Synthesis of new serine-based phosphinooxazoline ligands and iridium complexes for asymmetric hydrogenations

Article abstract of DOI:10.1016/j.tet.2011.02.021

A series of serine-based phosphinooxazoline ligands was synthesized and the corresponding iridum complexes were successfully applied in the asymmetric hydrogenation of various unfunctionalized olefines and acetophenone-N-phenyl- imine. The results show that these new derivatives are useful substitutes for the standard tert-leucine-derived PHOX ligands.

Full text of DOI:10.1016/j.tet.2011.02.021

Tetrahedron 67 (2011) 4358e4363
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of new serine-based phosphinooxazoline ligands and iridium
complexes for asymmetric hydrogenations
y
*
Axel Franzke , Felix Voss, Andreas Pfaltz
Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 January 2011
Received in revised form 4 February 2011
Accepted 8 February 2011
Available online 13 February 2011
A series of serine-based phosphinooxazoline ligands was synthesized and the corresponding iridum
complexes were successfully applied in the asymmetric hydrogenation of various unfunctionalized
olefines and acetophenone-N-phenyl-imine. The results show that these new derivatives are useful
substitutes for the standard tert-leucine-derived PHOX ligands.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric catalysis
Hydrogenation
Iridium
P,N-Ligands
1. Introduction
O
Iridium complexes with chiral P,N-ligands have considerably
enhanced the scope of asymmetric hydrogenation.1,2 In contrast to
rhodium and ruthenium diphosphine complexes, they do not
require a coordinating group near the C]C double bond and,
therefore, allow the highly enantioselective hydrogenation of
a wide range of unfunctionalized tri- and even tetrasubstituted
alkenes. In addition, they have also been successfully used for the
hydrogenation of various functionalized olefins, heterocycles, such
as furans and indoles, and imines.
The first efficient enantioselective iridium catalyst was the
phosphinooxazoline (PHOX) complex 1 reported in 1998.3 The tert-
butyl substituent at the stereogenic center proved to be essential
for achieving high asymmetric inductions, as less sterically
demanding groups, such as an iso-propyl substituent gave only
modest enantiomeric excesses. However, a drawback of the tert-
butyl moiety is the relatively high cost of tert-leucine (especially
the (R)-enantiomer), which serves as the precursor for this ligand.
oTol2P
N
BArF
Ir
1
F
F
F
O
B(C6F5)4
Ph2P
N
Ir
O
F
2
In the course of our studies on the pronounced counterion
effects observed with these catalysts,3,4 we developed a series of
zwitterionic complexes and their respective cationic analogs, such
as precatalyst 2.5 As complex 2 gave encouraging enantioselectiv-
ities, we thought that compounds of this type, which are easily
accessible from serine as chiral starting material, could be a valu-
able alternative to tert-butyl-substituted phosphinooxazoline cat-
alysts. An attractive feature of these serine-derived ligands is the
option to introduce a wide range of sterically demanding moieties
at the sterogenic center of the oxazoline ring by synthetic modifi-
cation of the serine carboxyl group. Although a few examples of
* Corresponding author. Tel.: þ41 61 2671108; fax: þ41 61 2671103; e-mail
address: andreas.pfaltz@unibas.ch (A. Pfaltz).
y
Present address: Intermediates Research, BASF SE, D-67056 Ludwigshafen,
Germany.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.02.021

A. Franzke et al. / Tetrahedron 67 (2011) 4358e4363
4359
serine-based phosphinooxazoline ligands have been reported,6,7
Table 1
Reduction of (E)-1,2-diphenyl-1-propene (23)
their corresponding iridium complexes have not been studied yet.
Herein, we report the synthesis of a library of serine-derived
phosphinooxazoline ligands and their evaluation in iridium-cata-
lyzed enantioselective hydrogenation reactions.
1 mol% 16-22
*
50 bar H2,
CH2Cl2, rt, 2 h
23
2. Results and discussion
Entry
Precatalyst
Conversion [%]a
ee [%]b
1
2
3
4
5
6
16
17
18
19
20
21
22
2
1
27
90
88
99
99
93
99
> 99
n.d.
92 (S)
92 (S)
92 (S)
92 (S)
86 (S)
97 (S)
93 (S)
97 (R)
Phosphinooxazoline ligands 9e15 were easily accessible in
36e84% yield over two steps from literature-known aryl fluoride
6,6 which was prepared by standard procedures starting from (S)-
serine methyl ester hydrochloride (3, Scheme 1). The nucleophilic
aromatic substitution to introduce the phosphine donors was ac-
complished in the presence of the free hydroxyl group, although
a second equivalent of n-butyl lithium had to be used in the case of
the ortho-tolyl derivative 8 for the in situ deprotonation of the
alcohol. This was necessary because of the higher basicity of the
intermediate di-(ortho-tolyl)-phosphide compared to the analo-
gous phenyl-substituted reagent.
7
85
93
1
n.d. denotes ‘not determined’.
a
Determined by GC.
b
Determined by HPLC on a chiral stationary phase.
OH
i)
ii)
iii)
H
N
H
N
O
HCI*H2N CO2Me
3
OH
OH
OH
F
O
CO2Me
F
O
F
N
6
4
5
HO
iv)
vi)
v)
O
O
O
BArF
R2P
N
R2P
N
R2P
N
Ir
OR'
R'O
R = Ph, R' = Me
HO
R = Ph
R = oTol
9
7
8
16 R = Ph, R' = Me
17 R = Ph, R' = Bn
18 R = Ph, R' = Ac
19 R = Ph, R' = Bz
20 R = oTol, R' = Ac
21 R = oTol, R' = Bz
22 R = oTol, R' = Piv
10 R = Ph, R' = Bn
11 R = Ph, R' = Ac
12 R = Ph, R' = Bz
13 R = oTol, R' = Ac
14 R = oTol, R' = Bz
15 R = oTol, R' = Piv
Scheme 1. Preparation of serine-derived iridium precatalysts 16e22: (i) 2-FC6H4COCl, NEt3, MeOH, 0 ꢀC, 2.5 h, 91%; (ii) MeMgBr, THF/Et2O, 0 ꢀC/rt, 18 h then NH4Cl, 0 ꢀC, 70%;
(iii) TsCl, NEt3, CH2Cl2, rt, 75 h, 92%; (iv) KPPh2, THF, 0 ꢀC, 2 h, 77% (7) or oTol2PH, nBuLi, THF, ꢁ78 ꢀC/0 ꢀC, 2.5 h, 89% (8); (v) KH, THF, 0 ꢀC/rt, 2 h then R0X, 0 ꢀC/rt, 15e24 h,
41e94%; (vi) [Ir(COD)Cl]2, CH2Cl2,
D, 2 h then NaBArF, H2O, rt, 30 min, 72% to quantitative.
