
can induce very pronounced effects in organopalladium catalysis
providing a further impetus for the investigations we describe here.
The reactions of 7,
8 and 11 with the common pre-
cursor [PdCl2(PhCN)2] were studied. Reaction of rac-7 with
[PdCl2(PhCN)2] occurs quantitatively at room temperature within
minutes, the product of the reaction being trans-[PdCl2(7)2], (com-
pound 12) which was fully characterised (Scheme 2 and Fig. 2).
Ligand 8 behaves similarly. In contrast, 11 gives no palladium com-
plexes even after several days at 20 ◦C or at higher temperatures.
Although the diastereomer that crystallised was the meso
isomer, in which both phosphine units are of the opposite con-
figuration, the rac isomer, in which the phosphines are of the same
3. Results and discussion
The preparation of the new ligands, 7, 8, and 11 is
straightforward.
(tert-butyl)methyl(ortho-trifluoromethyl-
phenyl)phosphine, 7 was prepared from the chlorophosphine
6 by the addition of an excess of methyllithium (Scheme 1). The
reaction proceeded cleanly to give a very air sensitive oil with
the 31P NMR spectrum showing no significant impurities. The
19F NMR spectrum displays a doublet at 55.2 ppm due to the 4J
coupling to phosphorus (JF–P 57 Hz). The corresponding coupling
1
configuration, is also present in solution (judging by the 31P { H}
NMR spectrum), in a 1:2.5 ratio (rac:meso).
A crystal structure of the meso isomer of 12 was successfully
obtained and this shows that a 2:1 complex forms between the
is seen in the quartet observed in the 31P{ H} NMR spectrum at
1

A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
23
Scheme 2. Reaction of rac-7 and rac-8 with Pd(PhCN)2Cl2 showing the two
stereoisomers of complexes 12 and 13.
ligand and palladium (Fig. 2). The unit cell of the complex con-
sists of two distinct molecules with slightly different dimensions.
Both molecules are made up of two phosphorous ligands that are
of opposite configuration and arranged trans to each other. They
adopt a staggered conformation about the P–Pd–P axis such that
each of the substituents on phosphorous is anti to its counterpart
when viewed along this axis. The arrangement of ligands around
Pd is distorted from square planar with two acute and two obtuse
Cl–Pd–P angles of 84.72(5)◦ for Cl syn P-methyl, and 95.28(5)◦ for
Cl syn P–t-Bu (from independent molecule 1). There is some dis-
order in all of the trifluoromethyl groups. The distance from Pd to
the closest F atoms at 2.90(1) Å (molecule 1) and 2.97(1) (molecule
2), and as such is slightly shorter than the van der Walls radii of Pd
and F; it is possible that a weak electrostatic interaction locates the
CF3 groups in the vacant axial positions above the Pd square plane.
The structure of complex 13 shows some similar trends, but there
is no sign of a weak F–Pd interaction. The structure of 13 is shown
in Fig. 3.
The performance of the Pd complexes of the monophosphines 7
and 8 was compared with triphenylphosphine (cone angle = 145◦,
[PdCl2(PPh3)2] = complex 14) and tricyclohexylphosphine (cone
angle = 170◦; [PdCl2(PCy3)2] = complex 15) in the hydroxycarbony-
lation of styrene was investigated (Scheme 3 and Table 1) [7,8].
It is well established that simple monophosphine ligands can
give excellent regioselectivity and activity in this reaction, but the
effects of bulky electron rich ligands such as 7 were not known.
Fig. 3. X-ray crystal structure of meso-13. Hydrogens omitted for clarity.
The reactions were carried out by running the 4 catalysts in paral-
lel at the relatively low temperature of 80 ◦C, since we have tended
to find that temperatures below 100 ◦C lead to improved branched
regioselectivity, albeit at the expense of activity. The results were
quite striking, and somewhat unexpected. Bulky phosphines such
as Cy3P are known to give poor Pd catalysts for this reaction [4], and
the tricyclohexylphosphine-based catalyst, 15 did give low yields,
(Table 1, entries 2 and 6). Triphenylphosphine is known to give
very good catalysts for this reaction [6d], and this is the case, since
very good regioselectivity can be observed with reasonable yields
using the PPh3 catalyst, 14 (Table 1, entries 1 and 5). However, it
is clear from the NMR spectra of the isolated carboxylic acid that
the linear acid is a significant impurity (and cannot be separated
by column chromatography). In contrast, using the Pd catalysts, 12
derived from tert-butyl(ortho-trifluoromethylphenyl)methyl phos-
phine, good yields that sometimes exceed those achieved with
[PdCl2(PPh3)2] are observed, but in this case the regioselectivity
is essentially perfect (Table 1, entries 3 and 7). This does have some
synthetic significance in that even a few % of a difficult to sepa-
rate impurity can be a serious inconvenience that could ultimately
prevent the use of this clean, atom-efficient synthetic method. Fur-
thermore, we envisaged that other substrates might have a lower
in-built preference for branched regioselectivity, making this new
catalyst potentially useful. Catalyst 13 although closely related to
12, gives lower reactivity in these reactions; presumably the reac-
Scheme 3. Hydroxycarbonylation of styrene, 4-butyl styrene, 9-methoxy-
naphthalene and indene gives mainly branched carboxylic acids.
