Ferrocenyl bis-phosphine ligands bearing sulfinyl, sulfonyl or sulfenyl groups: Applications in asymmetric hydrogenation and allylic alkylation reactions

Article abstract of DOI:10.1016/j.tetasy.2005.08.036

A new series of chiral ferrocenyl bis-phosphine ligands have been synthesized. Elements of planar and central chirality have been incorporated into a ferrocene backbone through sulfinyl, sulfonyl and sulfenyl groups at the ortho-position to the phosphines

Full text of DOI:10.1016/j.tetasy.2005.08.036

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3676–3681
Ferrocenyl bis-phosphine ligands bearing sulfinyl, sulfonyl
or sulfenyl groups: applications in asymmetric hydrogenation
and allylic alkylation reactions
Malati Raghunath, Wenzhong Gao and Xumu Zhang*
Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA
Received 10 August 2005; accepted 19August 2005
Available online 10 November 2005
Abstract—A new series of chiral ferrocenyl bis-phosphine ligands have been synthesized. Elements of planar and central chirality
have been incorporated into a ferrocene backbone through sulfinyl, sulfonyl and sulfenyl groups at the ortho-position to the phos-
phines. The effectiveness of these ligands has been demonstrated in Rh-catalyzed hydrogenations and Pd-catalyzed allylic
alkylations.
ꢀ
2005 Elsevier Ltd. All rights reserved.
1. Introduction
[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine (PPFA)
0
1
b and (R)-N,N-dimethyl-1-[(S)-1 ,2-bis(diphenylphos-
Bisphosphine ligands with a ferrocenyl backbone are an
important class of ligands for homogenous catalysis. For
example, 1,1 -bis(diphenylphosphino)ferrocene (dppf)
phino)ferrocenyl]ethylamine (BPPFA) 1c were some
of the first ligands to be successfully employed in vari-
0
7
ous asymmetric transformations. Knochelꢀs C -sym-
2
1
a is recognized as one of the most effective bis-phos-
metric Ferriphos type ligand 1d and Taniaphos 1e
1
phine ligands for organometallic transformations. Pio-
neering work was carried out by Kumada et al. in the
late 1970s on the use of dppf in Pd-catalyzed cross-
coupling of Grignard reagents and organic bromides
and allylic alcohols. Dppf has also been tested for
other nucleophilic substitutions and olefin-hydrogena-
tions. Introducing elements of central and planar chi-
rality in the dppf backbone is a well studied area.
Hayashi and Kumadaꢀs ligands (R)-N,N-dimethyl-1-
also constitute significant contributions in this area
8
,9
(Fig. 1). In summary, the planar chiral 1,2-disubsti-
tuted ferrocene unit has become one of the most use-
ful backbones in designing new ligands. Herein, we
report the synthesis and applications of ferrocenyl
bis-phosphine ligands, which have tert-butyl-sulfinyl
2, -sulfonyl 3 and -sulfenyl 4 groups at the ortho-
position of each diphenylphosphino groups of dppf
(Fig. 2).
2
,3
4
5
6
NMe2
NMe2
PPh2
Ph
NMe2
PR2
PPh2
PPh2
PPh2
Fe
Fe PPh
2
Fe PPh
2
Fe
Fe PR2
Ph
PPh2
PPh2
PPh2
1
a
1b
1c
1d
1e
Figure 1. Ferrocenyl bis-phosphine ligands.
*
0
Corresponding author. Tel.: +1 814 865 4221; fax: +1 814 865 3292; e-mail: xumu@chem.psu.edu
957-4166/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.08.036

M. Raghunath et al. / Tetrahedron: Asymmetry 16 (2005) 3676–3681
3677
known compound,14 as the starting material. By prepar-
ing this compound from a pure dilithiumferrocene
1
5
S
SO t-Bu
S
(TMEDA) salt, we obtained disulfide 7 in up to 76%
2
O
0
yield. Kaganꢀs asymmetric oxidation of 7 led to 1,1 -bis-
(tert-butylsulfinyl)ferrocene 8. The overall yield after two
recrystallizations was 40%. Crystallizations eliminated
meso-8 (as evidenced from H NMR) and gave the enan-
PPh2
PPh2
S
PPh2
PPh2
SO t-Bu
PPh2
PPh2
S
Fe
Fe
Fe
1
O
2
tiomerically pure bis-sulfoxide. Based on Kaganꢀs results,
we assigned an (R ,R )-configuration to 8. ortho-Lithia-
S
S
tion followed by the introduction of PPh groups gave
2
2
3
4
the primary desired ligand (R ,R ,R ,R )-bis(tert-butyl-
Fc
S
Fc
S
sulfinyl) phosphino ferrocene 2 (Scheme 2). The planar
Figure 2. Bis-sulfinyl 2, -sulfonyl 3a and 3b and -sulfenyl 4 ligands.
