Novel planar chiral diphosphines and their application in asymmetric hydrogenations and asymmetric Heck reactions

Article abstract of DOI:10.1016/j.tetasy.2003.11.014

Nine planar chiral diphosphines 8a-i have been synthesised by a versatile approach: The diphosphines have been assayed in an asymmetric hydrogenation reaction and an asymmetric Heck reaction and were found to give active catalysts that generated products

Full text of DOI:10.1016/j.tetasy.2003.11.014

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 465–473
Novel planar chiral diphosphines and their application in
asymmetric hydrogenations and asymmetric Heck reactions
Susan E. Gibson,* Hasim Ibrahim, Corinne Pasquier and Vishwanath M. Swamy
Department of Chemistry, Imperial College, South Kensington Campus, London SW7 2AY, UK
Received 20 October 2003; accepted 14 November 2003
Abstract—Nine planar chiral diphosphines 8a–i have been synthesised by a versatile approach: The diphosphines have been assayed
in an asymmetric hydrogenation reaction and an asymmetric Heck reaction and were found to give active catalysts that generated
products of moderate to good enantiopurity.
ꢀ 2003 Elsevier Ltd. All rights reserved.
[RhCODCl]2 (0.1 mol%)
1. Introduction
COOR'
COOR'
S
4 a-c (0.2 mol%)
100 bar H2, MeOH, 40 oC, 24 h
As a result of the success of planar chiral ligands such as
the ferrocene ÔJosiphosÕ, 1,1 and the [2,2]paracyclophane
ÔPhanephosÕ, 22 (Fig. 1), in the arena of asymmetric
catalysis, interest in other types of ligands possessing
planar chirality has increased rapidly in recent years.
Planar chiral ligands based on (arene)tricarbonylchro-
mium(0) complexes are no exception,3 and the increased
activity in this area in the last few years4 has led to the
successful application of planar chiral (arene)tricar-
bonylchromium(0) complexes as catalyst ligands in
several quite diverse reactions, including rhodium-
catalysed hydrogenation of ketones,5 palladium-cataly-
sed hydrosilyations of styrene6 and Lewis acid-catalysed
Diels–Alder reactions.7
R"
NHCOCH3
R"
NHCOCH3
4a, 66% ee
4b, 78% ee
4b, >95% ee
4c, 3% ee
(R' = H, R" = Ph)
(R' = H, R" = Ph)
PR2
(R' = Me, R" = Me)
(R' = H, R" = Ph)
CH3
H
PPh2
(CO)3Cr
4a R = Ph
4b R = Cy
4c R = tBu
Scheme 1.
bine the diphosphine motif with planar chirality and
develop routes to diphosphine derivatives of (arene)tri-
carbonylchromium(0) complexes. Complexes of gener-
alised structure 3 have been synthesised to date and
tested in palladium-catalysed allylic alkylations,8 palla-
dium-catalysed allylic sulfonations,9 rhodium-catalysed
hydrogenations9 and iridium-catalysed hydroamina-
tions.9 For example, complexes 4a–c have been shown to
give a very wide range of selectivities for the hydroge-
nation of dehydroamino acid derivatives (Scheme 1).9
Complexes of general formula 3 are synthesised using
a-methylbenzyl alchol8 or a-methylbenzylamine9 as the
source of chirality. The benzylic phosphine substituent is
introduced by nucleophilic displacement of either oxy-
gen8 or nitrogen9 substituents either directly8 or indi-
rectly9 via a chloro substituent.
Me
PPh2
PtBu2
PR2
PPh2
Fe
Me
PPh2
Cr(CO)3
PPh2
1
2
3
Figure 1.
Chelating diphosphines play an important role in tran-
sition metal catalysis, and it is thus of interest to com-
Some time ago, we demonstrated that tricarbonyl-
chromium(0) complexes of benzyl ethers could be
asymmetrically functionalised in high yields and
* Corresponding author. Fax: +44-207-594-5804; e-mail: s.gibson@
imperial.ac.uk
0957-4166/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.014

466
S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
enantioselectivities by reaction with a chiral base fol-
lowed by an electrophilic quench.10 More recently, we
reported that this reaction could be used to create a
new approach to planar chiral (arene)tricarbonylchro-
mium(0) complexes.11;12 We report herein that this
chemistry can be used to generate a range of novel planar
chiral diphosphine ligands, and that we have started to
probe the utility of these diphosphines in asymmetric
catalysis with investigations of an asymmetric hydroge-
nation reaction and an asymmetric Heck reaction. The
hydrogenation reaction was chosen for study because it
was anticipated that it would give clean and high con-
versions to product, and thus provide direct insight into
the effectiveness of a new ligand, whilst the Heck reaction
was selected because to the best of our knowledge there
have been no other reports to date of the application of
(arene)tricarbonylchromium(0) based ligands in the
Heck reaction. Some of the results described herein have
been reported in communication form.13
to give 7. Finally it was proposed that a third variable
step (step iii) involving a diastereoselective ortho-lithia-
tion of 7 followed by an electrophilic quench with a
second chlorodiphosphine R3Cl would be used to give
a range of planar chiral complexes 8.
Preliminary studies in which complex 5 had been con-
verted to diphosphine 8a via methyl ether 6a and
monophosphine 7a (Scheme 3) had demonstrated that
the introduction of asymmetry in step ii and the diaste-
reoselective installation of the second phosphine in step
iii proceeded smoothly to generate the required diphos-
phine 8a in high diastereo- and enantiopurity and good
yield.12 During the course of the hydrogenation and
Heck studies reported below, one new ether complex 6b
was synthesised, together with four new monophos-
phines 7b–e and eight new diphosphines 8b–i. With one
exception, the syntheses of these compounds proceeded
in good to excellent yields providing monophosphines
and diphosphines of very high enantiopurity. The
exception to this is the low enantiopurity of 8i. The origin
of the loss of enantiopurity during the conversion of 7e–
8i was not investigated during the course of this study
due to the inactivity of complex 8i in both the hydroge-
nation and Heck assays (see below).
