Chiral 2-(2-diphenylphosphinophenyl)-oxazolines: Synthesis and use in Pd-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1080/10426500600781367

The synthesis of 2-(2-diphenylphosphinophenyl)-oxazolines from o-fluoroben-zonitrile and (-)-norephedrine or (+)-endo-2-hydroxy-endo-3- aminobornane is described. The Pa-catalyzed alkylation of (E)-1,3-diphenylallyl acetate with the sodium salt of dimethy

Full text of DOI:10.1080/10426500600781367

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Chiral 2-(2-
Diphenylphosphinophenyl)-
oxazolines: Synthesis and Use
in Pd-Catalyzed Asymmetric
Allylic Alkylation
Benjamin Ganchegui a , Carole Chevrin a , Sandrine
Bouquillon a , Jean Le Bras a , Françoise Hénin a &
Jacques Muzart a
a Unité Mixte de Recherche “Réactions Sélectives
et Applications,” CNRS Université de Reims
Champagne–Ardenne, France
Published online: 01 Feb 2007.
To cite this article: Benjamin Ganchegui , Carole Chevrin , Sandrine
Bouquillon , Jean Le Bras , Franoise Hnin & Jacques Muzart (2006) Chiral 2-(2-
Diphenylphosphinophenyl)-oxazolines: Synthesis and Use in Pd-Catalyzed Asymmetric
Allylic Alkylation, Phosphorus, Sulfur, and Silicon and the Related Elements, 181:11,
2635-2639, DOI: 10.1080/10426500600781367
To link to this article: http://dx.doi.org/10.1080/10426500600781367
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Phosphorus, Sulfur, and Silicon, 181:2635–2639, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600781367
Chiral 2-(2-Diphenylphosphinophenyl)-oxazolines:
Synthesis and Use in Pd-Catalyzed Asymmetric
Allylic Alkylation
Benjamin Ganchegui
Carole Chevrin
Sandrine Bouquillon
Jean Le Bras
´
Franc¸oise Henin
Jacques Muzart
Unite´ Mixte de Recherche “Re´actions Se´lectives et Applications,” CNRS
Universite´ de Reims Champagne–Ardenne, France
The synthesis of 2-(2-diphenylphosphinophenyl)-oxazolines from o-fluoroben-
zonitrile and (−)-norephedrine or (+)-endo-2-hydroxy-endo-3-aminobornane is de-
scribed. The Pa-catalyzed alkylation of (E)-1,3-diphenylallyl acetate with the
sodium salt of dimethylmalonate using these chiral ligands occurs with an 82–87%
yield and 88–93% ee.
Keywords η3-allylpalladium; allylic alkylation; asymmetry; catalysis; oxazolines
Over the last 20 years, we have been strongly involved in the enan-
tioselective protonation of prochiral enolic species produced either
photochemically1 or from Pd catalysis.2 The chiral protic sources were
ephedrine-type compounds, (+)-endo-2-hydroxy-endo-3-aminobornane
(1),3 and its N-alkylated derivatives. Being also interested in Tsuji–
Trost reactions,4 we have prepared oxazolines 2 and 3 from (−)-
norephedrine and 1, respectively, (Scheme 1) to test them for the
Pd-catalyzed asymmetric alkylation of (E)-1,3-diphenylallyl acetate (4).
Indeed, homochiral phosphinoaryloxazolines are a class of ligands com-
monly used in metal-catalyzed enantioselective reactions, in particular
Received February 9, 2006; accepted April 22, 2006.
We are grateful to “Ministe`re de la Recherche et de la Technologie” and “Re´gion
Champagne-Ardenne” for PhD studentships to Benjamin Ganchegui and Carole Chevrin,
respectively.
Address correspondence to Jacques Muzart, Unite´ Mixte de Recherche “Re´actions
Se´lectives et Applications,” UMR 1039, CNRS–Universite´ de Reims, Champagne–
Ardenne, B.P. 1039, Reims, cedex 2, 51687 France. E-mail: jacques.muzart@univ-reims.fr
2635

