Threonine-Derived Phosphinite-Oxazoline Ligands for the Ir-Catalyzed Enantioselective Hydrogenation

Article abstract of DOI:10.1002/1615-4169(200201)344:1<40::AID-ADSC40>3.0.CO;2-7

A series of chiral phosphinite-oxazolines was synthesized in four steps starting from carboxylic acids and threonine methyl ester. In the asymmetric hydrogenation of a number of alkenes, iridium complexes of these ligands induced significantly higher enan

Full text of DOI:10.1002/1615-4169(200201)344:1<40::AID-ADSC40>3.0.CO;2-7

COMMUNICATIONS
Threonine-Derived Phosphinite-Oxazoline Ligands for the Ir-Catalyzed
Enantioselective Hydrogenation
Frederik Menges, Andreas Pfaltz*
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland
Fax: ( ‡ 41)-61-267-1103, e-mail: andreas.pfaltz@unibas.ch
Received October 23, 2001; Accepted November 22, 2001
prepared PHOX analogues (PyrPHOX; Figure 1) in which the
Abstract: A series of chiral phosphinite-oxazolines was
phenyl bridge was replaced by a pyrrole ring. These ligands
synthesized in four steps starting from carboxylic acids and
gave high enantioselectivities in the hydrogenation of the a,b-
threonine methyl ester. In the asymmetric hydrogenation
of a number of alkenes, iridium complexes of these ligands
induced significantly higher enantioselectivities than the
corresponding serine-derived complexes. Enantiomeric
unsaturated ester 9 (92% ee, structure see Table 1) and the
dihydronaphthalene derivative 10 (92% ee).[7] The most
promising class of ligands that we have found so far are the
phosphinite-oxazolines 1.[8,9] They gave good to excellent
excesses of 89 to 99% were obtained for unfunctionalized
alkenes with turnover numbers of up to 5000.
HO
*
Keywords: asymmetric catalysis; hydrogenation; iridium;
OH
*
O
O
ligand design; N,P-ligands.
.
HCl NH2
COOMe
R1
X
R1
N
H
COOMe
X = Cl: MeOH, Et3N, 0 °C (97%)
X = OH: CH2Cl2, Et3N, EDC,
HOBt, 0 °C (86 - 98%)
4
5
Iridium complexes derived from chiral phosphinooxazolines
(PHOX ligands)[1] are efficient catalysts for the enantioselec-
tive hydrogenation of imines[2] and olefins.[3] Particularly
promising results were obtained in the hydrogenation of
unfunctionalized olefins, a class of substrates that cannot be
handled by conventional rhodium- and ruthenium-phosphine
catalysts.[4] Although iridium-PHOX catalysts gave excellent
enantioselectivities and high turnover numbers in the hydro-
genation of certain olefins such as 1,2-diaryl-1-alkyl-substitut-
ed alkenes, the substrate scope of these catalysts proved to be
limited. Therefore, we and others started a search for new P,N-
ligands which enhance the application range of iridium-
catalyzed hydrogenation.
