Synthesis of Josiphos-type bisphospholane ligands

Article abstract of DOI:10.1055/s-0032-1316755

Bisphospholane Josiphos-type ligands were synthesized in high yields employing electrophilic and nucleophilic phospholane synthons. Full characterization data including solid-state structures of the diastereomeric ligands are reported. These ligands resul

Full text of DOI:10.1055/s-0032-1316755

PAPER
▌2793
paper
Synthesis of Josiphos-Type Bisphospholane Ligands
Josiphos-Type Bisphospholane Ligands
Tim Hammerer,a Andrea Dämbkes,a Wolfgang Braun,b,1 Albrecht Salzer,b Giancarlo Franciò,*a Walter Leitner*a
a
Institut für Technische Chemie und Makromolekulare Chemie, RWTH Aachen University, Worringerweg 1, 52074 Aachen, Germany
Fax +49(241)8022177; E-mail: francio@itmc.rwth-aachen.de; E-mail: leitner@itmc.rwth-aachen.de
b
Institut für Anorganische Chemie, RWTH Aachen University, Landoldtweg 1, 52074 Aachen, Germany
Received: 21.05.2012; Accepted after revision: 23.06.2012
been successfully used for the synthesis of numerous of li-
Abstract: Bisphospholane Josiphos-type ligands were synthesized
gand structures.6
in high yields employing electrophilic and nucleophilic phos-
pholane synthons. Full characterization data including solid-state
structures of the diastereomeric ligands are reported. These ligands
resulted in active and enantioselective iridium catalysts for the
asymmetric hydrogenation of imines. Pronounced cooperative ef-
fects of the chiral elements within the ligand structure were ob-
served and enantioselectivities of up to 74% ee were achieved.
Following this reaction sequence, in 2004 Salzer and co-
workers7 reported the first example of a Josiphos deriva-
tive bearing a phospholane moiety in the side chain (α-po-
sition). The resulting hybrid phosphine-phospholane
ligand led to excellent results in the asymmetric hydroge-
nation of dimethyl itaconate with >99% ee. Recently,
Börner and co-workers introduced a phospholane unit in
the ortho position of Ugi’s amine through an electrophilic
phospholane synthon resulting in a bidentate P,N-ligand.8
Key words: ferrocene ligands, chiral phospholane, asymmetric hy-
drogenation, iridium, imine hydrogenation
In 1994, Togni2 developed an efficient and modular ap-
proach for the synthesis of ferrocene-based bidentate
phosphorous ligands (Josiphos-type) elaborating a proce-
dure of Kumada and Hayashi.3 Josiphos-type bisphos-
phines are extremely useful ligands for asymmetric
catalysis and have been applied up to now in four different
industrial processes including the large-scale production
of (S)-Metolachlor.4
Intrigued by the possibility to integrate the privileged
structural motifs of the Josiphos backbone, based on pla-
nar and central chirality, with two chiral phospholane
units, we sought to synthesize bisphospholane counter-
parts of the Josiphos bisphosphine ligands.
(R1)2P
Ph2P
P(R2)2
P
Fe
Fe
Fe
P
NMe2
The Josiphos ligands are available via a two-step synthe-
sis starting from enantiomerically pure Ugi’s amine.5 Due
to the consecutive introduction of the phosphorus moi-
eties, the synthesis is quite flexible and allows for func-
tionalization with two different donor groups.
Josiphos
Salzer 2004
Börner 2007
Figure 1 Josiphos and related derivatives
Both the nucleophilic synthons (2R,5R)-2,5-dimethyl-
phospholane (2) and the electrophilic synthon (R,R)-1-
chloro-2,5-dimethylphospholane (3)9 could be conve-
niently obtained from (R,R)-2,5-dimethyl-1-(trimethylsi-
lyl)phospholane (1) in a one-step procedure (Scheme 2).
By treating 1 with either an excess of degassed water or
methanol, quantitative conversion into the corresponding
secondary phospholane was achieved.10 After distillation
(bp 132–133 °C), analytically pure secondary phos-
pholane 2 was obtained as colorless oil in 82% yield.
