Hindered diarylether and diarylsulfone bisphosphine ligands: Atropisomerism and palladium complexes

Article abstract of DOI:10.1016/j.tetasy.2010.06.017

Phosphines and bisphosphines derived from hindered ortho-substituted diaryl ethers and diarylsulfones by lithiation are, with appropriate substitution patterns, resolvable atropisomeric ligands which form crystalline complexes with palladium dichloride.

Full text of DOI:10.1016/j.tetasy.2010.06.017

Tetrahedron: Asymmetry 21 (2010) 1355–1360
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Hindered diarylether and diarylsulfone bisphosphine ligands:
atropisomerism and palladium complexes
*
Jonathan Clayden , Stephen P. Fletcher, James Senior, Christopher P. Worrall
School of Chemistry, University of Manchester, Oxford Rd., Manchester M13 9PL, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Phosphines and bisphosphines derived from hindered ortho-substituted diaryl ethers and diarylsulfones
by lithiation are, with appropriate substitution patterns, resolvable atropisomeric ligands which form
crystalline complexes with palladium dichloride.
Received 24 February 2010
Accepted 3 June 2010
Available online 6 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Dedicated to Professor Henri Kagan on the
occasion of his 80th birthday
1. Introduction
phenyl or substituted isoquinolinyl or pyridinyl rings.1b,c Use of
non-biaryl atropisomers2 in catalytic applications has to date been
Atropisomeric phosphine ligands have a long and illustrious
history, which has encompassed a Nobel Prize (Noyori, 2001, for
applications involving BINAP) and many powerful catalytic syn-
thetic applications.1 The combination of gross chirality with the
potential for subtle modulation of bite angle means that atrop-
isomerism is ideally matched with the requirements of ligand de-
sign. Almost invariably, however, atropisomeric ligands have been
based on an Ar–Ar axis, usually between two naphthyl, substituted
limited.3
We have recently shown that diaryl ethers,4a,b sulfides4c and
sulfones4c 1 exhibit atropisomerism provided they fulfill certain
structural conditions: for example, compounds 2–4 are all chiral
and have half-lives to racemisation long enough to allow resolu-
tion by HPLC on a chiral stationary phase (Fig. 1).4 Diarylether
bisphosphines such as DPEPhos 5, Xantphos and their analogues5a
are wide bite angle ligands which have been used to promote
HO
R1
R3
R4
X
O
S
O2S
R2
HO
1
(X = O, S, SO2)
2
3
4
R1
R1
R2
PPh2
PPh2
PPh2
PPh2
PPh2
X
X
O
R2
6
7
5
(X = O, SO2)
(X = O, SO2)
(DPEPhos)
Figure 1. Atropisomeric diaryl ethers, sulfides and sulfones as potential ligand scaffolds.
* Corresponding author.
E-mail address: clayden@man.ac.uk (J. Clayden).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.06.017

1356
J. Clayden et al. / Tetrahedron: Asymmetry 21 (2010) 1355–1360
metal-catalysed hydroformylation,5a but recently also for conju-
gate additions,5a C–H insertions,5b carboetherifications,5c and
aminations.5e With few exceptions,6 chiral analogues of these li-
gands are unknown. Heavily encumbered diarylether bisphos-
phines and diarylsulfone bisphosphines have the potential to
exhibit atropisomerism, and hence when used as ligands may com-
bine the architecture and reactivity profile of DPEPhos with the
stereochemical opportunities offered by atropisomeric ligands. In
this paper we describe the synthesis, resolution and palladium
complexes of some phosphines 6 and bisphosphines 7 based on
hindered diarylether or diarylsulfone structures.
Reduction and methylation gave bromophenylethers 13–15 which
were converted to the phosphines by bromine–lithium exchange
to the unstable lithioethers and quenching with freshly distilled
chlorodiphenylphosphine.
A complementary route (Scheme 2) gave bisphosphines 7b and
7c. Bis(iodophenyl) ethers 20 and 21 were made by a previously
reported route from di-p-tolyl ether 16.7 Rapid iodine–lithium
exchange and trapping with freshly distilled chlorodiphenyl-
phosphine yielded 7b and 7c.