Burgess reagent,
COOMe
R2MgCl
THF, reflux (74 - 83%)
*
O
N
or: SOCl2, neat, 0 °C
Et2O, −78 °C to rt
(78%)
(77 - 86%)
R1
6
R2
N
R2
R2
R2
O
1. n-BuLi, TMEDA,
5
*
pentane, −78 °C to rt
*
OH
4
O
O
N
PAr2
2. ClPAr2 (53 - 78%)
R1
R1
7a-f
2a-f
Burgess and coworkers reported the JM-Phos ligands[5]
(Figure 1) and, more recently, analogous oxazolines connected
to an imidazolylidene instead of a phosphine group.[6] We
R2
N
R2
1. [Ir(COD)Cl]2, CH2Cl2, reflux
*
O
O
BArF
PAr2
2. NaBArF, CH2Cl2, H2O
(75 - 87%)
Ir
O
R1
O
N
PR'2
O
N
N
PR'2
N
PAr2
3a-f
R
R
R
PHOX
PyrPHOX
JM-Phos
a: R1 = Ph;
b: R1 = Ph;
c: R1 = Ph;
d: R1 = Ph;
e: R1 = 3,5-Me2C6H3;
f: R1 = 3,5-t-Bu2C6H3;
R2 = Bn;
R2 = Bn;
R2 = Bn;
R2 = Me;
R2 = Bn;
R2 = Bn;
Ar = Ph;
Ar = Ph;
4S,5S
4S,5R
4S,5S
4S,5S
4S,5S
4S,5S
Ar = o-Tolyl;
Ar = Ph;
R2
N
R2
O
R2
N
R2
O
*
Ar = Ph;
O
O
Ar = Ph;
PPh2
PAr2
R1
R1
Scheme 1. Synthesis of threonine derived phosphinite-oxazo-
line ligands. EDC: N-(3-dimethylaminopropyl)-N'-ethylcarbodi-
imide hydrochloride, HOBt: 1-hydroxybenzotriazole, BArF: tet-
rakis[3,5-bis(trifluoromethyl)phenyl]borate.
1
2
Figure 1. P,N-Ligands for enantioselective iridium-catalyzed
hydrogenation.
40
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Adv. Synth. Catal. 2002, 344, No. 1

Threonine-Derived Phosphinite-Oxazoline Ligands
COMMUNICATIONS
enantioselectivities for a much wider range of substrates than
the other P,N-ligands studied so far. Another advantage of this
ligand system is its modular architecture allowing the intro-
duction of many different substituents atthe oxazoline ring, the
backbone and the phosphine group. The synthesis is straight-
forward, starting from serine methyl ester as an inexpensive
precursor which is available in both enantiomeric forms.
As an extension of this work, we report here the synthesis of
analogous phosphinite-oxazolines 2 derived from threonine
and their application in the Ir-catalyzed hydrogenation.
Surprisingly, the additional methyl group in the oxazoline
ring was found to have a remarkably strong effect on the
enantioselectivity resulting in distinctly higher enantiomeric
excesses for a number of substrates.
The synthesis starts with threonine methyl ester hydro-
chloride which is coupled with the carboxylic acid 4 using either
EDC/HOBt or thionyl chloride for activation (Scheme 1).
Formation of the oxazolines 6 can be achieved with Burgess
reagent[10] or with neat SOCl2.[11,12] This ring closure follows an
SN2-like pathway, so the stereogenic center at C(5) is invert-
ed.[11] Therefore, starting from l-(2S,3R)-threonine, the
(4S,5S)-product 6 is formed.[13] Addition of a Grignard reagent
to the ester 6 results in the corresponding hydroxyoxazoline 7
in good yield. After deprotonation of the tertiary alcohol with
n-butyllithium/TMEDA and condensation with a chlorophos-
phine, the phosphinite-oxazolines 2 are obtained in moderate
to good yields. The corresponding iridium-complexes 3 are
synthesized according to standard procedures.[3] The resulting
complexes are air- and moisture-stable and can be purified by
column chromatography on silica gel.
