Enantiopure 1-r-H-2-c,5-t-diphenylphospholane as ligand in Rh-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1016/j.tetasy.2006.08.020

Chiral enantiopure secondary phospholane 1-r-H-2-c,5-t-diphenylphospholane and the corresponding oxide are unusual and efficient ligands in the rhodium catalyzed hydrogenation of olefins.

Full text of DOI:10.1016/j.tetasy.2006.08.020

Tetrahedron: Asymmetry 17 (2006) 2354–2357
Enantiopure 1-r-H-2-c,5-t-diphenylphospholane as ligand in
Rh-catalyzed asymmetric hydrogenation
Aurore Galland, Cristian Dobrota, Martial Toffano* and Jean-Claude Fiaud*
ˆ
Institut de Chimie Mole´culaire et des Mate´riaux d’Orsay, Equipe Catalyse Mole´culaire, Universite´ Paris Sud Bat,
420 91405 ORSAY Cedex, France
Received 25 July 2006; accepted 29 August 2006
Abstract—Chiral enantiopure secondary phospholane 1-r-H-2-c,5-t-diphenylphospholane and the corresponding oxide are unusual and
efficient ligands in the rhodium catalyzed hydrogenation of olefins.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
parent of P-substituted-2,5-diphenylphospholane family
offers good activity and enantioselectivity in Rh-catalyzed
hydrogenations.
Enantiomerically pure phosphines have been—and still
are—widely used as chiral ligands in a variety of metal-
catalyzed enantioselective reactions.1 Among them,
binaphthyl-, ferrocenyl and phospholanyl-containing
frameworks are important structures, which give good re-
sults in a broad range of applications.2 However, all these
are tertiary phosphines with three P–C bonds. The only
example of using a secondary phosphine in asymmetric
catalysis was described by Helmchen and co-workers.3
The authors reported the synthesis and use of secondary
phosphinane 2 in asymmetric hydrogenation (Fig. 1). Fur-
thermore, chiral secondary phospholanes were found to be
unknown as ligands.
2. Results and discussion
The synthesis of 1 was carried out from the chiral enantio-
pure phospholanic acid 3.5 The acid was transformed
quantitatively into phosphinyl chloride 4 using oxalyl chlo-
ride. Reduction of 4 with lithium aluminium hydride gave
the expected phospholane 1 in an enantiopure form and
quantitative yield (Scheme 1). This easy procedure offers
an efficient and rapid pathway to this simple ligand.
Ph
P
Ph
P
Ph
P
O
(COCl)2
THF
LiAlH4
Et2O
O
O
H
Ph
Ph
Alk
P
H
Alk
OH
Cl
P
H
Ph
Ph
Ph
(S,S)-1
2
(
S
,
S
)-3
(S,S)-1
4
Figure 1.
Scheme 1. Synthesis of secondary phospholane 1.
As part of our efforts to synthesize new, enantiopure 2,5-
diphenylphospholane ligands,4 we decided to fill this void
and examined the potential of secondary (S,S)-1-H-2,5-
diphenylphospholane 1 as a ligand. Herein we report that
secondary phospholane, which may be considered as the
Due to the sensitivity of 1 towards oxidation, we decided to
protect the ligand as a rhodium complex Rh(COD)P2BF4
5. This complex was prepared from Rh(COD)2BF4 precur-
sor and 2 equiv of (S,S)-1 in dichloromethane, as a brown,
air-stable powder (Scheme 2).
The 31P NMR analysis of complex 5 showed one clean
sharp doublet (d = 27.2 ppm, J = 142 Hz), revealing the
*
Corresponding authors. Tel.: +33 1 69 15 47 40; fax: +33 1 69 15 46
80; e-mail addresses: mtoffano@icmo.u-psud.fr; fiaud@icmo.u-psud.fr
0957-4166/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.08.020

A. Galland et al. / Tetrahedron: Asymmetry 17 (2006) 2354–2357
2355
Ph
P
spheric pressure of dihydrogen. A moderate conversion
(62%) was obtained under pressure after 24 h reaction time.
This result could be explained by the steric hindrance of the
substrate. However the less sterically hindered compound
13 did not react, either at a low or a higher pressure. This
suggests that steric hindrance is not solely responsible for
the low reactivity. A common feature for substrates 8, 12,
13 and 14 is the presence of an a-phenyl substituent, which
could inhibit the reactivity. The lack of reactivity of the
simple substrate 14 seems to confirm this hypothesis. How-
ever, compound 10 reacted readily to give quantitatively
the hydrogenated product with good enantioselectivity
(82% ee).