chirality configuration is assigned on the basis of the
1
0
known ortho-lithiation of sulfoxide 5.
2
. Results and discussion
To test the activity of bis-phosphine ligand 2, we set up
Rh-catalyzed hydrogenation reactions of some common
substrates (Fig. 3). Unfortunately, we found that the
reaction did not occur with this ligand. A possible expla-
nation for this is that the presence of two sulfur and two
phosphorus donor atoms inhibits the catalytic activity.
As a consequence, the idea of having only planar chiral-
ity, yet retaining the dppf 1a motif appealed to us.
Ligand 2 became our chiral synthon and we envisaged
the conversion of the chiral sulfoxide of 2 to achiral sul-
fone 3 and sulfide 4. Thus, the coordinating ability of S
atoms would be altered.
2
.1. Ligand synthesis
In 1993, Kagan et al. described the ortho-lithiation of
the readily available (R)-tert-butyl sulfinyl ferrocene 5
as directed by the sulfinyl group occurring with complete
selectivity at the C-2 (and not C-5). The directing influ-
ences of the sulfinyl group have been explored by a few
groups to prepare a variety of planar chiral ferro-
1
0
1
1,12
cenes.
Amongst these, the bidentate P,S-ferrocenyl
ligand 6 has been successfully employed by Carretero
et al. in asymmetric allylic alkylations and aza Diels–
Alder reactions (Scheme 1).
1
3
To obtain sulfone 3, we developed a synthesis method
(Scheme 3, Route A). A dibromo sulfoxide intermediate
9a was oxidized by m-CPBA to give dibromo sulfone 9b.
A lithium bromide exchange reaction followed by the
However, this idea has not been extended to bis-sulfinyl
ferrocene. Our goal herein was to bring planar chirality
elements at the ortho-positions of the two diph-
enylphosphino groups in dppf to make a new chiral
0
ligand. We chose 1,1 -bis(tert-butylthio)ferrocene 7, a
[
Rh(NBD) SbF ] / Ligand 2
2
6
Substrates
No Conversion
NHAc
2
MeOH, H (45 psi)
S
S
S
O
O
2
CO Me
CO Me
a
b
2
Fe
Fe PPh2
Fe PPh2
NHAc
Ph
NHAc
HO C
CO
2
Me
2
5
6
AcHN
2
MeO C
Scheme 1. Directing influence of sulfinyl group. Reagents and condi-
tions: (a) t-BuLi, THF, À78 ꢁC; Ph
2
PCl; (b) HSiCl
3
, Et
3
N, toluene,
Figure 3. Common test substrates for Rh-catalyzed asymmetric
hydrogenation.
1
10 ꢁC.
S
S
S
S
t-Bu
O
a, b
0%
O
c, d
80%
PPh2
PPh2
Fe
Fe
Fe
4
t-Bu
O
S
O
S
7
(R
S
,R
S
)-8
(RFc,R ,RFc,R )-2
S S
Scheme 2. Synthesis of (RFc,R
S
,RFc,R
S
)-bis(tert-butylsulfinyl)phosphino ferrocene 2. Reagents and conditions: (a) Kaganꢀs oxidation Ti(Oi-Pr)
4
/
(
+)DET/CHP/water, CH Cl
2
2
, À23 ꢁC; (b) recrystallization CH
2
Cl /hexanes; (c) n-BuLi/hexane, THF, 0 ꢁC; (d) PPh Cl, rt.
