Diastereoselective hydrogenation of folic acid esters with the Daniphos ligand

Article abstract of DOI:10.1016/j.jorganchem.2005.11.026

Folic acid dimethylester benzenesulfonate was hydrogenated homogeneously in a rhodium-catalyzed diastereoselective reaction employing a set of the previously published planar-chiral "Daniphos" ligands, which are based on an arene chromium tricarbonyl scaf

Full text of DOI:10.1016/j.jorganchem.2005.11.026

Journal of Organometallic Chemistry 691 (2006) 2263–2269
www.elsevier.com/locate/jorganchem
Diastereoselective hydrogenation of folic acid esters
with the Daniphos ligand
a
a
a,
b
Wolfgang Braun , Beatrice Calmuschi-Cula , Albrecht Salzer *, Viola Groehn
a
Institut fu¨r Anorganische Chemie, RWTH Aachen, Professor-Pirlet-Strasse 1, D 52074 Aachen, Germany
b
Merck Eprova AG, Im Laternenacker 5, CH 8200 Schaffhausen, Switzerland
Received 23 September 2005; received in revised form 8 November 2005; accepted 8 November 2005
Available online 19 December 2005
Abstract
Folic acid dimethylester benzenesulfonate was hydrogenated homogeneously in a rhodium-catalyzed diastereoselective reaction
employing a set of the previously published planar-chiral ‘‘Daniphos’’ ligands, which are based on an arene chromium tricarbonyl scaf-
fold. Diastereoselectivities of up to 42% de were achieved, almost matching the benchmark ligand BINAP. An X-ray structure of the
most successful ligand P(i-Pr2)/PPh2 is presented and discussed.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Rhodium; Diphosphines; Planar chirality; Asymmetric hydrogenation
1. Introduction
Boscalid (Nicobifen) [5] by Suzuki-coupling and the pro-
duction of Ibuprofene by Pd-catalyzed carbonylation and
the fragrance Civetone by Ru-catalyzed metathesis by
BASF [5]. L-Tetrahydrofolic acid is a versatile intermediate
for the manufacturing of different folates e.g., L-leucovorin
[7], which is used in cancer therapy or Metafolin which is
used as a vitamin in functional food. To our knowledge
optically pure L-tetrahydrofolic acid is still obtained by
repeated fractional crystallisation from an equimolar mix-
ture of diastereoisomers formed by non-diastereoselective
hydrogenation of folic acid. In order to increase the yield
of L-tetrahydrofolic acid and to avoid recrystallisation
steps, we checked the utility of our recently developed pla-
nar-chiral ligand, ‘‘Daniphos’’ [6] for the diastereoselective
hydrogenation of folic acid dimethylester-benzenesulfo-
nate. A sketch of the Daniphos ligand is given in Fig. 1.
Asymmetric catalysis is undoubtfully the most powerful
method for the synthesis of optically active compounds as
it is possible to gain a maximum amount of enantiomeri-
cally enriched product at the expense of only catalytic
amounts of a chiral catalyst which normally consists of a
transition metal and an enantiomerically pure ligand. The
nobel-prize winners Knowles, Noyori and Sharpless [1]
layed the foundation of a modern transition-metal catalysis
used on an industrial scale for the production of fine chem-
icals [2c], fragrances, agrochemicals and pharmaceutical
intermediates (API, active pharmaceutical ingredients).
Besides the well-known cases of the Takasago-process for
the production of (ꢀ)-menthol [1b,1d] and the Syngenta
herbicide (S)-Metolachlor [2a,2b], which involves an asym-
metric hydrogenation employing the JOSIPHOS-ligand,
more recent examples are AstraZenecaÕs heartburn drug
Esomeprazole by an asymmetric oxidation [3], NovartisÕ
antihypertensive drug Valsartan [4] and BASFÕs fungicide
2. Results and discussion
The hydrogenation of folic acid dimethyl ester benzene-
sulfonate is presented in Fig. 2. In this reaction the diazadi-
ene system of the pteridine ring of the substrate is
hydrogenated, giving a new stereogenic center at position
*
Corresponding author. Tel.: +49 241 809 4646; fax: +49 241 809 2288.
E-mail address: albrecht.salzer@ac.rwth-aachen.de (A. Salzer).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.11.026

2264
W. Braun et al. / Journal of Organometallic Chemistry 691 (2006) 2263–2269
They are summarized in Fig. 3, together with the bench-
mark ligands Josiphos and BINAP, which also were
included in this examination for reasons of comparison
(all ligands are configured (R) with respect to central as
well as planar chirality except for ligand 1, where also the
(S,S)-enantiomer was employed). The results are collected
in Table 1.