Tostudy the influence of the relative configurationat the two
stereogenic centers, both diastereomers (2a and 2b) of one
ligand were synthesized. For examining the role of the R1
substituent, the steric demand in this position was increased
stepwise by replacing the phenyl (2a) by a 3,5-dimethylphenyl
(2e) and a 3,5-di(tert-butyl)phenyl (2f) group. The substituent
at the phosphorus atom was also varied by introduction of
ortho-tolyl substituents (2c). To investigate if bulky R2 groups
are required for good selectivities, the dimethyl derivative 2d
was synthesized. In initial experiments the iridium complexes
3a and 3b were tested in the enantioselective hydrogenation of
a series of olefins (Scheme 2) and the results were compared
with the enantioselectivities previously obtained with the
corresponding serine-derived catalyst.[8]
In the hydrogenation of substrates 8, 9 and 10, the threonine-
derived catalysts 3a and 3b proved to be superior to the
corresponding serine-derived complex [Ir(COD) (1)] (R1 ˆ
Ph, R2 ˆ Bn, Table 1). In the hydrogenation of trans-a-
Table 1. Enantioselective hydrogenation of olefins with catalysts 3a 3f.[a]
Entry
Substrate
Catalyst
Cat. loading [mol %]
Conv.[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
9
3a
1
0.3
1
1
100
100
100
100
100
100
100
100
100
> 99
100
54
99 (R)
89 (S)
97 (R)
98 (R)
98 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
99 (R)
[Ir(COD) (1)][d]
3b
3c
3d
3e
3f
3a
3a
3a
3a
3a
1
1
1
Ph
0.5[e]
0.1[e]
8
[e]
10
11
12
0.05
0.02[e, f]
0.01[g]
13
14
15
16
17
18
19
3a
1
0.1
1
1
1
> 99
61
97
> 99
> 99
> 99
96
92 (R)
85 (S)
85 (R)
70 (R)
88 (R)
94 (R)
61 (R)
[Ir(COD) (1)][d]
COOEt
3b
3c
3d
3e
3f
1
1
9
20
21
22
23
24
25
26
3a
1
0.6
1
1
1
100
100
100
100
100
100
100
71 (S)
55 (R)
85 (S)
66 (S)
65 (S)
74 (S)
64 (S)
[Ir(COD) (1)][d]
3b
3c
3d
3e
3f
MeO
1
1
10
[a]
All reactions were performed using 0.1 mmol of alkene and 1 mL of dichloromethane at 50 bar of hydrogen pressure at rt (reaction time: 2 h).
Conversion was determined by GC. In all cases a clean reaction was observed with a single product peak in the GC. In a preparative experiment on
a 1-g scale, the hydrogenation product of 8 was isolated in > 94% yield.
Determined by HPLC (see ref.[3]).
[b]
[c]
[d]
[e]
[f]
R1 ˆ Ph, R2 ˆ Bn, from d-serine (see ref.[8]).
2 mL of dichloromethane, up to 2.5 mmol of substrate.
Reaction time: 4 h.
3 mL of dichloromethane, 5 mmol of substrate, reaction time: 24 h.
[g]
Adv. Synth. Catal. 2002, 344, 40 44
41

Frederik Menges, Andreas Pfaltz
COMMUNICATIONS
with all ligands (Table 2). The corresponding Z-isomer 12 gave
lower enantiomeric excesses, but again catalyst 3e (92% ee)
was more selective than the serine-derived complex.
R'
R'
3a-f
R
R
*
Ar
Ar
H2, CH2Cl2, 2h
In the hydrogenation of the terminal olefin 13 similar results
were obtained as with the corresponding serine-derived
ligands. As previously observed,[8] the ee increases with
decreasing hydrogen pressure. By lowering the temperature
from 23 to 08C, the enantioselectivity of catalyst 3a was raised
from 84 to 89% ee. At À 788C virtually no conversion was
observed. For this substrate, the threonine-derived catalysts
offered no advantages over the serine-derived catalysts.
Similar ee values in the hydrogenation of 2-arylbut-1-enes
have also been reported for a DuPhos-ruthenium catalyst in
the presence of t-BuOK (up to 89% ee)[15] and for organo-
lanthanide catalysts (64% ee at 258C, 96% ee at À 788C).[16]
The hydrogenation of the N-phenylimine 14 was also briefly
investigated (Table 3). With catalysts 3c and 3f better enantio-
selectivities were obtained than with the serine-derived
catalysts (80 vs. 75% ee). However, these catalysts cannot
compete with the best Ir-PHOX catalysts (up to 89% ee)[2] or
the titanocene catalysts reported by Buchwald et al.[17] (up to
99% ee for a range of imines).