Both activated alkyl halogenides, such as methyl iodide or
benzyl bromide and acid chlorides could be used in step (v) with
similar efficiencies to furnish the corresponding ethers or esters.
The desired iridium complexes 16e22 were readily obtained by
metalation of the respective phosphinooxazolines 9e15 with
[Ir(COD)Cl]2 followed by anion exchange. The pathway shown in
Scheme 1 offers the advantage that the structural elements, which
define the chiral pocket around the catalytically active metal center,
namely the substituents at the phosphorus atom and especially in
the oxazoline moiety, are introduced in the last two steps of the
ligand synthesis. This allows an efficient fine-tuning of the catalysts
to meet the specific demands of different substrates.
With the new complexes in hand, the asymmetric hydrogena-
tion of benchmark substrate (E)-1,2-diphenyl-1-propene (23) was
studied. The results are summarized in Table 1 together with the
corresponding data for the literature-known, structurally related
catalysts 13 and 2.5
enantiomeric excesses, with the most selective catalyst 22 match-
ing the asymmetric induction induced by the tert-leucine-based
derivative 1.
In Scheme 2 the performance of the new iridium complexes in
the enantioselective reduction of other unfunctionalized olefins
24e27 as well as allylic alcohol 28, a,b-unsaturated ester 29 and
imine 30 is compared with that of the standard tert-butyl phos-
phinooxazoline catalyst 1.1d,3,8,9
The serine-based complexes yielded significantly higher enan-
tioselectivities in most cases (substrates 24e27 and 30) than the
well-known phosphinooxazoline catalyst 1. For the allylic alcohol
28 the enantiomeric excesses obtained with catalysts 22 and 1 were
similar. Only in the hydrogenation of ester 29 the tert-butyl
derivative 1 performed better. In general, ortho-tolyl substituents at
the phosphorus donor proved to be advantageous for achieving
high asymmetric inductions. Overall, the pivalate 22 was the most
effective precatalyst. However, most of the unfunctionalized olefins
gave better results with other complexes. Like this, higher selec-
tivities were obtained for the three substrates 24, 26, and 27 with
acetate-substituted catalysts 18 and 20, furnishing 88% ee, 89% ee
and 85% ee, respectively, while with 89% ee the best result for 24
was provided by benzyl ether 17. Since the ligand synthesis is
While the O-alkyl-substituted derivatives 16 and 17 showed
very low reactivities, all ester-functionalized complexes 18e22
furnished high conversions under standard conditions, which were
only slightly lower than the value reported for phosphinooxazoline
catalyst 1. All serine-based complexes yielded good to excellent

4360
A. Franzke et al. / Tetrahedron 67 (2011) 4358e4363
25
26
24
MeO
MeO
MeO
17 > 99% / 89% ee (S)
20 > 99% / 89% ee (R)
21 88% / 69% ee (R)
20 > 99% / 88% ee (S)
22 > 99% / 88% ee (R)
20 93% / 65% ee (R)
1
> 99% / 81% ee (R)
1
> 99% / 63% ee (S)
1
> 99% / 72% ee (S)
OH
28
27
MeO
22 > 99% / 95% ee (+)
18 > 99% / 92% ee (+)
18 > 99% / 85% ee (R)
19 > 99% / 82% ee (R)
1
95% / 96% ee (-)
1
> 99% / 60% ee (S)
CO2Et
29
N
30
22 > 99% / 75% ee (S)
21 > 99% / 71% ee (S)
22 > 99% / 85% ee (R)
20 > 99% / 82% ee (R)
1
96% / 84% ee (R)
1
> 99% / 77% ee (R)
Scheme 2. Conversions and enantioselectivities for the asymmetric hydrogenation of substrates 24e30 (conditions: 50 bar H2, CH2Cl2, rt, 2 h except for 27 (1 bar H2, 30 min) and 30
(4 h)). For the data of catalyst 1 see Ref. 1d (24e27), Ref. 3 (28, 29), and Ref. 8 (30).
highly flexible with the introduction of the P- and O-substituents in
the last two steps, structural optimization can be accomplished
easily and very efficiently.
To find an explanation for the unexpectedly low reactivity of the
methoxy-substituted catalyst 16, it was treated with hydrogen gas
in the absence of substrate (Scheme 3). Subsequent analysis of the
crude reaction mixture indicated a quantitative, selective trans-
formation of 16 into a new species. The latter was unequivocally
identified as hydride-bridged dimeric iridium complex 31 by NMR
spectroscopy and X-ray crystallography (Fig. 1).10
spectroscopy, when it was stirred under the conditions shown in
Scheme 3. However, formation of this complex was slower.
Remarkably, this class of precatalysts does not form trinuclear
complexes with an Ir3 core and a single bridging hydride upon
deactivation,12 as this is the case for complexes derived from other
amino acids like valine or tert-leucine.13 This can be explained by
the observed coordination of the methoxy groups in the crystal
structure of 31, which stabilizes the dimeric complex. In contrast,
no bonding IreO interactions can be detected in the solid state
structures of the cyclooctadiene derivatives 16, 21, and 22 with
a stable square-planar coordination geometry characteristic of a d8
16-electron configuration.14 Obviously, the iridium atoms in these
complexes show no tendency to coordinate additional ligands for
electronic and steric reasons.
2
O
O
O
O
O
CD2Cl2
H
H
N
N
P
Ph2P
N
BArF
2 BArF
Ir
Ir
1 bar H2, rt,
45 min
Ir
O
P
H
H
Ph
Ph
Ph
Ph
16
31
3. Conclusion
Scheme 3. Preparation of the dimeric iridium hydride complex 31.
A series of iridium complexes with serine-derived P,N-ligands
was readily synthesized in six steps from commercially available
starting materials in 18e49% overall yields. The catalysts were
evaluated in the enantioselective hydrogenation of representative
olefins and an imine, where theygenerally outperformed previously
developed, structurally similar phosphinooxazoline complexes.
A significant advantage of the serine-based ligands over the tert-
leucine-derived analogs is their flexible synthesis, which allows the
introduction of a wide range of sterically demanding substituents at
the stereogenic center in the oxazoline ring. In this way the ligand
structure can be optimized for a specific application. In addition,
enantiomerically pure (S)- and (R)-serine are much less expensive
precursors than (S)- and especially (R)-tert-leucine. Thus, it seems
worthwhile to evaluate serine-based phosphinooxazolines as
cheap alternatives for their tert-butyl-substituted analogs in other
reactions.
Fig. 1. Crystal structure of the dimeric iridium hydride complex 31. The counterions as
well as all hydrogen atoms (except of the two bridging hydrides) and solvent mole-
cules have been omitted for clarity.
4. Experimental section
4.1. General
In contrast to the two bridging hydrides the terminal hydrides in
the apical positions of the distorted coordination octahedrons
around the metal centers were not located in the refinement of the
structure, but these were assigned by NOESY NMR spectroscopy.