Chlorophospholane 3 was synthesized from 1 via an
umpolung reaction with hexachloroethane (yield: 73%).8
Both transformations were carried out using enantiomeri-
cally pure (R,R)-2,5-dimethyl-1-(trimethylsilyl)phos-
pholane (1) as the starting material and proceeded without
loss of optical purity.
ortho-position
α-position
Fe
P1
P2
electrophilic
synthon
nucleophilic
synthon
electrophilic
synthon
nucleophilic
synthon
P1
Fe
Fe
P1 Fe
NMe2
NMe2
P2
Scheme 1 Togni’s ferrocene ‘construction kit’2b
In the first step an electrophilic synthon is introduced in
the ortho position of Ugi’s amine, while in the second step
the dimethylamino group is substituted by a nucleophilic
phosphine synthon. This synthetic approach, known as
‘Togni’s ferrocene construction kit’ (Scheme 1),2b has
H
P
TMS
P
Cl
P
C2Cl6
73%
H2O
82%
SYNTHESIS 2012, 44, 2793–2797
Advanced online publication: 01.08.2012
DOI: 10.1055/s-0032-1316755; Art ID: SS-2012-T0455-OP
© Georg Thieme Verlag Stuttgart · New York
2
1
3
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Scheme 2 Synthesis of the nucleophilic and electrophilic phos-
pholane synthons 2 and 3, respectively

2794
T. Hammerer et al.
PAPER
Ligand precursors (RC,SFc)-4 and (SC,RFc)-4 were synthe-
sized via the route published by Börner.8 The synthesis is
straightforward and pure products (RC,SFc)-4 and (SC,RFc)-
4 were obtained after recrystallization from hot methanol
in 81% and 83% yield, respectively. For the introduction
of the phospholane moiety into the side chain of the ligand
precursors (Scheme 3), the standard method was adapt-
ed.2a The precursors (RC,SFc)-4 and (SC,RFc)-4 were re-
fluxed in glacial acetic acid together with secondary
phospholane 2 leading to the desired bisphospholanes L1
and L2, respectively, in good yields after recrystallization
from hot ethanol (L1, 78%; L2, 74%). Single crystals suit-
able for X-ray diffractometric analysis were obtained
from cold ethanol and the molecular structures of L1 and
L2 in the solid state were determined.
P
P1
Fe
Fe
P2
NMe2
Figure 2 ORTEP representation of L1 (50% probability, hydrogen at-
oms omitted for clarity)
P
(Rc,SFc)-4
, AcOH
H
L1 (78%)
85–90 °C, 2–3 h
P1
Me2N
P2
P
Fe
Fe
L2 (74%)
(Sc,RFc)-5
Scheme 3 Synthesis of ligand L1 and L2
In the solid state structure of L1 the two phosphorus atoms
are quite far apart (5.272 Å) and their lone pairs have an
almost antiperiplanar orientation (Figure 2). This arrange-
ment is unusual for Josiphos-type ligands as confirmed by
the torsion angles α1(C11–C1–P1–C2) of –106.03° and
α2(C9–C8–C12–C19) of –73.20°, which are well beyond
the range of values typically found for free (RC,SFc)-Josi-
phos derivatives (α1 = –60° to –82°; α2 = –10° to –32°).11
In contrast, the two phosphorus atoms in the solid state
structure of (SC,RFc)-L2 (Figure 3) are much closer (3.803
Å), the lone pairs are almost synperiplanar, and the torsion
angles α1(C17–C16–P2–C12) (+58.83°) and α2(C19–
C15–C7–C8) (+30.35°) in line with the values measured
for other (RC,SFc)-Josiphos ligands, upon inverting the
sign because of the opposite chirality at the ferrocene
backbone. The arrangement of the cyclopentadienyl rings
in L1 is almost staggered (25.76°), whereas in L2 is nearly
eclipsed (6.31°). Selected crystallographic data, bond
lengths and angles for L1 and L2 are summarized in
Tables 1–3.