Multiple ortho-functionalisation of diarylsulfones is facilitated
by the lithiation-directing power of the sulfonyl group.8 2,20-Diiso-
propyl diphenylsulfone 228a and 2,20-di-tert-butyl diphenylsulfone
238a were thus lithiated with 3 equiv of s-BuLi and the resulting
organolithiums were trapped with chlorodiphenylphosphine
(Scheme 3). A bisphosphine 7d was formed cleanly from 22. How-
ever, even after repeated attempts under various conditions, we
were unable to trap a dilithio derivative of (or even sequentially
lithiate) the more hindered 23: the only phosphine isolated from
these reactions was the monophosphine 6c.
In general, diaryl ethers and diaryl sulfones are atropisomeric
provided (1) they carry at least three ortho substituents and (2)
at least two of those substituents are bulky.4 The diphenylphos-
phinyl group was not surveyed by either Sternhell9a or Lunazzi9b
in their studies of the effects of substituent size on atropisomerisa-
tion rates, although our own studies3a suggest that the relatively
long C–P bond limits its ability to block bond rotation. NMR and
chromatographic studies of 6 and 7 were therefore used to estab-
lish how much additional steric bulk was required for bond rota-
tion to be sufficiently hindered to allow the existence of
resolvable, stable atropisomers. Relevant data are presented in
Table 1.
2. Results and discussion
Hindered diaryl ethers may be conveniently synthesised either
by SNAr reactions of 2-chlorobenzonitriles with hindered phenox-
ides4a,b or via lithiation of the dibenzosiloxane 17.7 Mono- and
bisphosphines 6a, 6b and 7a (Scheme 1) were made from 3-bro-
mobenzonitrile by lithiation, chlorination and substitution with
2-substituted phenoxides, yielding cyanophenylethers 10–12.
R
1. LDA, THF,
–78 °C, 1 h
2. C2Cl6, 20 °C,
16 h
1. ArOH,
Cl
O
KOH, tol, Δ,
NC
Br
NC
Br
NC
Br
2 h
2. DMF, Δ,
86%
16 h
10 (R = i-Pr) 74%
11 (R = t-Bu) 66%
12 (R = Br) 32%
8
9
1. DIBAL.
–78-20 °C, 16 h
2. HCl, H2O
1. n-BuLi ,
THF,
–78 °C, 60 s
R
The trisubstituted bisphosphinoether 7a showed no evidence of
diastereotopicity on the NMR timescale in its room temperature
NMR spectrum (the CH2O group appeared as a 2H singlet) and
therefore presumably racemises rapidly. Trisubstituted monophos-
O
Br
3. NaBH4, THF,
20 °C, 16 h
2. ClPPh2
MeO
4. NaH, THF
then MeI, 16 h
13 (R = i-Pr) 91%
14 (R = t-Bu) 80%
15 (R = Br) 97%
1. s-BuLi (3 equiv.),
THF, 30 min, –78 °C
2. ClPPh2 (excess)
R
PPh2
PPh2
O2S
O2S
O2S
PPh2
PPh2
PPh2
O
O
O
R
PPh2
PPh2
22 (R = H)
MeO
MeO
MeO
7a 3%
23 (R = Me)
7d 92%
6c 84%
6a 31%
6b 34%
Scheme 3. Synthesis of diaryl sulfone phosphines.
Scheme 1. Synthesis of phosphinophenyl ethers by SNAr reactions.
1. s-BuLi,
TMEDA, Et2O,
0-20 °C, 16 h
2. Cl2SiMe2, 2 h
1. s-BuLi (1.3
or 3.5 equiv.)
TMEDA,
R
O
O
SiMe2
O
SiMe2
66%
Et2O, 0-20 °C,
2 or 16 h
2. MeI
18 (R = H) 51%
19 (R = Me) 47%
16
17
1. n-BuLi , THF,
–78 °C, 90 s
2. ClPPh2
R
ICl, CH2Cl2,
0-20 °C, 16 h
PPh2
PPh2
PPh2
PPh2
I
I
O
O
O
20 (R = H) 55%
21 (R = Me) 64%
7b 68%
7c 74%
Scheme 2. Synthesis of phosphinophenyl ethers by multiple lithiation of di-p-tolyl ether.