All reactions were performed in flame-dried glassware under ar-
gon using Schlenk techniques. Solvents and NEt3 were dried
employing standard procedures and distilled under nitrogen or
argon.15 All other commercial reagents were used as received. Deu-
teratedsolvents forNMR spectroscopyweredegassed bythreefreeze-
ꢀ
The distance between the two iridium atoms (2.62 A) is slightly
ꢀ
shorter than IreIr distances in analogous complexes (2.66 A and
11
ꢀ
2.70 A, respectively). The more reactive acetate derivative 18
furnished an analogous dimeric complex 32 according to NMR

A. Franzke et al. / Tetrahedron 67 (2011) 4358e4363
4361
ꢀ
pump-thaw cycles, dried over 4 A molecular sieves and stored under
(3ꢂ50 mL). The combined organic layers were dried over MgSO4, fil-
trated, and all volatiles removed under reduced pressure. Purification
of the brownish residue by column chromatography under argon
argon. Solvents for workup and chromatographic purification of air-
sensitive compounds were purged with a stream of argon for at least
15 min prior to use. Catalytic hydrogenations were set up under a nitro-
gen atmosphere in a MBraun Labmaster 130 glovebox using absolute
solvents purchased from Fluka. Chromatographic separations were per-
formed on Merck silica gel 60 (Darmstadt, 40e63 nm). For TLC analyses
pre-coated MachereyeNagelPolygram SIL G/UV254 plateswereused, and
the compounds were visualized with the help of UV light. NaBArF16 and
oTol2PH (33)17 were prepared following modified literature procedures.
NMR experiments were performed on Bruker Avance 400 or 500
spectrometers. 1H and 13C spectra were referenced relative to SiMe4
using the solvent residual peaks and the solvent signals, respectively,
as internal standards.18,19 31P, 19F, and 11B spectra were calibrated us-
ing H3PO4 (85%), CFCl3 and BF3$OEt2 as external standards. All NMR
shifts are given in parts per million (ppm). Mass spectra were mea-
sured on VG70-250, Finnigan MAT 95Q (EI), Finnigan MAT 312, Fin-
nigan MAR8400 (FAB) or FinnianMAT LCQ apparatus(ESI). Elemental
analyses were performed by the Micro Analysis Laboratory of the
University of Basel. IR spectra were measured on a PerkineElmer
(silica gel, 5ꢂ17 cm, hexanes/EtOAc 3:2) yielded PHOX 8 (1.86 g, 89%)
20
as colorless solid. Rf (hexanes/EtOAc 3:2) 0.28; [
a
]
þ126 (c 1.01 in
D
~
CHCl3);
1249, 1202, 1170, 1135, 1095, 1038, 964, 868, 785, 753, 718, 674, 582,
554, 524, 461 cmꢁ1
dH (400.1 MHz, CDCl3, 300 K) 0.99 (3H, s,
n
(KBr) 3462, 3053, 2972, 2905, 1653, 1586, 1465, 1351, 1288,
;
C(CH3)(CH3)OH), 1.09 (3H, s, C(CH3)(CH3)OH), 2.32 (3H, s, oTol-CH3),
2.38 (3H, s, oTol-CH3), 4.18 (1H, dd, J 9.7, 8.4 Hz, Ox-40-H), 4.25e4.35
(2H, m, Ox-50-H), 6.75 (1H, dd, J 7.3, 4.2 Hz, oTol-6000-H), 6.79 (1H, ddd, J
7.6,4.3,1.2Hz,oTol-6000-H), 6.95 (1H, ddd, J7.7, 3.7, 0.8Hz,Ar-300-H), 7.08
(2H, mc, oTol-5000-H), 7.16e7.29 (4H, m, oTol-3000-H and oTol-4000-H), 7.32
(1H, td, J 7.6, 1.4 Hz, Ar-400-H), 7.42 (1H, td, J 7.6, 1.3 Hz, Ar-500-H), 7.91
(1H, br s, Ar-600-H) (despite prolonged data aquisition time, the signal
for the exchangeable proton OH was not detected); dC (100.6 MHz,
CDCl3, 300 K) 21.2 (d, J 14 Hz, oTol-CH3), 21.4 (d, J 12 Hz, oTol-CH3), 24.3
(s, C(CH3)(CH3)OH), 27.5 (s, C(CH3)(CH3)OH), 68.4 (s, Ox-50-CH2), 71.0
(s, C(CH3)2OH), 76.7 (s, Ox-40-CH),126.1 (s, oTol-5000-CH),126.4 (s, oTol-
5000-CH), 128.6e128.9 (m, oTol-4000-CH and Ar-500-CH), 129.7 (br s, Ar-
CH),130.1 (d, J 5 Hz, oTol-3000-CH),130.5 (d, J 5 Hz, oTol-3000-CH),130.9 (s,
Ar-CH), 132.6 (s, Ar-CH), 133.6 (s, Ar-CH), 134.9 (s, Ar-CH), 135.7 (d, J
10 Hz, Ar-C),136.3 (br s, Ar-C),137.0 (br s, Ar-C),137.2 (br s, Ar-C),142.0
(br s, oTol-2000-C), 142.2 (br s, oTol-2000-C), 164.0 (s, Ox-20-C); dP
(162.0 MHz, CDCl3, 300 K) ꢁ21.4; m/z (FAB, NBA) 418 (100, [MþH]þ),
402 (12, [MꢁMe]þ), 358 (33, [MꢁCMe2OH]þ), 333 (13), 326 (35,
[MꢁoTol]þ), 316 (11%); C26H28NO2P requires: C, 74.80; H, 6.76; N, 3.36;
found: C, 74.30; H, 6.62; N, 3.42%.
€
1600 FTIR spectrometer. Melting points were determined on a Buchi
535 apparatus and are uncorrected. Specific rotations were measured
on a PerkineElmer 314 polarimeter. HPLC analyses were performed
on a Shimadzu system, GC measurements on equipment from Carlo
Erba Instruments. The abbreviation BArF refers to the tetrakis[3,5-
bis(trifluoromethyl)phenyl]borate anion, whilst ArF denotes the 3,5-
bis(trifluoromethyl)phenyl substituent in general.