Figure 3 ORTEP representation of L2 (50% probability, hydrogen at-
oms omitted for clarity)
Table 1 Comparison of Principal Crystallographic Data of L1 and
L2
Ligand
L1
L2
crystal system
space group
monoclinic
P21
orthorhombic
P212121
The 31P NMR of L1 shows two singlets, at δ = –2.0 and
+24.1 arising from the phospholanes in the ortho position
and in the α-position, respectively. In contrast, the 31P
NMR spectrum of L2 shows two doublets, at δ = –11.6
and 16.6 for the phospholane in the ortho position and the
α-phospholane, respectively, with a coupling constant of
P1,P2 distance
5.272 Å
25.76°
3.803 Å
6.31°
dihedral angle Cp–Cp′
Synthesis 2012, 44, 2793–2797
© Georg Thieme Verlag Stuttgart · New York

PAPER
Josiphos-Type Bisphospholane Ligands
2795
(Table 5). The coupling constant JSe,P is a suitable tool for
classifying phosphorus ligands, whereby a smaller cou-
pling constant reflects a higher P-basicity.14 The 31P–77Se
coupling constants for the bisselenides of L1 and L2 (Ta-
ble 5) lie within the range reported for phospholane sele-
nides (710–780 Hz).15 The phosphorus atoms of L1 and
L2 in the ortho position showed JSe,P = 713 and 718 Hz,
respectively, similar to the value registered for the corre-
sponding MeDuPhos derivative (712 Hz). The coupling
constants of the phospholane selenides in the α-position
are significantly higher (727 Hz for L1 and 726 Hz for
L2) and closer to the value reported for Se=PPh3 (732
Hz).14a
Table 2 Selected Distances and Angles for L1
Distances (Å)
Angles (°)
P1–C1
P1–C2
P1–C5
P2–C12
P2–C13
P2–C16
1.820(4)
1.861(3)
1.872(3)
1.882(3)
1.882(3)
1.879(3)
C1–P1–C2
104.40(1)
92.70(1)
105.30(1)
104.67(1)
92.98(1)
104.54(1)
–106.03
C2–P1–C5
C1–P1–C5
C12–P2–C16
C16–P2–C13
C12–P2–C13
α1(C11–C1–P1–C2)
Table 5 31P NMR Data of Selected P-Selenides
α2(C9–C8–C12–C19) –73.20
Selenide
31P NMR
P1 (δ)
+48.7
+53.4
+61.0
+35.9
JSe,P1 (Hz) P2 (δ)
JSe,P2 (Hz)
Table 3 Selected Distances and Angles for L2
L1
713
718
712
732
+74.0
+68.6
–
727
726
–
Distances (Å)
Angles (°)
L2
MeDuPhos
PPh3
P2–C16
P2–C9
P2–C12
P1–C7
P1–C4
P1–C1
1.831(3)
1.887(3)
1.887(3)
1.879(3)
1.874(3)
1.865(3)
C16–P2–C12
C9–P2–C12
C9–P2–C16
C1–P1–C7
C1–P1–C4
C4–P1–C7
101.64(1)
92.43(1)
102.02(1)
106.06(1)
92.78(1)
103.00(1)
–
–
The diastereomeric ligands L1 and L2 were applied in the
iridium-catalyzed asymmetric hydrogenation of N-(1-
phenylethylidene)aniline (5) as a model substrate
(Scheme 4).
Ph
α1(C17–C16–P2–C12) +58.83
α2(C19–C15–C7–C8) +30.35
Ph
HN
∗
N
[Ir(cod)Cl]2, L, I2
Ph
Ph
toluene, H2 (40 bar), r.t., 16 h
5
6
L1 74% (R)
L2 32% (S)
JP1,P2 = 23.3 Hz (Table 4). As the presence and magnitude
of through space coupling constant between two phospho-
rus atoms depends on their distance and the relative orien-
tation of their lone pairs,12 the preferential conformation
in solution of the phospholane groups in L1 and in L2
should be significantly different, far apart in L1 and close
to each other in L2.13 This qualitative assumption corre-
lates very well with the arrangements found in the solid-
state structure of L1 (Figure 2) and L2 (Figure 3).
Scheme 4 Iridium-catalyzed imine hydrogenation with L1 and L2
Full conversion was obtained with both ligands. Ligand
L1 led to 74% ee in favor of the (R)-product, whereas L2
led to the preferential formation of the opposite enantio-
mer with significantly lower enantioselectivity of 32% ee.