2. Results and discussion
2.1. Synthesis of diphosphines
We planned to synthesise the planar chiral diphosphines
based on the (arene)tricarbonylchromium(0) unit using
the route shown in Scheme 2. The approach is based on
complex 5, which is readily formed in high yield from
commercially available 4-tert-butylbenzyl alcohol and
hexacarbonylchromium(0). In the first variable step
(step i) we proposed to react tricarbonyl(4-tert-butyl-
benzyl alcohol)chromium(0) 5 with an alcohol R1OH
under acid catalysis to give an ether complex 6. We then
proposed to introduce asymmetry into complex 6 in a
second flexible step (step ii) by its treatment with a chiral
base [the diamine precursor of which is readily available
from (R)- or (S)-a-methylbenzylamine in two steps14 and
an electrophilic quench with a chlorodiphosphine R2Cl
2.2. Asymmetric hydrogenations
The discovery of WilkinsonÕs hydrogenation catalyst in
the late 1960s15 stimulated much interest in the enan-
tioselective hydrogenation of alkenes using optically
active transition-metal complexes in order to generate
stereogenic carbon centres. Many chiral ligands have
been examined in the ensuing years and very high
selectivities have been achieved.16 In many cases the
efficiency of the catalysts generated has been probed
using (Z)-2-(acetamido)cinnamic acid, 2-(acetam-
ido)acrylic acid, or their methyl or ethyl esters, with the
reaction being performed in alcoholic solvents under 1–
10 atm of hydrogen using cationic complexes of rho-
dium. As asymmetric hydrogenation is one of the key
test reactions for chiral diphosphine ligands, we decided
to determine how well planar chiral diphosphine ligands
synthesised by our approach would perform in an
asymmetric hydrogenation reaction. We decided to
determine the effect of varying (i) the phosphine sub-
stituent on the aromatic ring, (ii) the phosphine sub-
stituent on the benzylic ring and (iii) the ether
substituent R1 that is to exploit the flexibility of our
synthesis by changing all the possible variables intro-
duced in steps i–iii. Thus ligands 8a–i were synthesised
and subjected to the standard hydrogenation reaction
depicted in Scheme 4.
Cr(CO)6
tBu
tBu
(97%)
OH
OH
(CO)3Cr
5
R1OH,
cat. H2SO4
i
tBu
OR1
(CO)3Cr
6
Ph
Ph
1.
N
Li
N
The diphosphines 8a–i all cleanly hydrogenated methyl
(Z)-2-(acetamido)cinnamate, apart from the ethyl ether
complex 8i, which did not form an active catalyst. Mod-
erate to good enantioselectivities were observed, and,
interestingly, the presence of a dialkyl phosphine unit on
the aromatic ring, rather than a diaryl phosphine group,
led to an inversion in product stereochemistry. Compar-
ing our results with the results depicted in Scheme 1,9 it
can be seen that the highest selectivity obtained in this
ii
Li
Ph
Ph
2. R2Cl
R2
R2
1. LiTMP
But
tBu
2. R3Cl
OR1
OR1
iii
R3
(CO)3Cr
(CO)3Cr
7
8 a-i
Scheme 2.

S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
467

468
S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
[Rh(COD)2] BF4 (1mol%)
2.3. Asymmetric Heck reactions
COOCH3
COOCH3
8a-i (1 mol%)
Ph
NHCOCH3
Ph
NHCOCH3
Transition metal catalysed carbon–carbon bond form-
ing reactions have become an invaluable tool for syn-
thetic chemists. Among the most successful and widely
applied of such transformations is the Heck reaction,
which has been known since the late 1960s. Many new
and exciting developments concerning the Heck cou-
pling reaction have appeared in recent years, such as the
utilisation of aryl bromides and chlorides as coupling
partners.17 One of the most significant developments has
been the discovery that the Heck reaction could be
carried out in an asymmetric manner.18 This reaction,
which utilises chiral palladium catalysts, can be carried
out in an intramolecular or intermolecular fashion.
MeOH, H2 (5 bar), 24 h
Scheme 4.
Table 1
Entry
Ligand
Ee (%)a;b
Configuration
of the major
enantiomer
PPh2
t Bu
OMe
1
2
3
4
45
69
41
48
R
R
R
S
PPh2
PiPr2
PCy2
PPh2
(CO)3Cr
8a
Hayashi reported the first example of an intermolecular
asymmetric Heck reaction in 1991.19 It involved the
phenylation of 2,3-dihydrofuran with phenyl triflate
catalysed by a Pd(OAc)2/(R)-BINAP combination.
Although several other substrates were examined, much
of the investigation into the mechanism and reaction
parameters focused around the phenylation of 2,3-di-
hydrofuran, and thus this has become one of the
benchmark reactions for the intermolecular Heck reac-
tion. We thus decided to conduct a second assay of
ligands 8a–i using this reaction (Scheme 5). Standard
conditions were employed to perform the catalyst,
perform the coupling reaction and assess the yield and
enantiopurity of the product.20
PPh2
tBu
OMe
(CO)3Cr
8b
PPh2
tBu
OMe
(CO)3Cr
8c
PiPr2
tBu
OMe
(CO)3Cr
8e
PCy2
OMe
tBu
The reaction was initially performed using the bis
diphenylphosphine complex 8a. This gave (R)-2-phenyl-
2,3-dihydrofuran in 60% yield and 60% ee (Table 2,
entry 1). Encouraged by this result, given that this was
the first asymmetric Heck reaction conducted using a
planar chiral (arene)tricarbonylchromium(0) complex,
we decided to assay the other diphosphines synthesised.
Changing the diphenylphosphine aromatic substituent
to a dialkylphosphine substituent resulted in no reaction
taking place (Table 2, entries 2 and 3), while, in contrast,
changing the benzylic diphenylphosphine substituent to
a dialkylphosphine substituent maintained catalyst
activity, but gave no significant improvement in selec-
tivity (Table 2, entries 4 and 5). Attempts to examine the
effect of placing tert-butyl phosphine or methyl phos-
phine substituents at the benzylic position were thwarted
by problems encountered in the introduction of the
aromatic substituent in the former case (presumably due
to steric effects), and the highly unstable nature of
chlorodimethylphosphine in the latter case. Changing
the methyl ether to an ethyl ether resulted in no reaction
(Table 2, entry 6). This effect was also observed in the
hydrogenation assay (see above). It is possible that this
inactivity is caused by poor co-ordination of the two
phosphines to the transition metal (rhodium or palla-
dium). Co-ordination of both phosphines leads to the
alkoxy substituent being forced towards the tricarbon-
5
6
60
S
PPh2
(CO)3Cr
8f
PPh2
tBu
No reaction
OEt
PPh2
PAr2
(CO)3Cr
8i
PPh2
tBu
7
8
9
48
36
31
R
OMe
(CO)3Cr
8d
PAr2
OMe
8g
tBu
R
R
PPh2
(CO)3Cr
PAr2
tBu
OMe
PAr2
(CO)3Cr
8h
a Ees were determined by HPLC using a Chiracel OD-H column and
95:5 hexane isopropanol as eluent with a flow rate of 900 lL/min.
b All reactions proceeded with 100% conversion.
ylchromium(0) rotor,
a situation, which may be
study (69% with complex 8b, Table 1, entry 2) is broadly
comparable with the selectivities recorded for the hydro-
genation of (Z)-2-(acetamido)cinnamic acid with
diphosphines 4a and 4b (66% and 78% ee, respectively).
