Preparation of optically pure 1,2,5-triphenylphospholane. Use as ligand for enantioselective transition-metal catalysis

Article abstract of DOI:10.1016/S0040-4039(00)93435-X

Base-catalyzed isomerization of achiral (E,E)-1,2,5-triphenylphospholane oxide leads to the racemic (E,Z)-isomer. Resolution by Supercritical Fluid Chromatography (SFC) followed by reduction gives the two enantiomers. The activity of this new ligand is tested in palladium-catalyzed coupling of cyclohex-2-enyl acetate with nucleophiles.

Full text of DOI:10.1016/S0040-4039(00)93435-X

Tetxahedron Letters, Vol.32, No.38, pp 5089-5092, 1991
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Preparation of Optically Pure 1,2,5-Triphenylphospholane.
Use as Ligand for Enantioselective Transition-Metal Catalysis.
Jean-Claude Fiaud and Jean-Yves Legros
Laboratoire de Synlh~se Asym6trique Associ6 au C.N.R.S.,
B~fiment 420, Universit6 de Paris-Sud, 91405 Orsay, France.
Key Words: Chiralphosphines; Chiralphosphine oxides; Base-catalyzed isomerization;
Chiral Chromatography; Palladium-catalyzed allylic substitution
Abstract: Base-catalyzed isomerization of achiral (E,E)-l ,2,5-triphenylphospholane oxide leads to the racemic (E,Z)-
isomer. Resolution by Supercritical Fluid Chromatography (SFC) followed by reduction gives the two enantiomers.
The activity of this new ligand is tested in palladium-catalyzed coupling of cyclohex-2-enyl acetate with nucleophiles.
Monophosphine ligands have been less useful than chelating biphosphines in enantioselective transition-
metal catalysis.1 In palladium-catalyzed coupling of allyl acetates and phenylzinc chloride however,
monophosphines showed higher reactivity and enantioselectivity than chelating diphosphines. 2 Optically active
monophosphines have been shown to be efficient chiral inductors (up to 80%ee) in Ziegler-Natta type nickel
complexes for the hydrovinylation reaction (codimerization between ethylene and cycloocta-l,3-diene or
norbornene). 3 Basic phosphines such as dialkylarylphosphines or trialkylphosphines have been reported to
display better catalytic activity than alkyldiarylphosphines or triarylphosphines in rhodium-catalyzed
hydrogenation of simple, non-functionalized ketones.4 Moreover optically active monophosphines (such as
menthyldimethylphosphine) have been used for the resolution of cyclododecatrienylnickel(0) complex.5
R
Ph
R
Ph
la: R = Ph
lb: R = Me
le: R = Et
ld: R = i P r
2
Recent reports on the preparation and use of 1-phenyl-2,5-dialkylphospholanes 1 (lb-d, R=Me,6,7 Et,
iPr 7) prompted us to disclose our work dealing with the preparation of racemic (E,Z)-l,2,5-
5089

