Chiral carborane-derived thiophosphites: A new generation of ligands for Rh-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1016/j.jorganchem.2008.09.032

A new class of chiral monodentate ligands - carborane-containing thiophosphites have been synthesized and tested in the Rh-catalyzed asymmetric hydrogenation of prochiral olefins with the result of up to 99% ee. The dependence of the enantioselectivity on

Full text of DOI:10.1016/j.jorganchem.2008.09.032

Journal of Organometallic Chemistry 693 (2008) 3689–3691
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Chiral carborane-derived thiophosphites: A new generation of ligands for
Rh-catalyzed asymmetric hydrogenation
Sergey E. Lyubimov a, , Vadim A. Davankov , Pavel V. Petrovskii , Evamarie Hey-Hawkins ,
a
a
b
*
a
a
a
Andrey A. Tyutyunov , Evgeny G. Rys , Valery N. Kalinin
Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov street 28, 119991 Moscow, Russia
Institut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
a
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 July 2008
Received in revised form 19 September
A new class of chiral monodentate ligands – carborane-containing thiophosphites have been synthesized
and tested in the Rh-catalyzed asymmetric hydrogenation of prochiral olefins with the result of up to 99%
ee. The dependence of the enantioselectivity on the electronic properties of the carboranyl substituent
has been studied.
2
008
Accepted 22 September 2008
Available online 27 September 2008
Ó 2008 Elsevier B.V. All rights reserved.
Keywords:
Thiophosphite ligands
Carboranes
Asymmetric hydrogenation
Rhodium
1
. Introduction
Transition metal-catalyzed hydrogenation of prochiral olefins
2. Results and discussion
The new monodentate thiophosphites 4 and 5 were synthesized
by a convenient one-step phosphorylation of the corresponding
ortho- and meta-9-mercapto-dicarba-closo-dodecaboranes (2 and
belongs to the most practical ways of producing many optically ac-
tive organic compounds including intermediates for the pharma-
ceutical industry [1,2], and a broad range of chiral hydrogenation
catalysts has been developed, most of which rely on chiral biden-
tate phosphorus ligands [3,4]. In recent years, increasing attention
has been directed to chiral monodentate phosphites and phospho-
ramidites, due to their ready accessibility and efficiency in the Rh-
catalyzed hydrogenation [5–8] and references cited therein. Never-
theless, another type of chiral trivalent phosphorus derivatives –
3
1
1
3, Scheme 1). The products 4, 5 were characterized by P,
H
1
1
and B NMR spectroscopy and by elemental analysis (see Section
3). They are white solids and are air stable under ambient
conditions.
Reaction of the thiophosphites 4,
2 4
5 with [Rh(COD) ]BF
(COD = 1,5-cyclooctadiene) afforded the cationic rhodium com-
plexes 6, 7 (Scheme 2). These compounds are stable in air and have
moderate solubility in common organic solvents (especially com-
thiophosphites
– has not been previously reported. Such
3
1
compounds are promising as novel unexploited ligands for asym-
metric metal complex catalysis.
plex 7). P NMR data for complexes 6 and 7 showed chemical
shifts and JP,Rh coupling constants (see Section 3) similar to those
of rhodium complexes with monodentate phosphite and phospho-
ramidite ligands [6,12–14].
Recently, we designed a novel class of chiral mono- and biden-
tate phosphite-type ligands containing sterically congested carbo-
rane fragments and showed their high efficiency for the Rh-
catalyzed asymmetric hydrogenation of functionalized olefins (up
to 99.8% ee) [9–11]. Encouraged by these results we have now pre-
pared the first representatives of chiral thiophosphite ligands bear-
ing bulky ortho- and meta-9-dicarba-closo-dodecaborane fragments
for an application in the Rh-catalyzed asymmetric hydrogenation.
Ligands 4 and 5 were first used in the Rh-catalyzed hydrogena-
tion of the benchmark substrate, dimethyl itaconate (8, Scheme 3).
