Cymantrene-derived monodentate phosphites: New ligands for Rh-catalyzed enantioselective hydrogenation

Article abstract of DOI:10.1016/j.jorganchem.2006.08.027

Novel chiral monodentate phosphite ligands bearing cymantrene fragment have been prepared. Phosphite 4 with PPh₃, instead of CO-ligand, in cymantrene moiety provided higher enantioselectivity than its unsubstituted analogue 3 in hydrogenation of (Z)-methyl-2-acetamido-3-phenylacrylate.

Full text of DOI:10.1016/j.jorganchem.2006.08.027

Journal of Organometallic Chemistry 691 (2006) 5980–5983
www.elsevier.com/locate/jorganchem
Note
Cymantrene-derived monodentate phosphites: New ligands
for Rh-catalyzed enantioselective hydrogenation
a,
a
a
a
Sergey E. Lyubimov *, Vadim A. Davankov , Nikolay M. Loim , Lyudmila N. Popova ,
a
a
b
Pavel V. Petrovskii , Petr M. Valetskii , Konstantin N. Gavrilov
a
Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov street, 119991 Moscow, Russian Federation
b
Department of Chemistry, Ryazan State University, 46 Svoboda street, 390000 Ryazan, Russian Federation
Received 29 June 2006; received in revised form 8 August 2006; accepted 10 August 2006
Available online 22 August 2006
Abstract
Novel chiral monodentate phosphite ligands bearing cymantrene fragment have been prepared. Phosphite 4 with PPh3, instead of CO-
ligand, in cymantrene moiety provided higher enantioselectivity than its unsubstituted analogue 3 in hydrogenation of (Z)-methyl-2-acet-
amido-3-phenylacrylate.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Phosphite ligands; Cymantrene; Asymmetric hydrogenation
1. Introduction
ferrocenylethyamine-derived phosphoramidites showed up
to 99.5% ee in hydrogenation of enamides and dehydro-
amino acids [12]. But ligands containing only axial chirality
are more attractive because of their synthetic availability
and low cost [14].
Herein, we report synthesis of BINOL-based monoden-
tate phosphites derived from accessible cymantrenylcarbi-
nol and its derivative obtained by changing a CO-ligand
for PPh3. Due to the lack of additional stereocentres, cor-
rect correlation between the ligands structure and their effi-
ciency in the Rh-catalyzed asymmetric hydrogenation can
be made.
Bidentate derivatives of ferrocene, cymantrene, and
some tricarbonyl complexes of chromium and rhenium
have been actively investigated and demonstrated from
good to excellent enatioselectivity in asymmetric hydroge-
nation, allylation, hydrosilylation and conjugate addition
(for example, see [1–8]). Despite the encouraging perfor-
mance of many bidentate ligands, especially phosphines,
recent breakthroughs have shown that the use of bidentate
ligands is not essential to obtain high enantioselectivity.
Chiral monodentate phosphines [9], phosphonites [10],
phosphites [11] and phosphoramidites [12] have been
reported to be excellent ligands in the rhodium-catalyzed
asymmetric hydrogenation. Undoubted leaders among
modern P-monodentate ligands are phosphite and phos-
phoramidite derivatives of BINOL [11–13, and references
cited therein]. They may have either only axial chirality
or contain additional stereogenic centers. The latter group
has been well developed during the last years; for example,
2. Results and discussion
Cymantrenylcarbinol was easily prepared from formyl-
cymantrene [15]. To increase the electron-donor and steric
demands of 1 the photochemical substitution of a CO
ligand by PPh3 was carried out (Scheme 1). Compound 2
showed two multiple signals for Cp-protons at d 4.16
1
(2H) and d 4.52 (2H) in the H NMR spectrum in ace-
tone-d6 but only first of them possessed a PH-coupling of
3.2 Hz. Analysis of the NOESY spectrum of 2 and synthe-
*
Corresponding author. Tel./fax: +7 495 135 6471.
E-mail address: lssp452@mail.ru (S.E. Lyubimov).
0022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.08.027