J. Clayden et al. / Tetrahedron: Asymmetry 21 (2010) 1355–1360
1357
Table 1
Racemisation of the phosphines
Compound
R1
R2
Barrier to
Half-life for
racemisation
racemisation
at 25 °C
(298 K)/kJ molꢀ1
6a (X = O)
6b (X = O)
6c (X = SO2)
7a (X = O)
7b (X = O)
7c (X = O)
7d (X = SO2)
MeOCH2
MeOCH2
t-Bu
MeOCH2
Me
i-Pr
t-Bu
t-Bu
H
H
Me
i-Pr
73a
<1 s
102 2b
<90c
<60d
<90c
113e
<90c
Hours to days
<10 min
<0.01 s
<10 min
12 weeks
<10 min
Me
i-Pr
Hzrac ¼ þ66:4 kJ molꢀ1
;
D
Szrac
¼
a
By lineshape analysis from NMR studies:
D
ꢀ22 J molꢀ1 Kꢀ1
.
b
Separable by HPLC but complete racemisation within 9 days.
Separation impossible by HPLC.
No diastereotopicity observed by NMR at 23 °C.
By equilibration at 63 °C after HPLC resolution.
c
d
e
phinoethers 6a and 6b by contrast displayed anisochronous signals
arising from diastereotopic CHAHBO protons. In the case of 6a coa-
lescence between 90 and 100 °C allowed an estimate of 73 kJ molꢀ1
to be made for its barrier to racemisation at room temperature.9
This figure, which corresponds to a half-life for racemisation of
<1 s, is far too low to allow resolution at ambient temperature.
Comparison with related compounds4a suggests that the –PPh2
group blocks rotation only as effectively as a –CH(R)OH group.
No comparable coalescence was observed for 6b, which was fur-
thermore resolvable by HPLC on a chiral stationary phase, but
which subsequently racemised in solution over a period of hours
at ambient temperature. Neither sulfones 6c and 7d nor ether 7b
could be resolved by HPLC on related chiral stationary phases.
Bisphosphine 7c was resolvable on the Chiralcel OT+ stationary
phase (Fig. 2, 250 ꢁ 4.6 mm; eluent 85:15 hexane/i-PrOH; flow
rate 1.0 ml minꢀ1; retention times 8.8 and 15.6 min)—loading
heavily the analytic column and collection of the fraction eluting
between 8 and 10 min returned a sample with 97% ee; collection
of the fractions eluting between 11 and 15 min returned a sample
of the other enantiomer with 85% ee. No loss of ee was evident in
either sample over a period of 21 days in the solid state; heating
the latter sample for 21 h at 63 °C in 1:1 hexane/i-PrOH returned
Figure 3. X-ray crystal structure of 7cꢂPdCl2. Bite angle P–Pd–P = 99.8°.
Figure 4. X-ray crystal structure of 7dꢂPdCl2. Bite angle P–Pd–P = 98.1°.
material with 40% ee, suggesting a half-life for racemisation in this
case of the order of 20 h at this temperature, which approximates
to a barrier to rotation about the C–S axis of about 113 kJ molꢀ1
(and hence a room temperature half-life for racemisation of about
6 months).9
Palladium complexes of the bisphosphines 7b, 7c and 7d were
formed by stirring with (MeCN)2PdCl2. Coloured complexes
7bꢂPdCl2 (56%), 7cꢂPdCl2 (60%) and 7dꢂPdCl2 (60%) were formed,
which were characterised by NMR, MALDI MS and IR. In the case
of the Pd complexes of 7c and 7d, crystals of 7cꢂPdCl2ꢂCH2Cl2 and
7dꢂPdCl2ꢂCH2Cl2 suitable for X-ray crystallography were obtained
and Figures 3 and 4 show these structures.10 P–Pd–P bite angles
were determined as 99.8° for 7cꢂPdCl2 and as 98.1° for 7dꢂPdCl2.
Both of these are close to, but marginally smaller than, crystallo-
graphic bite angles in the PdCl2 complexes of DPEPhos 5 (100.8°)
and sixantphos (104.3°) and are considerably greater than the cor-
responding bite angle for BINAP (92.7°).11
3. Conclusion
In conclusion, we show that wide bite angle chiral bisphos-
phines based on atropisomeric diaryl ether and sulfone scaffolds
may be made, although barriers to racemisation in even the most
hindered of the phosphines we report here are clearly too low
Figure 2. HPLC resolution of 7c (Chiralcel OT+).