2
2

3678
M. Raghunath et al. / Tetrahedron: Asymmetry 16 (2005) 3676–3681
Route A
S
SO t-Bu
SO2t-Bu
S
S
8
2
O
O
a
b
c
Br
Br
Br
Br
PR2
PR2
Fe
Fe
Fe
Fe
86%
40%
3
5%
O
O
S
SO t-Bu
SO t-Bu
2
2
(RFc,RFc)-3
9a
9b
{3a R = Ph; 3b R = Cyclohexyl}
Route B
SO t-Bu
S
SO t-Bu
2
2
O
d
80%
POPh
2
e
PPh2
PPh2
PPh2
PPh2
Fe
Fe
Fe
POPh2
30%
O
SO t-Bu
SO t-Bu
2
S
2
2
10
(RFc,RFc)-3a
Scheme 3. Synthesis of (RFc,RFc)-bis(tert-butylsulfonyl)phosphino ferrocene 3. Route A: (a) n-BuLi/hexane, THF, 0 ꢁC, C
2 2 4
H Br ; (b) m-CPBA,
acetone, 0ꢁC–rt; (c) n-BuLi/hexane, THF, À78 ꢁC, 1 h; PR Cl, rt. Route B: (d) m-CPBA, CH Cl , 0 ꢁC; (e) HSiCl , Et N, toluene, 110 ꢁC.
2
2
2
3
3
addition of a phosphine electrophile led to the desired
R ,R )-bis(tert-butylsulfonyl)phosphino ferrocene 3.
Table 1. Optimization of the reaction solvent for the Rh-catalyzed
hydrogenation with 3a
(
Fc Fc
Based on Route A, we prepared two ligands 3a and
b. In order to improve the synthesis of 3, we also
CO
2
Me [Rh(NBD) SbF ] / Ligand 3a
2
CO Me
2
6
3
NHAc
Solvent, H
2
(45 psi)
NHAc
devised an alternate route (Route B). Synthon 2 was
completely oxidized at the sulfur and phosphorus centres
and intermediate 10 was formed. Reduction of 10 with
HSiCl /Et N in refluxing toluene gave the desired sulfo-
1
1
12
a
b
Entry
Solvent
Conversion (%)
ee (%)
3
3
nyl phosphine 3. The synthesis of bis-sulfenyl phosphine
ligand 4 was carried out according to Carreteroꢀs proce-
1
2
3
4
5
6
7
Methanol
Dichloromethane
Ethanol
THF
Toluene
99.7
>99.9
95.9
>99.9
76.4
93
88
91
92
73
1
1
dure who synthesized the first P,S-bidentate ligands
possessing planar chirality. Following their methodology
of HSiCl /Et N reduction, we synthesized ligand 4 by
3
3
Isopropanol
Ethyl acetate
46.984
>99.9
reducing the sulfoxides of 2 to sulfides (Scheme 3).
88
a
See Section 4 for details.
2
.2. Applications in asymmetric catalysis
b
Enantiomeric excess (ees) were determined by chiral GC (Chiralsil-
VAL III FSOT). The (S)-configuration was assigned by the com-
parison of the specific rotation with the reported data.
The planar chiral sulfones 3a and 3b, and sulfides 4 were
tested for Rh-catalyzed asymmetric hydrogenation. The
catalytic complex was prepared in situ by mixing
[
Rh(NBD) ]SbF and the ligand in solvent. Of the three
acetate 13, a typical substrate, was tested in conjunction
2
6
ligands tested, 3a offered the best results. Hydrogenation
of commercially available a-(N-acetamido)acrylate 11
was initially chosen to demonstrate the ligandꢀs effective-
ness. The hydrogenated product 12 was obtained in up
to 93% ee and over 99% conversion. Both conversion
and ees were poor for ligands 3b and 4. We also screened
a few solvents for the reaction with MeOH being found
as the best choice (Table 1).
with dimethyl malonate as the anion. Under standard
conditions with [Pd(p-allyl)Cl] as the catalyst precursor
2
and 3a as the ligand, alkylation product 14 was obtained
in high yields (up to 98%) and 86% ee (Scheme 4). The
product was assigned an (S)-configuration based on its
1
6
specific rotation. In the literature, it is known that
additive effects play a role in the Pd-catalyzed AAA
1
7
+
reaction. We tested alkali metal acetates from Li
+
through Cs to see if there was any effect on the reactiv-
ity and enantioselectivity of this transformation.
