New enantiopure cyclic β-iminophosphine ligands: Applications in Pd-catalyzed asymmetric allylic substitution

Article abstract of DOI:10.1016/S0040-4039(03)00182-5

New enantiopure cyclic β-iminophosphines were applied as ligands in Pd-catalyzed asymmetric allylic substitution reactions.

Full text of DOI:10.1016/S0040-4039(03)00182-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2413–2415
New enantiopure cyclic b-iminophosphine ligands: applications in
Pd-catalyzed asymmetric allylic substitution
Maria Zablocka,a,* Marek Koprowski,a Bruno Donnadieu,b Jean-Pierre Majoral,b,* Mathieu Achardc
and Ge´rard Buonoc,*
aCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
bLaboratoire de Chimie de Coordination, 205 route de Narbonne, 31077 Toulouse Cedex 4, France
cENSSPICAM, CNRS, UMR 6516, Faculte´ St Je´roˆme, Av. Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France
Received 12 December 2002; accepted 16 January 2003
Abstract—New enantiopure cyclic b-iminophosphines were applied as ligands in Pd-catalyzed asymmetric allylic substitution
reactions. © 2003 Elsevier Science Ltd. All rights reserved.
Transition metal-catalyzed asymmetric reactions per-
formed with phosphorusꢀnitrogen mixed donor biden-
tate ligands generally led to excellent levels of
stereocontrol.1 A large variety of phosphorusꢀnitrogen
ligands was used but very few of them concern linear or
cyclic iminophosphines.2–4 Among them, chiral linear
g-iminophosphines 1 have shown a versatile behaviour
in some catalytic asymmetric transformations such as
for example palladium-catalyzed asymmetric allylic
substitutions.3 However to the best of our knowledge,
no similar work has been conducted with cyclic
iminophosphines. Electronically and sterically different
chiral arrangements as well as variation in the ligand
flexibility might induce better enantioselectivities. In
this paper we report the synthesis of new enantiomeri-
cally pure cyclic b-iminophosphines, the crystal struc-
ture characterization of an enantiomer and preliminary
results concerning the catalytic properties of Pd(0) com-
plexes in asymmetric allylic alkylation and amination.
pure enantiomeric form. These two enantiomers were
1
characterized by H, 13C, 31P NMR and by mass spec-
trometry analysis.6 The enantiomeric purity of 5 was
1
determined by either chiral HPLC7 or H NMR using
the chiral shifting agent (+)-Eu(hfc)3. The structure of
the 5-(RP) enantiomer {[h]2D0=−252 (c 3.1, CHCl3)} was
solved by X-ray diffraction studies which confirm its
absolute configuration at the level of the phosphorus
atom.8 Absolute configuration for carbons C8(S) and
C(11)(S) was also established (see Fig. 1). NMR data of
the 5-(SP) enantiomer {[h]2D0=+254 (c 2.3, CHCl3)}
were similar to that observed for 5-(RP).
According to the procedure already published5 we have
prepared and separated the (R)- and (S)-phospholene
enantiomers 2-(RP) and 2-(SP) (Scheme 1). Each of
these enantiomeric forms was reacted first with
diphenyl zirconocene—a precursor of zirconabenzyne—
to give the tricyclic zirconaindanephospholanes 3-(RP)
and 3-(SP), respectively.6 Further treatment of 3-(RP)
and 3-(SP) with the isocyanide 4 (R=2,6-Me2C6H3)
afforded the b-iminophosphines 5-(RP) and 5-(SP) in
Scheme 1. Synthesis of the enantiopure cyclic b-iminophos-
phines 5.
* Corresponding authors. Tel.: +33-5-6133-3123; fax: +33-5-6155-
3003; e-mail: majoral@lcc-toulouse.fr
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00182-5