Rh(COD)2BF4
67%
Rh(COD)P2BF4
2
H
5
Ph
Scheme 2. Synthesis of (S,S)-1 rhodium complex 5.
formation of the C2-symmetric [Rh(COD)(P*)2] complex.
The results of asymmetric hydrogenation of activated
olefins 6–14 catalyzed by the new chiral complex 5 are
reported in Table 1.
Table 1. Catalytic asymmetric hydrogenation using 1-Rh complexa
Under the same reaction conditions, compound 10 was
hydrogenated in the presence of 1 mol % of Rh(COD)2BF4
and 2.2 mol % of (S,S)-1 to generate the catalytic active
species in situ, under rigorous exclusion of oxygen. Only
12 min were required for the total conversion, and the
product was obtained in 90% ee (Scheme 3).
Substrate
H2
(bar)
Conversionb
(%)
t1/2
(min)
eec
(%)
CO2H
6
1
100
30
8
52 (R)
CO2H
CO2Me
7
8
9
1
1
1
100
95
39 (R)
28 (R)
68 (S)
1 mol% Rh(COD)2BF4
CO2Me
Ph
CO2Me
NHAc
CO2Me
NHAc
2.2 mol % (S,S)-1
Ph
Ph
d
H2 (1 atm.) / MeOH
R = 12 min. , rt
—
NHAc
(S
)-90 % ee
t
conv. 100%
CO2H
100
8
Scheme 3. Catalyzed hydrogenation reaction with (S,S)-1 and
Rh(COD)2BF4.
Ph
NHAc
CO2Me
NHAc
10
11
1
1
100
100
23
4
82 (S)
58 (S)
This result indicated that the secondary phospholane 1 is
an efficient ligand in rhodium catalyzed hydrogenations.
Compound 1 offers enantioselectivities, which compare
well with P-substituted-2,5-diphenylphospholane.6
Ph
AcHN
CO2H
The corresponding oxidized analogue of (R,R)-1 is the sec-
ondary phospholane oxide 15. This compound described in
our previous paper,5 has been used in Ir-catalyzed asym-
metric hydrogenation of imines.7 It offers the advantage
of not being sensitive towards oxygen. Considering the
well-known equilibrium8 between the secondary phosphine
oxide and the hydroxy phosphine 16 it is suggested that 15
could be the precursor of the active species 16 as ligand.
The Rh-catalyzed hydrogenation of (Z)-methyl-acetamido-
cinnamate 10 gave the product with total conversion and
83% ee (Scheme 4).
12
13
1
40
0
62
—
—
—
8 (S)
e
Ph
CO2H
Ph
AcHN
Ph
1
40
0
0
—
—
—
—
14
1
0
—
—
Ph
OAc
a All reactions were carried out in methanol at room temperature in the
presence of 1 mol % of complex 5 under one atmosphere of dihydrogen
unless otherwise noted.
b Determined by 1H NMR.
c Determined by HPLC or CPG analysis using Chiralcel OD-H or
Chiraldex b-PM column, respectively.
1 mol% Rh(COD)2BF4
CO2Me
NHAc
CO2Me
NHAc
d The reaction was carried out for 24 h under dihydrogen.
e The reaction was carried out for 5 days under dihydrogen.
2.2 mol % (R,R
)-15
Ph
MeO2C
H2 (1 atm.) / MeOH
tr = 1 h 30, rt
(S)-83 % ee
conv. 100%
Ph
We observed an excellent reactivity of the secondary phos-
phine complex for substrates 6–11. A total conversion was
obtained in most cases in less than 1 h reaction time under
an atmospheric pressure of dihydrogen at room tempera-
ture. The reactions were rapid, with the exception of sub-
strates 8, 12, 13 and 14. Compound 8 needed 24 h of
reaction time to reach 95% conversion. The tetrasubsti-
tuted compound 12 was not hydrogenated under atmo-
Ph
Ph
Ph
P
R
P
OH
O
H
(R,
)-15
(R,R)-16
Scheme 4. Rh-catalyzed hydrogenation reaction with (R,R)-15 and
Rh(COD)2BF4 in methanol.

