An evaluation of phosphine and carbene adducts of phosphite- and phosphinite-based palladacycles in the coupling of alkyl bromides with aryl boronic acids

Article abstract of DOI:10.1016/j.tet.2005.07.097

A range of palladacyclic catalysts and their phosphine and carbene adducts were tested in the Suzuki coupling of an alkyl bromide with phenylboronic acid and showed modest activity in some cases. Unlike with aryl halide substrates it appears that there is no particular benefit in the use of palladacycles as the palladium source. Initial data indicate that the rate determining step is not the oxidative addition of the alkyl halide substrate, but rather lies later in the catalytic cycle.

Full text of DOI:10.1016/j.tet.2005.07.097

Tetrahedron 61 (2005) 9663–9669
An evaluation of phosphine and carbene adducts of phosphite-
and phosphinite-based palladacycles in the coupling
of alkyl bromides with aryl boronic acids
a
b
c
Robin B. Bedford,a, Michael Betham, Simon J. Coles, Robert M. Frost
*
and Michael B. Hursthouseb
aSchool of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, UK
bEPSRC National Crystallography Service, Department of Chemistry, University of Southampton, Highfield Road,
Southampton, SO17 1BJ, UK
cDepartment of Chemistry, University of Exeter, Exeter, EX4 4QD, UK
Received 12 May 2005; revised 14 July 2005; accepted 15 July 2005
Available online 24 August 2005
Abstract—A range of palladacyclic catalysts and their phosphine and carbene adducts were tested in the Suzuki coupling of an alkyl
bromide with phenylboronic acid and showed modest activity in some cases. Unlike with aryl halide substrates it appears that there is no
particular benefit in the use of palladacycles as the palladium source. Initial data indicate that the rate determining step is not the oxidative
addition of the alkyl halide substrate, but rather lies later in the catalytic cycle.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
bond strength compared with aryl halides.3 Secondly,
b-elimination of the Pd–alkyl complex formed after
oxidative addition can lead to competitive alkene formation
rather than subsequent coupling, depending on the relative
rates of the two processes (Scheme 2).
Coupling reactions leading to the formation of new C–C
bonds, typically catalysed by ubiquitous palladium
complexes, form the bedrock of many contemporary
syntheses.1 Despite the undoubted usefulness of such
processes, there are still holes in the general methodologies
currently available that limit their applicability. Much
research is focused on addressing these shortcomings and
the last few years have seen substantial advances. One area
that has proved particularly problematic is the extension of
Suzuki coupling of aryl boron nucleophiles to alkyl halides
bearing b-hydrogens (Scheme 1).2
As long ago as 1992 Suzuki and co-workers showed that
alkyl iodides could be coupled with alkyl- and aryl-(9-BBN)
reagents (9-BBNZ9-borabicyclo[3.3.1]nonane) using
[Pd(PPh3)4] as catalyst and K3PO4 as base at 60 8C, giving
the coupled products in reasonable yield.4 By contrast, no
activity was seen with alkyl bromides. Fu and co-workers
have focused on the problem of using substrates other than
alkyl iodides and found that primary alkyl bromides can be
coupled with both alkyl- and vinyl-(9-BBN) reagents at rt in
THF using palladium acetate/tricyclohexylphosphine as the
catalyst and potassium phosphate as a mild base.5 When the
base is replaced with cesium hydroxide and the reactions
performed in dioxane at 90 8C, then primary alkyl chlorides
can be used as coupling partners with alkyl-(9-BBN)
reagents.6 Both alkyl- and aryl-(9-BBN) reagents can be
coupled with alkyl tosylates at 50 8C in dioxane using
sodium hydroxide as base employing a catalyst formed
in situ from palladium acetate and PMe(tBu)2.7 Caddick,
Cloke and co-workers have shown that N-heterocyclic
carbene adducts of palladium, formed in situ from
palladium bis(dibenzylideneacetone) and the salt 1, can
Scheme 1. Suzuki coupling of aryl boron nucleophiles with alkyl halides.