Fig. 1. The ‘‘Daniphos’’-ligand.
From the results achieved with ligand 1, it can be seen
that the use of the other enantiomer of the ligand results
in a reversal of the configuration in the product together
with (nearly) the same induction, as is to be expected.
Moreover, it is remarkable that all derivatives that carry
only aromatic substituents on the phosphorus donor atoms
deliver preferably the undesired (6R,S) diastereomer. In
contrast to this, the desired isomer is formed in excess when
the ligands contain aliphatic side chains on the donor cen-
ters as well (it should be kept in mind that all ligands are
configured (R,R)). Here, an especially high stereochemical
induction and chemical yield of tetrahydrofolic acid ester
is achieved in case of the P(i-Pr)2/PPh2 derivative 2. So
one might conclude that a sterically demanding, Lewis-
basic group in the ortho-position influences the reaction
in the desired direction. In case of the purely aromatic can-
didates the differences in optical yields are less pronounced:
they range between 20% and 30% de. Better values are
6. The distance of the stereogenic center of the glutamic
acid residue is too far from the newly formed chiral center
and therefore it does not cause any measurable stereochem-
ical induction in the hydrogenation and the outcome of the
reaction is governed by the chiral ligand alone. Quite a
number of experiments have been undertaken so far to
reach a reasonable induction, but the best results achieved
do not exceed some 40% de, in which the desired product is
the (S,S)-diastereomer [8]. In the course of the reaction, a
significant percentage of an undesired cleavage product is
observed in varying amounts (ABGAMe2, aminobenzoyl-
gluamic acid dimethylester), depending on the ligand used,
diminishing the yield of the valuable tetrahydrofolic acid
dimethylester (THFMe2).
A number of candidates from our ligand library has
been employed in this survey, bearing aliphatic as well as
aromatic substituents on the phosphorus donor atoms.
Fig. 2. Hydrogenation of folic acid dimethylester.

W. Braun et al. / Journal of Organometallic Chemistry 691 (2006) 2263–2269
2265
Fig. 3. Overview of the ligands employed in this investigation.
Table 1
Results of the hydrogenation of folic acid ester employing the Daniphos ligand
Ligand
No./R
Form
Stereoselectivity
Yield (%)
THFMe2
R0
d.r.(6S,S):(6R,S)
de (%)a
ABGAMe2
1/Ph
1/Ph
2/i-Pr
3/Ph
4/Ph
5/Ph
6/Ph
7/o-Tol
8/o-Tol
9/Ph
10/m-Xyl
11/m-Xyl
12 Josiphos
13 BINAP
a
Cy
Cy
Ph
S,S
R,R
R,R
R,R
R,R
R,R
R,R
R,R
R,R
R,R
R,R
R,R
S,S
R
43.0:57.0
58.5:41.5
71.2:28.8
54.0:46.0
34.2:65.8
39.2:60.8
39.6:60.4
37.2:62.8
32.5:67.5
41.3:58.7
36.1:63.9
34.0:66.0
61:39
ꢀ14.0
17.0
42.4
70.1
64.0
81.5
69.5
87.9
77.6
80.6
63.0
76.1
71.3
83.1
79.8
60
26.9
18.6
16.7
16.8
7.2
21.0
9.9
20.9
21.7
14.9
14.2
10.4
Unknown
Unknown
i-Bu
o-Tol
m-Tol
p-Tol
Ph
o-Tol
m-Xyl
Ph
8.0
ꢀ31.6
ꢀ21.6
ꢀ20.8
ꢀ25.6
ꢀ35.0
ꢀ17.4
ꢀ27.8
ꢀ32.0
22
m-Xyl
73:27
46
90
The de values were determined by HPLC analysis (see Section 4 for details).
obtained here if the ortho-group is quite bulky (o-Tol,
m-Xyl versus Ph). This effect cannot be observed for the
a-position, but it seems that the presence of a methyl group
close to the phosphorus center has a benefitial effect here as
well.