4.2. Introduction of phosphine donors by nucleophilic
aromatic substitution
4.3. Preparation of ligands by ether or ester formation
4.2.1. (40S)-2-[20-(200-Diphenylphosphanylphenyl)-40,50-dihydro-ox-
azol-40-yl]-propan-2-ol (7)5. To oxazoline 6 (2.23 g, 10.0 mmol) in
absolute THF (15 mL) KPPh2 in THF (0.5 M, 20.0 mL, 10.0 mmol) was
slowly added at 0 ꢀC. After the red solution had been stirred for 2 h
at this temperature, H2O (50 mL) was added. The mixture was
extracted with CH2Cl2 (3ꢂ70 mL), the combined organic phases
were dried over MgSO4, filtrated, and evaporated under reduced
pressure. Purification of the yellow crude product by column
chromatography under argon (silica gel, 5ꢂ19 cm, hexanes/EtOAc
3:2) yielded PHOX 7 (3.01 g, 77%) as colorless, foamy solid. Rf
4.3.1. (4S)-4-(10-Methoxy-10-methylethyl)-2-(200-diphenylphosphanyl-
phenyl)-4,5-dihydrooxazole (9). To a suspension of KH (44.1 mg,
1.10 mmol) in absolute THF (10 mL) PHOX 7 (389 mg,1.00 mmol) was
added at 0 ꢀC and the mixture was stirred at room temperature, until
no further gas evolution was detected (about 2 h). After MeI (filtered
over basic Al2O3 directly before use, 75 mL, 1.20 mmol) had been
added at 0 ꢀC, the mixture was stirred for 24 h at room temperature.
The resulting yellow suspension was treated with aqueous Na2S2O3
(5%, 20 mL) and the mixture was extracted with CH2Cl2 (4ꢂ20 mL).
The combined organic phases were dried over MgSO4, filtered, and
evaporated to dryness under reduced pressure. The yellowish crude
product was purified by column chromatography under argon (silica
20
~
(hexanes/EtOAc 3:2) 0.25; [
a
]
þ97.5 (c 1.14 in CHCl3);
n
(KBr)
D
3424, 3054, 2971, 2902, 1953, 1887, 1824, 1760, 1650, 1584, 1473,
1433, 1354, 1293, 1246, 1174, 1134, 1092, 1034, 960, 906, 871, 745,
gel, hexanes/EtOAc 4:1) to yield ligand 9 (263 mg, 65%) as colorless,
20
696, 579, 503 cmꢁ1
;
dH (400.1 MHz, CDCl3, 300 K) 0.97 (3H, s, CH3),
waxy solid. Rf (hexanes/EtOAc 4:1) 0.15; [
a
]
þ40.7 (c 0.935 in
D
~
1.15 (3H, s, CH3), 1.74 (1H, br s, OH), 4.16 (1H, dd, J 10.0, 8.4 Hz, Ox-
40-H), 4.23 (1H, t, J 8.2 Hz, Ox-50-H), 4.31 (1H, dd, J 10.0, 8.0 Hz, Ox-
50-H), 6.91 (1H, dddd, J 7.7, 3.9, 1.4, 0.5 Hz, Ar-300-H), 7.20e7.29 (4H,
m, Ar-H), 7.29e7.37 (7H, m, Ar-H), 7.41 (1H, td, J 7.5, 1.3 Hz, Ar-H),
7.94 (1H, ddd, J 7.7, 3.7, 1.3 Hz, Ar-600-H); dC (100.6 MHz, CDCl3,
300 K) 24.4 (s, CH3), 27.6 (s, CH3), 68.6 (s, Ox-50-CH2), 71.0 (s,
C(CH3)2OH), 76.4 (s, Ox-40-CH), 128.5e128.8 (m, several Ar-CH),
129.8 (d, J 3 Hz, Ar-CH), 130.9 (s, Ar-CH), 131.8 (br d, J 22 Hz, Ar-100-
C), 133.4 (d, J 20 Hz, PPh2-o-CH), 134.4 (d, J 20 Hz, PPh2-o-CH), 134.7
(s, Ar-300-CH), 138.0 (d, J 10 Hz, Ar-C), 138.5e138.8 (m, several Ar-C),
164.2 (br s, Ox-20C); dP (162.0 MHz, CDCl3, 300 K) e6.1; m/z (FAB,
NBA) 390 (100, [MþH]þ), 330 (79, [MꢁCMe2OH]þ), 302 (21), 183
(14), 59 (14%, Me2COHþ); C24H24NO2P requires: C, 74.02; H, 6.21; N,
3.60; found: C, 73.63; H, 6.24; N, 3.55%.
CHCl3);
1582, 1562, 1470, 1432, 1340, 1305, 1254, 1154, 1087, 1031, 960, 902,
850, 748, 699, 580, 552, 501 cmꢁ1
dH (500.1 MHz, CDCl3, 295 K) 0.77
n
(KBr) 3043, 2969, 2933, 2889, 2823, 1965, 1828, 1768, 1647,
;
(3H, s, C(CH3)(CH3)O), 1.10 (3H, s, C(CH3)(CH3)O), 3.13 (3H, s, OCH3),
4.11e4.21 (2H, m, Ox-4-H and Ox-5-H), 4.25 (1H, br t, J 6.2 Hz, Ox-5-
H), 6.87 (1H, ddd, J 7.7, 4.0, 1.0 Hz, Ar-300-H), 7.21e7.35 (11H, m, PPh2-H
and Ar-400-H), 7.37 (1H, t, J 7.5 Hz, Ar-500-H), 7.96 (1H, br s, Ar-600-H); dC
(125.8 MHz, CDCl3, 295 K) 18.9 (s, C(CH3)(CH3)O), 23.0 (s, C(CH3)(CH3)
O), 49.6 (s, OCH3), 68.6 (br s, Ox-5-CH2), 74.7 (br s, Ox-4-CH), 76.6 (s,
C(CH3)2O), 128.3 (s, Ar-CH), 128.4e128.6 (m, several Ar-CH), 128.8 (s,
Ar-CH), 130.1 (br s, Ar-600-CH), 130.7 (br s, Ar-CH), 133.7 (d, J 20 Hz,
PPh2-o-CH), 134.4 (s, Ar-300-CH), 134.5 (d, J 21 Hz, PPh2-o-CH),
138.4e139.2 (br m, several Ar-C) (despite prolonged data aquisition
time, the signal for Ox-2-C was not detected); dP (202.5 MHz, CDCl3,
295 K) ꢁ5.4; m/z (FAB, NBA) 404 (66, [MþH]þ), 372 (12, [MꢁOMe]þ),
330 (62, [MꢁCMe2OMe]þ), 304 (27), 220 (11), 183 (15), 57 (100%);
C25H26NO2P requires: C, 74.43; H, 6.50; N, 3.47; found: C, 74.47; H,
6.64; N, 3.55%.
