Facile axial chirality control by using a precursor with central chirality. Application to the preparation of new axially chiral diphosphine complexes for asymmetric catalysis

Article abstract of DOI:10.1039/b207399d

A diastereoselective synthesis of a new chiral diphosphine with planar chirality is performed in 2 steps from (S)-p-tolylferrocenyl sulfoxide with 60% overall yield. The ligand gives enantioselectivities up to 98% ee in Pd(0)-catalyzed allylic substitutio

Full text of DOI:10.1039/b207399d

Facile axial chirality control by using a precursor with central chirality.
Application to the preparation of new axially chiral diphosphine
complexes for asymmetric catalysis
Matthias Lotz, Gernot Kramer and Paul Knochel*
Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstr. 5-13, Haus F, D-81377
München, Germany. E-mail: Paul.Knochel@cup.uni-muenchen.de; Fax: (+49)-89-2180-7680;
Tel: (+49)-2180-7681
Received (in Cambridge, UK) 29th July 2002, Accepted 6th September 2002
First published as an Advance Article on the web 1st October 2002
A diastereoselective synthesis of a new chiral diphosphine
with planar chirality is performed in 2 steps from (S)-p-
tolylferrocenyl sulfoxide with 60% overall yield. The ligand
gives enantioselectivities up to 98% ee in Pd(0)-catalyzed
allylic substitution reactions.
Molecules having axial chirality have found important applica-
tions as ligands in asymmetric catalysis.1 The enantioselective
synthesis of axially chiral compounds can be troublesome,2
however, an elegant approach for the synthesis of axially chiral
binaphthyls has been recently reported by Lipshutz3 and
Bringmann.4 Herein, we report the synthesis of a new class of
Scheme 1 Synthesis of ligand 1. Reagents and conditions: (a) LDA (1.1
planar chiral diphosphines such as 1 using the chiral building
equiv), THF, 278 °C, 30 min; (b) ZnBr2 (1.3 equiv), THF, 278 °C to room
block 2.5 The diphosphine 1 forms, upon complexation to a
metallic salt, axially chiral complexes such as 3. Due to steric
temp., 1 h; (c) Pd(dba)2 (5 mol%), tfp (10 mol%), THF, 65 °C, 16 h,
(2-iodophenyl)diphenylphosphine (4; 0.7 equiv); (d) t-BuLi (2.0 equiv),
hindrance, the complexation of a metal with ligand 1 will only
occur on the upper face away from the bulky ferrocenyl moiety.
Furthermore, the diphenylphosphinyl group attached to the
upper Cp-ring (see complex 3) will allow a further right–left
differentiation, so that the metallic moiety (L2M) will be in a
well defined steric environment (see Fig. 1).
THF, 278 °C, 5 min; (e) ClPPh2 (3.5 equiv), 278 °C to room temp.
substitution product (8) in high yield and 92–98% ee depending
on the temperature. The highest enantiomeric excess is obtained
at 220 °C (98% ee) (Scheme 2).
Similarly, the substitution of 1,3,3-triphenylprop-2-enyl
acetate (9)10 with dimethyl malonate furnishes with complete
regioselectivity the triphenyl derivative 10 in 94% yield and
85% ee (Scheme 2). Pd(0)-catalyzed substitution reactions with
amine derivatives have also been examined. Thus, the reaction
of the potassium salt of benzoylhydrazine leads to the product
12b in 86% ee at 20 °C and in 95% ee at 220 °C in 96–98%
yield. Finally, benzylamine furnishes at 20 °C the allylic amine
12c under the standard conditions in 71% yield and 82% ee.
Only very little conversion was observed, when the same
reaction was attempted at 220 °C (Scheme 3).
Fig. 1 Structures of the diphosphine 1 and complexes 2 and 3.
The complexation to the metal center locks the conformation
of the aryl ring attached to the ferrocene and thus creates a
chirality axis.
In summary, we have developed a new simple synthesis of
axially chiral diphosphine complexes. The presence of the
planar chiral ferrocenyl unit avoids the need of resolution since
The ferrocenyl sulfoxide 2 can be readily prepared in
optically pure form according to Kagan.5 Its ortho-lithiation
using LDA (278 °C to room temp., 1 h) followed by
transmetallation with ZnBr2 furnishes the corresponding zinc
reagent. Negishi cross-coupling6 of this intermediate ferroce-
nylzinc derivative with (2-iodophenyl)diphenylphosphine (4) in
the presence of Pd(dba)2 (5 mol%), tris-o-furylphosphine (tpf,
10 mol%) in THF (65 °C, 16 h) afforded the chiral sulfoxide 5
in 74% yield. Sulfoxide–lithium exchange of 5 with t-BuLi in
THF (278 °C, 5 min) and trapping of the lithium intermediate
with ClPPh2 provides the diphosphine 1 in 81% yield. Thus, the
diphosphine 1 was obtained in 2 steps from the sulfoxide 2 in ca.
60% overall yield (Scheme 1).
The mode of complexation of the new ligand 1 was verified
by forming complex 6 with [Pd(C3H5)Cl]2 (0.5 equiv) and
LiClO4. The X-ray structure7 of 6 indicates that only the
predicted diastereomeric complex is formed. Therefore, the
ferrocenyl moiety efficiently shields the bottom side and the
back side (Fig. 2).
The diphosphine 1 was tested in several reactions.8 Allylic
substitution9 of 1,3-diphenylallyl acetate (7) with dimethyl
malonate in the presence of [Pd(C3H5)Cl]2 (1 mol%) and the
chiral ligand 1 (2 mol%) provides the expected allylic
Fig. 2 ORTEP-Plot of the molecular structure of Pd-complex 6 (anion and
H-atoms were omitted for clarity). The thermal ellipsoids represent a 50%
probability.
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This journal is © The Royal Society of Chemistry 2002