For the most successful ligand, P(i-Pr)2/PPh2 (2), we
were able to obtain a single crystal suitable for X-ray dif-
fraction measurements by slow evaporation of an etheral
solution. The structure is depicted in Fig. 4, some selected
bond lengths are given in Table 2. The experimental X-ray

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W. Braun et al. / Journal of Organometallic Chemistry 691 (2006) 2263–2269
Table 3
Experimental X-ray diffraction parameters and the crystal data for
compound 2
Compound
2
Empirical formula
Formula mass
C29H32CrO3P2
542.49
Crystal habit, color
Crystal dimensions (mm)
Crystal system
Rod, yellow
0.40 · 0.13 · 0.12
Orthorhombic
P212121
Space group
˚
a (A)
9.7035(15)
13.995(2)
19.993(3)
2715.1(7)
4
1.327
1136
0.567
Bruker Smart CCD
110(2)
˚
b (A)
˚
c (A)
3
˚
V (A )
Z
Dcalc (g cmꢀ1
F(000)
l (Mo Ka) (cmꢀ1
Diffractometer
T (K)
)
)
h Range (ꢁ)
2.33–27.45
35642
6213
Reflections collected
Unique reflections
Rint
Fig. 4. Displacement elipsoids plot (30%) of 2. The H atoms are shown
0.0598
with arbitrary radius.
Reflections used
Parameters refined
R1
5663
321
0.0378
wR2
FlackÕs parameter
Goodness-of-fit
0.0887
ꢀ0.010(17)
Table 2
˚
1.001
Selected distances (A) and angles (ꢁ) for complex 2
˚
Distances (A)
3
˚
Largest difference in peak/hole (e/A )
0.50/ꢀ0.25
P2–C5
P2–C18
P2–C24
C6–C5
1.876(2)
1.831(2)
1.832(3)
1.514(3)
P1–C11
P1–C13
P1–C16
C5–C4
1.856(2)
1.872(3)
1.874(2)
1.534(3)
3. Conclusion
We have proved that the ‘‘Daniphos’’ class of ligands
has indeed a high potential for the reaction under investiga-
tion and that with a suitable choice of the substitution pat-
tern it is in fact competitive to the BINAP system and
superior to the Josiphos ligand and its derivatives [9].
Angles (ꢁ)
C24–P2–C5
C18–P2–C5
C5–C6–C11
100.68(11)
103.62(11)
122.2(2)
C16–P1–C11
C13–P1–C11
P1–C11–C6
99.59(11)
99.91(11)
121.92(17)
4. Experimental
diffraction parameters and the crystal data are summarized
in Table 3. The structure exhibits the typical features that
were found in numerous other examples of diphosphines
of that kind [6d–i,6k]. The chromium tricarbonyl rotator
shows the typical piano stool arrangement, staggered with
regard to the chiral a-chain, causing this moiety to adopt a
conformation in which the hydrogen atom on the stereo-
genic carbon atom points down towards the chromium
atom to avoid steric hindrance. The diphenylphosphino
group points upwards, exhibiting a dihedral angle of
78.1(2)ꢁ between the planes defined by P2–C5–C6 and
C5–C6–C11. The disk-like shaped phenyl rings point away
from the lone-pair, whereas the isopropyl groups of the
other phosphine moiety can be regarded as rigid rotators,
which presumably helps to create a chiral environment in
the active catalyst and to force the substrate to coordinate
facial-selectively, yielding a relatively high de value. A sim-
ilar observation we made recently in the asymmetric ring
opening of oxanorbornadiene, where a ligand bearing a
bulky and rigid P(t-Bu)2-group gave the best selectivities
[6k].
The ligands were synthesized according to our published
method [6d]. Analytical data are given below for those can-
didates that were not published previously (compounds 4–8
and 10; for1 see Ref. [6d], for 2,9 and 11 see Ref. [6j] and
for 3 see Ref. [6k]). All substances were handled under
argon atmosphere using standard inert gas techniques.
NMR spectra were recorded on a Varian Unity 500 (1H:
500 MHz, 13C: 125 MHz, 31P: 200 MHz) spectrometer at
ambient temperature. IR spectra were recorded on a Nico-
let Avatare 360 E.S.P.e spectrometer. Mass spectra were
recorded on a Finnigan MAT 95 spectrometer using the
chemical ionisation (CI) technique and isobutane as react-
and gas. Solvents were purified applying standard proce-
dures. Flash chromatography was performed using
Merck grade silica gel 60 (0.04–0.063 mm).
4.1. General hydrogenation procedure
8.12 mg [Rh(COD)2]BF4 (20 lmol) and the diphosphine
ligand (25 lmol) were degassed in a Schlenk tube and

W. Braun et al. / Journal of Organometallic Chemistry 691 (2006) 2263–2269
2267
suspended in 5 ml methanol. 1.25 g (2 mmol) of folic acid
dimethylester benzenesulfonate were suspended in 25 ml
methanol and added via a narrow tube to the catalyst.