These results indicate a pronounced cooperative effect of
the chiral information from the ferrocene backbone and
the chirality of phospholane moieties. For this particular
reaction, ligand L1 provides the matched diastereomer.
Comparable effects have been observed by Togni16 using
P-chiral Josiphos diastereomers and by Zheng13 with re-
lated phosphine-phosphoramidite ligands.
Table 4 Selected Analytical Data for L1 and L2
24
Ligand
31P NMR (δ)
[α]D
P1
P2
JP1,P2 (Hz)
In conclusion, the first bisphospholane Josiphos-type li-
gands were synthesized. The ligands have been fully char-
acterized both in solution and in the solid state via X-ray
diffractometry. The coupling constants JSe,P of the corre-
sponding bisselenides indicated, that the electronic fea-
tures of these ligands resemble that of phosphine-
phospholanes. Strong cooperative effects of the chiral el-
ements within the ligand structure were observed in the
L1
L2
–2.0
–11.6
+24.1
+16.6
–
+71.63
+266.8
23.3
To evaluate the σ-donor properties of the distinct phos-
pholane groups of L1 and L2, they were converted into
the corresponding phospholane selenides by treating them
with elemental selenium at 60 °C for two hours in benzene
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2793–2797

2796
T. Hammerer et al.
PAPER
EtOH, 3 mL) to give the pure product as an orange solid; yield:
394.4 mg (0.79 mmol, 78%).
[α]D24 +71.6 (c 0.393, CH2Cl2).
iridium-catalyzed asymmetric hydrogenation of an imine
and enantioselectivities of up to 74% ee have been ob-
tained with the matched diastereomer L1.
1H NMR (400 MHz, C6D6): δ = 0.97–1.04 (m, 1 H, CH2), 1.10 (dd,
J
H,H = 6.9 Hz, JH,P = 17.3 Hz, 3 H, CH3), 1.16–1.25 (br m, 1 H, CH),
All reactions were carried out under an inert atmosphere of dry and
O2-free argon either with the use of standard Schlenk techniques or
1.20 (t, JH,H,P = 7.1 Hz, 3 H, CH3), 1.31 (dd, JH,H = 7.4 Hz, JH,P = 18.7
Hz, 3 H, CH3), 1.42 (dd, JH,H = 7.3 Hz, JH,P = 10.4 Hz, 3 H,
CH3),1.47–1.61 (br m, 1 H, CH2), 1.67–1.77 (br m, 1 H, CH2), 1.69
(dd, JH,H = 7.0 Hz, JH,P = 15.1 Hz, 3 H, CH3), 1.79–1.87 (m, 2 H, CH
+ CH2), 1.90–2.06 (br m, 4 H, 2 CH + 2 CH2), 2.09–2.17 (m, 1 H,
CH2), 2.37–2.52 (m, 1 H, CH2), 2.92–3.02 (m, 1 H, CH), 3.88–3.96
(m, 1 H, CCpH), 3.99–4.08 (m, 1 H, CCpH), 4.12 (s, 5 H, CCpH), 4.42
(s, 1 H, CCpH).
1
in a glove box. H, 13C, and 31P NMR spectra were recorded with
Bruker AV 300 spectrometer operating at 300.1 MHz (1H), 75.5
MHz (13C), and 121.5 MHz (31P) and Bruker AV 400 spectrometer
operating at 400.1 MHz (1H), 100 MHz (13C), and 162 MHz (31P);
1H and 13C{1H} NMR are relative to TMS with use of the residual
solvent signals as internal standards and 31P NMR are relative to
85% H3PO4 as external standard. The multiplicities of the signals
were analyzed by assuming spectra of first order. The signals were
13C NMR (101 MHz, C6D6): δ = 15.6 (CH3), 15.9 (CH3), 21.6 (d,
J
1
assigned on the basis of 2D NMR spectra (31P-1H HMBC, H-1H
C,P = 31.6 Hz, CH3), 22.1 (d, JC,P = 31.0 Hz, CH3), 25.0 (CH3), 25.3
COSY, 13C-1H HMBC, 13C-1H HSQC). Mass spectra were recorded
on a Varian 1200L Quadrupole GC-MS, Finnigan MAT 8200 (MS
and HRMS-EI) or a Bruker FTICR-Apex III spectrometer (HRMS-
ESI). HRMS were performed with a Finnigan-MAT 95 spectrome-
ter (EI, 70 eV). Optical rotations were measured on a Jasco P-1020
polarimeter. The concentrations used for measuring specific rota-
tions are given as g/100 mL. Toluene was dried over alumina with
a solvent purification system from Innovative Technology. Et2O,
MeOH, and EtOH were distilled and then dried over molecular
sieves. All other organic solvents were purged with argon for 2 h
prior to use. Deuterated solvents were degassed through freeze–
pump–thaw cycles and stored over molecular sieves. Compounds
2,10 3,8 and 48 were synthesized according to literature procedures.