Encouraged by the hydrogenation results, we explored
the application of sulfone phosphine ligand 3a in C–C
bond formation reactions such as Pd-catalyzed asym-
metric allylic alkylations (AAA). 1,3-Diphenylpropenyl
The reaction yields remained similar (96–98% isolated
yields) upon changing the additive. However, we

M. Raghunath et al. / Tetrahedron: Asymmetry 16 (2005) 3676–3681
3679
MeO2C
CO Me
2
OAc
Ph
2
.5mol%[Pd(allyl)Cl] ; 5mol% ligand 3a
2
MeO C
CO Me
2
2
+
BSA; Metal Acetate; CH Cl ; rt; 12hrs
2 2
Ph
Ph
Ph
1
3
(S)-14
Scheme 4. Pd-catalyzed allylic alkylations with ligand 3a.
100
(Chiral Technologies, Inc.). Column chromatography
was performed using EM silica gel 60 (200–400 mesh).
9
8
94
9
0
0
0
0
4
4
.2. Ligand synthesis
8
6
8
3
0
.2.1. (R ,R )-1,1 -Bis-(tert-butylsulfinyl)ferrocene
S
8.
S
8
7
6
Titanium tetra-isopropoxide (14.6 mL, 0.05 mol) was
added to solution of (R,R)-diethyl tartarate
(17.5 mL, 0.10 mol) in dichloromethane (60.0 mL) at
room temperature. The mixture was stirred for ca.
77
a
5
2
min and 0.9mL of distilled water added. After
0 min, the solution was cooled to À23 ꢁC while main-
Li
Na
K
Rb
Cs
taining an inert atmosphere and bis(tert-butylthio)ferro-
cene 37 (9.0 g, 0.025 mol) then added. The stirring was
continued for an additional 20 min. Cumene hydroper-
oxide (18.9mL, 0.10 mol) was added dropwise and the
whole system kept at À23 ꢁC for ca. 3 days (unstirred).
A solution of FeSO Æ7H O (140.0 g, 0.50 mol), citric
Alkali metal ions
Figure 4. Effect of alkali metal acetates on the enantioselectivity of
product 14.
4
2
observed a dramatic increase in the enantioselectivity
acid (54.0 g, 0.25 mol) in water (1800 mL) was prepared
for work-up. The organic layer was extracted with
diethyl ether (3 · 250 mL). The combined organics were
washed with 900 mL of 2 M aq NaOH solution. The
biphasic mixture was stirred vigorously for 1 h to
remove diethyl tartarate. After separation, the organic
+
+
while changing the alkali metal ions Li through Cs
Fig. 4). By using CsOAc as the additive, up to 98% ee
has been observed.
(
3. Conclusion
layer was dried over MgSO and concentrated to give
4
a yellow oily mixture. Flash silica gel chromatography
with ethyl acetate/hexanes (1/1 to 2/1) as eluent gave
bis-sulfoxide 8 (4.5 g, 50% yield). H NMR revealed
In conclusion, we have developed bis-sulfoxide 2, sul-
fone 3 and sulfide 4 ferrocenyl bisphosphine ligands.
Preliminary results demonstrating the asymmetric
potentials of these ligands in hydrogenation and allylic
alkylation reactions are encouraging. Further investiga-
tions on these ligands are underway and will be reported
in due course.
1
the presence of nearly 20% of meso-sulfoxide as impu-
rity. Two recrystallizations with CH Cl /hexanes (1:4)
2
2
afforded the desired pure chiral (R ,R )-bis-sulfoxide 8
S
S
25
(3.8 g, 42% yield) as a yellow solid. ½aŠ ¼ À566:0 (c
D
1
1, CHCl ); H NMR (360 MHz, CDCl ) d 4.83 (s,
3
3
2
H), 4.76 (s, 2H), 4.69(s, 2H), 4.63 (s, 2H), 1.16 (s,
1
3
18H); C NMR (75 MHz, CDCl ) d 88.88, 72.96,
3
4
. Experimental
72.84, 71.75, 67.12, 55.62, 23.14; APCI-MS (m/z):
+
4
17.0 [M +Na]; APCI-HRMS: calculated for
+
4
.1. General procedure
C H FeNaO S [M +Na]: 417.0616; found: 417.0621.