2356
A. Galland et al. / Tetrahedron: Asymmetry 17 (2006) 2354–2357
In dichloromethane, the same catalyst gave the product
with only 24% ee as the (R)-enantiomer. This surprising
inversion of configuration and the longer reaction time sug-
gest a different mechanism and stereochemical course for
hydrogenation in methanol or dichloromethane (Scheme
5). This could be the result of a different equilibrium of
ligands 15 and 16.
minium hydride (1.5 mmol) was added portionwise. The
solution was stirred at room temperature for 16 h, then
hydrolyzed with a minimum of water and filtered under ar-
gon to give a colourless solution. The solvent was removed
in vacuo and phospholane 1 was obtained as a white solid
20
and used without further purification. ½aꢁD ¼ þ104 (c 0.95,
1
CHCl3). H NMR (360 MHz, CDCl3): d = 7.25 (9H, m),
7.10 (1H, m), 3.90 (1H, m), 3.35 (1H, ddd, JPH = 190 Hz,
JHH = 11 Hz and 11 Hz), 3.35 (1H, m), 2.45–2.55 (2H,
m), 2.00–2.15 (1H, m), 1.75–1.90 (1H, m). 31P NMR
(101.2 MHz, CDCl3): d = ꢀ17.8 (d, JPH = 190 Hz). 13C
NMR (62.9 MHz, CDCl3): d = 38.8 (d, JPC = 5 Hz), 39
(s), 41.10 (d, JPC = 9 Hz), 44.80 (d, JPC = 12 Hz), 126.00
(d, JPC = 13 Hz), 127.15 (d, JPC = 14 Hz), 127.65 (d,
JPC = 8 Hz), 128.55 (s). HRMS (IE): m/z = 240.1063
found. Calcd for C16H17P: 240.1068.
1 mol% Rh(COD)2BF4
CO2Me
NHAc
CO2Me
NHAc
2.2 mol % (R,
R)-15
Ph
MeO2C
H2 (1 atm.) / CH2Cl2
tr = 15 h, rt
(R
)-24 % ee
conv. 100%
Scheme 5. Catalyzed hydrogenation reaction with (R,R)-15 and
Rh(COD)2BF4 in dichloromethane.
4.2. Bis((S,S)-2,5-trans-diphenylphospholane)(cyclo-octa-
1,5-diene)rhodium tetrafluoroborate 5
3. Conclusions
In conclusion, we have shown that a simple synthesis
allows us to obtain the monodentate, secondary phos-
phine 1. This simple compound appears as an active
ligand for Rh-catalyzed hydrogenation of olefinic comp-
ounds. Investigations on the ability of 1 to give active
chiral transition-metal complexes for the catalysis in
other reactions are currently underway.
A Schlenk tube was charged with the desired enantiopure
(S,S)-trans-2,5-diphenylphospholane
freshly distilled DCM (15 mL).
1
(1.7 mmol) in
A solution of
Rh(COD)2BF4 (347 mg, 0.8 mmol) in DCM (5 mL) was
then added at room temperature via cannula. The mixture
was stirred for 3 h and the solvent was removed under re-
duced pressure to give an orange solid. This was washed
with cold diethyl ether giving the complex as a powder
(443 mg, 67%). 1H NMR (400 MHz, CD2Cl2): d = 7.4–
7.0 (m, 20H, Ph); 5.6 (m, 1H, CH Bn); 5.0 (m, 2H, CH al-
kene); 4.4 (m, 2H, CH alkene); 4.3 (m, 2H, CH Bn); 3.3–3.2
(m, 1H, CH Bn); 2.7–2.6 (m, 4H, CH2 phosphine); 2.3–2.1
4. Experimental
Proton NMR spectra were recorded on Bruker 250, 360 or
400 MHz spectrometers. 1H and 13C NMR analyses of sen-
sitive phosphorus compound 1 were realized under an
argon atmosphere. Proton chemical shifts are reported in
parts per million (d) relative to tetramethylsilane as internal
reference (TMS, d = 0.0). J values are given in hertz (Hz).
Carbon NMR spectra were recorded on Bruker 250 MHz
(62.9 MHz) or 300 MHz (75.45 MHz) spectrometers with
complete proton decoupling. Phosphorus NMR spectra
were recorded at 101.2 MHz spectrometer with complete
proton decoupling. The corresponding chemical shifts are
reported in parts per million (d) relative to the residual deu-
terated solvent or external phosphoric acid (H3PO4,
d = 0.0). Flash column chromatography was performed
using silica gel Merck (0.04–0.063 lm). Optical rotations
were recorded at the sodium D line with a Perkin Elmer
341 polarimeter. The specific rotation [a] is given without
the units (understood to be deg cm2 gꢀ1). High-resolution
mass spectra were obtained with a MAT95 Thermo-Finni-
gan spectrometer using electrospray or GC analysis. All
reactions were carried out in Schlenk tubes under an argon
atmosphere. All solvents were distilled from appropriate
drying agents prior to use. The synthesis and experimental
data of (R,R)-1-oxo-2,5-diphenylphospholane 15 were
reported in our previous paper.5
(m, 4H, CH2 phosphine); 2.1–1.5 (m, 8H, CH2 (COD)). 31
P
NMR (101.2 MHz, CD2Cl2), d = 27.2 (d, JRh–P = 142 Hz).