Fig. 2. X-ray crystal structure of meso-12. Hydrogens omitted for clarity.

24
A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
Table 2
the possible significance of an inherently more regioselective cata-
Alkoxycarbonylation of styrene
lyst, since ethoxycarbonylation gave only moderate regioselectivity
to the branched ester using the PPh3 catalyst (7:1), but this is sig-
nificantly improved using catalyst 12 (43:1). Similar trends were
seen in the alkoxycarbonylation using n-propanol or iso-propanol
as nucleophiles.
We have successfully used complex 12 in several cross-
couplings we have needed to carry out in other projects. It is an
efficient catalyst that surpasses many of the plethora of Suzuki
coupling catalysts, although thus far, we have not found any
particularly special properties that distinguish it beyond the state-
of-the-art ligands. An example that was examined and compared
under controlled conditions and is relevant to this discussion is
shown in Scheme 4. Coupling of 4-fluorophenylboronic acid with
4-chloroacetophenone takes place in the presence of 0.5 mol% of
12 within 2.5 h at 90 ◦C (T.O.F ∼150 mol prod./mol cat./h). Under
similar conditions, [PdCl2(PPh3)2] returned only starting material,
while [PdCl2(PCy3)2] was an excellent catalyst for this reaction.
Catalyst 13 does promote this reaction, but does not reach full con-
version, perhaps suggesting that catalysts derived from this more
bulky phosphine are less stable, consistent with the observations
in hydroxycarbonylation.
.
Entrya
Catalyst [% Pd]a
ROH
Conv.b
%
b:lc
Yieldd
%
1
2
3
4
5
6
14, 1.0
12, 1.0
14, 1.0
12, 1.0
14, 0.5
12, 0.5
EtOH
EtOH
58
84
>99
>99
>99
>99
7:1
43:1
7:1
73:1
10:1
64:1
40
58
73
73
92
84
PrnOH
PrnOH
PriOH
PriOH
Reactions carried out at 30 bar of CO, at 80 ◦C, 24 h, in 1.5 mL of degassed alcohol
a
using the [PdCl2(L)2] precatalysts.
1H NMR spectroscopy of reaction mixtures before work-up does not reveal
any side products, hence, conversion is calculated as acids/(acids + styrene) × 100
b
determined.
Ratio of branched/linear acid in the isolated products determined by 1H NMR
c
integration.
d
Isolated yield of pure acids.
tion is sensitive to the cone angle of the phosphine, and 8 is just
too bulky either diminishing the Pd complexes ability in one of the
steps of the mechanism, or perhaps more likely giving catalysts
with lower stability (Table 1, entries 4 and 8). We have not per-
formed kinetic studies of these catalysts, since the main focus here
is on understanding selectivity, but the average turnover frequen-
cies for catalyst 12 are in the order of 15–25 mol/mol/hr at these
relatively low reaction temperatures and moderate S/C ratios, and
are broadly similar to triphenylphosphine-based catalysts.
Interestingly, if the LiCl additive, previously found to be impor-
tant in regioselective hydroxycarbonylations is omitted [3b,6d], the
selectivity for the PPh3 catalyst is reduced significantly, but selec-
tivity using catalyst 12 is unaffected, albeit at the expense of rate
(Table1, compare entries 9and 10). This resultis consistentwith the
proposal of Claver and co-workers that chloride can displace one
of the phosphine ligands to give a neutral intermediate that gives
enhanced selectivity [7a]; Perhaps in the case of the bulky fluori-
nated ligand, even tosylate anions are sufficient to displace one of
the phosphines. The enhanced regioselectivity of catalyst 12 was
also observed in the other vinyl arenes, 17 and 18, with essentially
perfect branched selectivity and high yield. Notably, Indene, a di-
substituted alkene that to the best of our knowledge had not been
investigated in hydroxycarbonylation, gave nearly perfect selectiv-
ity and high yield.