The problems associated with this process are two-fold.
Firstly, the oxidative addition of the C–X bond is believed to
be more difficult for alkyl halides as a result of the higher
Keywords: Alkyl halide; Suzuki reaction; Palladacycles; Coupling;
Catalysis.
Corresponding author. Fax: C44 117 925 1295;
e-mail: r.bedford@bristol.ac.uk
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.097

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R. B. Bedford et al. / Tetrahedron 61 (2005) 9663–9669
Scheme 2. Simplified catalytic cycles for competing coupling and b-elimination pathways.
also be used to couple primary alkyl bromides with alkyl-
and vinyl-(9-BBN) reagents, using potassium tert-butoxide
as base at 40 8C in THF.8
aryl halides with aryl and alkyl boronic acids.12,13 Often the
phosphines tested show far better activity when used in
conjunction with palladacyclic precursors than classical
palladium sources such as palladium acetate or palladium
dibenzylideneacetone complexes.14 We were interested to
see whether this would hold true in the Suzuki coupling of
alkyl halides with aryl boronic acids (Scheme 1, YZOH),
the results of an evaluative study are presented below.
2. Results and discussion
2.1. Synthesis and characterisation of catalysts
We have previously found that the reaction of the
palladacyclic phosphite complex 4 with tricyclohexylphos-
phine at rt in dichloromethane leads to the formation of the
phosphine adduct 5a. However, under these conditions, the
reaction does not go to completion, but rather gives a
mixture of 4, 5a and PCy3.12b Pure complex 5a can be
synthesized by the reaction of 4 with PCy3CS2, however, we
wished to design a synthesis that exploits the free
phosphine. This proves to be straightforward; the use of
acetonitrile as solvent gives clean 5a from 4 and PCy3,
presumably via the intermediate formation of a mono-
nuclear acetonitrile complex 6 (Scheme 3).
While such reactions are useful, the low commercial
availability of alkyl- and aryl-(9-BBN) reagents and their
air-sensitivity limits their appeal. In contrast aryl boronic
acids reagents are widely available and easily handled.
Therefore, Fu and co-workers investigated the possibility of
using them as coupling partners with alkyl halides.9 They
found that the catalyst formed in situ from Pd(OAc)2/
PMe(tBu)2 couples primary alkyl bromides with aryl- and
vinyl-boronic acids at rt when KOtBu is used as the base in
tert-amyl alcohol. Capretta and co-workers recently
demonstrated that palladium catalysts containing the
phosphaadamantyl ligand 2 can be used to good effect in
the rt coupling of primary alkyl bromides and chlorides with
aryl boronic acids, using potassium tert-butoxide in
dioxane.10 Interestingly, they even found that a moderate
yield of coupled product results when the secondary alkyl
bromide bromocyclohexane is used as a substrate. Zhou and
Fu have also investigated the coupling of secondary alkyl
halides with aryl- and vinyl-boronic acids and find that
optimum activity is obtained with a nickel-based catalyst
formed in situ from [Ni(COD)2] and bathophenanthroline,
3, in sec-butanol using potassium tert-butoxide as base.11
We have been interested in the use phosphite- and
phosphinite-based palladacyclic catalysts and their phos-
phine and carbene adducts in a range of Suzuki couplings of
Scheme 3. Synthesis of phosphine adducts of a phosphite palladacycle.
Conditions: (i) PRCy2, MeCN, rt, 18 h.

R. B. Bedford et al. / Tetrahedron 61 (2005) 9663–9669
9665
Figure 1. The molecular structure of 5a with an ethanol solvate and disorder in two tert-butyl groups removed for clarity.
The 31P spectrum of 5a shows doublets at d 136.0 and
26.2 ppm corresponding to the phosphite and phosphine
donors, respectively, with a mutual coupling of 40.7 Hz.