acceptable for the methoxy substituent but not for the
more bulky ethoxy substituent. Finally, the diphenyl-
phosphine substituents of 8a were replaced with di(3,5-
dimethylphenyl)phsophine groups, but this lead to

S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
469
providing a new set of planar chiral diphosphines for use
in asymmetric catalysis. The diphosphines have been
assayed to date in two asymmetric catalytic reactions: an
asymmetric hydrogenation, a reaction that is used
widely to test the efficiency of new chiral diphosphines,
and an asymmetric Heck reaction, a reaction that to
date has not been investigated using (arene)tricarbon-
ylchromium(0) based ligands. Almost all of the
diphosphines synthesised in this study formed active
catalysts that proved stable under the catalytic condi-
tions employed. Although the enantioselectivities mea-
sured were only moderate to good, and much lower than
some of the best results obtained with some planar
chiral ferrocene complexes in asymmetric catalysis, it is
anticipated that future investigations using different
catalyst systems and substrates will identify highly
enantioselective processes mediated by these ligands.
8a-i (6 mol%),
OTf
Pd(OAc)2, (3 mol%)
+
2 eq. iPr
2NEt
THF, r.t., 3 days
Ph
O
O
Scheme 5.
Table 2
Entry
Ligand
Yield (%)
60
Ee (%)a
60
PPh2
t Bu
1
2
3
4
OMe
PPh2
PiPr2
PCy2
PPh2
(CO)3Cr
8a
PPh2
tBu
No reaction
OMe
(CO)3Cr
8b
PPh2
tBu
No reaction
OMe
4. Experimental
(CO)3Cr
8c
All reactions and manipulations involving organome-
tallic compounds were performed under an inert atmo-
sphere of dry nitrogen, using standard vacuum line and
Schlenk tube techniques.21 Reactions and operations
involving (arene)tricarbonylchromium(0) complexes
were protected from light. THF was distilled from
sodium benzophenone ketyl. The concentration of al-
kyllithums was determined by titration against diphe-
nylacetic acid in THF.22 Tetramethylpiperidine was
purchased from Aldrich and stored without further
purification over potassium hydroxide, or alternatively
it was distilled over CaH2 and stored over potassium
hydroxide. Chlorodiphenylphosphine was distilled prior
to use. Flash column chromatography was performed
using Merck silica gel 60 (230–400 mesh). All other re-
agents were used as obtained from commercial sources.
Melting points were recorded in open capillaries on a
PiPr2
tBu
55
58
42
62
OMe
(CO)3Cr
8e
PCy2
tBu
5
OMe
PPh2
(CO)3Cr
8f
PPh2
tBu
6
7
No reaction
OEt
PPh2
PAr2
(CO)3Cr
8i
PPh2
tBu
5248
OMe
€
Buchi 510 melting point apparatus, and are uncorrected.
(CO)3Cr
8d
IR spectra were recorded on a Perkin Elmer 1600 FT-IR
spectrometer. NMR spectra were recorded at room
PAr2
OMe
8g
€
temperature on Bruker AM 360, DRX 400 and DRX
tBu
8
9
54
50
500 instruments and J values are reported in Hz. Mass
spectra were recorded at the mass spectroscopy facility
at KingÕs College London on JEOL AX 505W and
Kratos MS890MS spectrometers and the EPSRC mass
spectral facility, Swansea. Elemental analyses were per-
formed by the London Metropolitan University micro-
analytical service.
PPh2
PAr2
(CO)3Cr
PAr2
tBu
2
0
62
OMe
(CO)3Cr
8h
a Ees were determined by HPLC using a Chiracel OD-H column and
HPLC analysis was performed using a Unicam Crystal
200 pump, Unicam Spectra 100 UV–vis detector (set at
330 nm) and Chiracel OD-H or AD columns. Racemic
monophosphines 7c–e and diphosphines 8b–i, used as
standards for the HPLC analysis, were synthesised using
t-BuLi as the base instead of the chiral diamide in step ii.
99.6:0.4 hexane isopropanol as eluent with a flow rate of 900 lL/min.
reduced selectivity (Table 2, entries 7 and 8) or reduced
activity (Table 2, entry 9).
3. Conclusions
The chiral diamine14 and bis(3,5-dimethylphenyl) chlo-
rophosphine23 were prepared according to literature
methods. Complexes 6a, 7a, 7b and 8a were prepared
following our reported literature procedures.12
We have synthesised a series of planar chiral diphos-
phines using an efficient and versatile approach, thus

470
S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
4.1. Tricarbonyl(1-ethoxymethyl-4-tert-butylbenzene)-
chromium(0) 6b
min (minor); (R)-enantiomer tR ¼ 16:5 min (major): 96%
24
D
ee; ½aŠ ¼ þ83:4 (c 0.5, CH2Cl2); mmax (CH2Cl2), cmꢀ1
1959s (CBO), 1880s (CBO); dH (360 MHz, CDCl3)
1.05–1.30 (10H, m, Cy), 1.27 [9H, s, (CH3)3C], 1.62–1.84
(12H, m, Cy), 3.58 (3H, s, OCH3), 4.51 (1H, d, J 5.0,
CHPCy2), 5.17 (1H, dd, J 8.7, 1.8, CCrH), 5.49–5.57
(3H, m, CCrH); dP{1H} (146 MHz, CDCl3) 28.9 (PCy2);
dC{1H} (125 MHz, CDCl3) 25.7 (d, J 2.9, CH2), 26.4–
26.8 (m, CH2), 29.5 (t, J 12.6, CH2), 30.3 [(CH3)3C], 32.2
[(CH3)3C], 33.2(C cyHP), 59.6 (OCH3), 78.8 [d, J 26.7
Hz, CHP(OMe)], 88.1 [d, J 1.9, CCrHCCrCH(PCy2)
OMe], 88.3 [d, J 12.0, CCr HCCrCH(PCy2)OMe], 90.2
[CCr(t-Bu)CCrH], 90.7 [CCr(t-Bu)CCrH], 109.4 (d, J 17.4,
CCrCHPCy2OMe), 122.3 [CCr(t-Bu)], 233.2 (CBO); m=z
(EI, %) 510 (Mþ, 1), 482(M )CO, 68), 454 (M)2CO,
100), 426 (M)3CO, 100), 396 (M)3CO)H2CO, 9), 177
[M)Cr(CO)3)PCy2, 45]; HRMS (ESI) found 555.1755,
C31H35O4CrP+H requires 555.1751.