5090
triphenylphospholane oxide 2, its resolution and the reduction of each enantiomer to give optically pure la (R =
Ph). Some preliminary results concerning the use of la as ligand for transition-metal complexes in
enantioselective catalytic organic reactions are also reported.
The synthesis of racemic 1,2,5-triphenylphospholane oxide 5 (Scheme 1) has already been reported by
Ezzell and Freedman, but with no indication about the stereochemistry of the product.8 1,2,5-triphenyl-
phosphole 3 was readily prepared according to a reported procedure,9 oxidized (H202, THF) and quantitatively
hydrogenated (10%Pd/C, AcOEt)8 to give a stereochemically homogeneous compound 5. 13C NMR data
indicate a symmetry plane in the molecule and hence a cis relationship between the two phenyl substituents in 2
and 5 positions. 10 The stereochemistry at phosphorus was tentatively assigned as (E,E), assuming a
coordination of the substrate 4 by its less hindered face on the heterogeneous hydrogenation catalyst.
Ph
Ph
Ph
Ph
+ C12PPh
~
P--Ph
Ph
~
P~
AcOEt
(ref.8)
- 2 HCI
(ref. 9)
THF
(ref. 8)
Ph
k
Ph
Ph
Ph
Ph
3
4
Scheme 1: Synthesis of (E,E)-l,2,5-Triphenylphospholane oxide 5
Isomerization of this compound with one equivalent of methyl lithium in THF at room temperature gave
a mixture of the starting material and two new diastereoisomers, the other achiral (Z,Z)-6 [31p NMR (CDC13):
= 42.5 ppm relative to 85% H3PO4] and the expected chiral (E,Z)-2 (Scheme 2). Equilibration in the presence
of catalytic amounts of methyl lithium (2 mol%) as a base afforded 2 as the sole product. On proper
concentration conditions (0.5 M), 2 crystallized out and could be readily recovered from the THF solution by
filtration. 13C NMR data indicate no symmetry plane in the molecule, in agreement with a trans relationship
between the two phenyl substituents in 2 and 5 positions.11
Ph
Ph
Ph
Ph
0
0
0
'
0
2 + S
+
,~
~
leq. MeLi
2mol%MeLi I~
+
h
i
Ph
Ph
i
Ph
Ph
Ph
Ph
Ph
6
5
2 (racemic)
Scheme 2: Isomerizations of (E,E)-5
Calculations of the relative energies of 2, 5 and 6 by a molecular modeling program (PCmodel, MMX
program) indicated that, among the three isomers, (E,Z)-2 was favored over (E,E)-$ by 11.4 KJ.mol-l, and
over (Z,Z)-6 by 13.2 KJ.mo1-1.
Analytical enantiomer separation of 2 was carried out by liquid chromatography (LC) using the
previously described 12 chiral stationary phase (S)-thio-DNB-Tyr-E . However, due to the low (o~ = 1.1)
separation factor value, preparative separation was performed by chiral SFC (Supercritical Fluid

5091
Chromatography) [carbon dioxide with a polar modificator as eluent]. 13 Each enantiomer could be obtained
enantiomerically pure (>99%ee)14 by a single recrystallization (EtOH: H20 60:40) from an elution fraction
showing 84% ee.
Since the phosphorus atom is not a stereogenic center in (E,Z)-2, one has not to pay attention to the
stereochemistry of reduction of 2. However one should avoid epimerization at benzylic carbon atoms C2 or C5
which would either produce the (Z,Z)-6 or (E,E)-5 diastereomer or lead to enantiomerization of 2. From this
point of view, both phenylsilane and LiA1H4 gave satisfactory results. The phospholane la obtained by
reduction of (-)-2 with these reagents was enantiomerically pure (as shown by chiral HPLC analysis of the
reoxidation product from la).
Activity and enantioselectivity of phospholane (-)-la [31p NMR (CDC13): fi = 21.2 ppm relative to 85%
H3PO4] as figand were evaluated in the following palladium-catalyzed aUylic coupling reactions of cyclohex-2-
enyl acetate with sodium dimethylmalonate and phenylzinc chloride:
cat. Pd(dba)2 + (-)- la ~ G *
OAc
OAc
CH(CO2CH3)2
NaCH(CO2CH3) 2
7
cat. Pd(dba)2 + (-)- la
~
,
~
~
Ph
PhZnCI
8
The catalyst was prepared in situ by stirring a THF solution of bis(dibenzylideneacetone)palladium(0)
and crude (-)-la (1:2 ratio) resulting from PhSiH3 reduction of enantiomerically pure (-)-2. The catalytic
activity was very high, the reaction led rapidly to allylated dimethylmalonate 7 (74% isolated yield) and 3-
phenylcyclohexene 8 (60% isolated yield) respectively, as a single product in each case. Unfortunately, the
enantioselectivities were low (10% ee in each case), but comparable to reported results [6% ee for 7 using (+)-
DIOP 15 as chiral ligand and 9.4% ee for 8 with (+)-NMDPP]. 16
Work is currently in progress in our laboratory to find out appropriate reactions using this new chiral
phosphine ligand.
Acknowledgements: Authors are indebted to Dr. A. Tambut6 (Centre d'.Etudes du Bouchet, Vert le Petit,
France) for the analytical resolution (HPLC) of racemic 2 and to G.Fuchs and L.Doguet (Laboratoire de
Physicochimie industrielle, ENSIC, Nancy, France) for the preparative resolution of 2 by SFC.
References and Notes:
1.
Kagan, H.B. Chiral ligands for Asymmetric Synthesis. In Asymmetric Synthesis; Morrison, J.D. Ed.;
Academic Press, Inc.: Orlando, 1985; pp. 1-39.
Kagan, H.B.; Sasaki, M. Optically Active Phosphines: Preparation, Uses and Chiroptical Properties.
In The chemistry of Organophosphorus Compounds, Vol. 1, Hartley, F.R. Ed.; John Wiley and Son,
Inc.: New York, 1990; pp. 51-102.
2.
3.
Fiaud, J.-C.; Aribi-Zouioueche, L. J. Organometal. Chem. 1985, 295, 383-387.
Bogdanovic,B. Angew. Chem., Int. Ed. Engl. 1973, 12,954-989, and references cited herein.