The suspension was added to a 100 ml autoclave flushed
with nitrogen. The autoclave was sealed and the hydroge-
nation run at 70 ꢁC at a constant pressure of 80 bar. After
17 h a sample for HPLC analysis was taken.
134.38 (d, JCP = 2.2 Hz, ar-C(PAr2)), 132.99 (dd,
JCP = 23.0 Hz, JCP = 1.1 Hz, ar-CipsoP-Tol or ar-Cipso
(PPh2)), 130.72 (d, JCP = 3.3 Hz, ar-C(PAr2)), 130.64 (ar-
C(PAr2)), 130.14 (d, JCP = 6.1 Hz, ar-C(PAr2)), 129.61–
125.93 (10C, ar-C(PAr2)), 124.26 (dd, JCP = 25.8 Hz,
-
JCP = 22.4 Hz, ar-Cipso), 104.32 (dd, JCP
= 22.4 Hz,
JCP = 3.2 Hz, ar-Cipso), 99.21 (d, JCP = 2.2 Hz, ar-C),
94.04 (ar-C), 89.75 (ar-C), 88.74 (dd, JCP = 4.2 Hz,
4.2. HPLC method for the separation of diastereoisomers of
tetrahydrofolic acid dimethylester
JCP = 4.2 Hz, ar-C), 31.53 (dd, JCP = 24.7 Hz, JCP =
21.9 Hz, PTol2CHMe), 22.46 (d, JCP = 23.5 Hz, Me-
Tol)21.70 (d, JCP = 20.3 Hz, Me-Tol), 15.75 (PTol2CHMe)
ppm.
The content and diastereomeric excess of tetrahydrofolic
acid dimethylester was determined by using the following
HPLC method: 6.8 g of b-cyclodextrine and 270 ml of
37% formaldehyde were dissolved in 1 L of water to give
the sample dilution solution. 1 ml of this sample dilution
solution was mixed with 15 mg of the hydrogenation mix-
ture or 1 mg isolated product was dissolved in 100 ml of
the sample dilution solution and analysed (flow rate 1 ml/
min) on an OS column (Macherey and Nagel, Nucleosil,
240 · 4 mm) with UV detection at 300 nm. The eluent
was prepared by mixing 6.8 g b-cyclodextrine, 8.5 ml trieth-
ylamine, 850 ml water and 150 ml acetonitrile. By addition
of acetic acid the pH was adjusted to pH 7.5 and then
270 ll of 37% formaldehyde were added.
4.4. [g6-(R,R)-{(Pm-Tol2)CHMe}(C6H4PPh2)]Cr(CO)3
(5)
Compound 5 was prepared according to the method
published in Ref. [6d] from the corresponding chloro deriv-
ative [g6-(R,R)-{(Cl)CHMe}(C6H4PPh2)]Cr(CO)3 (0.50 g,
1.09 mmol), di-(3-methylphenyl)-phosphine (0.26 g, 1.09
mmol) and TlPF6 (0.36 g, 1.03 mmol). It was purified
by column chromatography (first pentane, then ether).
Yield: 0.51 g (0.80 mmol, 73%). IR (CHCl3): mmax 1967,
1895 (CO) cmꢀ1. MS (CI): m/z = 696.0 (M+58+Å), 639.0
(M+1+Å). 31P NMR (200 MHz, C6D6) d = 9.81 (d,
JPP = 20.4 Hz, a-P), ꢀ18.1 (d, JPP = 20.4 Hz, ortho-P)
4.3. [g6-(R,R)-{(Po-Tol2)CHMe}(C6H4PPh2)]Cr(CO)3
(4)
ppm. H NMR (500 MHz, C6D6) d = 7.46–6.80 (m, 18H,
1
ar-H(PPh2) and ar-H(PTol2)), 5.31 (mbr, 1H, ar-H), 5.12
(mbr, 1H, ar-H), 5.02 (mbr, 1H, ar-H), 4.60 (mbr, 1H,
PTol2CHMe), 4.55 (mbr, 1H, ar-H), 2.31 (s, 3H, Me-
Tol), 2.28 (s, 3H, Me-Tol), 1.27 (tr, 3H, J = 5.7 Hz,
PTol2CHMe) ppm. 13C NMR (125 MHz, C6D6)
d = 232.48 (CO), 137.68 (d, JCP = 5.5 Hz, ar-CipsoMe-
Tol), 137.50 (d, JCP = 7.7 Hz, ar-CipsoMe-Tol), 136.49–
127.84 (22C) (ar-C(PPh2) and ar-C(PTol2)), 123.79 (ar-
Cipso), 104.09 (d, JCP = 21.4 Hz, ar-Cipso), 98.57 (ar-C),
97.44 (ar-C), 90.25 (ar-C), 89.24 (br, ar-C), 33.47 (tr,
JCP = 23.9 Hz, PTol2CHMe), 21.53 (Me-Tol), 21.44 (Me-
Tol), 15.98 (PTol2CHMe) ppm.
