Chirality control in 2,2′-biphosphole ligand leading to enantiopure Pd complex

Article abstract of DOI:10.1039/b301613g

Asymmetric alkylation of the 3,4-dimethyl-5-phenyl-2,2′-biphospholyl anion with the (2R, 4R)-(-)-pentaneditosylate leads to a new chirally flexible 2,2′-biphosphole ligand as a mixture of three diasteroisomers. By complexation with Pd(II), a chirality con

Full text of DOI:10.1039/b301613g

Chirality control in 2,2A-biphosphole ligand leading to enantiopure Pd
complex†
Carmen Ortega, Maryse Gouygou* and Jean-Claude Daran*
Laboratoire de Chimie de Coordination, CNRS, 205 route de Narbonne F-31077 Toulouse, Cedex France.
E-mail: gouygou@lcc-toulouse.fr, daran@lcc-toulouse.fr; Fax: 33 (0)5 61 55 30 03; Tel: 33 (0)5 61 33 31
74
Received (in Cambridge, UK) 12th February 2003, Accepted 20th March 2003
First published as an Advance Article on the web 9th April 2003
Asymmetric alkylation of the 3,4-dimethyl-5-phenyl-2,2A-
biphospholyl anion with the (2R, 4R)-(2)-pentaneditosylate
leads to a new chirally flexible 2,2A-biphosphole ligand as a
mixture of three diasteroisomers. By complexation with
Pd(II), a chirality control occurs to afford enantiopure Pd
complex.
Considerable efforts have been devoted to the development of
new chiral ligands owing to the growing importance of
transition metal catalysed asymmetric synthesis.1 Among these
chiral ligands, diphosphanes have played a dominant role, in
particular chirally rigid atropoisomeric ligands (e.g. BINAP,
DuPHOS).1 Recently, a new approach has emerged where
conformationnally flexible diphosphanes (e.g. BIPHEP) are
used in asymmetric activation process.2 The dynamic chirality
control takes place in inert metal coordination sphere by using
a chiral controller. We have recently reported the use of the
chirally flexible BIPHOS ligand in asymmetric catalysis owing
Scheme 1 Reagents and conditions : i, Na-naphthalene, THF, 25 °C; ii,
to the combination of a crystallisation induced spontaneous
(2)-(R,R)-TsOCH(CH3)–CH2–CH(CH3)OTs, THF, 25 °C; iii, S8, CH2Cl2,
resolution of this diphosphane and its kinetic stabilisation by
25 °C.
coordination with PdCl2.3 This chiral flexible ligand exists in
solution as an equilibrium of six stereoisomers (Fig. 1) because
been converted into their more air-stable disulfides derivatives
4 (Scheme 1), a process that occurs with retention of
configuration at phosphorus.6 Disulfides 4, obtained as a
mixture of 4a–c could be separated by column chromatography
and characterised by 1H, 13C, 31P NMR spectroscopy and mass
spectroscopy. The molecular structures of 4a and 4c have been
established by X-ray diffraction studies7 (Fig. 2 and 3). For both
Fig. 1 The different stereoisomers of BIPHOS that possess two chiral
centers and one chiral axis; each stereoisomer is also represented in a
Newman projection along the axis of the C–C linking the phosphole
rings.
of the configurational instability of the axial chirality generated
by the 2,2A-biphosphole framework and of the central chiralities
of the phosphorus atoms.4 In order to generalise the use of 2,2A-
biphosphole type ligands in asymmetric catalysis, it’s necessary
to control the chirality of this ligand. This can be achieved in
two steps : first by introducing a chiral controller on the 2,2A-
biphosphole framework such as a chiral chain to connect the
two phosphorus atoms and secondly by complexation to select
the best configuration to accommodate the metal centre. In
order to prepare this new type of 2,2A-biphosphole ligand, we
have investigated the asymmetric alkylation of the 3,4-dime-
thyl-5-phenyl-2,2A-biphospholyl anion 2 with the enantiomer-
ically pure (2R,4R)-(2)-pentaneditosylate.†
Fig. 2 Molecular view of 4a with atom labelling scheme. Ellipsoids at
50%.
compounds all structural parameters, distances and angles, are
in good agreement with reported structures.4,8 The molecular
structure of the major diastereoisomer 4a shows that the (S,S)
phosphorus stereochemistry is associated with the (R) axial
chirality of the 2,2A-biphosphole framework as shown by the
P(1)–C(11)–C(21)–P(2) torsion angle of 255.4(2)°. For the
diastereoisomer 4c, the (R,R) central chirality is associated with
the (S) axial chirality as shown by the P(1)–C(11)–C(21)–P(2)
torsion angle of 84.3(3)°[mean value]. The large difference
observed with the torsion angle in 4a is certainly related to the
strain introduced by the chiral bridge in the S[Rp,Rp] configura-
tion.9 Concerning compound 4b, its absolute configuration
could not be established. However, the two phosphorus
The 2,2A-biphospholyl anion 25 was obtained from the
phosphole tetramer 1 after cleavage of the two phosphorus–
phosphorus bonds by naphthalene sodium in THF (Scheme 1).
2 reacted with the enantiomerically pure ditosylate to afford the
2,2A-biphosphole compound 3 in 65% yield as a mixture of three
diastereoisomers 3a (dp 18), 3b (dp 31 (d), dp 27(d), JPP 42) and
3c (dp 16) in the ratio 80+15+5. These diastereoisomers have
† Electronic supplementary information (ESI) available: selected spectro-
scopic NMR data. See http://www.rsc.org/suppdata/cc/b3/b301613g/
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CHEM. COMMUN., 2003, 1154–1155
This journal is © The Royal Society of Chemistry 2003