The catalysts were formed in situ by mixing [Rh(COD)
2 equiv of the chiral ligand 4 or 5 in CH Cl under argon (Table
1). The enantioselectivities are influenced by the donor/acceptor
2 4
]BF , with
2
2
properties of the 9-ortho- and 9-meta-carboranyl substituents
[
11]. The rhodium catalyst with ligand 4, which has a strongly elec-
tron-donating 9-ortho-carboranyl group (d = - 0.23), exhibited
excellent enantioselectivity (98% ee) and complete conversion. It
should be noted that changes in H pressure in this case had no
i
*
Corresponding author. Tel./fax: +7 495 135 6471.
E-mail address: lssp452@mail.ru (S.E. Lyubimov).
2
0
022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.09.032

3
690
S.E. Lyubimov et al. / Journal of Organometallic Chemistry 693 (2008) 3689–3691
O
O
O
+
H , CH C
2 2 l2
cat*
O
O
*
HS
O
P
O
,
NEt3
HN
HN
HN
HN
2
S
S
-
HNEt3Cl
10
11
4
O
O
O
P Cl
O
O
O
+
H , CH C
O
O
2
2
l2
*
HN
HS
O
P
O
cat*
3
, NEt3
HNEt Cl
1
-
3
13
1
2
5
O
O
O
Scheme 1. Synthesis of chiral carborane-containing thiophosphites.
O
H2, CH2Cl2
cat*
O
*
HN
F
F
1
4
15
9
O
O
+
BF4
+
-
+2L
L
BF4-
Scheme 4. Asymmetric hydrogenation of a-dehydro amino acids esters 10, 12, 14.
Rh
Rh
-
COD
L
6
7
L = 4
L = 5
Table 2
Asymmetric hydrogenation of a-dehydro amino acids esters
Scheme 2. Synthesis of complexes 6 and 7.
Conversiona (%)
Eeb (%)
Entry
Catalyst
Substrate
p (atm)
t (h)
1
2
3
4
5
6
7
8
9
4/Rh
4/Rh
5/Rh
5/Rh
4/Rh
5/Rh
4/Rh
5/Rh
5/Rh
10
10
10
10
12
12
14
14
14
5
10
5
10
10
10
10
10
10
18
14
16
12
16
18
18
18
22
100
100
100
100
100
100
100
85
94 (S)
94 (S)
95 (S)
95 (S)
88 (S)
70 (S)
75 (S)
50 (S)
50 (S)
O
O
O
O
O
O
H2
,
CH Cl
*
2
2
cat*
O
100
8
9
O
a
Determined by 1H NMR spectroscopy.
b
Scheme 3. Asymmetric hydrogenation of dimethyl itaconate.
Ee of 11 determined by HPLC (Daicel Chiralcel OJ-H) 95/5 hexane/i-PrOH,
.0 mL/min, 219 nm, t(R) = 14.01 min, t(S) = 16.01 min). Ee of 13 determined by
1
HPLC (Daicel Chiralcel OD-H) 9/1 hexane/i-PrOH, 0.9 mL/min, 219 nm,
t(R) = 11.8 min, t(S) = 15.8 min). Ee of 15 determined by HPLC (Daicel Chiralcel OD-
Table 1
Asymmetric hydrogenation of 8
H) 9/1 hexane/i-PrOH, 0.9 mL/min, 219 nm, t(R) = 12.2 min, t(S) = 15.2 min),
14 = 18 min).
t
Entry
Catalyst
Substrate
p (atm)
t (h)
Conversiona (%)
eeb (%)
1
2
3
4
5
4/Rh
4/Rh
6
5/Rh
7
8
8
8
8
8
5
10
5
10
5
18
14
18
14
16
100
100
100
100
100
98 (R)
98 (R)
99 (R)
88 (R)
93 (R)
2, entries 1–4). Hydrogenation of the more sterically hindered sub-
strate 12 with the electron-withdrawing phenyl substituent
showed that ligand 4 (bearing a stronger electron-donating 9-
ortho-carboranyl group) gave product 13 with better enantiomeric
excess, compared to the catalytic system based on ligand 5 (Table
a
Determined by 1H NMR spectroscopy.
b
Ee of 9 determined by HPLC (Daicel Chiralcel OD-H) 98/2 hexane/i-PrOH,
.8 mL/min, 219 nm, t(R) = 9.21 min, t(S) = 16.14 min).