Compound 4 was prepared according to the method
published in Ref. [6d] from the corresponding chloro deriv-
ative [g6-(R,R)-{(Cl)CHMe}(C6H4PPh2)]Cr(CO)3 (0.85 g,
1.85 mmol), di-(2-methylphenyl)-phosphine (0.396 g, 1.85
mmol) and TlPF6 (0.612 g, 1.75 mmol). It was purified
by column chromatography (first pentane, then ether).
Yield: 0.91 g (1.43 mmol, 76%). IR (CHCl3): mmax 1968,
1899 (CO) cmꢀ1. MS (CI): m/z = 639.0 (M+1+Å). 31P
NMR (200 MHz, C6D6) d = 13.21 (d, JPP = 30.5 Hz, a-
P), ꢀ9.00 (d, JPP = 30.5 Hz, ortho-P) ppm. 1H NMR
(500 MHz, C6D6) d = 7.61 (m, 3H, ar-H(PPh2) and ar-
H(PTol2)), 7.32 (trm, 2H, ar-H(PPh2) and ar-H(PTol2)),
7.12 (trm 2H, ar-H(PPh2) and ar-H(PTol2)), 7.06–6.94
(m, 8H, ar-H(PPh2) and ar-H(PTol2)), 6.88 (dd, 1H,
JPH = 3.1 Hz, JPH = 1.2 Hz, ar-H(PPh2) and ar-H(PTol2)),
6.82 (trm, 1H, ar-H(PPh2) and ar-H(PTol2)), 6.75 (trm, 1H,
ar-H(PPh2) and ar-H(PTol2)), 4.97 (m, 2H, ar-H), 4.54 (tr,
1H, J = 6.4 Hz, ar-H), 4.28 (m, 1H, PTol2CHMe), 2.05 (s,
3H, Me-Tol), 1.64 (d, 3H, JPH = 1–5 Hz, Me-Tol), 1.35
(dd, 3H, J = 7.0 Hz, JPH = 4.6 Hz, PTol2CHMe) ppm.
13C NMR (125 MHz, C6D6) d = 232.88 (CO), 143.84 (d,
JCP = 31.8 Hz, ar-CipsoMe-Tol), 141.20 (d, JCP = 24.6 Hz,
ar-CipsoMe-Tol), 136.10 (dd, JCP = 6.9 Hz, JCP = 3.0 Hz,
ar-CipsoP-Tol or ar-Cipso(PPh2)), 135.83 (dd, JCP = 13.5 Hz,
JCP = 2.5 Hz, ar-CipsoP-Tol or ar-Cipso(PPh2)), 135.69 (d,
JCP = 19.2 Hz, ar-CipsoP-Tol or ar-Cipso(PPh2)), 135.54
(d, JCP = 1.5 Hz, ar-C(PAr2)), 134.97 (ar-C(PAr2)), 134.81
(ar-C(PAr2)), 134.53 (d, JCP = 2.2 Hz, ar-C(PAr2)),
4.5. [g6-(R,R)-{(Pp-Tol2)CHMe}(C6H4PPh2)]Cr(CO)3
(6)
Compound 6 was prepared according to the method
published in Ref. [6d] from the corresponding chloro deriv-
ative [g6-(R,R)-{(Cl)CHMe}(C6H4PPh2)]Cr(CO)3 (0.63 g,
1.50 mmol),
di-(4-methylphenyl)-phosphine
(0.32 g,
1.50 mmol) and TlPF6 (0.48 g, 1.37 mmol). It was purified
by column chromatography (first pentane, then ether).