4.2.2. (40S)-2-{20-[200-(Di-ortho-tolylphosphanyl)-phenyl]-40,50-dihy-
drooxazol-40-yl}-propan-2-ol (8). To oxazoline 6 (1.12 g, 5.00 mmol)
and (oTol)2PH (33, 1.18 g, 5.50 mmol) in absolute THF (20 mL) was
added nBuLi in hexanes (1.6 M, 6.41 mL, 10.3 mmol) dropwise within
14 min at ꢁ78 ꢀC. After the dark red solution had been stirred for 2.5 h
at 0 ꢀC, H2O (40 mL) was added and the mixture extracted with CH2Cl2
4.3.2. (40S)-1-Methyl-1-{20-[200-(di-ortho-tolylphosphanyl)-phenyl]-
40,50-dihydrooxazol-40-yl}-ethyl pivalate (15). In analogy to the

4362
A. Franzke et al. / Tetrahedron 67 (2011) 4358e4363
synthesis of 9, PHOX 8 (1.04 g, 2.50 mmol) was reacted with KH
(110 mg, 2.75 mmol) and PivCl (369 L, 3.00 mmol) in absolute THF
Ox-5-CH2), 73.7 (s, Ox-4-CH), 75.9 (s, C(CH3)2O), 95.5 (d, J 13 Hz,
COD-CH), 97.7 (d, J 11 Hz, COD-CH), 117.6 (sept, J 4 Hz, ArF-p-CH),
122.7 (d, J 58 Hz, PPh2-i-C), 124.7 (q, J 273 Hz, CF3), 128.4 (d, J 47 Hz,
Ar-200-C), 128.6e129.4 (m, ArF-m-C, PPh2-m-CH and Ar-100-C), 129.6
(d, J 11 Hz, PPh2-m-CH), 130.1 (d, J 52 Hz, PPh2-i-C), 132.1 (d, J 2 Hz,
PPh2-p-CH), 132.5 (d, J 2 Hz, Ar-500-CH), 132.6 (d, J 2 Hz, PPh2-p-CH),
133.3 (d, J 10 Hz, PPh2-o-CH), 134.1 (d, J 8 Hz, Ar-600-CH), 134.3 (d, J
7 Hz, Ar-400-CH), 134.7e134.9 (m, ArF-o-CH, PPh2-o-CH and Ar-300-
CH),161.8 (q, J 50 Hz, ArF-i-C),164.9 (d, J 6 Hz, Ox-2-C); dF (376.5 MHz,
CDCl3, 300 K) e62.7; dP (202.5 MHz, CDCl3, 295 K) 17.0; m/z (ESIþ,
CH2Cl2) 704 (100%, [MeBArF]þ); C65H50BF24IrNO2P requires: C,
49.82; H, 3.22; N, 0.89; found: C, 49.91; H, 3.30; N, 1.09%.
m
for 22 h at room temperature. In contrast to the preparation of 9,
half-saturated aqueous NaHCO3 (20 mL) was added during workup.
Purification of the yellowish crude product by column chroma-
tography under argon (silica gel, 4ꢂ19 cm, hexanes/EtOAc 5:1)
furnished ligand 15 (1.19 g, 94%) as colorless, foamy solid. Rf (hex-
20
~
anes/EtOAc 5:1) 0.33; [
2971,1725,1650,1588,1468,1356,1289,1247,1174,1135, 1093, 1031,
968, 901, 841, 749, 718, 677, 556, 521, 455 cmꢁ1
dH (400.1 MHz,
a
]
þ36.9 (c 0.990 in CHCl3);
n
(KBr) 3055,
D
;
CDCl3, 300 K) 1.08 (12H, s, C(CH3)3 and C(CH3)(CH3)O), 1.40 (3H, s,
C(CH3)(CH3)O), 2.36 (3H, d, J 1.9 Hz, oTol-CH3), 2.37 (3H, d, J 1.6 Hz,
oTol-CH3), 4.18 (1H, dd, J 10.1, 8.8 Hz, Ox-50-H), 4.27 (1H, dd, J 8.6,
7.3 Hz, Ox-50-H), 4.44 (1H, dd, J 10.2, 7.2 Hz, Ox-40-H), 6.71 (2H, ddd,
J 7.6, 4.0, 0.9 Hz, oTol-6000-H), 6.92 (1H, dddd, J 7.7, 3.5, 1.3, 0.4 Hz, Ar-
300-H), 7.03 (2H, mc, oTol-5000-H), 7.14e7.27 (4H, m, oTol-3000-H and
oTol-4000-H), 7.31 (1H, td, J 7.6, 1.4 Hz, Ar-400-H), 7.39 (1H, td, J 7.6,
1.3 Hz, Ar-500-H), 7.96 (1H, dd, J 7.2, 3.2 Hz, Ar-600-H); dC (100.6 MHz,
CDCl3, 300 K) 20.5 (s, C(CH3)(CH3)O), 21.2 (s, oTol-CH3), 21.5 (s, oTol-
CH3), 23.9 (s, C(CH3)(CH3)O), 27.2 (s, C(CH3)3), 39.5 (s, C(CH3)3), 68.2
(s, Ox-50-CH2), 75.3 (s, Ox-40-CH), 82.5 (s, C(CH3)2O), 126.1 (s, oTol-
5000-CH), 126.3 (s, oTol-5000-CH), 128.3 (s, Ar-500-CH), 128.6 (s, oTol-4000-
CH),128.6 (s, oTol-4000-CH),130.1 (m, several Ar-CH),130.9 (s, Ar-CH),
132.3 (br d, J 24 Hz, Ar-100-C), 133.1 (s, oTol-6000-CH), 133.5 (s, oTol-
6000-CH), 134.6 (s, Ar-300-CH), 136.4e136.7 (m, oTol-1000-C), 138.0 (d, J
25 Hz, Ar-200-C), 142.2 (d, J 27 Hz, oTol-2000-C), 142.6 (d, J 27 Hz, oTol-
2000-C), 164.1 (br s, Ox-20-C), 177.6 (s, CO2); dP (162.0 MHz, CDCl3,
300 K) ꢁ21.2; m/z (EI, 70 eV) 501 (7, Mþ), 486 (9, [MꢁMe]þ), 410
(50, [MꢁoTol]þ), 400 (43, [MꢁOPiv]þ), 358 (65, [MꢁCMe2OPiv]þ),
332 (100), 316 (39), 308 (46), 57 (27%, tBuþ); C31H36NO3P requires:
C, 74.23; H, 7.23; N, 2.79; found: C, 73.94; H, 7.24; N, 2.87%.
4.4.2. (40S)-[(h4-1,5-Cyclooctadiene)-(1-methyl-1-{20-[200-(di-ortho-
tolylphosphanyl)-phenyl]-40,50-dihydrooxazol-40-yl}-ethyl
pivalate)-
iridium(I)] tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (22). In
analogy to the synthesis of 16, ligand 15 (150 mg, 0.300 mmol) was
reacted with [Ir(COD)Cl]2 (111 mg, 0.165 mmol), and NaBArF
(346 mg, 0.390 mmol). Purification of the crude product by column
chromatography under argon (silica gel, 4ꢂ20 cm, CH2Cl2) yielded
precatalyst 22 (503 mg, quantitative) as orange-red solid. According
to 31P NMR spectroscopy 22 is in equilibrium between two con-
formers in a ratio of 5:1 at 295 K, when it is dissolved in CDCl3. Single
crystals suitable for X-ray analysis were obtained by layering a con-
centrated solution of 22 in CDCl3 with hexane at room temperature.