2, entries 5 and 6). Ligands 4, 5 showed the same trend in the
0
hydrogenation of the fluor-containing enamide 14 (Scheme 4, Ta-
ble 2); the stronger electron-donating thiophosphite 4 showed bet-
ter enantioselectivity. The ligand 5 bearing the weaker electron-
donating 9-meta-carboranyl substituent gave not only lower ee,
but also incomplete conversion in 18 h.
In summary, we have designed and synthesized the first exam-
ples of sterically congested carborane-containing chiral thi-
ophosphite ligands for use in asymmetric catalysis. Initial studies
of the monodentate carboranylthiophosphite ligands resulted in
excellent enantioselectivities in the Rh-catalyzed asymmetric
hydrogenation of prochiral olefins (up to 99% ee). These ligands
can also be regarded as attractive candidates for other asymmetric
transition metal-catalyzed reactions in traditional and alternative
effect on the enantioselectivity (Table 1, entries 1 and 2). The less
electron-donating 9-meta-carboranyl group (d
leads to a decrease in enantioselectivity (88% ee), compared to the
i
= ꢀ0.12) in ligand 5
isomeric ligand 4. The use of the isolated cationic complexes 6 and
7
in the Rh-catalyzed hydrogenation of dimethyl itaconate showed
some improvement in enantioselectivity (99% ee for complex 6 and
3% for 7) compared to the catalytic systems formed in situ, when
9
low (5 atm) hydrogen pressures were used.
To expand the utility of these ligands and further investigate the
influence of the carborane component, we also examined the Rh-
‘
green’ solvents, such as scCO
3. Experimental
All reactions were carried out under dry argon atmosphere in
2
[8–9].
catalyzed enantioselective hydrogenation of
a-dehydro amino
acids esters: methyl 2-acetamidoacrylate (10), (Z)-methyl 2-acet-
amido-3-phenylacrylate (12) and (Z)-methyl 2-acetamido-3-(4-
fluorophenyl)acrylate (14) (Scheme 4).
In the hydrogenation of 10, for both ligands 4 and 5 complete
conversion and high enantioselectivity (94% and 95% ee) was ob-
served, independent of the hydrogen pressure (5 or 10 atm, Table
1
11
freshly dried and distilled solvents.
(128.38 MHz) and P (161.98 MHz) NMR spectra were recorded
H
(400.13 MHz),
B
3
1

S.E. Lyubimov et al. / Journal of Organometallic Chemistry 693 (2008) 3689–3691
3691
with an Avance 400 instrument. Chemical shifts (ppm) are given
relative to Me Si ( H), BF (OEt ) ( B NMR) and 85% H PO ( P
4 3 2 3 4
Calc. for C52
48.96; H, 4.65; B, 17.70.
H
58
B
21
F
4
O
4
P
2
RhS
2
: C, 48.83; H, 4.57; B, 17.75. Found: C,
1
11
31
NMR). Elemental analyses were performed at the Laboratory of
Microanalysis (Institute of Organoelement Compounds, Moscow).
3.6. [Rh(COD)(5)
2 4
]BF (7)
0
0
(
[
R)-2-Chloro-dinaphtho[2,1-d:1 ,2 -f][1,3,2] dioxaphosphine (1)
15], ortho- and meta-9-mercapto-dicarba-closo-dodecarboranes 2
Yellow solid, moderately soluble in organic solvents, m.p. 120–
3
1
and 3 were prepared as published [16].
124 °C (dec), P{H} NMR (CDCl
Calc. for C52 RhS : C, 48.83; H, 4.57; B, 17.75. Found: C,
48.92; H, 4.68; B, 17.86.