This relatively small coupling is indicative of a cis-
disposition of the two phosphorus donors. Both this 31P
doublets at d 131.4 (phosphite) and 4.4 (phosphine) ppm
with a mutual cis coupling of 46.2 Hz. These data are
consistent with complex 5b adopting a similar structure to
5a. The proton-coupled 31P spectrum shows a doublet of
doublets at 134.2 ppm corresponding to the phosphite donor
with a 47 Hz coupling to the phosphine phosphorus and a
3JPH of 14 Hz to the phosphine P–H and a doublet of
doublets at 4.5 ppm with a large 1JPH of 312 Hz and a 2JPP of
41 Hz. The resonance for the P–H hydrogen is seen as a
1
and the H NMR spectral data are consistent with those
obtained previously.12b The structure of complex 5a was
confirmed by single crystal X-ray analysis and the molecule
is shown in Figure 1, whilst selected data are presented in
Table 1. The structural analysis confirms the cis-disposition
of the two P-donor groups. This is in marked contrast to the
related carbene adducts 7, which show the carbene ligand
trans to the phosphite donor.13
1
doublet of doublets of triplets in the H NMR spectrum at
1
3
3.57 ppm with a large JPH of 310.5 Hz, a small JPP
coupling of 15 Hz to the phosphite and a small 3JHH of 7 Hz
to the two equivalent cyclohexyl PCHs. The JPH coupling
1
is considerably larger than that of the free phosphine
(170 Hz).
Attempts to produce phosphine adducts of 4 with the larger
t
phosphines PtBu3, PR2(o-biphenyl) (RZCy, Bu), PPhtBu2
using this method either failed or gave mixtures. The
reaction of the two orthometallated phosphinite complexes
8a and 8b with PCy3 again gave a mixture of products.
The synthetic methodology outlined above can also be
applied to the synthesis of the novel secondary alkylphos-
phine adduct 5b. The 31P{1H} NMR spectrum of 5b shows
Table 1. Selected bond lengths and angles for complex 5a
˚
Bond lengths (A)
Pd1–P1
Pd1–C42
2.1770(5)
2.0842(18)
Pd1–P2
Pd1–Cl1
2.4052(5)
2.3488(5)
Bond angles (8)
P1–Pd1–C42
P2–Pd1–Cl1
P1–Pd1–Cl1
2.2. Catalysis
77.83(5)
84.946(17)
168.029(18)
P1–Pd1–P2
C42–Pd1–Cl1
P2–Pd1–C42
106.044(17)
91.37(5)
175.64(5)
In the first instance we performed an optimisation study
using the complex 5a as catalyst in the coupling of

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R. B. Bedford et al. / Tetrahedron 61 (2005) 9663–9669
Table 2. Optimisation of solvents and basesa
Entry
Solvent
Base
Conversion to 1,2-diphenyl ethane (%)b
Conversion to styrene (%)b
1
2
3
4
5
6
7
8
NMP
NMP
NMP
Toluene
Toluene
Toluene
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
DME
DME
DME
DME
sec-Butanol
sec-Butanol
sec-Butanol
sec-Butanol
tert-Amyl alcohol
tert-Amyl alcohol
tert-Amyl alcohol
tert-Amyl alcohol
Cs2CO3
K3PO4
K2CO3
Cs2CO3
K3PO4
K2CO3
Cs2CO3
K3PO4
K2CO3
KOtBu
KF
KF/K3PO4 1:1
K3PO4
K2CO3
Cs2CO3
KF
K3PO4
K2CO3
Cs2CO3
KOtBu
K3PO4
K2CO3
Cs2CO3
KOtBu
0
1
0
2
30
18
29
6
5
4
13
4
1
64
7
6
12
2
26
10
10
8
31
49
8
15
41
77
30
5
6
31
36
0
24
11
20
4
13
8
47
23
11
0
30
48
22
0
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
a Conditions: BrCH2CH2Ph (5.0 mmol), PhB(OH)2 (7.5 mmol), base (15.0 mmol), solvent (10 ml), 110 8C (external temperature).
b Conversion determined by GC (hexadecane internal standard).