Scheme 2. Enantioselective hydrogenation of olefins catalyzed
by iridium complexes 3a f (see Tables 1 and 2).
methylstilbene 8, the enantiomeric excess increased from 89%
to 99% ee for the (4S,5S) complex 3a. The allo-threonine-
derived ligand (3b) was slightly less selective (97% ee), but still
superior to 1. For the b-methylcinnamic ester 9 the iridium
complex 3a (92% ee) was the most efficient catalyst, while
catalyst 3b and [Ir(COD) (1)] both gave 85% ee. With the
cyclic substrate 10, on the other hand, complex 3b was the most
selective catalyst (85% ee).
Encouraged by these results, we synthesized four additional
metal complexes with different substituents (3c f) and carried
out further hydrogenations varying the reaction conditions.
Introduction of two meta-methyl substituents at the R1 group
(complex 3e) showed a further improvement in selectivity for
the ester 9 (94% ee, Table 1, Entry 18).[14] Full conversion was
obtained with catalyst loadings as low as 0.02 mol % (Entries
7
12, Table 1). For E-2-(4-methoxyphenyl)-but-2-ene 11,
In summary, threonine-derived phosphinite-oxazolines are a
useful addition to the previously reported serine-derived
excellent enantioselectivities (98 99% ee) were observed
Table 2. Enantioselective hydrogenation of 2-arylbutenes 11 13.[a]
Entry
Substrate
Complex
p [bar]
T [8C]
Cat. loading [mol %]
Conv.[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3f
50
50
50
50
50
50
50
50
23
23
23
23
23
23
23
23
1
1
1
1
1
1
0.1
0.1
100
100
100
100
100
100
> 99
100
99 (R)
98 (R)
98 (R)
98 (R)
99 (R)
99 (R)
99 (R)
96 (R)
MeO
[Ir(COD) (1)][d]
11
9
10
11
12
13
14
15
3a
3b
3c
3d
3e
3f
50
50
50
50
50
50
50
23
23
23
23
23
23
23
1
1
1
1
1
1
0.4
100
100
100
100
100
100
100
89 (S)
88 (S)
83 (S)
88 (S)
92 (S)
84 (S)
85 (S)
MeO
[Ir(COD) (1)][e]
12
16
17
18
19
20
21
22
23
24
25
3a
3a
3a
3a
3a
3e
3e
3f
50
1
1
1
1
50
1
50
1
23
23
23
0
À78
23
0
23
0
23
1
1
0.1
1
1
1
1
1
1
100[g]
62 (R)
84 (R)
85 (R)
89 (R)
n.d.
66 (R)
86 (R)
60 (R)
85 (R)
88 (R)
100[g, h]
100[g, h]
100[g, h]
< 1[g, h]
100[g]
MeO
100[g, h]
100[g]
100[g, h]
100[g]
13
3f
[Ir(COD) (1)][f]
1
0.1
[a]
All reactions were performed using 0.1 mmol of alkene and 1 mL of dichloromethane at 50 bar of hydrogen pressure at rt (reaction time: 2 h).
[b]
[c]
[d]
[e]
[f]
Determined by GC.
Determined by HPLC (see ref.[3]).
R1 ˆ ferrocenyl, R2 ˆ Bn (from ref.[8]).
R1 ˆ ferrocenyl, R2 ˆ i-Pr (from ref.[8]).
R1 ˆ 3,5-(t-Bu2)C6H3, R2 ˆ Bn (from ref.[8]).
Reaction time: 30 min.
[g]
[h]
3 mL of dichloromethane.
42
Adv. Synth. Catal. 2002, 344, 40 44

Threonine-Derived Phosphinite-Oxazoline Ligands
COMMUNICATIONS
Table 3. Enantioselective hydrogenation of imine 14 with catalysts 3a 3f.[a]
Entry
Substrate
Catalyst
Cat. loading [mol %]
Conv.[b] [%]
ee[c] [%]
1
2
3
4
5
6
7
3a
3b
3c
3d
3e
3f
1
1
1
1
1
1
0.1
100
100
100
100
100
100
100
66 (R)
53 (R)
80 (R)
46 (R)
39 (R)
80 (R)
75 (S)
Ph
N
14
[Ir(COD) (1)][d]
[a]
All reactions were performed using 0.1 mmol of imine and 1 mL of dichloromethane at 50 bar of hydrogen pressure at rt (reaction time: 4 h).