20
~
Rf (CH2Cl2) 0.74 (tailing); [
1731, 1598, 1565, 1480, 1356, 1279, 1128, 974, 889, 839, 751, 713, 677,
567, 533, 454 cmꢁ1
dH (500.1 MHz, CDCl3, 295 K, main conformer)
a
]
þ114 (c 0.215 in CHCl3);
n
(KBr) 2975,
D
;
0.28 (3H, br s, C(CH3)(CH3)O), 1.06 (9H, br s, C(CH3)3), 1.51 (1H, br s,
COD-CHH), 1.57e1.74 (4H, br m, C(CH3)(CH3)O and COD-CHH),
2.02e2.22 (2H, br m, COD-CHH), 2.26e2.52 (7H, br m, COD-CH2 and
oTol-CH3), 3.04 (1H, br s, COD-CH), 3.15 (3H, br s, oTol-CH3), 3.40 (1H,
br s, COD-CH), 4.38 (1H, br t, J 9.6 Hz, Ox-50-H), 4.71 (1H, br d, J
9.5 Hz, Ox-50-H), 4.88 (1H, br s, COD-CH), 5.02 (2H, br s, COD-CH and
Ox-40-H), 6.47 (1H, br mc, oTol-6000-H), 6.80 (1H, br dd, J 11.1, 7.8 Hz,
oTol-6000-H), 7.07 (1H, br s, oTol-5000-H), 7.18e7.32 (2H, br m, Ar-H),
7.33e7.69 (10H, br m, Ar-H and ArF-p-H), 7.73 (8H, s, ArF-o-H), 8.19
(1H, br s, Ar-600-H); dC (125.8 MHz, CDCl3, 295 K, main conformer)
19.2 (s, C(CH3)(CH3)O), 23.3 (s, C(CH3)(CH3)O), 24.7 (d, J 5 Hz, oTol-
CH3), 25.6 (s, COD-CH2), 25.8 (d, J 7 Hz, oTol-CH3), 26.9 (s, C(CH3)3),
28.3 (s, COD-CH2), 32.6 (s, COD-CH2), 35.6 (d, J 3 Hz, COD-CH2), 39.5
(s, C(CH3)3), 67.6 (s, COD-CH), 67.6 (s, COD-CH), 69.6 (s, Ox-40-CH),
70.0 (s, Ox-50-CH2), 80.9 (s, C(CH3)2O), 91.6 (d, J 13 Hz, COD-CH), 95.9
(d, J 10 Hz, COD-CH), 117.6 (br s, ArF-p-CH), 119.2 (d, J 53 Hz, oTol-1000-
C), 124.7 (q, J 273 Hz, CF3), 127.4e127.6 (m, oTol-5000-CH), 128.6 (d, J
49 Hz, Ar-200-C),129.0 (q, J 32 Hz, ArF-m-C),129.9 (d, J 47 Hz, oTol-1000-
C), 132.5e132.9 (m, several Ar-CH), 133.7 (d, J 10 Hz, oTol-6000-CH),
134.0 (d, J 3 Hz, oTol-6000-CH), 134.3 (d, J 8 Hz, Ar-600-CH), 134.6e134.9
(m, ArF-o-CH and several Ar-CH), 141.0 (d, J 11 Hz, oTol-2000-C), 142.8
(d, J 16 Hz, oTol-2000-C), 161.8 (q, J 50 Hz, ArF-i-C), 165.7 (s, Ox-20-C),
178.1 (s, CO2) (despite prolonged data aquisition time, the signal for
Ar-100-C was not detected); dF (376.5 MHz, CDCl3, 300 K) ꢁ62.7; dP
(202.5 MHz, CDCl3, 295 K) 10.7 and 18.7 (in a ratio of 5:1); m/z (ESIþ,
CH2Cl2) 802 (100%, [MꢁBArF]þ); C71H60BF24IrNO3P requires: C, 51.21;
H, 3.63; N, 0.84; found: C, 51.33; H, 3.71; N, 1.01%.
4.4. Synthesis of iridium complexes
4.4.1. (4S)-[(h4-1,5-Cyclooctadiene)-{4-(10-methoxy-10-methylethyl)-
2-(200-diphenylphosphanylphenyl)-4,5-dihydrooxazole}-iridium(I)] tet-
rakis[3,5-bis(trifluoromethyl)phenyl]borate (16). To
a solution of
[Ir(COD)Cl]2 (73.9 mg, 0.110 mmol) in absolute CH2Cl2 (3 mL) ligand
9 (80.7 mg, 0.200 mmol) in absolute CH2Cl2 (2 mL) was added
dropwise at room temperature. After the resulting red solution had
been stirred in a closed vessel for 2 h at 50 ꢀC, the mixture was
cooled to room temperature and NaBArF (230 mg, 0.260 mmol) was
added. The slightly turbid solution was stirred for 5 min and then
treated with H2O (5 mL). After the mixture had vigorously been
stirred for 30 min at room temperature, the phases were separated
and the aqueous layer was extracted with CH2Cl2 (3ꢂ10 mL). The
combined organic phases were dried over MgSO4, filtered, and
evaporated under reduced pressure. Purification of the crude prod-
uct by column chromatography under argon (silica gel, CH2Cl2) fur-
nished precatalyst 16 (227 mg, 72%) as red solid. Single crystals
suitable for X-ray analysis were obtained by layering a concentrated
solution of 16 in CDCl3 with hexane at room temperature. Rf (CH2Cl2)
20
~
0.74 (tailing); [
1566, 1484, 1437, 1356, 1279, 1127, 967, 889, 839, 778, 743, 710, 677,
564, 510, 440 cmꢁ1
dH (500.1 MHz, CDCl3, 295 K) 0.64 (3H, s,
a
]
þ173 (c 0.225 in CHCl3);
n
(KBr) 2976, 2839, 1603,
D
;
C(CH3)(CH3)O), 0.79 (3H, s, C(CH3)(CH3)O), 1.42 (1H, mc, COD-CHH),
1.64 (1H, mc, COD-CHH), 2.01 (2H, mc, COD-CHH), 2.33e2.62 (4H, m,
COD-CH2), 2.95 (1H, mc, COD-CH), 3.01 (3H, s, OCH3), 3.28 (1H, br s,
COD-CH), 4.12 (1H, dd, J 9.3, 3.1 Hz, Ox-4-H), 4.39 (1H, t, J 9.6 Hz, Ox-
5-H), 4.59 (1H, dd, J 9.9, 3.0 Hz, Ox-5-H), 4.99 (1H, br s, COD-CH), 5.39
(1H, quint, J 7.0 Hz, COD-CH), 7.09 (2H, br s, PPh2-o-H), 7.34e7.58