(2-bromoethyl)benzene with phenylboronic acid with a
range of solvents and bases; the results from this are
summarized in Table 2. As can be seen, with respect to
conversion to the desired 1,2-diphenylethane, the use of
potassium phosphate in sec-butanol or potassium carbonate
on tert-amyl alcohol gives the best activities (entries 17 and
22, respectively). However, in both cases substantial
amounts of styrene are formed. While the use of potassium
carbonate in 1,4-dioxane gives lower conversion to the
desired product, the selectivity is much higher with very
little styrene observed (entry 9). In stark contrast with the
findings outlined in the introduction, potassium tert-
butoxide proves to be a very poor choice of base with this
catalyst (entries 10, 20, 24) giving little or no conversion to
the desired product and substantial amounts of styrene via
b-elimination, particularly when tert-amyl alcohol is used as
the solvent.8–11
that the rate-determining step is reductive elimination, in
which case b-elimination may also occur from the
intermediate B. If this is true then an intermediate of the
form C would be produced (Scheme 4), which would
undergo reductive elimination to reform the active catalysts
and an arene, in this case benzene. This certainly appears to
be occurring; GC analysis of the product mixture formed in
the reaction with cesium carbonate as base in tert-amyl
alcohol (Table 2, entry 23) shows the presence of a
substantial quantity of benzene, although at this stage we
have not been able to determine the precise amount.
Scheme 4.
It is apparent from the relative conversions to the desired
coupled product 1,2-diphenylethane and styrene that when
the former is relatively low then the latter is relatively high.
This is consistent with a manifold in which the rate
determining step is not the oxidative addition of the alkyl
bromide, but occurs after the formation of a palladium alkyl
intermediate (Scheme 2, A). It is to be expected that the base
plays an intimate role in the formation of the Pd-aryl
intermediate (B) and if the rate-determining step is
associated with this process a slow rate of formation of B
from A would lead to greater amounts of b-eliminated
product, in line with observation. Alternatively it is possible
We next examined the effect of varying catalyst loading in
the reaction in dioxane with K2CO3 acting as base and the
results of this are shown in Figure 2. As can be seen the
optimum conversion is achieved at 1.5 mol% catalyst
loading but lowering the loading to 0.1 mol% leads to a
maximum TON (turn-over number, mol product/mol
catalyst) of 70. This is as expected since lowering the
catalyst concentration would lead to a lower rate of catalyst
decomposition by aggregation.
Then we examined the use of a range of catalysts, both

R. B. Bedford et al. / Tetrahedron 61 (2005) 9663–9669
9667
Table 3 (continued)
Entry
Catalyst
Conversion to 1,2-
Conversion to
diphenylethane (%)b styrene (%)b
10
11
25
4
4
9
11
12
13
14
15
C2 PPhtBu2
Figure 2. Variation in catalyst loading.
pre-formed or formed in situ, in the standard reaction.
Dioxane was chosen as solvent and potassium carbonate as
base for this study despite the fact that these conditions do
not give the highest conversion, but rather because they
26
11
C2 PCy2(o-biphenyl)
C2 PtBu2(o-biphenyl)
C2 PtBu3
Table 3. Variation in catalysta
Entry
Catalyst
Conversion to 1,2-
Conversion to
diphenylethane (%)b styrene (%)b
3
6
1
2
8
0
18
4
2
3
4
0
6
16
7
8a
8b
C2 PMetBu2
Pd(OAc)2C2 PMetBu2
Pd(OAc)2C2 PCy3
Pd2(dba)3C4 PCy3
16
17
18
1
32
15
39
10
7
0
10
a Conditions: BrCH2CH2Ph (5.0 mmol), PhB(OH)2 (7.5 mmol), K2CO3
(15.0 mmol), 1,4-dioxane (10 ml), 110 8C (external temperature).
b Conversion determined by GC (hexadecane internal standard).