Determined by GC.
[b]
[c]
[d]
Determined by HPLC on a Daicel OD-H column (n-heptane/2-propanol ˆ 99: 1).
R1 ˆ Ph, R2 ˆ Bn, from d-serine (see ref.[8]).
7.50 (m, 23H, CH2Ph, Ph, PPh2), 8.01 (d, J ˆ 7.3 Hz, 2H, Ph); 31P{1H}-NMR
analogues and other oxazoline-based P,N-ligands. In the
hydrogenation of unfunctionalized trisubstituted arylalkenes,
unprecedented enantioselectivities could be obtained with
these new ligands. The surprisingly strong effect of the
additional methyl group in the oxazoline ring suggests that
the scope of iridium-catalyzed hydrogenation can be further
enhanced by variation of the substitution pattern in the
oxazoline ring.
(162 MHz, CDCl3): d ˆ 88.7 (s). The product contained a small amount (ca.
1-5 mol %) of the corresponding phosphinate [31P{1H}-NMR: d ˆ 25.6]. It
was used in the next step without further purification.
Complex 3a
Ligand 2a (125 mg, 0.22 mmol) was dissolved in anhydrous dichloromethane
(5 mL) under an argon atmosphere. [Ir(COD)Cl]2 (83 mg, 0.12 mmol) was
added and the mixture heated at reflux for 1 h. Then, with vigorous stirring,
sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (227 mg, 0.24 mmol)
was added and, after 1 min, 3 mL of water. The layers were separated and the
aqueous phase was extracted with dichloromethane (2 Â 10 mL). The
combined organic extracts were dried over MgSO4 and evaporated under
reduced pressure. The residue was purified by column chromatography
(silica gel, dichloromethane) to give iridium complex 3a as an orange
powder; yield: 262 mg (68%); 1H-NMR (400 MHz, CDCl3): d ˆ 1.73 (d, J ˆ
7.0 Hz, 3H, CH3), 1.75 2.05 [br m, 6H, CH2(COD)], 2.05 2.25 [br m, 1H,
CH2(COD)], 2.27 2.33 [br m, 1H, CH2(COD)], 2.95 (dd, J ˆ 5.3 Hz, J ˆ 14.9
Experimental Section
(4S,5S)-2-(5-Methyl-2-phenyl-4,5-dihydrooxazol-4-yl)-1,3-
diphenylpropan-2-ol (7a)
(4S,5S)-4-Methyl-2-phenyl-4,5-dihydrooxazole-4-carboxylic acid methyl es-
ter 6[11,12] (500 mg, 2.28 mmol) was dissolved in anhydrous diethyl ether
(15 mL). Benzylmagnesium chloride solution (1 M in diethyl ether, 6.80 mL,
6.80 mmol) was added at À 788C. The cooling bath was removed, the
reaction mixture stirred for 4 h and then poured on aqueous NH4Cl/ice
(10 mL). The organic layer was washed with water (10 mL) and brine
(10 mL). After drying over MgSO4 the solvent was evaporated under
reduced pressure. The light yellow oil was purified by column chromatog-
raphy (silica gel, pentane/diethyl ether, 6:1) to afford 7a as a white powder;
À
À
Hz, 1H, Ph CH2), 3.04 (d, J ˆ 14.4 Hz, 1H, Ph CH2), 3.15- À 3.38 [br m, 2H,
À
CH(COD)], 3.42 (d, J ˆ 14.9 Hz, 1H, Ph CH2), 4.10 4.35 [br m, 2H,