13C NMR (62.9 MHz, CD2Cl2, d ppm): 141.3 (Cquat),
138.0 (Cquat), 134.8 (Cquat), 129.8 (CHPh), 129.4
(CHPh), 129.0 (CHPh), 128.8 (CHPh), 128.4 (CHPh),
128.1 (CHPh), 127.5 (CHPh), 99.2 (CH@CH), 95.4
(CH@CH), 43.5 (CH phosphine), 43.3 (CH phosphine),
43.1 (CH phosphine), 42.8 (CH phosphine), 38.5 (CH2
phosphine), 34.8 (CH2 phosphine), 32.7 (CH2 (COD)),
30.0 (CH2 (COD)), 27.8 (CH (COD)). HRMS (Electro-
spray): m/z = found: 691.2123. Calcd for C40H46P2Rh:
691.2130.
4.3. Rhodium-catalyzed asymmetric hydrogenation: general
procedure
A Schlenk tube placed in a glove box was charged with
(S,S)-1 (5.3 mg, 22 lmol) and bis(cyclooctadiene)rhodium
tetrafluoroborate (4.1 mg, 10 lmol). The tube was then
taken out of the glove box and charged with 5 mL of
degassed, anhydrous methanol. The mixture was stirred for
20 min, and the yellow solution obtained was cannulated
into a Schlenk tube containing 1 mmol of the chosen sub-
strate under a hydrogen atmosphere. The uptake of hydro-
gen began immediately upon stirring. After completion of
the reaction (no further hydrogen uptake), the resulting
solution was concentrated in vacuo, taken up in dichloro-
methane (10 mL) and stirred with activated carbon for
1.5 h. Filtration over Celite and removal of the solvent
afforded the hydrogenated product. Enantiomeric excesses
4.1. (2S,5S)-(+)-2,5-Diphenylphospholane 1
(2S,5S)-(ꢀ)-1-Chloro-1-oxo-2,5-diphenylphospholane
2
(1 mmol) was suspended in freshly distilled diethyl ether
(10 mL) after sonication and cooled at 0 °C. Lithium alu-

A. Galland et al. / Tetrahedron: Asymmetry 17 (2006) 2354–2357
2357
2. Oisaki, K.; Zhao, D.; Suto, Y.; Kanai, M.; Shibasaki, M.
Tetrahedron Lett. 2005, 46, 4325–4329.
3. Ostermeier, M.; Prieß, J.; Helmchen, G. Angew. Chem.
2002, 114, 625–628; Angew. Chem., Int. Ed. 2002, 41, 612–
614.
were determined by chiral HPLC on a Chiralcel OD-H col-
umn, with hexane/i-PrOH (90/10) as eluent or by chiral
capillary GC using Chiraldex b-PM column.
4. Toffano, M.; Dobrota, C.; Fiaud, J.-C. Eur. J. Org. Chem.
2006, 650–656.
Acknowledgements
5. Guillen, F.; Rivard, M.; Toffano, M.; Legros, J.-Y.; Daran,
J.-C.; Fiaud, J.-C. Tetrahedron 2002, 58, 5895–5904.
6. Toffano, M.; Dobrota, C.; Fiaud, J.-C. Unpublished results.
7. Jiang, X.-B.; Minnaard, A. J.; Hessen, B.; Feringa, B. L.;
Duchateau, A. L. L.; Adrien, J. G. O.; Boogers, J. A. F.; De
Vries, J. G. Org. Lett. 2003, 5, 1503–1509.
We wish to thank the Agence Universitaire de la Fran-
cophonie, the Romanian Ministry of Education, RHODIA
society and the Centre National de la Recherche Scientifi-
que (CNRS) for the financial support.
8. (a) Schlemminger, I.; Saida, Y.; Gro¨ger, H.; Maison, W.;
Durod, N.; Sasai, H.; Shibasaki, M.; Martens, J. J. Org. Chem.
2000, 65, 4818–4825; (b) Dubrovina, N. V.; Bo¨rner, A. Angew.
Chem. 2004, 116, 6007–6010; Angew. Chem., Int. Ed. 2004, 43,
5883–5886.
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