independent and used in refinement, 7195 with I 4 2s(I), Rint = 0.0619,
mean s(I)/I = 0.0419, C-bonded H are refined with a riding model. The
center-C-atom of the allyl ligand is disordered, 468 parameters, R(Fobs
)
= 0.0400, Rw(F2) = 0.1100, S = 1.111, Flack parameter: 20.04(2),
min. and max. residual electron density: 21.024, 0.650 e Å23, max.
shift/error: 0.002, programs used: ‘SIR97 (Cascarano et al., Acta
Crystallogr., Sect A, 1996, C79)’, ‘SHELXL-97 (G. M. Sheldrick.
University of Gottingen, 97-2 version)’, ORTEP (M. N. Burnett, C. K.
Johnson, ORTEP-III: Oak Ridge Thermal Ellipsoid Plot Program for
Crystal Structure Illustrations, Oak Ridge National Laboratory Report
ORNL-6895, 1996). CCDC 190672. See http://www.rsc.org/suppdata/
cc/b2/b207399d/ for crystallographic data in CIF or other electronic
format.
8 The new ligand 1 was patented in collaboration with Degussa AG: M.
Lotz, P. Knochel, A. Monsees, T. Riermeier, R. Kadyrov and J. Almena,
Ger. Pat. No. DE 10211250.
9 G. Helmchen and A. Pfaltz, Acc. Chem. Res., 2000, 33, 336; B. M. Trost,
Chem. Pharm. Bull., 2002, 50, 1.
Scheme 2 Pd-catalyzed allylic substitution of acetates 7 and 9 using ligand
1.
10 G. J. Dawson, J. M. J. Williams and S. J. Coote, Tetrahedron:
Asymmetry, 1995, 6, 2535.
11 Preparation of diphosphine 1. (a) Preparation of sulfoxide 5: LDA (2 M
in THF, 1.35 mL, 2.70 mmol, 1.1 equiv) was added dropwise at 278 °C
to a solution of (S)-ferrocenyl-p-tolylsulfoxide (2) (793 mg, 2.45 mmol)
in THF (15 mL). After 30 min of stirring, ZnBr2 (1.3 M in THF, 2.51
mL, 3.26 mmol, 1.3 equiv) was slowly added and the mixture allowed
to warm to room temperature. After 1 h the solvent was evaporated in
vaccuo and the resulting residue was dissolved in THF (10 mL).
Pd(dba)2 (61.2 mg, 5 mol%) and tfp (49.2 mg, 10 mol%) were dissolved
in THF (3 mL) and stirred for 10 min. A solution of (2-iodophenyl)di-
phenylphosphine (4) (633 mg, 1.63 mmol, 0.67 equiv) in THF (2 mL)
was added and the mixture stirred for an additional 10 min. The solution
of the ferrocenyl zinc compound was added and the reaction mixture
was stirred at 65 °C for 16 h. The solution was quenched with water, the
aqueous phase was extracted with Et2O (3 3 50 mL), the combined
organic phases were washed with brine and dried over MgSO4. The
solvent was removed under reduced pressure and the crude product was
purified by column chromatography (silica gel, pentane/Et2O 1+2)
affording 5 (707 mg, 1.21 mmol, 74 %) as a yellow solid (mp = 198 °C).
(b) Phosphorylation of 5 leading to 1. To a solution of ferrocenyl
sulfoxide 5 in THF (8 mL) was slowly added t-BuLi (1.6 M in pentanes,
0.64 mL, 1.03 mmol, 2.0 equiv) at 278 °C. After stirring for 5 min,
chlorodiphenylphosphine (0.32 mL, 1.80 mmol, 3.5 equiv) was added
dropwise, the mixture stirred for 5 min at 278 °C and for 30 min at room
temperature. The reaction was quenched with saturated aqueous NH4Cl