17
6
show good selectivity for the desired product. The results
from this study are presented in Table 3.
C2 PCy3
8aC2 PCy3
8bC2 PCy3
5
6
0
6
7
7
The dimeric phosphite- and phosphinite-based pallada-
cycles 4, 8a and 8b all show little or no activity (entries
1–3). Comparing the activity of the catalysts formed in situ
from dimer 4 and tricyclohexylphosphine (entry 4) with the
preformed catalyst 5a (Table 2, entry 9) indicates that it is
important to pre-synthesise the catalysts, if possible. It is,
therefore, perhaps not surprising that the catalysts formed
in situ from the dimers 8 and PCy3 show very poor activity
(Table 3, entries 5 and 6). Indolese, Studer and co-workers
have shown that palladacyclic catalysts with secondary
alkylphosphine co-ligands are effective in the Suzuki biaryl
coupling reaction of aryl chlorides.15 Therefore, we were
interested to see how the preformed catalyst 5b would fare,
unfortunately it proved to be disappointing (entry 7). It is
perhaps not surprising that the carbene-containing
complexes 7 did not prove to be any use (entries 8 and 9)
since we have found them to be unimpressive in the Suzuki
coupling of aryl chlorides.13 In contrast, we have shown that
7
6
4
5b
8
6
8
7a: ArZmesityl
9
8
7
7b: ZC6H3-2,6-iPr2

9668
R. B. Bedford et al. / Tetrahedron 61 (2005) 9663–9669
the preformed N-palladacyclic catalyst 9 shows good
activity in the Suzuki biaryl coupling of aryl chlorides and
were interested to see if it would work well in this instance.16
Unfortunately it too proved essentially ineffective (entry 10).
were performed under nitrogen, either in a glove-box or
using standard Schlenk techniques. Solvents were distilled
from appropriate drying reagents prior to use. Complexes
4, 7–9 were prepared according to literature pro-
cedures.12b,13,16b,17 All other material were obtained
commercially and used as received. GC analysis was
performed on a Varian 3800 GC fitted with a 25 m CP Sil
5CB column and data were recorded on a Star workstation.
All catalytic reactions were performed on a Radleys
Carousel Reactore. This consists of 12 ca. 45 ml tubes,
which are fitted with screw-on Teflon caps that are equipped
with valves for the introduction of inert gas and septa for the
introduction of reagents. The 12 reaction tubes sit in two
stacked aluminium blocks, the lower one fits on a hotplate-
stirrer and can be maintained at a constant temperature with
a thermostat, while the upper block has water circulating,
which cools the top of the tubes, allowing reactions to be
performed at reflux temperature.
Since we were unable to pre-form phosphine adducts of
5a with bulkier phosphines, we tested the performance of
catalysts produced in situ (entries 11–15). Both PPhtBu2 and
PCy2(o-biphenyl) (entries 11 and 12) show better con-
versions to product than the catalyst formed in situ with
PCy3 (entry 4), the latter at the expense of selectivity with
respect to competitive styrene formation. Neither P(o-bi-
phenyl)tBu2 or PtBu3 (entries 13 and 14) are promising.
The phosphine ligand PMetBu2 has been shown by Fu and
co-workers to give optimum activity under their conditions
in the Suzuki coupling of alkyl halides.9 When it is used in
conjunction with the palladacyclic complex 4 it shows poor
activity (entry 15). However, the catalysts formed in situ
from the phosphine and palladium acetate performed even
worse with no conversion to coupled product and substantial
styrene formation observed (entry 16). By contrast the catalyst
formed in situ from tricyclohexylphosphine and palladium
acetate shows similar activity (entry 17) to catalyst 5a
(Table 2, entry 9). Lower activity is seen when [Pd(dba)2] is
used as the palladium source (Table 3, entry 18).