All other chemicals were purchased from Sigma-Aldrich, Acros, or
Alfa Aesar and used as received.
(CH), 34.1 (CH), 34.9 (d, JC,P = 12.7 Hz, CH), 35.8 (d, JC,P = 8.1 Hz,
CH), 35.9 (CH2), 36.8 (CH2), 37.5 (CH2), 38.1 (d, JC,P = 3.6 Hz,
CH2), 38.6 (CH), 68.5 (CCpH), 68.9 (CCpH), 69.9 (5 CCpH), 71.3 (d,
J
C,P = 4.6 Hz, CCpH); the quaternary C-atoms of the Cp rings could
not be detected.
31P{1H} NMR (162 MHz, C6D6): δ = –2.0 (o-P), 24.1 (α-P).
HRMS (EI): m/z [M]+ calcd for C24H36FeP2: 442.16362; found:
442.16366.
(RFc)-1-[(2R,5R)-2,5-Dimethylphospholan-1-yl]-2-{(S)-1-
[(2R,5R)-2,5-dimethylphospholan-1-yl]ethyl}ferrocene
{(SC,RFc)-[C5H5]Fe[C5H3(CHMe{(R,R)-DMP}){(R,R)-DMP}],
L2}
The title compound was obtained as an orange solid starting from
(SC,RFc)-4 using the procedure described for L1; yield: 320.8 mg
(0.73 mmol, 74%).
(SFc)-2-[(R)-1-(Dimethylamino)ethyl]-1-[(2R,5R)-2,5-dimethyl-
phospholan-1-yl]ferrocene
[α]D24 +266.8 (c 0.393, CH2Cl2).
{(RC,SFc)[C5H5]Fe[C5H3(CHMeNMe2){(R,R)-DMP}], (RC,SFc)-
1H NMR (400 MHz, C6D6): δ = 1.04 (m, 1 H, CH2), 1.11 (dd, JH,H
=
4}8
7.1 Hz, JH,P = 17.1 Hz, 3 H, CH3), 1.16 (dd, JH,H = 7.2 Hz, JH,P = 9.1
Hz, 3 H, CH3), 1.19–1.23 (br m, 1 H, CH), 1.26 (dd, JH,H = 7.4 Hz,
A 1.5 M t-BuLi in pentane soln (1.01 mL, 1.51 mmol) was added at
–78 °C over 30 min through a syringe pump to a soln of (–)-(R)-
N,N-dimethyl-1-ferrocenylethylamine (Ugi-amine, 312.2 mg, 1.21
mmol, 1.0 equiv) in Et2O (10 mL). After stirring the soln at r.t. for
1 h, (2R,5R)-1-chloro-2,5-dimethylphospholane (3, 219.4 mg, 1.46
mmol, 1.2 equiv) was added and the resulting mixture heated to re-
flux for 2.5 h. The mixture was filtered through a short pad of Celite
and the solvent removed under reduced pressure. The pure product
was obtained as an orange solid after recrystallization (hot MeOH,
2 mL); yield: 356.4 mg (1.0 mmol, 81%).