Concentrated sulfuric acid (2.2 mL) was added dropwise
to a solution of complex 5 (1.0 g, 3.33 mmol) in nitrogen-
saturated methanol (10 mL). The mixture was heated at
50 ꢁC for 3 h and stirred for a further 2h at room tem-
perature. To neutralise the reaction mixture, saturated
aqueous Na2CO3 (10 mL) was added carefully followed
by the addition of diethyl ether (50 mL). The organic
layer was separated and the aqueous layer was extracted
with diethyl ether (3 · 50 mL). The combined organic
layers were dried over Na2SO4 and evaporated under
reduced pressure to give a yellow oil. Column chroma-
tography (SiO2; hexane/diethyl ether, 1:1) of this mate-
rial gave 1.01 g (95%) of title complex 6b as a yellow oil;
mmax (CH2Cl2), cmꢀ1 1950s (CBO), 1880s (CBO); dH
(360 MHz, CDCl3) 1.27–129 [12H, m, (CH3)3C and
CH3CH2O], 3.46 (2H, q, J 6.2, OCH2CH3), 4.14 (2H, s,
CH2OEt), 5.20 [2H, d, J 6.8, CCr(t-Bu)CCrHCCrH], 5.49
[2H, d, J 6.8, CCr(t-Bu)CCrHCrH]; dC{1H} (100 MHz,
CDCl3) 15.5 (CH3CH2), 31.5 [(CH3)3C], 34.3 [(CH3)3C],
67.5 (OCH2CH3), 71.2(C CrCH2O), 91.0 (CCrH), 93.0
(CCrH), 108.6 (CCrCH2OMe), 122.2 [CCr(t-Bu)], 233.0
(CBO); m=z (EI, %) 328 (Mþ, 68), 244 (M)3CO, 51), 52
(Cr, 100); HRMS (ESI) found 351.0642, C16H20CrO4Na
requires 351.0660.
4.4. (+)-(R)-Tricarbonyl[1-(1-di-3,5-dimethylphenyl-
phosphine-1-methoxymethyl)-4-tert-butylbenzene]chro-
mium(0) (+)-7d
Flash column chromatography (SiO2; hexane/ether,
10:0–95:5) of the crude product gave a 91% yield of the
title complex (+)-7d as a yellow solid; mp 128–129 ꢁC;
enantiomeric excess was determined by HPLC analysis
(Chiralcel AD, n-hexane/i-PrOH, 98:2, 0.6 mL/min,
4.2. General procedure for the synthesis of complexes
7c–e (step ii)
330 nm); (S)-enantiomer tR ¼ 8:5 min (minor); (R)-
24
enantiomer tR ¼ 10:3 min (major): 97% ee; ½aŠ ¼ þ36:4
D
(c 0.5, CH2Cl2); mmax (CH2Cl2), cmꢀ1 1955s (CBO),
1880s (CBO); dH (360 MHz, CDCl3) 1.18 [9H, s,
(CH3)3C], 2.18 (6H, s, CarCH3), 2.22 (6H, s, CarCH3),
3.23 (3H, s, OCH3), 4.60–4.64 (2H, m, CCrH and
CHPAr2), 5.08 (1H, dd, J 7.4, 1.4, CCrH), 5.24–5.29 (m,
2H, CCrH), 6.86 (1H, s, CarH), 6.88 (1H, s, CarH), 6.91
(1H, s, CarH), 6.94 (1H, s, CarH), 7.01 (1H, s, CarH), 7.03
(1H, s, CarH); dP{1H} (146 MHz, CDCl3) 10.7
n-Butyllithium (2n mmol) was added dropwise to a
stirred solution of the chiral diamine (1n mmol) in THF
(8n mL) at )78 ꢁC and the solution was allowed to reach
room temperature over 30 min. The resulting deep pink
solution was then re-cooled to )78 ꢁC and a solution of
heat gun-dried lithium chloride (1n mmol) in THF
(4n mL) was added via a cannula. Stirring was continued
for a further 5 min before a pre-cooled solution ()78 ꢁC)
of the complex 6a–b (1n mmol) in THF (4n mL) was
added dropwise (ca. 2min) via a short cannula. After
stirring the orange solution at )78 ꢁC for 30 min, chlo-
rodialkyl or chlorodiarylphosphine (2n mmol) was
added in one portion, which resulted in a colour change
of the solution from orange to yellow. Stirring was
continued at )78 ꢁC for 1.5 h before methanol (1n mL)
was added. The reaction mixture was warmed to room
temperature and the solvent was removed in vacuo to
give the crude complex, which was purified by flash
column chromatography. All the reactions were per-
formed on 1.0 mmol or 1.5 mmol scale.
(CHPAr2); dC{1H} (90 MHz, CDCl3) 2 1.8 (C CH3), 21.9
ar
(CarCH3), 31.6 [C(CH3)3], 34.4 [C(CH3)3], 60.5
(d, J 4.9, OCH3), 83.6 (d, J 13.4, CHPAr2OCH3),
89.9 [CCrHCCrC(CH3)3], 90.5 [CCrHCCrC(CH3)3], 91.1 (d,
J
4.0, CCrHCCrCHPAr2OMe), 91.4 (d,
J
5.4,
CCrHCCrCHPAr2OMe), 110.8 (d, J 17.4, CCrCHPAr2-
OMe), 124.5 [CCrC(CH3)3], 131.6 (d, J 3.9, CarH), 132.1
(d, J 18.5, CarH), 132.4 (d, J 19.3, CarH), 138.1 (d, J
18.2, CarP), 138.2(d, J 7.18, CarCH3), 234.38 (CrCBO);
m=z (EI, %) 555 (Mþ+H, 20), 419 [M+H)Cr(CO)3, 100],
313 [M)P(C8H9)2, 11], 177 [M)P(C8H9)2)Cr(CO)3, 13];
HRMS (ESI) found 555.1755, C31H35O4 CrP+H
requires 555.1751.