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J. Clayden et al. / Tetrahedron: Asymmetry 21 (2010) 1355–1360
for the reliable use of the ligands in asymmetric transformations.
We are currently developing analogues with greater stability to
racemisation obtainable by replacement of the methyl groups with
substituents of greater steric bulk and seeking to apply these li-
gands as chiral analogues of DPEPhos or xantphos in new asym-
metric reactions.
using OT+ column running 98:2 hexane/IPA at 0.6 ml/min, retention
times 9.9 and 11.2 min.
4.2.3. (2-(2-tert-Butylphenylsulfonyl)-3-tert-butylphenyl)
diphenylphosphane 6c
A solution of sec-BuLi (1.3 M in hexanes, 1.05 mL) was added
dropwise to a solution of sulfone 23 (150 mg) in anhydrous THF
(10 mL) in a flame-dried flask under an atmosphere of nitrogen
at ꢀ78 °C and stirred for 30 min. Chlorodiphenyl phosphine
(0.29 mL) was added dropwise and the reaction was stirred and al-
lowed to warm to rt over 16 h. The reaction was quenched by addi-
tion of solid silica gel (ꢃ300 mg) and the solvents were removed
under reduced pressure. Dry silica was loaded onto a pre packed
flash chromatography column and the crude product was purified
eluting with petrol increasing to 6:1 petrol/ethyl acetate to yield
the title compound as a white solid (196 mg, 84%); Rf = 0.65 (4:1
petrol/ethyl acetate); dC (75 MHz, CDCl3) 152.7, 152.7, 149.1,
148.8, 145.3, 143.5, 137.4, 133.4, 133.1, 133.0, 131.6, 131.4,
130.1, 129.7, 129.1, 129.1, 128.2, 128.1, 124.8, 38.7, 37.6, 33.1,
32.1; ES m/z 515 (100%, [M+H]+), 537 (50% [M+Na]+).
4. Experimental
4.1. General procedure for halogen?Li?PPh2 exchange
nBuLi (1 equiv) was added dropwise to a stirring solution of
halo arene (1 equiv) in anhydrous THF at ꢀ78 °C under N2 and stir-
red for 1 min, unless otherwise stated. The electrophile was added
and the mixture was stirred for 16 h with warming to rt. The reac-
tion was quenched by addition of saturated ammonium chloride
solution and the mixture was diluted using EtOAc. The layers were
separated and the organic fraction was washed with water, brine,
dried (Na2SO4), and the solvent was removed under reduced
pressure.
4.2.4. 1-Diphenylphosphanyl-2-(20-diphenylphospha-
4.2. Starting materials
nylphenoxy)-3-(methoxymethyl)benzene 7a
Dibromide 15 (250 mg, 0.67 mmol, 1 equiv), nBuLi (1.4 M solu-
tion in hexanes) (0.96 cm3, 1.34 mmol, 2 equiv), chlorodiphenyl-
phosphine (0.36 cm3, 2.02 mmol, 3 equiv) and THF (12 cm3) were
treated as described in Section 4.1 and stirred for 90 s before
quench. The crude product was purified several times by flash col-
umn chromatography (40:1 petrol/EtOAc), finally yielding the
product as a white solid (11 mg, 3%), mp 162–166 °C. Rf = 0.61
Aryl bromides 13–15 were made by the method of Clayden
et al.4a,b Aryl iodides 20 and 21 were made by the method of Betson
et al.7 Sulfones 22 and 23 were made by the method of Clayden
et al.4c,8a
4.2.1. [2-(20-Isopropylphenoxy)-3-(methoxymethyl)
phenyl]diphenylphosphane 6a
(19:1 petrol/EtOAc); mmax (film/cmꢀ1
) 1433, 1422 (PPh2); dH
Bromide 13 (44 mg, 0.13 mmol, 1 equiv), nBuLi (1.7 M solution
in hexanes) (0.08 cm3, 0.13 mmol, 1 equiv), chlorodiphenylphos-
phine (0.03 cm3, 0.14 mmol, 1.1 equiv) and THF (4 cm3) were trea-
ted as described in Section 4.1. The crude product was purified by
flash column chromatography (35:1 petrol/EtOAc) to yield the
product as a colourless oil (18 mg, 31%). Rf = 0.58 (19:1 petrol/
EtOAc); mmax (film/cmꢀ1) 1449, 1434, 1424 (PPh); dH (300 MHz;
CDCl3) 7.59 (1H, d, J 7.5, H-3), 7.41–7.20 (13H, m, ArH, H-1, H-2
and H-4), 6.94 (1H, m, H-5), 6.87 (1H, m, H-6), 6.32 (1H, m, H-7),
4.43–4.18 (2H, CH AB m, J 13, H-8), 3.32 (3H, s, H-9), 3.16 (1H, sept,
J 7, H-10) and 0.90 (6H, d, J 7, H-11).; dC (75 MHz; CDCl3) 155.2,
154.3, 154.1, 136.3, 135.0, 134.7, 134.4, 133.8, 133.4, 132.2,
130.1, 129.1, 128.7, 128.6, 128.5, 126.6, 126.5, 125.8, 121.9,
112.9, 110.0, 69.2, 58.7, 26.8 and 22.9.; CI m/z 441 (M+H); (found:
M+H, 441.1957. C29H30O2P requires M, 441.1978). VT NMR; In
DMSO-d6 run from rt to 150 °C, modelling H-8 coalescence ob-
served between 90 and 100 °C.