Yield: 0.56 g (0.88 mmol, 64%). IR (CHCl3): mmax 1961,
1892 (CO) cmꢀ1. MS (CI): m/z = 696.0 (M+58+Å), 639.0
(M+1+Å). 31P NMR (200 MHz, C6D6) d = 7.38 (d,
JPP = 25.6 Hz, a-P), ꢀ20.12 (d, JPP = 23.8 Hz, ortho-P)
1
ppm. H NMR (500 MHz, C6D6) d = 7.47–7.05 (m, 18H,
ar-H(PPh2) and ar-H(PTol2)), 5.31 (tr, 1H, J = 6.1 Hz,
ar-H), 5.11 (tr, 1H, J = 6.1 Hz, ar-H), 5.02 (tr, 1H,
J = 6.1 Hz, ar-H), 4.58 (m, 1H, PTol2CHMe), 4.55 (d,

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W. Braun et al. / Journal of Organometallic Chemistry 691 (2006) 2263–2269
1H, J = 6.4 Hz, ar-H), 2.36 (s, 3H, Me-Tol), 2.32 (s, 3H,
Me-Tol), 1.26 (tr, 3H, J = 6.1 Hz, PTol2CHMe) ppm. 13C
NMR (125 MHz, C6D6) d = 232.51 (CO), 139.85 (ar-
CipsoMe-Tol), 137.41 (ar-CipsoMe-Tol), 135.89–128.18
(22C) (ar-C(PPh2) and ar-C(PTol2)), 123.81 (ar-Cipso),
104.19 (d, JCP = 21.3 Hz, ar-Cipso), 99.56 (ar-C), 93.74
667.1 (M+1+Å). 31P NMR (200 MHz, C6D6) d = ꢀ12.12
(d, JPP = 46.9 Hz, a-P), ꢀ41.74 (d, JPP = 44.3 Hz, ortho-
P) ppm. 1H NMR (500 MHz, C6D6) d = 7.33 (d, 1H,
J = 7.3 Hz), 7.47 (dd, 1H, J = 7.6 Hz, JPH = 3.9 Hz), 7.14
(m, 1H), 7.11–6.95 (m, 8H), 6.84 (m, 3H), 6.73 (m, 2H)
(ar-H(PAr2)), 5.40 (dt, 1H, J = 6.0 Hz, JPH = 1.2 Hz, ar-
(ar-C), 90.22 (ar-C), 89.28 (br, ar-C), 33.59 (d, JCP
=
H), 4.86 (ddq, 1H, J = 7.3 Hz, JPH = 7.3 Hz, JPH =
24.2 Hz, PTol2CHMe), 21.40 (Me-Tol), 21.22 (Me-Tol),
15.89 (PTol2CHMe) ppm.
2.8 Hz, CHMe), 4.78 (t, 1H, J = 6.4 Hz, ar-H), 4.24 (m,
1H, ar-H), 4.17 (td, 1H, J = 6.4 Hz, JPH = 0.9 Hz, ar-H),
3.02 (s, 3H, Ph–Me), 2.14 (s, 3H, Ph–Me), 1.83 (d, 3H,
JPH = 2.1 Hz, Ph–Me), 1.60 (d, 3H, JPH = 1.2 Hz, Ph–
Me), 1.32 (dd, 3H, J = 7.0 Hz, JPH = 4.3 Hz, CHMe)
ppm. 13C NMR (125 MHz, C6D6) d = 232.87 (CO),
145.71 (d, JCP = 31.3 Hz), 145.15 (d, JCP = 31.2 Hz),
141.91 (d, JCP = 22.0 Hz), 141.70 (d, JCP = 19.2 Hz) (ar-
CipsoMe–Ph), 136.99 (dd, JCP = 7.2 Hz, JCP = 3.3 Hz, ar-
CipsoP–Ph), 135.64 (d, JCP = 18.6 Hz, ar-CipsoP–Ph),
135.18, 134.39 (d, JCP = 4.8 Hz) (ar-C(PAr2), 133.65 (dd,
JCP = 25.2 Hz, JCP = 2.8 Hz, ar-CipsoP–Ph), 132.65 (dd,
JCP = 12.6 Hz, JCP = 3.2 Hz, ar-CipsoP–Ph)), 131.43
(d, JCP = 5.5 Hz), 130.59 (d, JCP = 3.8 Hz), 130.36 (d,
JCP = 3.2 Hz), 130.26 (d, JCP = 5.5 Hz), 130.13 (d,
JCP = 5.5 Hz), 130.07, 129.22, 128.67, 128.33, 128.29 (ar-
C(PAr2), 126.50 (d, JCP = 20.3 Hz, ar-CipsoP), 126.35,
126.07, 125.98, 125.24 (ar-Cipso(PAr2)), 101.29 (ar-C),
99.77 (dd, JCP = 22.5 Hz, JCP = 3.9 Hz, ar-CipsoC), 96.22,
87.46, 87.15 (dd, JCP = 3.9 Hz, JCP = 3.9 Hz) (ar-C),
31.71 (dd, JCP = 23.3 Hz, JCP = 23.3 Hz, CHMe), 22.60
(d, JCP = 23.6 Hz, Ph–Me), 22.21 (d, JCP = 24.7 Hz, Ph–
Me), 20.95 (d, JCP = 22.0 Hz, Ph–Me), 20.70 (d,
JCP = 24.0 Hz, Ph–Me), 15.80 (CHMe) ppm.