4.3. (+)-(R)-Tricarbonyl[1-(1-dicyclohexylphosphine-1-
methoxymethyl)-4-tert-butylbenzene]chromium(0) (+)-7c
4.5. (+)-(R)-Tricarbonyl[1-(1-diphenylphosphine-1-
ethoxymethyl)-4-tert-butylbenzene]chromium(0) (+)-7e
Flash column chromatography (SiO2; hexane/dichloro-
methane, 10:0–7:3) of the crude product gave a 95%
yield of the title complex (+)-7c as a yellow solid; mp
140–142 ꢁC; enantiomeric excess was determined by
HPLC analysis (Chiralcel OD-H, n-hexane/i-PrOH,
99.8:0.2, 0.4 mL/min, 330 nm); (S)-enantiomer tR ¼ 14:2
Flash column chromatography (SiO2; hexane/diethyl-
ether, 100:0–95:5) of the crude product gave (90%) of
the title complex (+)-7e as a yellow solid; mp 113–
114 ꢁC; found C ¼ 65.41 H ¼ 5.86, C28H29CrO4P re-
quires C ¼ 65.62H ¼ 5.70; enantiomeric excess was
determined by HPLC analysis (Chiralcel AD, n-hexane/

S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
471
i-PrOH, 98:2, 0.6 mL/min, 330 nm); (S)-enantiomer
tR ¼ 13:5 min (minor); (R)-enantiomer tR ¼ 18:0 min
CCrHCCrHPi-Pr2], 5.74 (1H, dd, J 7.3, 4.0, CHPPh2),
7.25–7.31 (3H, m, CarH), 7.41–7.47 (5H, m, CarH), 7.91–
7.96 (2H, m, CarH); dP{1H} (146 MHz, CDCl3) 0.3 (d, J
16.2, CHPPh2), 0.6 [d, J 16.2, CCrP(i-Pr2)]; m=z (EI, %)
586 (Mþ)CO, 2), 558 (M)2CO, 4), 530 (M)3CO, 100),
293 [M)Cr(CO)3) PPh2, 52]; HRMS (ESI) found
637.1690, C33H40CrO4 P2Na requires 637.1704.
24
D
(major): 97% ee; ½aŠ ¼ þ133:4 (c 0.5, CH2Cl2); mmax
(CH2Cl2), cmꢀ1 1960s (CBO), 1882s (CBO). dH
(360 MHz, CDCl3) 1.08 (3H, t, J 7.2, CH3CH2), 1.16
[9H, s, (CH3)3C], 3.43–3.42(1H, m, CH 3CHH), 3.90
(1H, m, CH3CHH), 5.07 (2H, m, CHPPh2 and CCrH),
5.07 (1H, dd, J 8.0, 1.6, CCrH), 5.19 (1H, dd, J 8.6, 1.6,
CCrH), 5.28 (1H, d, J 6.9, CCrH), 7.18–7.31 (8H, m,
CarH), 7.45–7.50 (2H, t, J 7.4 CarH); dP{1H} (146 MHz,
CDCl3) 11.4 (CPPh2); dC{1H} (90 MHz, CDCl3) 14.2
(CH3CH2) 29.8 [(CH3)3C], 32.8 [(CH3)3C], 53.9 (d, J 4.2,
OCH2), 64.6 (d, J 14.3, CHPPh2), 80.6 [CCr(t-Bu)CCrH],
88.4 [CCr(t-Bu)CCrH], 88.7 [d, J 3.6, CCrHCCrCH(PPh2)
OMe], 89.4 [d, J 4.0, CCrHCCrCH(PPh2)OMe], 108.5 [d,
J 16.5, CCrCH(PPh2)OMe], 122.9 [CCr(t-Bu)], 125.6
(CarH), 126.8 (d, J 16.5, CarH), 127.1 (CarH), 127.2 (d, J
6.6, CarH), 132.4 (Car), 132.9 (d, J 19.0, CarH), 133.2(d,
J 20.4, CarH), 133.6 (Car), 140.5 (Car), 144.2(C ar), 233.7
(Cr-CBO); m=z (%) 512(M þ,1), 428 (M)3CO, 100), 384
(MH)3CO)C2H5O, 38), 332[MH )Cr(CO3))C2H5O,
3], 191 [M)Cr(CO)3)PPh2, 57], 52(Cr, 12); HRMS
(ESI) found 533.1878, C27H39O4 CrP+Na requires
533.1888.
4.8. ())-(1pR,10R)-Tricarbonyl[1-dicyclohexylphosphine-
2-(1-diphenylphosphine-1-methoxymethyl)-5-tert-butyl-
benzene]chromium(0) ())-8c
Flash column chromatography (SiO2; hexane/dichloro-
methane, 10:0–7:3) of the crude compound gave a 54%
yield of the title complex ())-8c as a yellow solid; mp
121–122 ꢁC; enantiomeric excess was determined by
HPLC analysis (Chiralcel OD-H, n-hexane/i-PrOH,
99.8:0.2, 0.15 mL/min, 330 nm); (pRR) enantiomer
tR ¼ 40:2min (major); ( pSS) enantiomer tR ¼ 44:2min
24
(minor): 97% ee; ½aŠ ¼ ꢀ111:2 (c 0.5, CH2Cl2); mmax
D
(CH2Cl2), cmꢀ1 1962s (CBO), 1889s (CBO); dH
(360 MHz, CDCl3) 0.84 (2H, t, J ¼ 7:0 Hz, Cy), 1.17
[9H, s, (CH3)3C], 1.13–1.95 (17H, m, Cy), 3.09–3.14
(3H, m, Cy), 3.40 (3H, s, OCH3), 4.88 [1H, ddd, J 7.0,
3.0, 1.2, CCr(t-Bu)CCrHCCrH], 5.25 [1H, d, J 7.0,
CHPPh2], 5.58 (1H, s, CCr(t-Bu)CCrHCCrH), 5.63 [1H,
dd, J 7.5, 4.0 Hz, (t-Bu)CCrCHCCrPCy2], 7.16–7.22 (6H,
m, CarH), 7.35 (2H, dt, J 7.1, 1.7, CarH), 7.84–7.88 (2H,
m, CarH); dP{1H} (146 MHz, CDCl3) 0.8 (d, J 55.5 Hz,
CHPPh2), )6.9 (d, J 55.5 Hz, CCrPCy2); m=z (EI, %) 695
(2%, MHþ), 612(100, M )2CO)CH3+H), 369 [33,
M)PCy2)Cr(CO)3], 197 (9, PCy2); HRMS (ESI) found
695.2496 C39H48CrO4P2+H, requires 695.2506.
4.6. General procedure for the synthesis of complexes
8b–c (step iii)
Methyllithium (1.1n mmol) was added dropwise to a
stirred solution of tetramethylpiperidine (1.1n mmol) in
THF (10n mL) at )78 ꢁC. The solution was allowed to
reach room temperature and re-cooled to )78 ꢁC.
Diphosphine complex 7a–e (1n mmol) in THF (4n mL)
was added via a cannula and the resulting orange solu-
tion was stirred for 1 h, Chlorodialkyl or chlorodiaryl
phosphine (2n mmol) was added in one portion and
stirring was continued for a further 1 h at )78 ꢁC. The
reaction mixture was warmed to room temperature and
stirred for 1 h before methanol (0.5 mL) was added.
Removal of solvent in vacuo gave the crude product,
which was purified by flash column chromatography. All
the reactions were performed on 0.35–0.50 mmol scale.