2636
B. Ganchegui et al.
SCHEME 1
in the Pd-catalyzed allylic alkylation of 4.5−7 Oxazoline 2 already has
been used with 4 to synthesize the corresponding η3-allylpalladium
complex,8 but its synthesis, analytical properties9 and use in cataly-
sis have not been disclosed. Our results are here reported.
The synthesis of 2 and 3 was attempted via the synthesis of the cor-
responding 2-(2-fluorophenyl)-4,5-dihydrooxazoles 2a and 3a. Reflux-
ing a mixture of o-fluorobenzonitrile, (−)-norephedrine and ZnCl2 in
chlorobenzene6,10 yielded 30% of 2a. The yield was improved to 76%
using o-fluorobenzoic acid10 under conditions depicted in Scheme 2.
These experimental conditions using 1 instead of (−)-norephedrine
SCHEME 2 (a) 1: PPh3 (1 equiv.), CCl4/MeCN (4:1), 0◦C, 2.5 h; 2: (−)-
norephedrine or 1 (1 equiv.), NEt3 (3.25 equiv.), r.t., 1 h; 3: 0◦C, PPh3 (0.37 equiv.);
4: r.t., 1 h (b) Ph2PK (1.1 equiv.), THF, 0◦C, 20–30 min.

Chiral Diphenylphosphinophenyl) Oxazolines
2637
afforded 3a in a 94% yield. The treatment of 2a and 3a with potassium
diphenylphosphide6 led to 2 and 3 in 86% and 71% yields, respectively.
The reaction of 4 with the sodium salt of dimethylmalonate in THF at
r.t. using [(η3-allyl)PdCl]2/2(or 3) as the catalytic system led to dimethyl
2-((E)-1,3-diphenylallyl)malonate in an 82–87% yield with 88–93% ee
(Eq.(1)).
(1)
In conclusion, we have synthesized two phosphorus-containing oxazo-
lines that have been used for the first time as chiral ligands for efficient
Pd-catalyzed Tsuji–Trost reactions.
EXPERIMENTAL
All reactions were carried out under an argon atmosphere using dry
solvents. The Pd-catalyzed reactions were carried out according to a
published procedure;6 the enantiomeric excesses were determined by
HPLC using a Daicel Chiracel OD column and hexane/i-PrOH (99:1)
as an eluent (254 nm, 0.5 mL/min). IR analyses were recorded on a
Spectrafile IR-TF plus Midac. NMR spectra were recorded on Bruker
spectrometers (1H, 250 or 500 MHz; 13C, 62.9 or 125.8 MHz, 19F, 235.4
MHz, 31P, 120.2 MHz) and referenced to TMS, CFCl3 and 85% H3PO4,
respectively. MS analyses were performed on a Q-TOF micro (Micro-
mass) with an electrospray source.
The Synthesis of 2a
MeCN (8 mL) and CCl4 (2 mL) were added to a round-bottom flask
containing o-fluorobenzoic acid (560 mg, 4 mmol) and PPh3 (1050 mg,
4 mmol) cooled at 0◦C. After stirring for 2.5 h, a solution of (−)-
norephedrine (605 mg, 4 mmol) and NEt3 (1315 mg, 13 mmol) in MeCN
(2 mL) was added. After stirring at r.t. for 1 h, the reaction was cooled
at 0◦C, and a supplementary portion of PPh3 (393 mg, 1.5 mmol) was
added. The mixture was stirred at r.t. for 1 h. The residue obtained af-
ter evaporation of the solvents under reduced pressure was dissolved
in CH2Cl2 (20 mL). This was washed with 2M of aqueous NaOH,