4.1.1. Synthesis of [PdCl{k2-P,C-(OC6H2–2,4-tBu2)
(OC6H3–2,4-tBu2)2}PCy3], 5a. A mixture of complex 4
(0.79 g, 0.50 mmol) and tricyclohexylphosphine (0.31 g,
1.10 mmol) in acetonitrile was stirred at rt overnight. The
solvent was then removed in vacuo, the resulting solid was
dissolved in dichloromethane (10 ml), ethanol (10 ml) was
added and the solution was concentrated in vacuo to induce
precipitation. The resultant precipitate was recrystallised
(dichloromethane/ethanol) to give complex 5a as a colour-
less solid (0.65 g, 61%). Anal. Calcd for C60H95O3P2PdCl:
C, 67.5; H, 9.0. Found: C, 66.9; H, 8.7. 1H NMR (300 MHz,
CDCl3): d 1.15 (br s, 30H, CH2 of Cy); 1.30 (br s, 18H, tBu
We were surprised that PMetBu2 performed so badly, given its
goodactivityinthecouplingofalkylhalidesandtosylateswith
alkyl- and aryl-(9-BBN) or boronic acid reagents.7,9 It is
possible that the temperature of the reaction is too high and
consequently the high relative rate of b-elimination precludes
substantial coupling. In order to test this we performed the
reaction again at 80 8C, at which temperature no product was
observeddespitethefactthattheformationofstyrenehadbeen
dramatically curtailed (4%). Similarly, when the reaction
catalysed by 5a was repeated at this temperature, very low
(3%) conversion to product was observed. No conversion to
product with either catalyst system is observed at rt or 50 8C.
t
of orthometallated ring); 1.48 (br s, 36H, Bu of non-
orthometallated rings); 2.32 (m, 3H, CH of Cy); 6.92 (d, 2H,
3JHHZ2.6 Hz, non-orthometallated ring H6); 6.94 (dd, 2H,
4
3JHHZ2.6 Hz, JHHZ2.45 Hz, non-orthometallated ring
H5); 7.27 (br m, 2H, non-orthometallated ring H3); 7.59
4
(d, 1H, JHHZ3.0 Hz, orthometallated ring), 7.62 (d, 1H,
4JHHZ3.0 Hz, orthometallated ring). 31P NMR
(121.5 MHz, CDCl3): d 27.0 (d, JPPZ41.6 Hz, PCy3);
136.6 (d, JPPZ41.6 Hz, P(OAr)3).
3. Conclusions
4.2. Crystal structure determination for complex 5a
In summary, unlike in the Suzuki biaryl coupling where the
use of palladacyclic pre-catalysts can have a substantial
benefit on activity compared with classical palladium
precursors, when alkyl halides are used as substrates there
is no discernible advantage in their use over palladium
acetate. Preliminary data indicate that the rate-determining
step in the coupling of alkyl bromides with aryl boronic
acids is not oxidative addition, but rather lies later in the
catalytic cycle. Mechanistic work is ongoing in our group to
try to help optimize future catalyst structures.
Data were collected at 120 K on an Nonius Kappa CCD area
detector diffractometer located at the window of a Nonius
FR591 rotating anode X-ray generator, equipped with a
˚
molybdenum target (l Mo kaZ0.71073 A). Structures were
solved and refined using the SHELX-97 suite of programs.18
Data were corrected for absorption effects by means of
comparison of equivalent reflections using the program
SORTAV19. Non-hydrogen atoms were refined aniso-
tropically, whilst hydrogen atoms were generally fixed in
idealised positions with their thermal parameters riding on
the values of their parent atoms. Positional disorder was
found to be present in two tertiary butyl groups and the
ethanol solvent molecule, which was modelled as 50%
partial occupancy for each orientation. C61H98ClO3.5P2Pd,
We thank the EPSRC (Advanced Research Fellowship for
RBB, DTA for RMF) and Kingston Chemicals for funding
and Johnson Matthey for the loan of palladium salts.