À
Ph CH2 and CH(COD)], 4.53 [br m, 1H, CH(COD)], 4.75 (d, J ˆ 8.1 Hz, 1H,
ˆ À
C N CH), 5.35 (m, 1H, CH-CH3), 6.93 (m, 2H, Ph), 7.08 (m, 4H, Ph), 7.18
(m, 2H, Ph), 7.23 7.36 (m, 7H, Ph), 7.51 [br s, 4H, ArH(BArF)], 7.52 7.69
(m, 7H, Ph), 7.72 [m, 8H, ArH(BArF)], 7.78 (m, 1H, Ph), 8.39 (br d, 2H, Ph);
1
yield: 690 mg (82%); H-NMR (400 MHz, CDCl3): d ˆ 1.73 (d, J ˆ 6.8 Hz,
31
1
À
Ä
P{ H}-NMR (162 MHz, CDCl3): d ˆ 93.6 (s); IR (KBr): n ˆ 3066w, 3033w,
3H, CH3), 2.00 (s, 1H, OH), 2.69 (d, J ˆ 13.6 Hz, 1H, Ph CH2), 2.93 (d, J ˆ
À
À
2953w, 2926w, 1608m, 1570m, 1496w, 1452w, 1438m, 1355vs, 1281vs, 1276vs,
1131vs, 1028w, 1000m, 936m, 886m, 839m, 774m, 744s, 712s, 700s, 682m, 670m
13.9 Hz, 1H, Ph CH2), 3.11 (d, J ˆ 13.9 Hz, 1H, Ph CH2), 3.19 (d, J ˆ 13.6
À
ˆ À
Hz, 1H, Ph CH2), 4.11 (d, J ˆ 9.6 Hz, 1H, C N CH), 4.84 (dq, J ˆ 9.6 Hz,
J ˆ 6.8 Hz, 1H, CH-CH3), 7.15 7.37 (m, 10H, CH2Ph), 7.44 (t, J ˆ 7.3 Hz,
2H, Ph), 7.50 (t, J ˆ 7.3 Hz, 1H, Ph), 8.05 (d, J ˆ 7.3 Hz, 2H, Ph).
cmÀ1. MS (FAB): 856 (M ); anal. calcd. for C77H58BF24IrNO2P: C 53.79, H
‡
3.40, N 0.81, O 1.86; found: C 53.74, H 3.57, N 0.68, O 2.00.
(4S,5S)-O-[1-Benzyl-1-(5-methyl-2-phenyl-4,5-
dihydrooxazol-4-yl)-2-phenylethyl] Diphenylphosphinite
(2a)
General Hydrogenation Procedure
To a 60-mL autoclave with a glass insert and a magnetic stir bar was added
the substrate, the metal complex and dichloromethane (inert atmosphere is
not necessary). The autoclave was sealed and pressurized with hydrogen.
After stirring at room temperature for 0.5 24 h (see Tables) the pressure
was released. The solvent was evaporated and heptane (3 mL) was added.
The resulting suspension was filtered through a syringe filter (CHROMA-
FIL O-20/15 MS 0.2 mm, Macherey-Nagel) and the filtrate was directly
analyzed by GC and chiral HPLC to determine the conversion and ee (for
analytical procedures and data, see ref.[3]). In a preparative experiment on a
gram scale (substrate 8), the catalyst was removed by filtration through a
short silica column (2 Â 1 cm) with hexane as solvent. After evaporation of
the solvent, analytically pure product was isolated in 94% yield. The
hydrogenations at 1 bar were carried out using an argon-flushed open
schlenk flask and a continuous slow flow of hydrogen.
(4S,5S)-2-(5-Methyl-2-phenyl-4,5-dihydrooxazol-4-yl)-1,3-diphenylpro-
pan-2-ol 7a (337 mg, 0.91 mmol) was dissolved in anhydrous pentane
(15 mL). At À 788C n-butyllithium (0.70 mL, 1.12 mmol) was added
dropwise followed by N,N,N×,N×-tetramethylethylenediamine (0.30 mL,
2.00 mmol). The cooling bath was removed and the mixture stirred for 1 h.