J
H,P = 8.7 Hz, 3 H, CH3), 1.31–1.37 (m, 1 H, CH2), 1.48 (dd, JH,H =
7.3 Hz, JH,P = 19.1 Hz, 3 H, CH3), 1.49 (dd, JH,H = 4.4 Hz, JH,P = 7.0
Hz, 3 H, CH3), 1.52–1.58 (br m, 1 H, CH2), 1.76 (m, 1 H, CH2),
1.85–1.97 (br m, 2 H, CH2), 2.00–2.10 (br m, 2 H, CH2), 2.10–2.19
(m, 1 H, CH), 2.20–2.37 (m, 1 H, CH), 2.59–2.73 (m, 1 H, CH),
3.39–3.49 (m, 1 H, CH), 3.84–3.92 (m, 1 H, CCpH), 4.06 (s, 1 H,
CCpH), 4.07–4.14 (m, 1 H, CCpH), 4.12 (s, 5 H, CCpH).
13C NMR (101 MHz, C6D6): δ = 14.7 (CH3), 17.8 (d, JC,P = 14.7 Hz,
CH3), 18.7 (CH3), 21.4 (d, JC,P = 33.0 Hz, CH3), 22.6 (d, JC,P = 37.3
1H NMR (400 MHz, C6D6): δ = 1.13 (d, JH,P = 6.7 Hz, 3 H, CH3),
1.21 (m, 1 H, CH2), 1.37 (dd, JH,H = 7.1 Hz, JH,P = 18.9 Hz, 3 H,
CH3), 1.54 (dd, JH,H = 7.7 Hz, JH,P = 2.3 Hz, 3 H, CH3), 1.74–1.87
(m, 1 H, CH2), 1.88–2.01 (m, 1 H, CH2), 2.10 (s, 6 H, 2 CH3), 2.09–
2.20 (br m, 3 H, CH, CH2), 3.95 (br s, 1 H, CHCp), 3.90–4.05 (m, 6
H, CHCp), 4.08 (br s, 1 H, CHCp), 4.14–4.25 (m, 1 H, CH).
Hz, CH3), 26.7 (CH), 30.7 (d, JC,P = 17.7 Hz, CH), 35.8 (d, JC,P
=
11.8 Hz, CH), 36.1 (d, JC,P = 17.6 Hz, CH), 36.5 (CH2), 36.8 (d,
J
J
C,P = 8.7 Hz, CH), 37.4 (CH2), 37.6 (d, JC,P = 2.5 Hz, CH2), 38.2 (d,
C,P = 3.8 Hz, CH2), 68.0 (CCpH), 68.5 (CCpH), 69.2 (5 CCpH), 70.8
(d, JC,P = 6.4 Hz, CHCp), 75.7 (CCp), 102.1 (CCp).
31P{1H} NMR (162 MHz, C6D6): δ = –11.6 (d, JP,P = 23.3 Hz, o-P),
16.6 (d, JP,P = 23.3 Hz, α-P).
HRMS (EI): m/z [M]+ calcd for C24H36FeP2: 442.16362; found:
13C NMR (101 MHz, C6D6): δ = 7.4 (CH3), 16.1 (CH3), 21.7 (d,
JC,P = 30.8 Hz, CH3), 36.1 (d, JC,P = 11.4 Hz, CH), 37.0 (d, JC,P = 3.8
Hz, CH2), 38.2 (d, JC,P = 5.2 Hz, CH2), 39.2 (2 CH3), 41.6 (d, JC,P
=
442.16338.
9.8 Hz, CH), 57.0 (d, JC,P = 8.7 Hz, CH), 67.9 (CHCp), 68.5 (CHCp),
70.2 (5 CHCp), 72.2 (d, JC,P = 4.7 Hz, CHCp), 79.4 (d, JC,P = 32.7 Hz,
CCp), 96.1 (d, JC,P = 19.2 Hz, CCp).
31P{1H} NMR (162 MHz, C6D6): δ = –5.8.
Selenide Formation; General Procedure
Bisselenides of L1 and L2 were prepared by treating a NMR sample
of the bisphospholanes with an excess of elemental Se for 2 h at 60
°C in C6D6. For spectroscopic data see Table 5.