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M. Zablocka et al. / Tetrahedron Letters 44 (2003) 2413–2415
plex.9 The PdꢀCl bond lenghts are significantly different
from one another, the chlorine atom trans to phospho-
,
rus displaying the expected longer distance (2.343 A as
,
compared to its partner trans to nitrogen (2.296 A).
This is the expression of the higher trans influence of
the phosphine ligand. We have tested the catalytic
properties of the palladium complexes formed in situ
from this new ligand 5-(RP) and 2 mol% of [Pd-
(allyl)Cl]2 in an allylic alkylation of 1,3-diphenylprop-
3-en-1-yl acetate 6 by the nucleophile generated from
dimethylmalonate with N,O-bis(trimethylsilyl) acet-
amide (BSA) and a catalytic amount of potassium
acetate in methylene dichloride solution at room tem-
perature (Table 1). The (S)-alkylated product 7 was
obtained in 95% yield and 57% e.e. with a ratio ligand/
Pd=2 (entry 1). The enantioselectivity decreases to 48%
with a ratio ligand/Pd=1 (entry 2). For the amination
the reaction solvents influenced the enantioselectivity of
the reaction and the best enantioselectivity e.e.=64%
was observed in CH2Cl2 as solvent (entries 3 and 4).
Both Pd(0)-allylic substitution alkylation and amina-
tion led to the same relative configuration for the
products 7 and 8 involving probably the same h3-allylic
diastereomer Pd-complex during the nucleophilic
attacks. By using 5-(SP), 7-(R) and 7-(S) were obtained
with practically the same enantioselectivity.
Figure 1. Molecular structure of 5-(RP) showing the atom
,
numbering scheme. Selected bond distances (A) and angles
(°): P(1)ꢀC(11) 1.880(4), P(1)ꢀC(10) 1.837(4), C(11)ꢀC(1)
1.521(5), C(8)ꢀC(7) 1.502(5), C(1)ꢀN(1) 1.272(5), N(1)ꢀC(18)
1.426(5), C(10)ꢀP(1)ꢀC(11) 92.27(19), P(1)ꢀC(11)ꢀC(1)
Although these preliminary results reveal a good yield
but a moderate enantioselectivity of allylation products,
the original strategy applied to synthesize these new
enantiopure chiral ligands should allow to modulate
electronic and steric effects for achieving higher enan-
tioselectivity in the asymmetric catalysis. The investiga-
tion on the application of these ligands in other
transition-metal-catalyzed asymmetric reactions is
ongoing in our laboratories.
112.7(3),
C(11)ꢀC(1)ꢀN(1)
130.3(4),
C(1)ꢀN(1)ꢀC(18)
118.9(3), C(11)ꢀC(8)ꢀC(7) 103.3(3), P(1)ꢀC(10)ꢀC(9) 107.4(3).
We shown that the ligand 5 is able to form five-mem-
bered ring chelates with both nitrogen and phosphorus
atoms coordinated to Pd(II) in the (PꢀN)PdCl2 com-
Table 1. Asymmetric Pd(0)-catalyzed substitution of racemic allylic substrate 6 with malonate and benzylamine as nucle-
ophile
Entry
Nucleophile
Solventd
Temp. (°C)
Time (h)
Yield (%)e
ee (%)f,g
1a
2b
3c
4c
CH2(COOMe)2
CH2(COOMe)2
PhCH2NH2
CH2Cl2
CH2Cl2
Toluene
CH2Cl2
20
20
−10
−10
16
16
24
24
95
90
96
72
57 (S)
48 (S)
57 (R)
64.(R)
PhCH2NH2
a [Pd(C3H5)Cl]2:5:KOAc:6:BSA:malonate=2:8:10:100:300:300. Ligand/Pd=2.
b [Pd(C3H5)Cl]2:5:KOAc:6:BSA:malonate=2:4:10:100:300:300. Ligand/Pd=1.
c [Pd(C3H5)Cl]2:5:6:benzylamine=2:8:100:300. Ligand/Pd=2.
d 0.15 M of 6.
e Isolated yield.
f For 7 the e.e. was determined by HPLC on a Chiralcel AD-H column at u=254 nm, eluent: hexane/isopropanol: 95/5; flow rate: 1 mL/min;
tS=14.34 min; tR=19.39 min.
g For 8 the e.e. was determined by HPLC on a Chiracel OD-H column at u=254 nm, eluent: hexane/isopropanol: 99/1; flow rate: 0.5 mL/min;
tS=20.98 min; tR=22.53 min.

M. Zablocka et al. / Tetrahedron Letters 44 (2003) 2413–2415
2415
Acknowledgements
ent: hexane/isopropanol: 90/10; flow rate: 1 mL/min; tS=
4.32 min; tR=7.11 min.
8. X-Ray analysis of C25H24NP: Data collection were col-
lected at low temperature T (160 K) on a Stoe imaging-
plate diffraction system (IPDS), equipped with an Oxford
Cryosystems cryostream cooler device and using graphite-
monochromated Mo Ka radiation. C25H24NP, Fw=
369.42, crystal dimensions: 0.25×0.20×0.07, colourless,
This work was performed with the support of the
Laboratoire Europe´en Associe´ (LEA) financed by
CNRS (France) and the Polish Committee for Scientific
Research (KBN grant 3TO9A03619).
platelet, orthorhombic, P212121, a=9.3523(9), b=
3
,
,
11.7112(9), c=18.3888(13) A, 2014.1(3) A , Dcalcd=1.218
mg m−3, v=0.145 mm−1, number of reflections collected/
unique 12960/3190 (Rint=0.1124). Structure was solved by
means of direct-methods using the program SIR-92, and
refined using the program SHELXL-97 included in the
package WINGX, R1=0.0470, wR2=0.0526 for [I>2|(I)],
R1=0.1067, wR2=0.0641 for all data, GOF=0.859, abso-
lute structure parameter x=0.04(15) All hydrogen atoms
were located on a difference Fourier map, but introduced
in the refinement as fixed contributors by using a riding
model and with an isotropic thermal parameter fixed at
20% higher than those of the carbon atoms to which they
are connected, excepted concerning the hydrogen atoms
H(8) and H(11) which were isotropically refined. All non-
hydrogen atoms were anisotropically refined, and in the
last cycles of refinement weighting schemes have been
used. Drawings of molecules are performed by using the
program ORTEP-32 with 50% probability displacement
ellipsoids for non-hydrogen atoms. Crystallographic data
(excluding structure factors) for the structure in this paper,
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers
CCDC.195494. Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK (Fax: +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
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