4. Conclusions
Monophosphines containing tert-butyl groups and ortho-
trifluoromethyl-phenyl groups are easily accessed and form trans
complexes, after reaction with [PdCl2(PhCN)2]. The ability of Pd
complex 12 to promote hydroxycarbonylation and alkoxycarbony-
lation with essentially perfect regioselectivity will hopefully make
a small contribution towards this reaction being employed more
often in organic synthesis, since high yielding, atom efficient reac-
tions that can directly give regioisomerically and chemically pure
building blocks like carboxylic acids compare favourably in terms
of convenience and environmental impact relative to established
methods. The methyl substituted phosphine (cone angle 178◦) con-
sistently gives more productive catalysts than the bulkier n-butyl
substituted ligands (cone angle = 182◦), while a phosphine with two
ortho-trifluoromethylphenyl substituents does not coordinate to
palladium precursors at all. The results obtained in the Suzuki reac-
tion combined with the carbonylation data point towards catalyst
stability being an issue when using the bulkier ligand, 8. While
there are many reports of the use of triphenylphosphine/Pd as
a catalyst for hydroxycarbonylation and alkoxycarbonylation, the
comparison made under controlled conditions here shows that this
is not the optimum ligand structure in terms of regioselectivity. It is
possible that the combination of a large cone angle (>170◦ <182◦)
and moderate electron donation contribute towards making lig-
and 7 more suited to this process compared to the PPh3 and PCy3
control systems. Future challenges in Pd catalysed alkene carbony-
lation reactions are the development of highly enantioselective
systems. Initial attempts to prepare 7 in enantio-enriched form
were not promising, and thus we are actively pursuing alternative
approaches towards asymmetric carbonylations.
We also briefly compared catalysts 12 with PPh3 catalyst in the
alkoxycarbonylation of styrene (Table 2). These results highlight
Acknowledgements
The authors thank EPSRC and SASOL Technology (UK) (JJRF) for
funding, the Royal Society of Edinburgh, the EPSRC national mass
spectrometry service and Johnson Matthey for the loan of some Pd
salts.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molcata.2010.06.026.
Scheme 4. Suzuki coupling using the Pd catalysts, 12, 13 and 15.

A. Grabulosa et al. / Journal of Molecular Catalysis A: Chemical 330 (2010) 18–25
25
References
to act as ligands. B. Croxtall, J. Fawcett, E.G. Hope, A.M. Stuart, Dalton Trans.
(2002) 491;
(b) S. Jääskeläinen, P. Suomalainan, M. Haukka, H. Riihimäki, J.T. Pursiainen, T.A.
Pakkanen, J. Organomet. Chem. 633 (2001) 69;
(c) M.L. Clarke, D. Elliss, K.L. Mason, A.G. Orpen, P.G. Pringle, R. Wingad, D.A.
Zaheer, Dalton Trans. (2005) 1294.
[1] (a) Some selected examples of the advantageous use of bulky phosphines in var-
ious types of carbonylation reactions: B. Breit, E. Fuchs, Chem. Commun. (2004)
694;
(b) M.L. Clarke, G.J. Roff, Chem. Eur. J. 12 (2006) 7978;
(c) M.L. Clarke, G.J. Roff, Green Chem. 9 (2007) 792;
(d) B. Breit, R. Winde, T. Mackewitz, R. Paciello, K. Harms, Chem. Eur. J. 7 (2001)
3106;
(e) A. van Rooy, E.N. Orij, P.C.J. Kamer, P.W.N.M. van Leeuwen, Organometallics
14 (1995) 34;
(f) R.A. Baber, M.L. Clarke, K. Heslop, A. Marr, A.G. Orpen, P.G. Pringle, A.M. Ward,
D.A. Zambrano-Williams, Dalton Trans. (2005) 1079;
(g) P.S. Bäuerleina, I.A. Gonzaleza, J.J.M. Weemersa, M. Lutz, A.L. Spek, D. Vogt, C.