(SFc)-1-[(2R,5R)-2,5-Dimethylphospholan-1-yl]-2-{(R)-1-
[(2R,5R)-2,5-dimethylphospholan-1-yl]ethyl}ferrocene
{(RC,SFc)-[C5H5]Fe[C5H3(CHMe{(R,R)-DMP}){(R,R)-DMP}],
L1}
(2R,5R)-2,5-Dimethylphospholane (117.6 mg, 1.01 mmol, 1 equiv)
was added to a soln of (RC,SFc)-4 (374.1 mg, 1.01 mmol, 1 equiv) in
glacial AcOH (5 mL) and heated to reflux for 2 h. The solvent was
removed in vacuo and the resulting solid was recrystallized (hot
Asymmetric C=N-Hydrogenation; General Procedure
A 10-mL stainless steel autoclave equipped with a glass inlet and a
magnetic stirring bar was charged under an argon atmosphere with
the imine 5 (0.5 mmol) and I2 (0.025 mmol). A Schlenk flask
equipped with magnetic stirring bar was charged with [Ir(cod)Cl]2
(1.68 mg, 2.5 μmol), the desired ligand L1 or L2 (5.5 μmol), and
toluene (2 mL). After 10 min under stirring, the resulting soln was
Synthesis 2012, 44, 2793–2797
© Georg Thieme Verlag Stuttgart · New York

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Josiphos-Type Bisphospholane Ligands
2797
transferred to the autoclave. The autoclave was pressurized with H2
(40 bar) and the mixture stirred at r.t. for 16 h. After carefully re-
leasing the pressure, conversion, and enantiomeric excess were de-
termined by GC (Chirasil-Dex-CB, 25 m, 100–160 °C, 5 °C/min,
1.0 bar H2): tR = 18.7 (S)-6, 18.9 min (R)-6.
U.; Federsel, H. J. Asymmetric Catalysis on Industrial Scale,
2nd ed.; Wiley-VCH: Weinheim, 2010.
(5) Marquarding, D.; Klusacek, H.; Gokel, G.; Hoffmann, P.;
Ugi, I. J. Am. Chem. Soc. 1970, 92, 5389.
(6) (a) Blaser, H.-U.; Pugin, B.; Spindler, F.; Mejía, E.; Togni,
A. In Privileged Chiral Ligands and Catalysts; Zhou, Q.-L.,
Ed.; Wiley-VCH: Weinheim, 2011, 93–136. (b) Togni, A.;
Halterman, R. Metallocenes: Synthesis, Reactivity,
Applications; Wiley-VCH: Weinheim, 1998. (c) Stepnicka,
P. Ferrocenes: Ligands, Materials and Biomolecules; John
Wiley & Sons: Chichester, 2008. (d) Dai, L. X.; Huo, X.-L.
Chiral Ferrocenes in Asymmetric Catalysis: Synthesis and
Applications; Wiley-VCH: Weinheim, 2009. (e) Gómez,
Arrayás. R.; Adrio, J.; Carretero, J. C. Angew. Chem. Int. Ed.
2006, 45, 7674. (f) Colacot, T. J. Chem. Rev. 2003, 103,
3101. (g) Atkinson, R. C. J.; Gibson, V. C.; Long, N. J.
Chem. Soc. Rev. 2004, 33, 313.
Single Crystal X-ray Diffraction
Data collection for L1 and L2 was done with MoKα radiation
(INCOATEC microsource, multilayer optics, λ = 0.71073 Å) on a
Bruker D8 goniometer with SMART CCD area detector; The
SADABS17 program was used for absorption correction of L2 and
PLATON18 was used for multi-scan absorption correction of L1.
The structures were solved by direct methods (SHELXS-97)19 and
refined by full matrix least-squares procedures based on F2 with all
measured reflections (SHELXL-97).19 All non-hydrogen atoms
were refined anisotropically. Hydrogen atoms were introduced in
calculated positions and refined using a riding model. Supple-
mentary crystallographic data for L1 (CCDC 882099) and L2
(CCDC 882100) can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html.
(7) Braun, W.; Calmuschi, B.; Haberland, J.; Hummel, W.;
Liese, A.; Nickel, T.; Stelzer, O.; Salzer, A. Eur. J. Inorg.
Chem. 2004, 2235.
(8) Holz, J.; Monsees, A.; Kadyrov, R.; Börner, A. Synlett 2007,
599.
(9) Hammerer, T.; Weisgerber, L.; Schenk, S.; Stelzer, O.;
Englert, U.; Leitner, W.; Franciò, G. Tetrahedron:
Asymmetry 2012, 23, 53.