(300 MHz; CDCl3) 7.50 (1H, ddd, J 7.5, 1 and 0.5, ArH), 7.34–7.21
(H, m, ArH), 7.17 (1H, t, J 8, ArH), 7.13 (1H, td, J 8 and 2, ArH),
7.03 (1H, ddd, J 8, 1 and 0.5, ArH), 6.86 (2H, m, ArH), 6.77 (1H,
dd, J 7.5 and 2, ArH), 6.75 (1H, dd, J 7.5 and 2, ArH), 6.30 (1H, dd,
8 and 4.5, ArH), 4.05 (2H, s, CH2OCH3) and 3.16 (3H, s, OCH3).; dC
(75 MHz; CDCl3) 159.9, 159.7, 137.3, 136.7, 136.6, 134.8, 134.6,
134.5, 134.4, 134.3, 134.0, 133.7, 133.4, 132.6, 132.4, 130.0,
129.6, 129.0, 128.9, 128.6, 128.5, 128.5, 128.4, 128.4, 128.4,
128.3, 126.0, 125.5, 122.1, 113.1, 68.8 and 58.6.; CI m/z 583
(M+H); (found: M+H, 583.1951. C38H33O2P2 requires M, 583.1950).
4.2.5. (2-(4-Methyl-2-(diphenylphosphino)phenoxy)-3,5-dimeth
ylphenyl)diphenylphosphane 7b
Diiodide 20 (679 mg, 1.62 mmol, 1 equiv), nBuLi (2.3 M solution
in hexanes) (1.4 cm3, 3.23 mmol, 2 equiv), chlorodiphenylphos-
phine (0.7 cm3, 3.88 mmol, 2.4 equiv) and THF (30 cm3) were trea-
ted as described in Section 4.1 H and stirred for 90 s before
quench. The crude product was purified by flash column chromatog-
raphy (150:1 petrol/EtOAc) to yield the product as a white foam
(342 mg, 68%), mp 74–78 °C. Rf = 0.79 (50:1 petrol/EtOAc); mmax
(film/cmꢀ1) 1434 (PPh).; dH (500 MHz; CDCl3) 7.22–7.09 (18H, m,
ArH), 6.99 (2H, td, J 7.5 and 1.5, ArH), 6.89 (1H, br s, ArH), 6.77 (1H,
dd, J 8 and 2, ArH), 6.45 (1H, dd, J 4.5 and 2, ArH), 6.41 (1H, br t, J 3,
ArH), 6.17 (1H, dd, J 8 and 4.5, ArH), 2.08 (3H, s, ArCH3), 2.03 (3H, s,
ArCH3) and 1.77 (3H, s, ArCH3).; dC (75 MHz; CDCl3) 157.9, 157.7,
153.7, 153.4, 137.8, 137.4, 137.1, 136.9, 136.9, 136.8, 134.9, 134.8,
134.6, 134.6, 134.5, 134.4, 134.2, 134.0, 133.6, 133.5, 133.4, 132.3,
132.0, 131.8, 131.4, 131.3, 130.8, 130.7, 128.7, 128.6, 128.5, 128.5,
128.4, 128.4, 126.3, 128.2, 128.2, 124.9, 124.7, 112.8, 21.2, 20.9
and 16.7.; APCI– m/z 580 (M); APCI+ m/z 581 (M+H).