Chlorodiphenylphosphine (0.18 mL, 0.99 mmol) was added at 08C. After
stirring for 5 h at room temperature the solvent volume was reduced to
0.5 mL. The residual suspension was transferred directly onto a silica gel
column. Chromatography with hexane/ethyl acetate (15:1) afforded the
product as a voluminous white powder; yield: 310 mg (62%); 1H-NMR (400
MHz, CDCl3): d ˆ 1.24 (d, J ˆ 6.6 Hz, 3H, CH3), 3.11 (d, J ˆ 14.1 Hz, 1H,
À
À
Ph CH2), 3.33 (br d, J ˆ 13.4 Hz, 2H, Ph CH2), 3.72 (d, J ˆ 13.1 Hz, 1H,
À
ˆ À
Ph CH2), 4.34 (d, J ˆ 9.6 Hz, 1H, C N CH), 4.73 (m, 1H, CH CH3), 7.05
Adv. Synth. Catal. 2002, 344, 40 44
43

Frederik Menges, Andreas Pfaltz
COMMUNICATIONS
catalysts, see: R. D. Broene, S. L. Buchwald, J. Am. Chem. Soc. 1993,
115, 12569 12570; M. V. Troutman, D. H. Appella, S. L. Buchwald, J.
Am. Chem. Soc. 1999, 121, 4916 4917.
[5] D.-R. Hou, J. H. Reibenspies, K. Burgess, J. Org. Chem. 2001, 66,
206 215; D.-R. Hou, J. Reibenspies, T. J. Colacot, K. Burgess,Chem.
Eur. J. 2001, 7, 5391 5400.
[6] M. T. Powell, D.-R. Hou, M. C. Perry, X. Cui, K. Burgess, J. Am.
Chem. Soc. 2001, 123, 8878 8879.
[7] P. G. Cozzi, N. Zimmermann, R. Hilgraf, S. Schaffner, A. Pfaltz, Adv.
Synth. Catal. 2001, 343, 450 454.
[8] J. Blankenstein, A. Pfaltz, Angew. Chem. 2001, 113, 4577 4579;
Angew. Chem. Int. Ed. 2001, 40, 4445 4447; J. Blankenstein,
Dissertation, University of Basel, 2001.
[9] Closely related ligands (1, R2 ˆ H) have been recently applied in Pd-
catalyzed allylic alkylation: G. Jones, C. J. Richards, Tetrahedron Lett.
2001, 42, 5553 5555.
Acknowledgements
[10] P. Wipf, C. P. Miller, Tetrahedron Lett. 1992, 33, 907 910; review of
Burgess reagent: C. Lambert, J. Prakt. Chem. 2000, 342, 518 522.
[11] P. M. Fischer, J. Sandosham, Tetrahedron Lett. 1995, 36, 5409 5412.
[12] Oxazoline (4S,5S)-6 with R1 ˆ Ph (CAS 82659-84-5) is commercially
available from Aldrich (No.: 29,217-6).
F. M. thanks the ™Fonds der Chemischen Industrie∫ (Frankfurt) and the
¬
German Federal Ministry for Science and Technology (BMBF) for a Kekule
Fellowship. Financial support by the Swiss National Science Foundation, the
Federal Commission for Technology and Innovation (KTI Project No. 5189.2
KTS) and Solvias AG (Basel) is gratefully acknowledged.
[13] The relative configuration was confirmed by NOESY and ROESY
À
À
NMR experiments [contact between C(4) H and C(5) H].
[14] For the influence of meta-substituents in arylphosphine ligands see:
K. Selvakumar, M. Valentini, P. S. Pregosin, A. Albinati, F. Eisen-
tr‰ger, Organometallics 2000, 19, 1299 1307.
References and Notes
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2001, 41, 9471 9475.
¬ √
[2] P. Schnider, G. Koch, R. Pretot, G. Wang, F. M. Bohnen, C. Kr¸ger,
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[4] Review: R. L. Haltermann in Comprehensive Asymmetric Catalysis
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¬
Giardello, V. P. Conticello, L. Brard, M. R. Gagne, T. J. Marks, J. Am.
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44
Adv. Synth. Catal. 2002, 344, 40 44