4.9. ())(1pR,10Rb)-Tricarbonyl[1-di-3,5-dimethylphenyl-
phosphine-2-(10-diphenylphosphine-10-methoxymethyl)-5-
tert-butylbenzene]chromium(0) ())-8d
Flash column chromatography (SiO2; hexane/diethyl
ether, 10:0–95:5) of the crude compound gave a 83%
yield of title complex ())-8d as a crystalline yellow solid;
mp 98–100 ꢁC; enantiomeric excess was determined by
HPLC analysis (Chiralcel OD-H, n-hexane/i-PrOH,
99.6:0.4, 0.5 mL/min, 330 nm); (pSS)-enantiomer
4.7. ())-(1pR,10R)-Tricarbonyl[1-diisopropylphosphine-2-
(10-diphenylphosphine-10-methoxymethyl)-5-tert-butylben-
zene]chromium(0) ())-8b
tR ¼ 10:8 min (minor); (pRR)-enantiomer tR ¼ 2:6 min
24
(major): 97% ee; ½aŠ ¼ ꢀ171 (c 0.5, CH2Cl2); mmax
D
Flash column chromatography (SiO2; hexane/dichloro-
methane, 10:0–7:3) of the crude compound gave a 56%
yield of the title complex ())-8b; enantiomeric excess was
determined by HPLC analysis (Chiralcel OD-H, n-hex-
ane/i-PrOH, 99.6:0.4, 0.3 mL/min, 330 nm); (pRR) enan-
(CH2Cl2), cmꢀ1 1962s (CBO), 1885s (CBO); dH
(360 MHz, CDCl3) 0.98, [9H, s, (CH3)3C], 2.20 (6H, s,
2 · PCarCH3), 2.25 (6H, s, 2 · PCarCH3) 3.02(3H, s,
OCH3), 4.75 [1H, t, J 1.1 (t-Bu)CCrCCrHCCrPAr2], 5.16
[1H, ddd, J 6.8, 3.6, 1.7, (t-Bu)CCrCCrHCCrH], 5.25 [1H,
dd, J 6.8, 1.1, CCr(t-Bu)CCrHCCrH], 5.47 (1H, dd, J 6.3,
4.3, CHPPh2), 6.82(1H, s, C arH), 6.98 (1H, s, CarH),
7.00 (1H, s, CarH), 7.02(1H, s, C arH), 7.31–7.47 (12H,
m, CarH); dP{1H} (146 MHz, CDCl3) )0.7 (d, J 10.3,
CHPPh2), )13.9 (d, J 10.3, CCrPAr2); m=z (EI, %) 738
(Mþ, 25), 710 (M)CO, 14), 682[MH )C(CH)3], 15), 654
(M)3CO, 100), 571 (M)Cr(CO)3)OCH3, 32), 377
[MH)P(C8H9)2)3CO)OCH3, 35]; HRMS (ESI) found
739.2186, C43H44CrO4P2+H requires 739.2194.
tiomer tR ¼ 18:0 min (major); (pSS) enantiomer tR ¼
24
20:3 min (minor): 97% ee; ½aŠ ¼ ꢀ48:2 (c 0.5, CH2Cl2);
D
mmax (CH2Cl2), cmꢀ1 1962s (CBO), 1889s (CBO); dH
(360 MHz, CDCl3) 1.01–1.08 (6H, m, 2 · CHCH3), 1.18–
1.25 (12H, m, (CH3)3C and CHCH3), 1.34 (3H, dd, J
16.0, 7.0, CHCH3), 1.98–2.05 [m, 1H, CH(CH3)2], 2.12–
2.20 [1H, m, CH(CH3)2], 3.11 (3H, s, OCH3), 5.06 [1H,
ddd, J 6.5, 2.8, 1.6, CCr(t-Bu)CCrHCCrH], 5.33 [1H, d, J
6.5, CCr(t-Bu)CCrHCCrH], 5.59 [1H, s, CCr(t-Bu)

472
S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
24
D
4.10. ())-(1pR,10R)-Tricarbonyl[1-diphenylphosphine-2-
(10-diisopropylphosphine-10-methoxymethyl)-5-tert-butyl-
benzene]chromium(0) ())-8e
½aŠ ¼ ꢀ132:0 (c 0.5, CH2Cl2); mmax (CH2Cl2), cmꢀ1
1960s (CBO), 1882s (CBO); dH (360 MHz, CDCl3) 0.98
[9H, s, (CH3)3C], 2.20 (6H, s, 2 · CarCH3), 2.28 (6H, s,
2 · CarCH3), 2.55 (s, 3H, OCH3), 4.70 [1H, t, J 1.4,
CCr(t-Bu) CCrHCCrPPh2)], 5.04–5.08 [1H, dt, J 6.5, 1.9,
CCr(t-Bu) CCrHCCrH)] 5.25 [1H, dd, J 6.5, 1.4, CCr(t-
Bu) CCrHCCrH] 5.57 (1H, dd, J 6.7, 4.7, CHPAr2), 6.91
(1H, s, CarH), 6.93 (1H, s, CarH), 6.95 (1H, s, CarH),
6.97 (1H, s, CarH), 6.99 (1H, s, CarH), 7.20–7.24 (4H,
m, CarH), 7.35–7.40 (4H, m, CarH), 7.86 (2H, t, J 6.8,
CarH); dP{1H} (146 MHz, CDCl3) )1.5 (d, J 10.4,
CHPAr2), )12.7 (d, J 10.4, CCrPPh2); m=z (EI, %)
682[15, MH þ-(t-Bu)], 654 [100, M)(CO)3], 571 [32,
MH) Cr(CO)3)OMe], 377 [48, MH)P(C8H9)2)3CO)
OMe].
Flash column chromatography (SiO2; hexane/dichlo-
romethane, 10:0–7:3) of the crude compound gave a
61% yield of the title complex ())-8e; mp 95–97 ꢁC;
enantiomeric excess was determined by HPLC analysis
(Chiralcel OD-H, n-hexane/i-PrOH, 99.9:0.1, 0.4 mL/
min, 330 nm); (pSS)-enantiomer tR ¼ 15:9 min (minor);
(pRR)-enantiomer tR ¼ 20:6 min (major): 96% ee;
24
½aŠ ¼ ꢀ104:6 (c 0.5, CH2Cl2); mmax (CH2Cl2), cmꢀ1
D
1959s (CBO), 1889s (CBO); dH (360 MHz, CDCl3) 1.09
[9H, s, (CH3)3C], 1.06–1.34 [12H, m, 2CH(CH3)2], 2.17–
2.25 [1H, m, CH(CH3)2], 2.28–2.35 [1H, m, CH(CH3)2],
2.73 (3H, s, OCH3), 4.74 [1H, t, J 1.4, CCr(t-Bu)
CCrHCCrPPh2], 4.84 [1H, t, J 3.4 CHP(i-Pr2)], 5.45 [1H,
dd, J 6.8, 1.5, CCr(t-Bu)CCrHCCrH], 5.65 [1H, dt, J 6.8,
2.6, CCr(t-Bu)CCrHCCrH], 7.36–7.45 (10H, m, CarH);
dP{1H} (146 MHz) 22.2 [d, J 28.2, CHP(i-Pr2)], )13.8 (d,
4.13. ())-(1pR,10R)-Tricarbonyl[1-(di-3,5-dimethylphe-
nylphosphine)-2-(10-di-3,5-dimethylphenylphosphine-10-
methoxymethyl)-5-tert-butylbenzene]chromium(0) ())-8h
J
28.2, CCrPPh2); HRMS (ESI) found 637.1699
C33H40CrO4P2Na, requires 637.1704.