5092
4.
Schrock, R.R.; Osborn, A, J. Chem. Soc., Chem. Commun. 1970, 567-568.
Fujitsu, H.; Matsumura, E.; Takeshita, K.; Mochida, I. J. Chem. Soc., Perkin Trans 1 1981, 2650-
2655.
Tani, K.; Suwa, K.; Tanigawa, E.; Ise, T.; Yamagata, T.; Tatsuno, Y.; Otsuka, S. J. Organometal.
Chem. 1989, 370, 203-221.
Wilke, G. Angew. Chem., Int. Ed. Engl. 1988, 27, 186-206.
5.
6.
7.
Wilson, S.R.; Pasternak, A. Synlett. 1990, 199-200.
Burk, M.J.; Feaster, J.E.; Harlow, R.L. OrganometaUics 1990, 9, 2653-2655.
Burk, M.J.; Harlow, R.L. Angew.Chem., lnt.Ed.Engl. 1990, 29, 1462-1464.
EzzeU, B.R.; Freedman, L.D.J. Org. Chem. 1970, 35, 241-242.
Lukas, B.; Roberts, R.M.G.; Silver, J.; Wells, A.S.J. Organometal. Chem. 1983, 256, 103-110.
Selected data for compound 5 (in CDC13):
b
8.
9.
10.
1H NMR (5, ppm): 2.5-2.8 (4H, m), 4.0 (2H, dt, J 24 and 9 Hz), 7.0-7.3 (15 H, m).
13C NMR (non aromatic carbons) (5, ppm): 26.6 (d, C3 and C4, 2J31p-13C 11 Hz), 47.4 (d, C2 and C5,
1J31p-13c 60 Hz): carbons 2 and 5 (as 3 and 4) are magnetically equivalent.
31p NMR: 5 = 61.7 ppm relative to 85% H3PO4.
11.
Selected data for compound 2 (in CDC13):
IH NMR (~5, ppm): 2.1-2.4 (1H, m), 2.4-2.9 (3H, m), 3.6 (IH, dt, J 12 and 8 Hz), 3.9 (1H, ddd, J
25, 12 and 7 Hz), 7.0-7.3 (15 H, m).
13C NMR (non aromatic carbons) (5, ppm): 27.9 (d, C3 or C4, 2J31p-13C 8 Hz), 31.6 (d, C3 or C4,
2J31p-13C 7 Hz), 46.8 (d, C2 or C5, 1J31p-13C 62 Hz), 51.0 (d, C2 or C5, 1J31p-13C 62 Hz): carbons 2
and 5 (as 3 and 4) are not magnetically equivalent.
31p NMR: ~ = 53.6 ppm relative to 85% H3PO4.
Elemental Analysis: found C, 79.25; H, 6.44; P, 9.15. C22H21OP calc.: C, 79.26; H, 6.35; P, 9.29.
Tambutt, A.; Btgos, A.; Lienne, M.; Macaudi~re, P.; Caude, M.; Rosset, R. New J. Chem. 1989,
13, 625-637.
12.
13.
14.
G. Fuchs, L. Doguet, M. Perrut, submitted for publication.
[tx]D = -150 (c 1, MeOH) for the f'trst-eluted enantiomer. X-Ray determination of the absolute
configuration is presently under way.
15.
16.
Malleron, J.L. Th~se, Universit6 de Paris-Sud, 1981. (+)-DIOP = 2,3-O-isopropylidene-2,3-
dihydroxy-l,4-bis(diphenylphosphinobutane: Kagan, H.B.; Dang, T.P.J.Am.Chem.Soc. 1972, 94,
6429-6433.
Reference 2. (+)-NMDPP (neomenthyldiphenylphosphine): Morrison, J.D.; Mosher, W.F.
J.Org.Chem. 1974, 39, 270-272.
(Received in France 24 June 1991)