18 26 2 2
All reactions were carried out under an inert atmosphere
of nitrogen using standard Schlenk line techniques. Sol-
vents were purified by standard procedures. All melting
points were determined in open capillary tubes and are
4.2.2. (R ,R ,R ,R )-Bis(tert-butylsulfinyl)phosphino
Fc S Fc S
ferrocene 2. To an ice-cold solution of bis-sulfoxide 8
(0.98 mg, 2.5 mmol) in 40 mL of dry THF was added
2.5 mL of n-BuLi (2.2 equiv, 2.5 M in hexanes) over
ca. 5 min. The lithiation was allowed to proceed at
1
13
31
uncorrected. H, C and P NMR spectra were
recorded in CDCl using Bruker DPX-300, DPX-400
0 ꢁC for 1 h followed by the addition of PPh Cl
3
2
and AMX-360 spectrometers. Mass spectra were
recorded on a KRATOS MS 9/50 for LR-ES and HR-
ES or LS-APCI and HR-APCI. GC analysis was carried
out on a Hewlett–Packard 6890 gas chromatograph with
a flame ionization detector and chiral capillary column
Chiralsil-VAL III FSOT (dimensions 25 m · 0.25 mm).
HPLC analysis was performed on a Waters 600 chro-
(1.3 mL, 7.0 mmol). The cooling bath was removed
and the solution allowed to warm to room temperature
and stirred for 1 h. As monitored by TLC (eluent ethyl
acetate/hexanes 1/1), upon consumption of the starting
material, work-up was done by adding 20 mL of satu-
rated brine solution. The organic phase was extracted
with 100 mL of CH Cl , washed with water, dried over
2
2
matograph using a UV absorbance detector set at
MgSO4 and concentrated to a red oil. Flash silica
gel chromatography with ethyl acetate/hexanes (1/1 to
ꢂ
2
54 nm for Chiralpak-AD chiral HPLC column

3680
M. Raghunath et al. / Tetrahedron: Asymmetry 16 (2005) 3676–3681
2
7
/1) as eluent gave bis-sulfinyl diphosphine 2 (1.34 g,
1% yield) as an orange solid. H NMR (360 MHz,
1 h. Work-up was done with the addition of 30 mL satu-
1
rated brine solution at 0 ꢁC, extracted with CH Cl
2
2
CD Cl ) d 7.27–7.09(m, 20H), 5.02–4. 98 (m, 4H), 3.37
(2 · 50 mL) and dried over MgSO . The solution was
2
2
4
1
3
(
m, 2H), 0.96 (s, 18H); C NMR (90 MHz, CD Cl ) d
concentrated and purified by silica gel column chroma-
tography with ethyl acetate/hexanes (10–25%) as eluent.
Concentration of pure fractions gave the pure bis-phos-
2
2
1
9
38.46, 135.57, 133.44, 129.99, 129.00, 128.93, 93.45,
3
1
3.23, 79.88, 79.56, 77.70, 56.97, 24.11; P NMR
1
(
145 MHz, CD Cl ) À25.77; APCI-MS (m/z): 763.1
phine ligand (55 mg, 41% yield). H NMR (300 MHz,
2
2
+
[
[
M +H]; APCI-HRMS: calculated for C H FeO P S
M +H]: 763.1720; found: 763.1714.
CDCl ) d 7.30–7.22 (m, 20H), 5.61 (s, 2H), 5.12 (s, 2H),
4
2
45
2
2
2
3
+
13
3.41 (s, 2H), 1.11 (s, 18H); C NMR (75 MHz, CD Cl )
2
2
d 139.28, 137.63, 135.64, 133.27, 130.32, 128.88, 92.71,
82.95, 81.69, 79.95, 77.02, 60.61, 24.19; P NMR
3
1
4
.2.3. Dibromosulfoxide 9a. Under an inert atmo-
sphere, bis-sulfoxide 8 (1.5 g, 3.8 mmol) was dissolved
in 60 mL of dry THF and cooled to below 0 ꢁC with
ice-salt bath. A solution of n-BuLi (3.8 mL, 2.5 M in
hexanes) was added over ca. 5 min and the lithiation
allowed to be completed over 1 h. To the red solution
was added 1,1,2,2-tetrabromoethane (2.0 mL, 17 mmol).