Müller, Chem. Commun. (2009) 4944;
(h) M. Dieguez, O. Pamies, A. Ruiz, S. Castillon, C. Claver, Chem. Eur. J. 7 (2001)
3086;
(i) C.J. Cobley, J. Klosin, C. Qin, G.T. Whiteker, Org. Lett. 6 (2004) 3277;
(j) P.W.N.M. Van Leeuwen, C. Claver, Rhodium Catalysed Hydroformylation,
Kluwer Academic Publishers, Dordrecht, 2000;
(k) M.L. Clarke, Curr. Org. Chem. 9 (2005) 701;
(l) B. Breit, W. Seiche, Synthesis (2001) 1;
[6] C.A. Tolman, Chem. Rev. 77 (1977) 313.
[7] (a) I. del Rio, C. Claver, P.W.N.M. van Leeuwen, Eur. J. Inorg. Chem. (2001)
2719;
(b) For a review on industrial use of Pd catalysts including Naproxen synthesis.
A. Zapf, M. Beller, Top. Catal. 19 (2002) 101;
(c) S. Jayasree, A. Seayad, R.V. Chaudhari, Chem. Commun. (2000) 1239;
(d) A. Seayad, S. Jayasree, R.V. Chaudhari, Org. Lett. 1 (1999) 459;
(e) M.S. Goedheijt, J.N.H. Reek, P.C.J. Kamer, P.W.N.M. Van Leeuwen, Chem. Com-
mun. (1998) 2431;
(f) A chiral phosphonic acid additive was communicated to give very good
e.e. in hydroxycarbonylation, but unfortunately yields were moderate and over
10% catalyst was required. H. Alper, N. Hamel, J. Am. Chem. Soc. 112 (1990)
2803;
(g) A. Ionescu, G. Laurenczy, O.F. Wendt, Dalton Trans. (2006) 3934;
(h) A. Aghmiz, M. Gimenez-Pedris, A.M. Masdeu-Bulto, F.P. Schmidtchen, Catal.
Lett. 103 (2005) 191;
(i) A. Ionescu, M. Ruppel, O.F. Wendt, J. Organomet. Chem. 691 (2006) 3806.
[8] (a) Selected references of alkoxycarbonylation: E. Guiu, M. Caporali, B. Munoz,
C. Muller, M. Lutz, A.L. Spek, C. Claver, P.W.N.M. Van Leeuwen, Organometallics
25 (2006) 3102;
(m) J. Klosin, C.R. Landis, Acc. Chem. Res. 40 (2007) 1251.
[2] (a) R.I. Pugh, E. Drent, P.G. Pringle, Chem Commun. (2001) 1476;
(b) C.J. Rodriguez, D.F. Foster, G.R. Eastham, D.J. Cole-Hamilton, Chem. Commun.
(2004) 1720;
(c) W. Clegg, G.R. Eastham, M.R.J. Elsegood, R.P. Tooze, X.L. Wang, K. Whiston,
Chem. Commun. (1999) 1877.
[3] (a) J.J.R. Frew, M.L. Clarke, U. Meyer, H. Van Rensburg, R.P. Tooze, Dalton Trans.
(2008) 1976;
(b) J.J.R. Frew, K. Damian, H. Van Rensburg, A.M.Z. Slawin, R.P. Tooze, M.L. Clarke,
R.P. Tooze, Chem. Eur. J. 15 (2009) 10504.
[4] I. del Rio, N. Ruiz, C. Claver, L.A. van der Veen, P.W.N.M. van Leeuwen, J. Mol.
Catal. A: Chem. 161 (2000) 39.
[5] (a) ortho-Trifluomethylphenyl phosphines are quite sparsely studied phos-
phines in any case, most likely due to their steric bulk hindering their ability
(b) C. Goddard, A. Ruiz, C. Claver, Helv. Chim. Acta 89 (2006) 1610;
(c) B. Munoz, A. Marinetti, A. Ruiz, S. Castillon, C. Claver, Inorg. Chem. Commun.
8 (2005) 1113;
(d) S. Oi, M. Nomura, T. Aiko, Y. Inoue, J. Mol. Catal. A 115 (1997) 289;
(e) G. Cometti, G.P. Chiousoli, J. Organomet. Chem. 236 (1982) C31;
(f) D.B.G. Williams, M.L. Shaw, M.J. Green, C.W. Holzapfel, Angew. Chem. Int. Ed.
47 (2008) 560;
(g) L.L. Da Rocha, A. de, O. Dias, E.N. dos Santos, R. Augusti, E. Gusevskaya, J. Mol.
Catal. Sect. A 132 (1998) 213;
(h) H. Ooka, T. Innoue, S. Itsuno, M. Tanaka, Chem. Commun. (2005) 1173.