(13H, m, Ar-H and ArF-p-H), 7.61 (2H, mc, Ar-400-H and Ar-500-H), 7.73
(8H, s, ArF-o-H), 8.19 (1H, dd, J 9.0, 4.3 Hz, Ar-600-H); dC (125.8 MHz,
CDCl3, 295 K) 18.0 (s, C(CH3)(CH3)O), 19.8 (s, C(CH3)(CH3)O), 26.0 (d, J
2 Hz, COD-CH2), 28.6 (s, COD-CH2), 32.5 (s, COD-CH2), 36.7 (d, J 5 Hz,
COD-CH2), 49.1 (s, OCH3), 61.0 (s, COD-CH), 62.2 (s, COD-CH), 70.2 (s,
4.4.3. (4S,4S)-{Diiridium(III)-bis(m1-hydrido)-bis(m2-hydrido)-bis[4-
(10-methoxy-10-methylethyl)-2-(200-diphenylphosphanylphenyl)-4,5-
dihydrooxazole]} bis{tetrakis[3,5-bis(trifluoromethyl)phenyl]borate}
(31). Precatalyst 16 (16.8 mg,10.7 mmol) in absolute CD2Cl2 (1.0 mL)
was stirred under an atmosphere of dihydrogen (about 1 bar) at
room temperature for 45 min. The NMR spectroscopic analysis of
the now yellowish solution revealed the complete, selective
transformation of 16 into iridium dimer 31. Layering this mixture
with absolute hexane (3.0 mL) at room temperature furnished

A. Franzke et al. / Tetrahedron 67 (2011) 4358e4363
4363
crystals, some of which were suitable for X-ray analysis. After re-
References and notes
moval of the mother liquor these were washed with pentane
1. Reviews: (a) Church, T. L.; Andersson, P. G. Coord. Chem. Rev. 2008, 252,
513e531; (b) Roseblade, S. J.; Pfaltz, A. Acc. Chem. Res. 2007, 40, 1402e1411; (c)
Cui, X.; Burgess, K. Chem. Rev. 2005, 105, 3272e3296; (d) Pfaltz, A.; Blanken-
(2ꢂ1 mL) and dried under high vacuum. Like this, complex 31
~
(8.4 mg, 50%) was isolated as yellow solid.
n
(KBr) 2990, 1639, 1487,
€
€
1438, 1357, 1280, 1127, 1023, 936, 890, 838, 776, 744, 712, 677, 553,
stein, J.; Hilgraf, R.; Hormann, E.; McIntyre, S.; Menges, F.; Schonleber, M.;
506, 444 cmꢁ1
;
dH (500.1 MHz, CD2Cl2, 295 K) ꢁ31.29 (2H, mc, m1-Ir-
€
Smidt, S. P.; Wustenberg, B.; Zimmermann, N. Adv. Synth. Catal. 2003, 345,
33e43.
H), ꢁ25.17 (1H, sept, J 4.7 Hz, m2-Ir-HcisP), ꢁ0.95 (1H, tt, J 78.5,
2.4 Hz, m2-Ir-HtransP), 0.14 (6H, s, C(CH3)(CH3)O), 1.14 (6H, s,
C(CH3)(CH3)O), 3.35 (6H, s, OCH3), 4.32e4.39 (4H, m, Ox-4-H and
Ox-5-H), 4.75 (2H, t, J 10.8 Hz, Ox-5-H), 6.62 (4H, dd, J 11.9, 7.2 Hz,
PPh2-o-H), 7.16 (4H, br s, PPh2-o-H), 7.22 (2H, dd, J 10.9, 7.6 Hz, Ar-
300-H), 7.38 (4H, t, J 7.2 Hz, PPh2-m-H), 7.45 (4H, br t, J 7.0 Hz, PPh2-
m-H), 7.55 (8H, s, ArF-p-H), 7.58 (4H, t, J 7.4 Hz, PPh2-p-H), 7.62e7.76
(18H, m, ArF-o-H and Ar-400-H), 7.78 (2H, t, J 7.6 Hz, Ar-500-H), 8.18
(2H, dd, J 7.7, 2.1 Hz, Ar-600-H); dC (125.8 MHz, CD2Cl2, 295 K) 14.4 (s,
C(CH3)(CH3)O), 21.4 (s, C(CH3)(CH3)O), 54.3 (s, OCH3), 70.8 (s, Ox-5-
CH2), 80.7 (s, Ox-4-CH), 81.4 (s, C(CH3)2O), 118.0 (sept, J 4 Hz, ArF-p-
CH), 125.1 (q, J 272 Hz, CF3), 128.2e128.3 (m, several Ar-C),
129.0e129.8 (m, PPh2-m-CH and ArF-m-C), 130.1 (mc, PPh2-m-CH),
132.6e132.8 (m, PPh2-o-CH, Ar-600-CH and Ar-C), 133.3e133.4 (m,
PPh2-o-CH and PPh2-p-CH), 133.8 (s, Ar-500-CH), 135.0 (mc, Ar-C),
135.2e135.3 (m, ArF-o-CH, Ar-300-CH and Ar-400-CH), 162.0 (br s, Ox-
2-C), 162.3 (q, J 50 Hz, ArF-i-C); dF (376.5 MHz, CD2Cl2, 300 K) ꢁ63.1;
dP (162.0 MHz, CD2Cl2, 300 K) ꢁ1.5; m/z (ESIþ, CH2Cl2) 598 (100%,
[Mꢁ2$BArF]2þ).
2. Selected, recent examples: (a) Verendel, J. J.; Zhou, T.; Li, J.-Q.; Paptchikhine, A.;
Lebedev, O.; Andersson, P. G. J. Am. Chem. Soc. 2010, 132, 8880e8881; (b) Zhu, Y.;
Fan, Y.; Burgess, K. J. Am. Chem. Soc. 2010, 132, 6249e6253; (c) Baeza, A.; Pfaltz, A.
Chem.dEur. J. 2010,16, 4003e4009; (d) Baeza, A.; Pfaltz, A. Chem.dEur. J. 2010,16,
2036e2039; (e) Woodmansee, D. H.; Muller, M.-A.; Neuburger, M.; Pfaltz, A.
Chem. Sci. 2010, 1, 72e78; (f) Zhao, J.; Burgess, K. J. Am. Chem. Soc. 2009, 131,
€
€
€
13236e13237; (g) Mazuela, J.; Verendel, J. J.; Coll, M.; Schaffner, B.; Borner, A.;
ꢂ
ꢁ
Andersson, P. G.; Pamies, O.; Dieguez, M. J. Am. Chem. Soc. 2009, 131,
12344e12353; (h) Cheruku, P.; Paptchikhine, A.; Church, T. L.; Andersson, P. G. J.
Am. Chem. Soc. 2009,131, 8285e8289; (i) Schrems, M. G.; Pfaltz, A. Chem. Commun.