4.2.2. [2-(20-tert-Butylphenoxy)-3-(methoxymethyl)
phenyl]diphenylphosphane 6b
Bromide 14 (103 mg, 0.31 mmol, 1 equiv), nBuLi (1.7 M solution
in hexanes) (0.18 cm3, 0.31 mmol, 1 equiv), chlorodiphenylphos-
phine(0.06 cm3, 0.34 mmol, 1.1 equiv)andTHF(8 cm3)weretreated
as described in Section 4.1. The crude product was purified by flash
column chromatography (50:1 petrol/EtOAc) to yield the product
as a white solid (48 mg, 34%), mp 100–103 °C. Rf = 0.55 (19:1 pet-
rol/EtOAc); m
max (film/cmꢀ1) 1422 (PPh); dH (300 MHz; CDCl3) 7.63
(1H, ddd, J 7.5, 1.5 and 0.5, H-3), 7.39–7.22 (12H, m, ArH, H-2 and
H-4), 6.97–6.89 (3H, m, H-1, H-5 and H-6), 6.32 (1H, m, H-7), 4.46–
4.13 (2H, CH AB m, J 12.5, H-8), 3.30 (3H, s, H-9) and 1.37 (9H, s, H-
10).; dC (75 MHz; CDCl3) 157.2, 154.4, 154.2, 136.9, 136.9, 136.7,
134.8, 134.6, 134.2, 133.7, 133.5, 132.5, 132.3, 132.0, 132.0, 130.4,
129.0, 128.6, 128.6, 128.5, 128.5, 127.3, 127.0, 125.9, 121.6, 113.9,
69.4, 58.7, 35.0 and 30.0.; EI m/z 455 (M); CI m/z 455 (M); (found:
M, 455.2143. C30H32O2P requires M, 455.2134). HPLC; separation
4.2.6. Bis(2,4-dimethyl-6-(diphenylphosphanyl)phenyl ether 7c
Diiodide 21 (254 g, 0.53 mmol, 1 equiv), nBuLi (2.3 M solution in
hexanes) (0.46 cm3, 1.06 mmol, 2 equiv), chlorodiphenylphosphine
(0.21 cm3, 1.17 mmol, 2.2 equiv) and THF (15 cm3) were treated as

J. Clayden et al. / Tetrahedron: Asymmetry 21 (2010) 1355–1360
1359
described in Section 4.1 H and stirred for 90 s before quench. The
crude product was purified by flash column chromatography
(petrol?19:1 petrol/EtOAc) to yield the product as a colourless oil
that crystallised on standing to a white solid (233 mg, 74%), mp
107–110 °C. Rf = 0.68 (petrol); mmax (film/cmꢀ1) 1434 (PPh).; dH
(500 MHz; CDCl3) 7.14–6.93 (16H, m, ArH), 6.86 (4H, m, ArH), 6.57
(2H, s, H-1), 6.17 (2H, s, H-2), 1.89 (6H, s, H-3) and 1.66 (6H, s, H-
4).; dC (100 MHz; CDCl3) 156.0, 137.8, 137.0, 134.5, 134.4, 134.3,
134.1, 134.0, 133.6, 133.4, 133.3, 132.7, 132.6, 128.6, 128.4, 128.4,
128.3, 128.2, 128.2, 128.1, 127.8, 29.9 and 18.1.; CI m/z 595 (M+H);
(found: M+H, 595.2314. C40H37OP2 requires M, 595.2314). HPLC;
separation using OT+ column running 0.6 ml/min with 98:2 hex-
ane/IPA, retention times 16.2 and 24.9 min.
J 7.5, ArH), 7.50–7.27 (15H, m, ArH), 7.21 (1H, d, J 7.5, ArH), 6.79
(2H, s, ArH), 6.29 (1H, s, ArH), 6.26 (1H, d, J 1, ArH), 1.98 (6H, s, ArCH3)
and 1.65 (6H, s, ArCH3) ; dC (75 MHz; CDCl3) weak 136.6, 135.3,
135.1, 134.6, 134.5, 133.9, 130.8, 130.5, 130.0, 129.3, 128.4, 128.3,
127.6, 127.4, 20.7 and 16.4.; MALDI TOF LD+I m/z 741, 740, 739,
738, 737, 736, 735, 734, 733 (MꢀCl).