3
): 182.6 (br d, JP,Rh = 238 Hz). Anal.
H
58
B
21
F
4
O
4
P
2
2
3.1. Preparation of ligands 4, 5 (general technique)
ortho- or meta-9-mercapto-dicarba-closo-dodecaborane (2 or 3)
3.7. General procedure for asymmetric hydrogenation
(
2
1
0.176 g, 1 mmol) was added to a vigorously stirred solution of (R)-
0
0
-chloro-dinaphtho[2,1-d:1 ,2 -f][1,3,2] dioxaphosphine (0.350 g,
mmol) and NEt (0.135 mL, 1 mmol) in benzene (25 mL). The
[Rh(COD)
0.012 mmol) or the corresponding complex 6 or 7 (0.006 mmol),
the appropriate substrate (8, 10, 12, 14, 0.6 mmol) and CH Cl
(5 mL) were placed in a 25-mL autoclave. The autoclave was closed
and flushed three times with argon, and then the hydrogenation
2 4
]BF (2.4 mg, 0.006 mmol), ligand (4 or 5, 5.8 mg,
3
mixture was stirred for 10 min. The reaction mixture was then
heated at reflux for 20 min, cooled and filtered. Benzene was re-
moved under reduced pressure (40 torr) and the crude products
2
2
4
or 5 were purified by flash column chromatography (silica gel,
2
was performed at room temperature under H pressure of 5 or
toluene) to give the desired thiophosphites as white powders after
evaporation of the solvent. Yield: 84% for 4 and 88% for 5.
10 atm during 12–22 h. After releasing the hydrogen gas, the reac-
tion mixtures were diluted with hexane, passed through a short sil-
ica gel plug using hexane as the eluent and analysed by HPLC and
0
0
1
3
.2. (Ra)-2-(ortho-Carboran-9-ylthio)-dinaphtho[2,1-d:1 ,2 -
H NMR spectroscopy.
f][1,3,2]dioxaphosphepine (4)
31P{H} NMR (CDCl
): 223.3 (q, JP,B = 18 Hz). 11B NMR (CDCl
3
):
Acknowledgement
3
4
.3 (s, 1B), ꢀ1.7 (d, J = 148 Hz, 1B), 8.4 (d, J = 153 Hz, 2B), ꢀ14.1
1
This work was supported by INTAS Open Call Grant No. 05-
000008-8064.
(
m, 6B). H NMR (CDCl
3
): 1.14–3.34 (m, 9H, carborane), 3.40 (s,
H, CH carborane), 3.54 (s, 1H, CH carborane), 7.23–7.52 (m, 8H,
PS: C,
3.86; H, 4.73; B, 22.04. Found: C, 53.98; H, 4.80; B, 22.11%.
1
1
23 10 2
aryl), 7.91–7.98 (m, 4H, aryl). Anal. Calc. for C22H B O
5
References
0
0
3
.3. (Ra)-2-(meta-Carboran-9-ylthio)-dinaphtho[2,1-d:1 ,2 -
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31P{H} NMR (CDCl ): 223.6 (q, JP,B = 14 Hz). 11B NMR (CDCl
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3
3
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): 1.33–3.65 (m, 9H, carborane),
3
4
2
.04 (s, 2H, CH carborane), 7.21–7.56 (m, 8H, aryl), 7.89–8.02 (m,
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H B O
[
[
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A solution of compound 4 or 5 (0.029 g, 0.06 mmol) in CH
6 mL) was added dropwise during 15 min to a vigorously stirred
solution of [Rh(COD) ]BF (0.012 g, 0.03 mmol) in CH Cl (6 mL).
2 2
Cl
[
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(
2
4
2
2
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[
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Yellow solid, poorly soluble in organic solvents, m.p. 112–
14 °C (dec), P{H} NMR (CDCl ): 184.4 (br d, JP,Rh = 240 Hz). Anal.
3
3
1
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1