2009, 6210e6212; (j) Paptchikhine, A.; Cheruku, P.; Engman, M.; Andersson, P. G.
Chem. Commun. 2009, 5996e5998; (k) Baeza, A.; Pfaltz, A. Chem.dEur. J. 2009,15,
2266e2269; (l) Dieguez, M.; Mazuela, J.; Pamies, O.; Verendel, J. J.; Andersson, P.
G. J. Am. Chem. Soc. 2008,130, 7208e7209; (m) Zhu, Y.; Burgess, K. J. Am. Chem. Soc.
2008, 130, 8894e8895; (n) Wang, A.; Wustenberg, B.; Pfaltz, A. Angew. Chem.
ꢁ
ꢂ
€
ꢁ
2008, 120, 2330e2332; Angew. Chem., Int. Ed. 2008, 47, 2298e2300; (o) Dieguez,
M.; Mazuela, J.; Pamies, O.; Verendel, J. J.; Andersson, P. G. Chem. Commun. 2008,
ꢂ
3888e3890; (p) Zhu, Y.; Burgess, K. Adv. Synth. Catal. 2008, 350, 979e983.
3. Lightfoot, A.; Schnider, P.; Pfaltz, A. Angew. Chem. 1998, 110, 3047e3050; Angew.
Chem., Int. Ed. 1998, 37, 2897e2899.
4. Smidt, S. P.; Zimmermann, N.; Studer, M.; Pfaltz, A. Chem.dEur. J. 2004, 10,
4685e4693.
5. Franzke, A.; Pfaltz, A. Chem.dEur. J. in press, doi:10.1002/chem.201003314.
6. Helmchen and coworkers synthesized ligand 7 and the related THP ether: Peer,
M.; de Jong, J. C.; Kiefer, M.; Langer, T.; Rieck, H.; Schell, H.; Sennhenn, P.;
Sprinz, J.; Steinhagen, H.; Wiese, B.; Helmchen, G. Tetrahedron 1996, 52,
7547e7583.
4.5. General procedure for enantioselective hydrogenations
7. Ligand 10 and the corresponding TBDMS ether were reported by Stoltz and
coworkers. In
a palladium-catalyzed enantioselective decarboxylative pro-
tonation the TBDMS derivative was found to be inferior to the tert-butyl
phosphinooxazoline ligand: (a) Marinescu, S. C.; Nishimata, T.; Mohr, J. T.;
Stoltz, B. M. Org. Lett. 2008, 10, 1039e1042; (b) Tani, K.; Behenna, D. C.;
McFadden, R. M.; Stoltz, B. M. Org. Lett. 2007, 9, 2529e2531; (c) Further ex-
ample of serine-based PHOX ligands: Caprioara, M.; Fiammengo, R.; Engeser,
Precatalyst (usually 1.0 mmol) and substrate (usually 100 mmol)
were weighed in a 2 mL screw cap glass vial equipped with a mag-
netic stir bar and the desired solvent was added (usually 0.5 mL
absolute CH2Cl2). In this connection, stock solutions of the iridium
complexes and alkenes were sometimes used leaving the overall
concentrations unchanged. Four vessels were placed in a 60 mL
autoclave (Premex), which was closed under an inert atmosphere.
After pressurizing the autoclave with hydrogen (usually 50 bar) the
transformationwasinitiatedbyswitchingon thestirrer(700 minꢁ1).
After the target reaction time the hydrogen was released and hex-
anes (2 mL) added. The resulting suspension was filtered over a pad
of silica gel, which was washed with Et2O/hexanes 1:1. The eluate
was concentrated under reduced pressure, the residue dissolved in
heptane (3 mL) and the conversion and enantioselectivity were di-
rectly determined by GC and HPLC analyses.3,20,21
€
M.; Jaschke, A. Chem.dEur. J. 2007, 13, 2089e2095.
8. Stohler, R. Ph.D. Thesis, University of Basel, 2006.
9. For reaction conditions and additional asymmetric hydrogenation experiments
see the Supplementary data.
10. Crystal data for 31 (from CD2Cl2/hexane): C114H78B2F48Ir2N2O4P2$2.75 CD2Cl2,
ꢀ
M¼3153.36, triclinic, a¼12.9269(1), b¼15.8510(1), c¼16.7145(2) A,
a
¼73.
3
ꢀ
0026(4),
group
b
¼73.5387(4),
g
¼89.7452(5)ꢀ, U¼3129.52(5) A , T¼173 K, space
P
1, Z¼1, 35,894 reflections measured, 35,886 unique (Rint¼0.00),
29,618 used in all calculations. The final wR was 0.0500 (all data). For a se-
lection of bond lengths and angles see the supplementary data. Crystallo-
graphic data (excluding structure factors) for 31 have been deposited with the
Cambridge Crystallographic Data Center as supplementary publication no.
CCDC-805973. Copies of the data can be obtained, free of charge, on appli-
cation to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: þ44 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk).
11. (a) Schnabel, R. C.; Carroll, P. S.; Roddick, D. M. Organometallics 1996, 15,
655e663; (b) Esteruelas, M. A.; García, M. P.; Lahoz, F. J.; Martín, M.; Modrego,
J.; Onate, E.; Oro, L. A. Inorg. Chem. 1994, 33, 3473e3480.
12. (a) Wang, H. H.; Pignolet, L. H. Inorg. Chem. 1980, 19, 1470e1480; (b) Crabtree, R.
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A. F. thanks the ‘Fonds der Chemischen Industrie’ (Frankfurt)
and the German Federal Ministry for Science and Technology
ꢁ
14. For details of the X-ray crystallograhic investigations see the Supplementary
(BMBF) for a Kekule Fellowship. Financial support by the Swiss
data.
National Science Foundation is gratefully acknowledged. We also
thank Markus Neuburger and Dr. Sylvia Schaffner for the crystal
structure analyses as well as Dr. Daniel Haussinger for the help with
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19. For CD2Cl2 the solvent shifts
d
¼5.32 (1H) and 54.0 (13C) ppm, respectively, were
Supplementary data
used to calibrate the spectra.
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Int. Ed. 2001, 40, 4445e4447; (b) Schnider, P.; Koch, G.; Pretot, R.; Wang, G.;
Supplementary data contain additional experimental pro-
cedures and hydrogenation results as well as X-ray structure
analyses of complexes 16, 21, and 22. Supplementary data related to
this article can be found online at doi:10.1016/j.tet.2011.02.021.
€
Bohnen, F. M.; Kruger, C.; Pfaltz, A. Chem.dEur. J. 1997, 3, 887e892.
21. The conversion of 28 was determined by GC (Restek Rtx 1701, 60 kPa He,
100 ꢀC/2 min/7 ꢀC mine1/250 ꢀC/10 min): tR 14.2 (product) and 16.1 (substrate)
min.