Fig. 3 Molecular view of 4c with atom labelling scheme. Ellipsoids at
50%.
Fig. 4 Molecular view of complex 6 with atom labelling scheme. Ellipsoids
at 50%. Selected bond lengths (Å) and bond angles(°): Pd–P(1) 2.2735(6);
Pd–P(2) 2.2479(6); Pd–Cl(1) 2.3381(7); Pd–Cl(2) 2.3515(6); P(1)–Pd–P(2)
78.02(2); P(1)–Pd–Cl(1) 169.31(2); P(2)–Pd–Cl(1) 91.29(2); P(2)–Pd–
Cl(2) 176.14(3); Cl(1)–Pd–Cl(2) 92.53(2).
resonances observed at dp = 67.3 and dp = 63.3 are consistent
with two diastereotopic phosphorus having opposite phospho-
rus configurations (R,S). According to these results, the chiral
controller have induced (1) a good carbon-to-phosphorus
induction as the original (R,R) chirality of the enantiomerically
pure ditosylate induces the preferred (S,S) stereochemistry of
the phosphorus atoms, (2) a partial chirality control of the 2,2A-
biphosphole framework as three diastereoisomers are obtained
among the six expected. The substitution of the two phenyl
groups by a short chain prevents the formations of (a) and (b)
forms and favour the (c), (d), (e) (or (f)) configurations (Figure
1). Among these three forms, the best candidate for chelating a
metal appears to be the isomer (e) (or (f)).
To confirm the stereolability of the 2,2A-biphosphole 3a, we
have carried out the desulfurization of compounds 4a and 4c
using a stereospecific method.10 Compound 4a reacted with
methyltrifluoromethane sulfonate to give compound 5a in
quantitative yield. Then at 270 °C, the reduction of 5a led to the
quantitative formation of 3a but an isomerization proceeded at
230 °C giving a mixture of 3a–c at room temperature in the
ratio 80+15+5 (Scheme 2). A similar reaction conducted on 4c
We thank the CNRS for financial support and the CON-
ACYT for a grant to Carmen Ortega-Alfaro.
Notes and References
1 E. N. Jacobsen, A. Pfaltz and H. Yamamoto, Comprehensive Asym-
metric Catalysis, Springer-Verlag, Berlin, 1999; R. Noyori, Asymmetic
Catalysis in Organic Synthesis, Wiley, New York, 1994.
2 K. Mikami, K. Aikawa, Y. Yusa, J. J. Jodry and M. Yamanaka, Synlett.,
2002, 10, 1561–1578 and references therein.
3 O. Tissot, M. Gouygou, F. Dallemer, J.-C. Daran and G. G. A.
Balavoine, Angew. Chem. Int. Ed., 2001, 40, 1076–1078.
4 O. Tissot, M. Gouygou, J.-C. Daran and G. G. A. Balavoine, Chem.
Commun., 1996, 2287–2288.
5 F. Laporte, F. Mercier, L. Ricard and F. Mathey, J. Am. Chem. Soc.,
1994, 116, 3306–3311.
6 W. E. McEven, Top. Phosphorus Chem., 1965, 2, 1; M. J. Gallaher and
J. D. Jenkins, Top. Stereochem., 1969, 3, 1.
7 Crystal data. R[Sp,Sp,Sc,Sc]-(+)4a: C29H32P2S2, M
= 506.61, or-
thorhombic, a = 6.568(1), b = 12.240(2), c = 33.217(7) Å, U =
2670.4(8) Å3, T = 180 K, space group P212121 (no 19), Z = 4, µ(Mo–
Ka) = 1.26 mm21, 20164 reflections measured, 5457 unique (Rint
=
0.048) which were used in all calculations. The final R and wR(F2) were
0.0327 and 0.0733 respectively (all data), Flack’s parameter = 0.00(6).
CCDC 203934. Crystal data. S[Rp,Rp,Sc,Sc]-(+)4c: C29H32P2S2, M =
506.61, monoclinic, a = 12.225(1), b = 16.667(1), c = 13.365(1) Å, b