After the addition, the reaction mixture was allowed to
warm to room temperature and the work-up carried out
after 3 h. A saturated brine solution (50 mL) was added
and organic layer extracted with CH Cl , dried over
(145 MHz, CD Cl ) À25.17; APCI-MS (m/z): 817.0
2
2
+
[M +Na]; APCI-HRMS: calculated for C H Fe-
4
2
44
+
NaO P S [M +Na]: 817.1398; found: 817.1403.
4
2 2
4.2.6. (R ,R )-Bis(tert-butylsulfonyl)dicyclohexylphos-
Fc Fc
phino ferrocene 3b. Ligand 3b was obtained in about
33% yield as an orange solid following the procedure de-
scribed for 3a and using dicyclohexylphosphine chloride
1
(0.1 mL, 0.72 mmol) as the electrophile. H NMR
(360 MHz, CD Cl ) d 5.34–5.29(s, 2H), 5.08–5.02 (s,
2
2
2
2
MgSO and concentrated to give a dark oily mixture.
Purification was done by silica gel column chromatogra-
phy with ethyl acetate/hexanes (1/1 to 2/1) as eluent.
2H), 4.62–4.51 (s, 2H), 2.41 (m, 2H), 2.15 (m, 2H),
4
1
3
1.94–1.16 (m, 58H); C NMR (75 MHz, CD Cl ) d
2 2
89.48, 88.36, 81.71, 78.72, 74.95, 60.73, 41.03, 34.76,
3
1
The desired product was obtained as a yellow solid
33.88, 32.55, 31.34, 27.16, 24.77; P NMR (145 MHz,
1
+
(
4
0.62 g, 30% yield). H NMR (300 MHz, CDCl ) d
CD Cl ) À10.20; APCI-MS (m/z): 819.3 [M +H];
3
2
2
1
3
.91–4.87 (m, 4H), 4.58 (m, 2H), 1.27 (s, 18H);
C
APCI-HRMS: calculated for C H FeNaO P S
42 68 4 2 2
+
NMR (75 MHz, CD Cl ) d 89.74, 73.06, 72.71, 71.97,
[M +Na]: 841.3276; found: 841.3281.
2
2
+
6
7.56, 55.60, 23.24; APCI-MS (m/z): 572.8 [M +Na];
APCI-HRMS: calculated for C H Br FeNaO S
2 2
M +Na]: 572.8832; found: 572.8826.
4.2.7. Bis(tert-butylsulfonyl) phosphonyl ferrocene
10. Bis-sulfinyl diphosphine 2 (1.0 g, 1.31 mmol) was
dissolved in 30 mL dry CH Cl in a Schlenk flask under
1
8
24
2
+
[
2
2
4
.2.4. Dibromosulfone 9b. Dibromosulfoxide 9a
N atmosphere and cooled to 0 ꢁC. Excess of m-Chloro-
2
(
0.50 g, 0.9mmol) was dissolved in 30 mL of acetone
and cooled to 0 ꢁC, under an inert atmosphere. A
0 mL acetone solution of m-chloroperbenzoic acid
400 mg, 2.3 mmol) was added to the reaction mixture
in ca. 2 min. The reaction was allowed to warm to
perbenzoic acid (3.65 g, 20 mmol) was dissolved in
40 mL of dry CH Cl and added slowly over ca.
2
2
1
(
10 min to the above solution. The reaction mixture
was allowed to stir for 1 h at this temperature. The pro-
gress of the reaction was monitored by TLC (eluent
methanol/ethyl acetate 20%). Work-up involved addi-
2
5 ꢁC and stirred for approx. 1 h. The solvent was
removed under vacuum and diluted with 100 mL
CH Cl . An aq NaOH solution (100 mL of 1 M) was
tion of 50 mL of saturated aq NaHCO solution and
3
extraction with 2 · 50 mL of CH Cl . The organic phase
2
2
2
2
used to wash the reaction and the organic phase was
was dried over MgSO and concentrated to an orange
4
extracted with CH Cl (3 · 50 mL), dried over MgSO
oily mixture. Purification was done by silica gel column
chromatography with methanol/ethyl acetate (5–10%)
as eluent to obtain the pure phosphine oxide 10 (0.9g,
2
2
4
and concentrated. Purification involved passing the red
oily mixture through a short silica gel plug with metha-
nol/CH Cl (1% v/v) as eluent. The desired product was
1
80% yield). H NMR (300 MHz, CD Cl ) d 8.00–7.29
2
2
2
2
1
obtained as a pure orange solid (423 mg, 80%).