Flash column chromatography (SiO2; hexane/diethyl
ether, 10:0–95:5) of the crude compound gave a 84%
yield of title complex ())-8h as a crystalline yellow solid;
mp 117–118 ꢁC; enantiomeric excess was determined by
HPLC analysis (Chiralcel OD-H, n-hexane/i-PrOH,
99.6:0.4, 0.5 mL/min, 330 nm); (pSS)-enantiomer
tR ¼ 16:0 min (minor); ( RR)-enantiomer tR ¼ 17:6 min
4.11. ())-(1pR,10R)-Tricarbonyl[1-diphenylphosphine-
2-(10-dicyclohexylphosphine-10-methoxymethyl)-5-tert-
butylbenzene]chromium(0) ())-8f
(major): 97% ee; ½aŠ ¼p ꢀ27:6 (c 0.75, CH2Cl2); mmax
Flash column chromatography (SiO2; hexane/dichloro-
methane, 10:0–7:3) of the crude compound gave a 73%
yield of the title complex ())-8f; mp 85–87 ꢁC; enantio-
meric excess was determined by HPLC analysis (Chi-
ralcel OD-H, n-hexane/i-PrOH, 99.8:0.2, 0.15 mL/min,
330 nm); (pRR)-enantiomer tR ¼ 41:8 min (major);
24
D
(CH2Cl2), cmꢀ1 1958s (CBO), 1880s (CBO); dH
(360 MHz, CDCl3) 1.05 [9H, s, (CH3)3C], 2.14 (12H, s,
4 · PCarCH3), 2.31 (6H, s, 2 · PCarCH3), 2.36 (6H, s,
2 · PCarCH3), 3.04 (3H, s, OCH3), 4.87 (1H, t, J 2.0,
CCr(t-Bu)CCrHCCrPAr2), 5.06 (1H, ddd, J 6.0, 3.0, 2.0,
CCr(t-Bu)CCrHCCrH), 5.22 [1H, dd, J 6.0, 2.0, CCr(t-
Bu)CCrHCCrH] 5.47 (1H, dd, J 6.0, 4.0, CHPAr2), 6.76
(1 H, s, CarH), 6.81 (1H, s, CarH), 6.92(1H, s, C arH),
6.94 (1H, s, CarH), 6.96–7.04 (6H, m, CarH), 7.42(1H, s,
CarH), 7.44 (1H, s, CarH); dP{1H} (146 MHz, CDCl3) 0.3
(d, J 10.4, CHPAr2), )13.4 (d, J 10.4, CCrPAr2); m=z
(EI, %) 710 (Mþ)3CO, 100), 627 [M)Cr(CO)3)OCH3,
18], 417 [Mþ)Cr(CO)3)P(C8H9)2, 52], 242 [P(C8H9)2+
H, 17]; HRMS (ESI) found 795.2831, C47H52CrO4P2+H
requires 795.2818.
(pSS)-enantiomer tR ¼ 49:8 min (minor): 97% ee;
24
½aŠ ¼ ꢀ82:9 (c 0.5, CH2Cl2); mmax (CH2Cl2), cmꢀ1 1962s
D
(CBO), 1889s (CBO); dH (360 MHz, CDCl3) 0.84–0.90
(3H, m, Cy), 1.08 [9H, s, (CH3)3C], 1.13–2.10 (19H, m,
Cy), 2.68 (3H, s, OCH3), 4.73 (1H, t, J 1.2, CCr(t-Bu)
CCrHCCrPPh2), 4.87 (1H, t, J 3.4, CHPCy2), 5.45 [1H,
dd, J 6.8, 1.2, CCr(t-Bu)CCrHCCrH], 5.61 [1H, dt, J 6.8,
2.4, CCr(t-Bu)CCrHCCrH], 7.35–7.44 (10H, m, CarH);
dP{1H} (146 MHz, CDCl3) 14.9 (d, J 31.0, CHPCy2),
)14.1 (d, J 30.7, CCrPPh2); m=z (EI, %) 638 (Mþ)2CO,
5), 610 (M)3CO, 100), 361 [M)Cr(CO)3) PCy2, 28];
HRMS (FAB): found 610.2592, C39H48CrO4 P2–3CO
requires 610.2586.
4.14. ())-(1pR,10R)-Tricarbonyl[1-diphenylphosphine-2-
(10-diphenylphosphine-10-ethoxymethyl)-5-tert-butylbenz-
ene]chromium(0)())-8i
4.12. ())-(1pR,10R)-Tricarbonyl[1-diphenylphoshine-2-
(10-di-3,5-dimethylphenylphosphine-10-methoxymethyl)-5-
tert-butylbenzene]chromium(0) ())-8g
Flash column chromatography (SiO2; hexane/diethyl
ether, 10:0–96:4) of the crude compound gave a 85%
yield of the title complex ())-8i as a crystalline yellow
solid; mp 74–76 ꢁC; enantiomeric excess was determined
by HPLC analysis (Chiralcel AD, n-hexane/i-PrOH,
99:1, 0.6 mL/min, 330 nm); (pSS)-enantiomer tR ¼ 11:2
Flash column chromatography (SiO2; hexane/diethyl
ether, 10:0–95:5) of the crude compound gave a 84%
yield of title complex ())-8g as a crystalline yellow
solid; found C ¼ 69.52% H ¼ 5.62%, C43H44CrO4P2
requires C ¼ 69.91% H ¼ 6.00%; mp 80–81 ꢁC;
enantiomeric excess was determined by HPLC analysis
(Chiralcel OD-H, n-hexane/i-PrOH, 99.6:0.4, 0.5 mL/
min, 330 nm); (pRR)-enantiomer tR ¼ 10:8 min (major);
(pSS)-enantiomer tR ¼ 12:6 min (minor): 97% ee;
min (minor); (pRR)-enantiomer tR ¼ 14:0 min (major):
24
84% ee; ½aŠ ¼ ꢀ162( c 0.25, CH2Cl2); (CH2Cl2), cmꢀ1
D
1964s (CBO), 1893s (CBO); dH (500 MHz, CDCl3) 0.23
(3H, t, J 6.9, CH3CH2O), 0.90 [9H, s, (CH3)3C], 2.45–
2.65 (2H, m OCH2CH3), 4.76 (1H, s, CCr(t-Bu)

S. E. Gibson et al. / Tetrahedron: Asymmetry 15 (2004) 465–473
473
CCrHCCrPPh2), 5.22–5.24 (1H, ddd, J 6.0, 3.2, 2.3,
CCr(t-Bu)CCrHCCrH), 5.31 [1H, d, J 6.0, CCr(t-Bu)
CrHCCrH], 5.74 [1H, dd, J 7.0, 4.6, CHPPh2], 7.21–7.47
(18H, m, CarH), 7.84 (2H, dt, J 7.7, 1.7, CarH); dP{1H}
(146 MHz, CDCl3) )1.4 (d, J 10.1, CHPPh2), )13.0 (d, J
10.1, CCrPPh2); m=z (EI, %) 640 (Mþ)2CO, 16), 612
(M)3CO, 100), 375 [M)Cr(CO)3)PPh2, 23]; HRMS
(ESI) found 719.1516, C40H38CrO4P2+Na, requires
719.1548.