solution, the aqueous phase was extracted with Et2O (3 3 50 mL), the
combined organic phases were washed with brine and dried over
MgSO4. The solvent was removed under reduced pressure and the crude
product was purified by column chromatography (silica gel, pentane/
Et2O 50+1) affording 1 (260 mg, 0.41 mmol, 81%) as a yellow solid (mp
= 187 °C).
12 Typical procedure for the allylic amination of 7. To a suspension of KH
(36.5 mg, 0.91 mmol) in THF (4 mL) was added portionwise p-
tolylsulfonamide 11a (200 mg, 1.17 mmol) and the mixture was stirred
for 2 h at room temperature. Allylpalladium chloride (dimer, 2.3 mg, 1.0
mol%) and ligand 1 (8.1 mg, 2.0 mol%) were dissolved in THF (1 mL),
stirred for 15 min at room temperature and then cooled to 220 °C.
Acetate 6 (168 mg, 0.64 mmol) and the suspension of 11a were added
and the reaction mixture was stirred at 220 °C for 48 h. The reaction
was quenched with saturated aqueous NH4Cl solution, the aqueous
phase was extracted with CH2Cl2 (2 3 50 mL), the combined organic
phases were washed with brine and dried over MgSO4. The solvent was
removed under reduced pressure and the crude product was purified by
column chromatography (silica gel, pentane/Et2O 2+1) affording 12a
(181 mg, 0.50 mmol, 78%, 97% ee) as a white solid.
Scheme 3 Pd-catalyzed allylic amination of acetate 7 using ligand 1.
only one diastereomer is formed in a metal complexation. From
central chirality (sulfoxide) we were able to generate ster-
eoselectively a chirality plan and a chirality axis. The new
ligand is useful for asymmetric allylic substitutions with
malonates and amino derivatives.10–12 Further applications in
asymmetric catalysis are currently underway.
We thank Degussa AG for financial support and for the
generous gift of chemicals.
Notes and references
1 R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New
York, 1994.
2 J. M. Brown, D. I. Hulmer and . Langzell, J. Chem. Soc., Chem.
Commun., 1993, 1673; T. Chiba, A. Miyashita and H. Nohira,
Tetrahedron Lett., 1993, 34, 2351; T. Chiba, A. Miyashita, H. Nohira
and H. Takaya, Tetrahedron Lett., 1991, 32, 4745.
3 B. H. Lipshutz and Y.-J. Shin, Tetrahedron Lett., 1998, 39, 7017.
4 G. Bringmann and D. Menche, Acc. Chem. Res., 2001, 34, 615.
5 D. Guillaneux and H. B. Kagan, J. Org. Chem., 1995, 60, 2502.
6 E. Negishi, L. F. Valente and M. Kobayashi, J. Am. Chem. Soc., 1980,
102, 3298; E. Negishi, Acc. Chem. Res., 1982, 15, 340; H. Pedersen and
M. Johannsen, Chem. Commun., 1999, 2517.
7 6: C43H37ClFeO4P2Pd, Mr = 877.42 g mol21, yellow needle, 0.32 3
0.06 3 0.04 mm, orthorhombic, P212121, a
= 9.74630(10), b =
18.7721(2), c = 20.4955(2) Å, a = 90, b = 90, g = 90°, V =
3749.83(7) Å3, Z = 4, r = 1.55421(3) g cm23, T = 200(2) K,
m(MoKa)
paCCD’, l(MoKa) = 0.71073, q range: 3.17–27.47, 59657 refls., 8570
=
1.066 mm21, numerical absorption correction, ‘Kap-
CHEM. COMMUN., 2002, 2546–2547
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