4.2.10. Complex 7dꢂPdCl2
In a similar manner, a solution of bisphosphine 7d (85 mg) in
anhydrous toluene (3 mL) was added to a stirred suspension of
bis(acetonitrile)dichloropalladium(II) (33 mg) in anhydrous tolu-
ene (2 mL) under N2 and stirred at room temperature for 16 h.
The precipitate was isolated by filtration under nitrogen and
washed with toluene and petrol. The crude product was dissolved
in a minimum amount of CH2Cl2 and precipitated by addition of
petrol. The product was isolated by filtration under nitrogen and
washed with petrol (2 ꢁ 5 mL) to yield an orange solid (64 mg,
60%). dH (400 MHz, CDCl3) 7.58–7.45 (12H, m, ArH), 7.40–7.29
(8H, m, ArH), 7.24 (2H, br s, ArH), 7.06 (2H, t, J 7, ArH), 6.63 (2H,
m, ArH), 4.00 (2H, sept, J 8, CHMe2), 1.17 (12H, d, J 8, CHMeAMeB),
0.95 (12H, d, J 8, CHMeAMeB); dC (75 MHz, CDCl3) 151.5, 135.8,
134.5, 133.7, 131.7, 131.4, 130.9, 128.3, 127.5, 29.2, 25.9, 22.3.
4.2.7. Bis(2-isopropyl-6-(diphenylphosphino)phenyl)sulfone 7d
A solution of sec-BuLi (1.3 M in hexanes, 2.29 mL) was added
dropwise to a solution of sulfone 22 (300 mg) in anhydrous THF
(10 mL) in a flame-dried flask under an atmosphere of nitrogen
at ꢀ78 °C and stirred for 30 min. Chlorodiphenylphosphine
(0.64 mL) was added dropwise and the reaction was stirred and al-
lowed to warm to rt over 16 h. The reaction was quenched by addi-
tion of solid silica gel (ꢃ1 g) and the solvents were removed under
reduced pressure. Dry silica was loaded onto a pre packed flash
chromatography column and the crude product was purified elut-
ing with petrol increasing to 6:1 petrol/ethyl acetate to yield the
title compound as a white solid (612 mg, 92%); mp 130–133 °C
(toluene/ether); Rf 0.38 (4:1 petrol/ethyl acetate); IR mmax (film)/
cmꢀ1 1158, 1325 (SO2), 2310 (P–C); dH (500 MHz, CDCl3) 7.33–
7.29 (10H, m, ArH), 7.27–7.20 (10H, m, ArH), 7.15 (4H, br s, ArH),
6.93–6.91 (2H, m, ArH), 3.72 (2H, sept, J 6, CHMe2), 0.94 (12H, d,
J 6, CHMeAMeB), 0.47 (12H, d, J 6, CHMeAMeB); dC (75 MHz, CDCl3)
150.2, 145.5, 145.7, 138.6, 137.9, 134.9, 134.7, 133.3, 133.2, 131.9,
128.7, 128.4, 127.9, 29.4, 24.7, 22.1; ES 671 (100%, [M+H]+), 693
(30%, [M+Na]+); HRMS found 693.2130, C42H40O2P2SNa requires
693.2122.
4.2.11. Determination of parameters for racemisation of 7a
NMR spectra were run at a series of seven temperatures and
gNMR was used to fit lineshapes to the resulting spectra (CH2OR
signal). An Eyring plot (below) of the resulting rate constants pro-
duced the following.2c
2
1.5
1
0.5
0
0
0.001
0.002
0.003
0.004
-0.5
-1
4.2.8. Complex 7bꢂPdCl2
By the method of Buchwald,12 a solution of 7b (60 mg, 0.1 mmol,
1 equiv)in anhydroustoluene(2 cm3)was added toa stirredsuspen-
sion of PdCl2(NCCH3)2 (27 mg, 0.1 mmol, 1 equiv) in anhydrous
toluene (1 cm3) at room temperature under N2 and stirred for 16 h.