4.6. [g6-(R,R)-{(PPh2)CHMe}(C6H4Po-Tol2)]Cr(CO)3
(7)
Compound 7 was prepared according to the method
published in Ref. [6d] from the corresponding chloro
derivative [g6-(R,R)-{(Cl)CHMe}(C6H4Po-Tol2)]Cr(CO)3
(0.92 g, 1.88 mmol), diphenylphosphine (0.40 g, 2.16
mmol) and TlPF6 (0.66 g, 1.88 mmol). It was purified by
column chromatography (first pentane, then ether). Yield:
0.82 g (1.28 mmol, 68%). IR (CHCl3): mmax 1968, 1897
(CO) cmꢀ1. MS (CI): m/z = 639.1 (M+1+Å). 31P NMR
(200 MHz, C6D6) d = 10.04 (d, JPP = 34.6 Hz, a-P),
ꢀ40.37 (d, JPP = 32.0 Hz, ortho-P) ppm. 1H NMR
(500 MHz, C6D6) d = 7.51 (m, 1H), 7.21–7.12 (m, 6H),
7.11–6.94 (m, 9H), 6.90–6.85 (tm, 1H), 6.77–6.74 (tm,
1H) (ar-H(PAr2)), 4.83 (dq, 1H, J = 7.0 Hz, JPH = 8.5 Hz,
CHMe), 4.73 (t, 1H, J = 6.4 Hz), 4.15 (td, 1H, J = 6.4 Hz,
JPH = 1.2 Hz), 4.11 (m, 1H) (ar-H), 3.08 (s, 3H, Ph–Me),
2.04 (d, 3H, JPH = 1.8 Hz, ar-H), 1.30 (dd, 3H,
J = 7.6 Hz, JPH = 4.3 Hz, CHMe) ppm. 13C NMR
(125 MHz, C6D6) d = 232.84 (CO), 145.07 (d,
JCP = 30.9 Hz, ar-CipsoMe-Tol), 141.68 (d, JCP = 26.9 Hz,
ar-CipsoMe-Tol), 136.97 (dd, JCP = 7.4 Hz, JCP = 2.5 Hz,
ar-CipsoPAr), 136.78 (d, JCP = 19.8 Hz, ar-CipsoPAr),
136.00, 135.82, 135.10, 134.42 (d, JCP = 5.2 Hz) (ar-
C(PAr2)), 134.26 (d, JCP = 1.9 Hz, ar-CipsoPAr), 132.84
(dd, JCP = 11.8 Hz, JCP = 2.5 Hz, ar-CipsoPAr), 131.68,
131.56, 130.50 (d, JCP = 4.9 Hz), 130.15, 129.65, 128.90,
128.61, 128.58, 128.29, 127.89, 126.18, 125.60 (ar-
C(PAr2), 125.39 (dd, JCP = 23.0 Hz, JCP = 23.0 Hz, ar-
Cipso), 101.00 (ar-C), 99.69 (dd, JCP = 22.0 Hz,
4.8. [g6-(R,R)-{(PPh2)CHMe}C6H4Pm-Xyl2)]Cr(CO)3
(10)
Compound 10 was prepared according to the method
published in Ref. [6d] from the corresponding chloro
derivative [g6-(R,R)-{(Cl)CHMe}C6H4Pm-Xyl2)]Cr(CO)3
(0.46 g, 0.89 mmol), diphenylphosphine (0.25 g, 1.34
mmol) and TlPF6 (0.30 g, 0.85 mmol). It was purified
by column chromatography (first pentane, then
ether:pentane = 1:3). Yield: 0.12 g (0.18 mmol, 20%). IR
(CHCl3): mmax 1964, 1895 (CO) cmꢀ1. MS (CI): m/z =
667.0 (M+1+Å).31P NMR (200 MHz, C6D6) d = 7.39
(d, JPP = 16.5 Hz, a-P), ꢀ18.17 (d, JPP = 14.7 Hz, ortho-
P) ppm. 1H NMR (500 MHz, C6D6) d = 7.67 (trd, 2H,
J = 8.1 Hz, J = 1.7 Hz, ar-Hortho-Xyl), 7.45 (trd, 2H,
J = 7.6 Hz, J = 1.7 Hz, ar-Hortho-Xyl), 7.11–6.99 (m,
10H, ar-H(PPh2)), 6.77 (s, 1H, ar-Hpara-Xyl), 6.62 (s,
1H, ar-Hpara-Xyl), 5.12–5.06 (mbr, 1H, ar-H), 5.00 (dtr,
1H, J = 6.4 Hz, J = 1.2 Hz, ar-H), 4.58–4.53 (mbr, 1H,
ar-H), 4.35–4.30 (mbr, 1H, ar-H), 4.26 (trd, 1H,
J = 6.1 Hz, J = 1.5 Hz, ar-H), 2.02 (s, 6H, Me-Xyl),