2638
B. Ganchegui et al.
evaporated, and then subjected to column chromatography to afford
2a (775 mg, 76%).
IR (KBr, cm−1): 699, 745, 766, 1455, 1497, 1584, 1613, 1649. 1H NMR
(CDCl3, δ ppm): 1.55 (d, 6.7 Hz, 3H), 4.22 (quint, 6.8 Hz, 1H), 5.08 (d,
7.9 Hz, 1H), 7.16 (m, 1H), 7.29 (m, 1H), 7.35 (m, 5H), 7.40 (m, 1H), 7.94
(dt, 1.7 and 7.4 Hz). 13C NMR (CDCl3, δ ppm): 21.2, 71.0, 87.4, 115.9 (d,
J
= 10.3 Hz), 116.6 (d, J = 21.9 Hz), 123.8 (d, J = 3.8 Hz), 125.4,
CF
CF
128.4, 128.6, 131.0 (d, J = 1.3 Hz), 132.8 (d, J CF= 8.7 Hz), 140.1,
CF
CF
159.2 (d, J = 5.7 Hz), 161.1 (d, J = 258.5 Hz). 19F NMR (CDCl3, δ
CF
CF
ppm): −108.9.
The Synthesis of 2
A 0.5-M Ph2PK solution in THF (11 mL, 5.5 mmol) was added dropwise
to a solution of 2a (1275 mg, 5 mmol) in THF (10 mL) at 0◦C. The mixture
was stirred at 0◦C until the color changed from red to yellow (20–30
min). After the addition of water (15 mL) and extraction of the aqueous
phase with CH2Cl2 (3 × 10 mL), the organic phases were washed with
brine and dried over MgSO4. Evaporation of the solvent followed by
column chromatography led to 2 (1810 mg, 86%).
[α]2D0 = +73.2 (c = 0.7, CH2Cl2). 1H NMR (CDCl3, δ ppm): 1.26 (d, 6.6
Hz, 3H), 4.02 (quint., 7.7 Hz, 1H), 4.71 (d, 8.3 Hz, 1H), 6.88 (m, 1H),
7.13 (d, 5.9 Hz, 2H), 7.34 (m, 15H), 7.98 (m, 1H). 13C NMR (CDCl3, δ
ppm): 20.6, 70.8, 87.8, 125.8, 127.9, 128.0, 128.3 (d, JCP = 6.8 Hz), 128.4
(d, J = 8 Hz), 128.5, 128.7, 130.0 (d, J = 2.5 Hz), 133.5 (d, J
=
CP
CP
CP
2.4 Hz), 133.9 (d, J = 20.9 Hz), 134.4 (d, J = 21.2 Hz), 138.0 (d,
CP
CP
J
= 10.8 Hz), 138.1 (d, JCP = 12.2 Hz), 139.4 (d, JCP = 25.9 Hz), 140.0,
CP
162.3 (d, J = 3.5 Hz). 31P NMR (CDCl3, δ ppm): −4.4. M. S. (E. S.):
CP
422(M + 1).
The same procedures were used for the synthesis of 3a and 3.
3a (770 mg, 94%) from o-fluorobenzoic acid (420 mg, 3 mmol). IR
1
(KBr, cm−1): 764, 1457, 1497, 1612, 1643. H NMR (CDCl3, δ ppm):
0.92 (s, 3H), 0.96 (s, 6H), 1.20 (m, 2H), 1.49 (m, 2H), 2.14 (wide s, 1H),
4.58 (d, 9.8 Hz, 1H), 4.72 (dd, 9.8 and 5.0 Hz, 1H), 7.14 (m, 2H), 7.37
(m, 1H), 7.83 (t, 7.4 Hz, 1H). 13C NMR (CDCl3, δ ppm): 15.0, 18.4, 19.9,
20.6, 27.1, 49.1, 49.3, 49.5, 71.8, 88.6, 116.6 (d, J = 22 Hz), 123.9 (d,
CF
J
J
CF
= 3.9 Hz), 131.0, 132.5, 132.6, 160.2 (d, J = 6.0 Hz), 161.2 (d,
CF
CF
= 273.8 Hz). 19F NMR (CDCl3, δ ppm): −109.7.
3 (312 mg, 71%) from 3a (723 mg, 2.65 mmol). [α]2D0 = +77.4 (c =
1
0.7, CH2Cl2). H NMR (CDCl3, δ ppm): 0.74 (s, 3H), 0.79 (s, 6H), 1.10
(m, 4H), 1.90 (t, 1.2 Hz, 1H), 4.28 (d, 9.9 Hz, 1H), 4.41 (dd, 4.9 and 9.9
Hz, 1H), 6.81 (m, 1H), 7.23 (m, 12H), 7.92 (m, 1H). 13C NMR (CDCl3,

Chiral Diphenylphosphinophenyl) Oxazolines
2639
δ ppm): 14.8, 18.3, 198.8, 20.3, 27.0, 49.1, 49.2, 49.2, 71.8, 88.6, 128.0,
128.2 (d, J = 7.3 Hz), 128.3 (d, J = 4.6 Hz), 129.9 (d, J = 2.9 Hz),
CP
CP
CP
130.2, 132.3 (d, JCP = 19.9 Hz), 133.9, 134.0, 134.1, 138.1 (d, JCP = 37.9
Hz), 138.4 (d, J = 39.2 Hz), 138.8 (d, J = 25.6 Hz), 163.4 (d, J
=
CP
CP
CP
2.5 Hz). 31P NMR (CDCl3, δ ppm): −5.7. M. S. (E. S.): 440 (M + 1).
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