Acknowledgement
We thank Dr. Renat Kadyrov (Evonik), Dr. Benoit Pugin (Solvias),
and W. C. Heraeus GmbH for a generous donation of (2R,5R)-2,5-
dimethyl-1-(trimethylsilyl)phospholane, Ugi’s amine tartrate, and
precious metal complexes, respectively. Ms Brigitte Pütz for the
measurement of MS data, Ms Julia Wurlitzer and Ms Hannelore
Eschmann for GC measurements, Prof. Dr. Ulli Englert (Inst. of In-
organic Chemistry, RWTH Aachen) for X-ray data collection, and
Ms Beatrice Braun for solving the X-ray structures are gratefully
acknowledged. The research leading to these results has received
funding from the European Community’s Seventh Framework Pro-
gram under grant agreement No. 246461.
(10) Roßenbach, S. Diploma Thesis; Bergische Universität-GH
Wuppertal: Germany, 1997.
(11) For comparing the conformational properties of Josiphos
derivatives, Togni6 chose the torsion angles α1 and α2
defining the relative orientation with respect to the ferrocene
core of the substituent at the ortho-P in the exo position and
of the methyl group in the α-position, respectively.
(12) Contreras, R. H.; Peralta, J. E. Prog. Nucl. Magn. Reson.
Spectrosc. 2000, 37, 321.
(13) Similar trend in 31P NMR was found for the two
diastereomers of ferrocene-derived phosphine-
phosphoramidite ligands: Hu, X.-P.; Zheng, Z. Org. Lett.
2004, 6, 3585.
(14) (a) Allen, D. W.; Taylor, B. F. J. Chem. Soc., Dalton Trans.
1982, 51. (b) Allen, D. W.; Nowell, I. W.; Taylor, B. F.
J. Chem. Soc., Dalton Trans. 1985, 2505.
(15) (a) Bilenko, V.; Spannenberg, A.; Baumann, W.; Komarov,
I.; Börner, A. Tetrahedron: Asymmetry 2006, 17, 2082.
(b) Holz, J.; Zayas, O.; Axel, M.; Kadyrov, R.; Börner, A.
Chem.–Eur. J. 2006, 12, 5001.
(16) (a) Buergler, J. F.; Niedermann, K.; Togni, A. Chem.–Eur. J.
2012, 18, 632. (b) Buergler, J. F.; Togni, A. Chem. Commun.
2011, 47, 1896.
References
(1) Current address: Department of Petroleum Engineering,
Texas A&M University, College Station, TX, USA.
(2) (a) Togni, A.; Breutel, C.; Schnyder, A.; Spindler, F.;
Landert, H.; Tijani, A. J. Am. Chem. Soc. 1994, 116, 4062.
(b) Togni, A.; Breutel, C.; Soares, M. C.; Zanetti, N.; Gerfin,
T.; Gramlich, V.; Spindler, F.; Rihs, G. Inorg. Chim. Acta
1994, 222, 213.
(3) (a) Hayashi, T.; Mise, T.; Fukushima, M.; Kagotani, M.;
Nagashima, N.; Hamada, Y.; Matsumoto, A.; Kawakami, S.;
Konishi, M.; Yamamoto, K.; Kumada, M. Bull. Chem. Soc.
Jpn. 1980, 53, 1138. (b) Hayashi, T.; Yamamoto, K.;
Kumada, M. Tetrahedron Lett. 1974, 15, 4405. (c) Hayashi,
T.; Tanaka, M.; Ogata, I. Tetrahedron Lett. 1977, 18, 295.
(4) (a) Blaser, H.-U.; Brieden, W.; Pugin, B.; Spindler, F.;
Studer, M.; Togni, A. Top. Catal. 2002, 19, 3. (b) Blaser, H.
(17) Sheldrick, G. M. SADABS program; University of
Göttingen: Germany, 1996.
(18) Spek, A. J. Appl. Crystallogr. 2003, 36, 7.
(19) Sheldrick, G. M. Acta Crystallogr. Sect. A 2008, 64, 112.
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Synthesis 2012, 44, 2793–2797