1.96 (s, 6H, Me-Xyl), 1.49 (d, 3H, J = 7.1 Hz, CHMe)
ppm. 13C NMR (125 MHz, C6D6) d = 233.02 (CO),
136.05 (d, JCP = 23.0 Hz, ar-CipsoXyl–Me), 135.55 (ar-
CipsoXyl–Me), 135.50 (ar-CipsoXyl–Me), 135.46 (ar-
JCP = 3.3 Hz, ar-Cipso), 96.31, 87.66, 87.43 (dd, JCP
=
3.8 Hz, JCP = 3.8 Hz) (ar-C), 34.12 (dd, JCP = 24.0 Hz,
JCP = 24.0 Hz, CHMe), 22.30 (d, JCP = 24.9 Hz, Me-Ph),
21.09 (d, JCP = 23.0 Hz, Me-Ph), 15.24 (CHMe) ppm.
4.7. [g6-(R,R)-{(Po-Tol2)CHMe}(C6H4Po-
Tol2)]Cr(CO)3 (8)
Compound 8 was prepared according to the method
published in Ref. [6d] from the corresponding
chloro derivative [g6-(R,R)-{(Cl)CHMe}(C6H4Po-Tol2)]-
Cr(CO)3 (0.68 g, 1.39 mmol), di-(2-methylphenyl)-phos-
phine (0.34 g, 1.59 mmol) and TlPF6 (0.49 g, 1.39 mmol).
It was purified by column chromatography (ethyl acetate/
pentane = 1/8). Yield: 0.62 g (0.93 mmol, 67%). IR
(CHCl3): mmax 1969, 1900 (CO) cmꢀ1. MS (CI): m/z =

W. Braun et al. / Journal of Organometallic Chemistry 691 (2006) 2263–2269
2269
CipsoXyl–Me), 127.12–131.65 (20C, ar-C(PPh2 and PXyl2)),
References
100.26 (ar-C), 88.05 (ar-C), 95.81 (ar-C), 88.05 (ar-C),
87.90 (ar-C), 33.68 (tr, JCP = 24.7 Hz, PPh2CHMe), 21.78
(d, JCP = 23.6 Hz, Xyl–Me), 21.37 (Xyl–Me), 20.94 (Xyl–
Me), 20.76 (d, JCP = 23.1 Hz, Xyl–Me), 15.89 (PPh2CHMe)
ppm.
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5. Supplementary material
Crystallographic data (excluding structure factors) for
the structure reported in this paper have been deposited
at the Cambridge Crystallographic Data Centre as supple-
mentary publication No. CCDC-262406. Copies of the
data can be obtained free of charge on application to
The Director, CCDC, 12 Union Road, Cambridge CB21
EZ, UK (fax: int. code +44 1223 336 033; e-mail: depos-
it@ccdc.cam.ac.uk; web, www: http://www.ccdc.cam.ac.
uk).
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Acknowledgements
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tures, University of Go¨ettingen, Go¨ettingen, Germany, 1997.
[11] G.M. Sheldrick, SHELXL-97: Program for Refinement of Crystal
Structures, University of Go¨ettingen, Go¨ettingen, Germany, 1997.
[12] G.M. Sheldrick, SADABS, University of Go¨ettingen, Go¨ettingen,
Germany, 1996.
The authors gratefully acknowledge financial support by
the Deutsche Forschungsgemeinschaft DFG within the
Collaborative Research Centre (SFB 380) ‘‘Asymmetric
Synthesis with Chemical and Biological Methods’’. B.C.
is grateful to the Graduiertenkolleg ‘‘Methods in asymmet-
ric synthesis’’ for a scholarship.
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