H
(m, 20H), 6.06–5.97 (m, 2H), 5.75 (m, 2H), 4.42–4.18
1
3
NMR (300 MHz, CDCl ) d 5.14 (m, 2H), 5.00 (s, 2H),
(m, 2H), 0.94 (s, 18H); C NMR (75 MHz, CD Cl ) d
3
2
2
1
3
4
.64 (s, 2H), 1.34 (s, 18H); C NMR (75 MHz, CDCl3)
132.78, 132.42, 129.19, 129.03, 128.86, 128.07, 92.97,
3
1
d 91.01, 86.90, 78.96, 75.45, 60.99, 42.80, 24.23; APCI-
88.36, 82.86, 81.71, 78.24, 61.90, 24.20; P NMR
+
MS (m/z): 604.8 [M +Na]; APCI-HRMS: calculated
(145 MHz, CD Cl ) 21.06; APCI-MS (m/z): 849.0
2
2
+
+
for C H Br FeNaO S [M +Na]: 604.8724; found:
[M +Na]; APCI-HRMS: calculated for C H Fe-
NaO P S [M +Na]: 849.1296; found: 849.1302.
1
8
24
2
4
2
42 44
+
6
04.8730.
6
2 2
4
.2.5. (R ,R )-Bis(tert-butylsulfonyl)diphenylphosphino
Fc Fc
4.2.8. (R ,R )-Bis-(tert-butyl-sulfenyl)diphenylphosph-
Fc Fc
ferrocene 3a. Dibromosulfone 9b (100 mg, 0.181 mmol)
was dissolved in 5 mL of dry THF in a Schlenk tube
ino ferrocene 4. Bis-sulfinyl phosphine 2 (115 mg,
0.15 mmol) was dissolved in 4 mL of dry toluene in a
Schlenk tube under an inert atmosphere. Trichlorosilane
(0.4 mL, 30 equiv) and triethylamine (0.4 mL, 20 equiv)
were added to the reaction mixture and heated to reflux
(110 ꢁC) for about 8 h. The progress of the reaction was
monitored by TLC (hexane/ethyl acetate 1/1). The reac-
tion mixture was diluted with 30 mL of CH Cl and
under a N atmosphere and cooled to À78 ꢁC with dry
2
ice/acetone bath. A solution of n-BuLi (0.26 mL 1.6 M
in hexanes) was added slowly and allowed 30 min for
the Li–Br exchange to take place. PPh Cl (0.2 mL,
2
0
.724 mmol) was added over ca. 5 min and the reaction
mixture allowed to warm to room temperature after
2
2

M. Raghunath et al. / Tetrahedron: Asymmetry 16 (2005) 3676–3681
3681
2
D
5b
1
0 mL of 3 M aq NaOH solution added to quench the
set at k = 254 nm. t = 15.3, 20.5 min. ½aŠ ¼ À17:2 (c
R
1
5
excess silane. The organic phase was washed with brine
1.6, ethanol) {literature À17.6 (c 1.68, ethanol)}, indi-
(
2 · 10 mL) and dried over MgSO . Purification was
cating (S)-enantiomer for 13.
4
done by column chromatography (ethyl acetate/hex-
ane = 5–10%). The pure bis-sulfide phosphine ligand 4
1
was obtained (60 mg, 55% yield). H NMR (360 MHz,
Acknowledgement
CD Cl ) d 7.31–7.25 (m, 10H), 7.21–7.12 (m, 10H),
2
2
4
.60 (s, 2H), 4.47 (s, 2H), 3.20 (s, 2H), 0.97 (s, 18H);
The authors wish to thank the National Institute of
Health for financial support (GM-58832).
1
3
C NMR (90 MHz, CD Cl ) d 140.82, 138.78, 135.46,
2
2
1
7
33.37, 129.75, 128.68, 86.83, 86.51, 82.91, 82.82,
3
1
5.41, 46.79, 31.76; P NMR (145 MHz, CD Cl )
2
2
+
À26.55; APCI-MS (m/z): 731.1 [M +H]; APCI-HRMS:
References
+
calculated for C H FeP S [M +H]: 731.1793; found:
4
2
45
2 2
1
. (a) Sollot, G. P.; Mertwoy, H. E. Chem. Abstr. 1965, 63,
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7
4
4
31.1787.