triclinic, P-1, aZ12.4913(1), bZ13.0629(1), cZ
˚
20.7063(3) A,
4. Experimental
4.1. General
aZ99.150(1),
bZ99.642(1)
gZ
3
˚
110.827(1)8, volumeZ3024.47(6) A , ZZ2, DcZ
1.198 Mg/m3, mZ0.445 mmK1, 57,222 measured, 13,800
unique (RintZ0.0476) and 12,220 (IO2s(I)) reflections,
R1 (obs)Z0.0345 and wR2 (all data)Z0.08795
All reactions and manipulations of air-sensitive materials

R. B. Bedford et al. / Tetrahedron 61 (2005) 9663–9669
9669
rmax/rminZ0.847/K0.613 eAK3. Supplementary data have
˚
G., Stone, F. G., Abel, E. W., Eds.; Comprehensive
Organometallic Chemistry; Pergamon: Oxford, 1982; Vol. 8,
pp 799–938.
been deposited with the Cambridge Crystallographic Data
Cente (Deposition numberZCCDC270788).
2. For recent reviews see: (a) Frisch, A. C.; Beller, M. Angew.
Chem., Int. Ed. 2005, 44, 674. (b) Netherton, M. R.; Fu, G. C.
Adv. Synth. Catal. 2004, 346, 1525.
4.2.1. Synthesis of [PdCl{k2-P,C-(OC6H2–2,4-tBu2)
(OC6H3–2,4-tBu2)2}PHCy2], 5b. This as prepared using
the same method for the synthesis of 5a, with PHCy2 in
place of PCy3. Complex 5b was obtained as a colourless
solid (0.304 g, 62%). Anal. Calcd for C54H85O3P2PdCl$(0.5
3. Hills, I. D.; Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed.
2003, 42, 5749.
4. Ishiyama, T.; Abe, S.; Miyaura, N.; Suzuki, A. Chem. Lett.
1992, 691.
1
CH2Cl2): C, 63.64; H, 8.43. Found: C, 63.61; H, 9.11. H
NMR (300 MHz, CDCl3): d 0.72 (br m, 2H Cy); 0.96 (br m,
5. Netherton, M. R.; Dai, C.; Neuschu¨tz, K.; Fu, G. C. J. Am.
Chem. Soc. 2001, 123, 10099.
t
4H, Cy); 1.07 (br s, 9H, Bu of orthometallated ring); 1.16
(br m, 4H, Cy); 1.24 (br s, 18H, tBu of non-orthometallated
rings); 1.32 (br m, 4H, Cy); 1.39 (br s, 9H, Bu of
6. Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem., Int. Ed.
2002, 41, 1945.
t
orthometallated ring); 1.46 (br m, 4H, Cy); 1.52 (br s, 18H,
tBu of non-orthometallated rings); 1.65 (br m, 2H, Cy); 1.80
7. Netherton, M. R.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41,
3910.
1
3
(br m, 2H, Cy); 3.57 (ddt, 1H, JPHZ310.5 Hz, JPH
Z
8. Arentsen, K.; Caddick, S.; Cloke, F. G. N.; Herring, A. P.;
Hitchcock, P. B. Tetrahedron Lett. 2004, 45, 3511.
9. Kirchhoff, J. H.; Netherton, M. R.; Hills, I. D.; Fu, G. C. J. Am.
Chem. Soc. 2002, 124, 13662.
15.0 Hz, 3JHHZ7 Hz PHCy2); 7.00 (dd, 2H, 3JHHZ8.5 Hz,
4JHHZ2.4 Hz, non-orthometallated ring H5); 7.12 (t, 2H,
3JHHZ2.4 Hz, non-orthometallated ring H6); 7.37 (br m,
4
2H, non-orthometallated ring H3); 7.39 (d, 1H, JHH
Z
10. Brenstrum, T.; Gerristma, D. A.; Adjabeng, G. M.; Frampton,
C. S.; Britten, J.; Robertson, A. J.; McNulty, J.; Capretta, A.
J. Org. Chem. 2004, 69, 7635.
4
2.2 Hz, orthometallated ring), 7.42 (d, 1H, JHHZ2.2 Hz,
orthometallated ring). 31P NMR (121.5 MHz, CDCl3): d
4.40 (d, JPPZ46.2 Hz, PCy3); 134.1 (d, JPPZ46.2 Hz,
P(OAr)3).
11. Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340.
12. Application of phosphine adducts of phosphite- and phosphi-
nite-based palladacycles in Suzuki catalysis: (a) Bedford,
R. B.; Coles, S. J.; Hursthouse, M. B.; Scordia, V. J. M. Dalton
Trans. 2005, 991. (b) Bedford, R. B.; Hazelwood, S. L.;
Limmert, M. E.; Albisson, D. A.; Draper, S. M.; Scully, P. N.;
Coles, S. J.; Hursthouse, M. B. Chem. Eur. J. 2003, 3126.
(c) Bedford, R. B.; Cazin, S. S. J.; Hazelwood, S. L. Angew.
Chem., Int. Ed. 2002, 41, 4120. (d) Bedford, R. B.; Hazelwood,
S. L.; Limmert, M. E. Chem. Commun. 2002, 2610.
13. Application of carbene adducts of phosphite-based pallada-
cycles in Suzuki catalysis: Bedford, R. B.; Betham, M; Blake,
4.3. Procedure for cross-coupling of (2-bromoethyl)
benzene with phenylboronic acid
A Radleys Carousel tube was loaded with the appropriate
amount of desired catalyst, then (2-bromoethyl)benzene
(0.68 ml, 5.0 mmol) was added followed by the solvent
(10 ml), base (15.0 mmol) and finally phenylboronic acid
(7.5 mmol). The mixture was then heated to 110 8C
(external temperature) for 18 h, allowed to cool to rt and
then aqueous HCl (2 M, 10 ml) was added. The mixture was
extracted with dichloromethane and the combined extracts
dried (MgSO4). Hexadecane (0.17 M in dichloromethane,
1.00 ml) was added and the product mixture analysed by
GC. GC, GC–MS and 1H spectroscopy of product mixtures
were consistent with data obtained using commercial
samples of styrene and 1,2-diphenylethane (Aldrich).
´
M. E.; Frost, R. F.; Horton, P. N.; Hursthouse, M. B.; Lopez-
´
Nicolas, R.-M. Dalton Trans. 2005, 2774.
14. For discussions see: (a) Bedford, R. B. Chem. Commun. 2003,
1787. (b) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord.
Chem. Rev. 2004, 248, 2283.
15. Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H.-U.
Angew. Chem., Int. Ed. 2002, 41, 3668.
16. (a) Bedford, R. B.; Cazin, C. S. J. Chem. Commun. 2001, 1540.
(b) Bedford, R. B.; Cazin, C. S. J.; Coles, S. J.; Gelbrich, T.;
Horton, P. N.; Hursthouse, M. B.; Light, M. E. Organo-
metallics 2003, 22, 987.
References and notes
17. Bedford, R. B.; Hazelwood, S. L.; Horton, P. N.; Hursthouse,
M. B. Dalton Trans. 2003, 4164.
1. For C–C coupling reactions see: (a) Heck, R. F. Palladium
Reagents in Organic Synthesis; Academic: New York, 1985.
(b) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G.
Principles and Applications of Organotransition Metal
Chemistry; University Science Books: Mill Valley, CA,
USA, 1987. (c) Trost, B. M.; Verhoven, T. R. In Wilkinson,
18. Sheldrick, G. M. SHELX-97: Programs for Structure Solu-
¨ ¨
tion and Refinement; University of Gottingen: Gottingen,
Germany, 1997.
19. Blessing, R. H. J. Appl. Crystallogr. 1997, 30, 421.