= 90.08(1)°, U = 2723.0(4) Å3, T = 180 K, space group P21 (no 4), Z
= 4, µ(Mo–Ka) = 1.236 mm21, 20784 reflections measured, 10919
unique (Rint = 0.045) which were used in all calculations. The final R
and wR(F2) were 0.0410 and 0.0862 respectively (all data), Flack’s
parameter = 0.07(6) ; the crystal is twinned (twin law: 1 0 0 0–1 0 0
0–1) and emulates orthorhombic. CCDC 203935. See http:/
/www.rsc.org/suppdata/cc/b3/b301613g/ for crystallographic data in
.cif or other electronic format.
Scheme 2 Reagents and conditions : i, CF3SO3Me, CH2Cl2, 25 °C; ii, t-
BuSLi, CH2Cl2/Et2O, 270 °C.
gave the same mixture at room temperature. These results
confirm that 2,2A-biphosphole 3 exists in solution at room
temperature as an equilibrium mixture of three diastereoi-
somers.
8 O. Tissot, J. Hydrio, M. Gouygou, F. Dallemer, J.-C. Daran and G. G.
A. Balavoine, Tetrahedron, 2000, 56, 85; J. Hydrio, M. Gouygou, F.
Dallemer, G. G. A. Balavoine and J.-C. Daran, Eur. J. Org. Chem.,
2002, 675–685.
9 To define absolute configuration, axial chirality is given first and central
chiralities are between square brackets.
10 J. Omelanczuk and M. Mikolajczyk, J. Am. Chem. Soc., 1979, 101,
7292; J. Omelanczuk, W. Perlikowska and M. Mikolajczyk, J. Chem.
Soc., Chem. Commun., 1980, 24.
11 According to 31P NMR, this unidentified product is a palladium
complex with four diastereotopic phosphorus having opposite phospho-
rus configurations [Rp,Sp) (dp 53.2 (d), dp 51.2(d), JPP 3.25 ; dp 52.9(s),
dp 50.9(s)).
12 Crystal data. [Rp,Sp,Sc,Sc]-(+)6: C29H32Cl2P2Pd,CH2Cl2, M = 704.71,
monoclinic, a = 9.1318(7), b = 12.1101(11), c = 14.1276(10) Å, b =
104.042(8)°, U = 1515.6(2) Å3, T = 180 K, space group P21 (no 4), Z
= 2, µ(Mo–Ka) = 1.09 mm21, 15118 reflections measured, 5886
unique (Rint = 0.046) which were used in all calculations. The final R
and wR(F2) were 0.0255 and 0.0512 respectively(all data), Flack’s
parameter = 0.00(2). CCDC 203936.
However, in presence of a transition metal, this equilibrium
shifts to one preferentially configuration. Treatment of 3a–c
with 1 equiv. of [PdCl2(CH3CN)2] led to complete consumption
of the ligand to afford [PdCl2(2,2A-biphosphole)] 6 (90%) and an
unidentified product (10%).11 The X-ray structure of 612 (Fig.
4) indicates that only the predicted [Rp,Sp] configuration of
2,2-biphosphole is complexed to the metal centre. The axial
chirality of the 2,2-biphosphole framework disappeared upon
complexation. Indeed, owing to the strain induced by chelation
on the metal, the P(1)–C(11)–C(21)–P2 torsion angle, 28.2(2)°,
is drastically reduced from the values observed in 4a and 4c .
The two rings P(1) C(11) C(12) C(13) C(14) P(2) C(21) C(22)
C(23) C(24) might be considered as planar with the largest
deviation being 20.261(2) Å at C(14).
In summary, we have developed a new simple access to
enantiopure 2,2A-biphosphole complex based on a two step
chirality control process. Applications in asymmetric catalysis
are currently underway.
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