(360 MHz, CDCl3) 2.57 (ddt, J 15.0, 8.4, 2.5, 1H,
CHHPh), 3.08 (ddt, J 15.0, 10.0, 2.5, 1H, CHHPh), 4.97
(dd, J 4.5, 2.5, 1H, OCHCH), 5.52(dd, J 10.0, 8.4, 1H,
OCHPh), 6.46 (dd, J 4.5, 2.5, 1H, OCHCH), 7.27–7.37
(m, 5H, Ph).
Acknowledgements
The authors acknowledge KingÕs College London for
the provision of a studentship (to H.I.) and post-doc-
toral fellowships (to C.P. and V.S.).
4.15. Procedure for asymmetric hydrogenation reaction
To
a
mixture of the ligand (0.01 mmol) and
[Rh(COD)2]BF4 (11 lmol) in a Schlenk tube was added
degassed methanol (5 mL) and the reaction mixture was
stirred at room temperature for 15 min under nitrogen.
The hydrogenation autoclave was charged with
1.0 mmol of the substrate and a magnetic stirrer bar.
The methanolic solution of the rhodium catalyst was
added very quickly to the substrate and the autoclave
was assembled and flushed 10 times with hydrogen. The
reaction mixture was stirred in the autoclave at room
temperature for 24 h under 5 bar pressure of hydrogen.
The reaction was filtered through a pad of Celite and
concentrated in vacuo to give the crude product, which
was purified by column chromatography (SiO2; 3:1,
toluene/ethyl acetate). Enantiomeric excess was deter-
mined by HPLC using a Chiracel OD-H column with
n-hexane/isopropanol (95:5) as the eluent with a flow
rate of 0.9 mL/min: tR ¼ 23:5 (R)-enantiomer, tR ¼ 33:6
(S)-enantiomer. The configuration of the major enan-
tiomer was identified as R by comparison of the optical
rotation of the product with literature data.24 dH
(360 MHz, CDCl3) 1.81 (s, 3H, NHCOCH3), 2.95 (dd,
1H, J 14.0, 5.5, CHHPh), 3.04 (dd, 1H, J 14.0, 6.2,
CHHPh), 3.60 (s, 3H, COOCH3), 4.77 (dd, J 6.2, 5.5,
1H, CHCH2Ph), 6.34 (br s, 1H, NH), 7.02(d, 2H, J 6.1,
CarH), 7.24–7.04 (m, 3H, CarH).
References and notes
1. Togni, A. Angew. Chem., Int. Ed. 1996, 35, 1475.
2. (a) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.;
Zanotti-Gerosa, A. Org. Lett. 2000, 26, 4173; (b) Pye, P.
J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R.
P.; Reider, P. J. J. Am. Chem. Soc. 1997, 119, 6207.
3. Bolm, C.; Muniz, K. Chem. Soc. Rev. 1999, 28, 51.
4. For a recent review of this area, see Gibson, S. E.;
Ibrahim, H. Chem. Commun. 2002, 2465.
5. Pasquier, C.; Naili, S.; Pelinski, L.; Brocard, J.; Mortreux,
A.; Agbossou, F. Tetrahedron: Asymmetry 1998, 9, 193.
6. Weber, I.; Jones, G. B. Tetrahedron Lett. 2001, 42, 6983.
7. Jones, G. B.; Guzel, M.; Heaton, S. B. Tetrahedron:
Asymmetry 2000, 11, 4303.
8. Hayashi, Y.; Sakao, H.; Kaneta, N.; Uemura, M. J.
Organometal. Chem. 1995, 503, 143.
9. Vasen, D.; Salzer, A.; Gerhards, F.; Gais, H.-J.; Sturmer,
R.; Bieler, N. H.; Togni, A. Organometallics 2000, 19, 539.
10. Cowton, E. L. M.; Gibson, S. E.; Schneider, M. J.; Smith,
M. H. Chem. Commun. 1996, 839.
11. Gibson, S. E.; Ibrahim, H. Chem. Commun. 2001, 1070.
12. Gibson, S. E.; Ibrahim, H.; Pasquier, C.; Steed, J. W.
Tetrahedron 2002, 58, 4617.
€
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A mixture of the phosphine (6 mol%), Pd(OAc)2
(3 mol%) and THF (5 mL) was stirred at room temper-
ature under a nitrogen atmosphere for 30 min. 2,3-Di-
hydrofuran (3 mmol), phenyl triflate (1 mmol) and
N,N-diisopropylethylamine (2mmol) were added and
the reaction was stirred at room temperature for 3 days.
Diethyl ether (10 cm3) was added and the resulting
mixture filtered through a pad of Celite. The filtrate was
carefully concentrated in vacuo to give the crude pro-
duct, which was purified by column chromatography
(SiO2; hexane/diethyl ether, 4:1) to give 2-phenyl-2,3-
dihydrofuran as a colourless oil. Enantiomeric excess
was determined by HPLC using a Chiracel OD-H col-
umn with n-hexane/isopropanol (99.6:0.4) as the eluent
with a flow rate of 0.6 mL/min; tR ¼ 12:0 min (major),
tR ¼ 13:8 (minor). The configuration of the major
enantiomer was identified as R by comparison of the
specific rotation of the product with literature data.8 dH
^
Vidal, V.; Genet, J.-P. Tetrahedron 2000, 57, 2563.