The precipitate was isolated by vacuum filtration, under a nitrogen
blanket, and washed with toluene and ether. The crude product
was dissolved in DCM and precipitated by addition of ether. The
product was isolated by vacuum filtration, under a blanket of nitro-
gen, and washed with two portions of ether to yield a dark yellow so-
lid (42 mg, 56%). dH (500 MHz; CDCl3) 8.00 (1H, d, J 7, ArH), 7.98 (1H,
d, J 7, ArH), 7.85 (1H, d, J 7, ArH), 7.83 (1H, d, J 7, ArH), 7.46–7.40 (3H,
m, ArH), 7.35 (1H, m, ArH), 7.29–7.27 (3H, m, ArH), 7.21–7.15 (4H, m,
ArH), 7.11–7.07 (4H, m, ArH), 6.94 (2H, br m, ArH), 6.69 (1H, dd, J 10.5
and 1.5, ArH), 6.66 (1H, dd, J 8.5 and 1, ArH), 6.09 (1H, dd, J 8.5 and 5,
ArH), 5.92 (1H, dd, J 9.5 and 2, ArH), 2.13 (3H, s, ArCH3), 2.01 (3H, s,
ArCH3) and 1.75 (3H, s, ArCH3). MALDI TOF LD+I m/z 726, 725, 723,
721, 720 (MꢀCl), 691, 690, 687, 686, 685, 684 (MꢀCl2).
-1.5
-2
y = -7991.3x + 21.08
R2 = 0.9978
-2.5
-3
-3.5
1/T / K-1
H–/
D
S–/
t1/2 at 298 K
D
G–298
/
D
kJ molꢀ1
J molꢀ1 Kꢀ1
kJ molꢀ1
+66.4
ꢀ22.3
73.1
0.4 s
Acknowledgments
We are grateful for support from the EPSRC and from Glaxo-
SmithKline, we thank Dr. James Raftery for determining the crystal
structures of 7cꢂPdCl2 and 7dꢂPdCl2.
4.2.9. Complex 7cꢂPdCl2
In a similar manner, a solution of 7c (55 mg, 0.09 mmol, 1 equiv)
in anhydrous toluene (3 cm3) was added to a stirred suspension of
PdCl2(NCCH3)2 (24 mg, 0.09 mmol, 1 equiv) in anhydrous toluene
(2 cm3) at room temperature under N2 and stirred for 16 h. The pre-
cipitate was isolated by vacuum filtration, under a nitrogen blanket,
and washed with toluene and ether. The crude product was dis-
solved in DCM and precipitated by addition of ether. The product
was isolated by vacuum filtration, under a blanket of nitrogen, and
washed with two portions of ether to yield a light orange solid
(37 mg, %). dH (300 MHz; CDCl3) 7.88 (1H, d, J 7.5, ArH), 7.86 (1H, d,
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10. X-ray crystallographic data for 7cꢂPdCl2ꢂCH2Cl2: C41H38Cl4OP2Pd; Mr = 856.85;
crystal dimensions 0.40 ꢁ 0.30 ꢁ 0.25 mm; monoclinic, P2(1)/c; a = 15.9510
(10) Å, b = 11.8310(7) Å, c = 20.4950(12) Å; V = 3825.4(4) Å3; b = 98.4850(10)°;
Z = 4; rcalcd = 1488 kg mꢀ3; m = 0.880 mmꢀ1; wavelength 0.71073 Å; T = 100
(2) K; reflections collected/unique: 22956/8886 [R(int) = 0.0558]; R1 = 0.0598;
wR2 = 0.0936. Cambridge Crystallographic Database deposition number
756411. X-ray crystallographic data for 7dꢂPdCl2ꢂCH2Cl2: C43H42Cl4O2P2PdS;
Mr = 932.97; crystal dimensions 0.30 ꢁ 0.20 ꢁ 0.15 mm; monoclinic, P2(1)/n;
a = 11.4202(9) Å, b = 37.959(3) Å, c = 19.3170(16) Å; V = 8364.6.2(12) Å3; b =
92.696(2)°; Z = 8; rcalcd = 1482 kg mꢀ3
;
m = 0.862 mmꢀ1
;
wavelength
0.71073 Å; T = 100(2) K; reflections collected/unique: 68430/19766 [R(int) =
0.1377]; R1 = 0.1368; wR2 = 0.1659. Cambridge Crystallographic Data Centre
deposition number 756410.
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2006, 25, 82.