1
.3. General catalytic procedure
2
3
4
. Hayashi, T.; Konishi, M.; Kumada, M. Tetrahedron Lett.
1
979, 1871.
.3.1. Asymmetric hydrogenation. A solution of [Rh-
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(
NBD) SbF ] (2.3 mg, 0.0050 mmol) and ligand 3a
2 6
(
4.4 mg, 0.0055 mmol) in solvent (5mL) was stirred in
a glove box for 10 min to allow the formation of cata-
lyst. The complex solution (1 mL) was then taken in
each of the hydrogenation vials. The commercially avail-
able substrate a-(N-acetamido)acrylate 11 (14.3 mg,
6
0
.1 mmol) was added and the mixture hydrogenated in
7
an autoclave for 12 h. After carefully releasing the
hydrogen, the reaction mixture was passed through a
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centration, the desired product was subjected to chiral
GC analysis to determine the enantiomeric excess.
8
9
(
. Tappe, K.; Knochel, P. Tetrahedron: Asymmetry 2004, 92,
4
.3.2. Asymmetric allylic alkylation. A Schlenk flask
under N2 was charged with [Pd(p-allyl)Cl]2 (4.5 mg,
.5 mol %), ligand (5 mol %) and CH Cl (2 mL). The
857.
10. (a) Rebiere, F.; Riant, O.; Ricard, L.; Kagan, H. B.
Angew. Chem., Int. Ed. Engl. 1993, 32, 568; (b) Riant, O.;
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2
2
2
catalyst solution was stirred for 30 min at 25 ꢁC before
adding (E)-1,3-diphenyl prop-2-enyl acetate 12
(
126 mg, 0.5 mmol) as a solution in 1 mL of solvent.
5, 549.
Dimethyl malonate (172 lL, 1.2 mmol) was then added
followed by alkali metal acetate (2.0 mol %) and BSA
1
1. Mancheno, O. G.; Priego, J.; Cabrera, S.; Arrayas, R. G.;
Llamas, T.; Carretero, J. C. J. Org. Chem. 2003, 68, 3679.
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Clapham, G.; Robinson, P. D. J. Org. Chem. 1996, 61,
4508.
(
8
0.37 mL, 1.2 mmol). The reaction was complete in ca.
h as evidenced by TLC (eluent hexanes/ethyl ace-
1
tate = 5/1; KMnO viewing). The mixture was concen-
4
trated and directly subjected to silica gel
chromatography with eluent hexanes/ethyl acetate (4/1)
to give product 13 (reaction yields 65–98%). H NMR
13. Mancheno, O. G.; Arrayas, R. G.; Carretero, J. C. J. Am.
Chem. Soc. 2004, 126, 456.
14. Sato, M.; Sekino, M. J. Organomet. Chem. 1989, 377,
1
3
27.
(
300 MHz, CDCl ) d 7.29–7.15 (m, 10H); 6.42 (d, 1H,
3
1
5. (a) Carroll, M. A.; Widdowson, D. A.; Williams, D. J.
Synth. Lett. 1994, 12, 1025; (b) Shevchenko, I.; Shakhnin,
D.; Zhang, H.; Lattman, M.; R o¨ schenthaler, G. V. Eur. J.
Inorg. Chem. 2003, 6, 1169.
J = 15.8 Hz); 6.30 (dd, 1H, J = 15.7 Hz and 8.4 Hz);
.19(dd, 1H, J = 10.1 Hz and 8.5 Hz); 3.93 (d, 1H,
4
J = 10.9Hz); 3.70 (s, 3H); 3.66 (s, 3H). The enantiomeric
excess was determined by chiral HPLC. The Chiralpak-
1
6. Mino, T.; Kashihara, K.; Yamashita, M. Tetrahedron:
Asymmetry 2001, 12, 287.
ꢂ
AD column was used with the mobile phase as 90/10
hexane/iso-propanol, flow rate 1 mL/min and detector
17. Bunt, R. C.; Trost, B. M. J. Am. Chem. Soc. 1998, 120, 70.