S.E. Lyubimov et al. / Journal of Organometallic Chemistry 691 (2006) 5980–5983
5981
OH
+
O
H
NaBH4, C2H5OH,
L
L
+ [Rh(COD)2]BF4
- COD
BF4
5 (L=3)
6 (L=4)
Rh
Mn
CO
2 L
Mn
CO
1
CO
OC
OC
OC
CO
CO
Scheme 3. Complexation of the ligand with Rh(I).
OH
P(Ph)3, UV
- CO
OH
Mn
CO
Mn
CO
P(Ph)3
OC
Table 1
2
Selected spectroscopic data for compounds 3–6
Compound IR, m(CO), cmꢀ1 (CHCl3) 31P NMR, dP (CDCl3)
Scheme 1. Synthesis of cymantrenylcarbinols.
3
4
5
6
2028, 1944
1940, 1872
2024, 1940
1932, 1864
137.7
142.9, 91.1
125.3 (1J(P,Rh), 241.9 Hz)
sis of its 2,5-D labeled analogue starting from 2,5-D labeled
alcohol 1 [15] revealed that a PH-coupling exists between
the P-atom of PPh3 and protons at 3,4-positions of the
Cp-ring. Selectivity of the observed coupling is connected
with the hindered conformational rotation of the
Mn(CO)2PPh3 moiety.
Novel BINOL-based ligands were readily synthesized by
direct phosphorylation of the corresponding cymantrene
alcohols 1 and 2 (Scheme 2).
125.4 (1J(P,Rh), 243.5 Hz), 91.85
CO2Me
NHAc
CO2Me
* NHAc
+ H2, cat*
Ph
Ph
7
8
Scheme 4. Hydrogenation of (Z)-methyl 2-acetamido-3-phenylacrylate.
They represent crystalline compounds stable in pro-
longed storage in dark place.
To examine the catalytic behavior of the both cymant-
rene-based ligands 3 and 4 in asymmetric hydrogenaton
cationic rhodium(I) complexes 5 and 6 were obtained
(Scheme 3).
Significantly larger m(CO) frequency for the ligand 3 and
its Rh(I) complex 5 (Table 1) prove higher p-acidity of
phosphite 3 in comparison to 4 having a more efficient elec-
tron-donating ligand P(Ph)3 than CO in the cymantrene
part. We supposed that the different electron-donating
properties of the ligands should have influence on the cat-
alytic behavior of the complexes.
Complexes 5 and 6 were first used in the hydrogenation
of (Z)-methyl 2-acetamido-3-phenylacrylate 7 (Scheme 4).
Both complexes showed excellent chemical yields. In the
case of 5 poor enantioselectivety were obtained in all sol-
vents used (Table 2, entries 1 and 2).
Influence of ligand structure on the enantioselectivity
and chemical yield was also examined in hydrogenation
of less sterical hindered substrate – dimethyl itaconate (9)
(Scheme 5).
In this case, moderate enantioselectivities were
obtained for both complexes 5 and 6. The use of complex
6 with bulky phosphite 4 led to a completely different
behavior during hydrogenation of 9. In this case not only
conversion was lower, but the enantioselectivity was
decreased due to increased steric demands of ligand 4 as
compared with 3 (Table 3). Solvent effect is also impor-
tant, complex 6 showed only 30% conversion in CH2Cl2
(Table 3, entry 3), however EtOAc as solvent afforded
product 10 with excellent chemical yield, but lower ees
(Table 3, entry 4).
Contrary, the use of the complex 6 dramatically
improved the enantioselectivity and gave product 8 in
91% ee (Table 2, entry 3). The result indicated that the
bulky electron-donating ligand 4 tended to increase enan-
tiomeric excess for the product 8. However, the nature of
the solvents showed no less important effect, changing the
solvent from CH2Cl2 to EtOAc reduced the ee value of
the product 8 from 91% to 27%. Closer effect was published
by Hua and van den Berg for bulky phosphites and phos-
phoramidites [16,17].
In summary, we have synthesized novel and easily pre-
pared cymantrene-derived monodentate phosphites. It has
been found that the more sterically hindered and better
electron-donating phoshite 4 with a P(Ph)3 group as ligand
in cymantrene was a better asymmetric catalyst in hydroge-
nation of a dehydroamino acid ester (up to 91% ee), but
less effective in hydrogenation of dimethyl itaconate. Fur-
ther modification of cymantrene part, for example, substi-
tution of second CO ligand by P(Ph)3, may improve
enatioselectivity. Such experiments are in progress.
X
+ 1 or 2, NEt3, CH2Cl2
O
O
O
P
Cl
P
O
3
4
CO
Mn
X
OC
O
CO
PPh3
Scheme 2. Synthesis of ligands 3 and 4.

5982
S.E. Lyubimov et al. / Journal of Organometallic Chemistry 691 (2006) 5980–5983
Table 2
and residue was crystallized from hexane to obtain 0.81 g
1
Hydrogenation of (Z)-methyl 2-acetamido-3-phenylacrylate (20 h, 5 atm
H2, 20 ꢁC)
(60%) of 2, mp 119–120 ꢁC. H NMR (acetone-d6): 4.03
2
(t, 1H, JH,H = 6.1, OH), 4.16 (m, 2H, JPH = 3.2,
3J + 4J = 4, bCp), 4.22 (d, 2H, 2J = 6.1, CH2OH), 4.52
Entry
Catalyst
Solvent
ee, %
Conversion, %
3
(dd, 2H, J + 4J = 4, aCp), 7.47–7.64 (m, 15H, Ph). IR,
1
2
3
4
5
5
6
6
CH2Cl2
EtOAc
CH2Cl2
EtOAc
25 (R)
20 (R)
91 (R)
27 (R)
100
100
100
97
m(CO), (CHCl3), cmꢀ1: 1875, 1942. Anal. Calc. for
C26H22PO3Mn (%): C, 66.68; H, 4.73; Found: C, 66.79;
H, 4.71%.
3.2. Preparation of ligands 3,4 (general technique)
*
A solution of the phosphorylating reagent [18] 0.74 g
(2.1 mmol) in CH2Cl2 (15 ml) was added to a vigorously
stirred solution of 1 or 2 (2.1 mmol) and NEt3 0.28 ml
(2.1 mmol) in CH2Cl2 (10 ml). The mixture was stirred
for additional 1 h. Obtained solution was washed with
water (80 ml), dried over Na2SO4, filtered, and concen-
trated. The residues were purified by flash column chroma-
tography (silica gel, CH2Cl2) to give the desired products as
yellow powders. Yields – (65% for 3 and 72% for 4).
+ H2, cat
CO2Me
MeO2C
MeO2C
CO2Me
9
10
Scheme 5. Hydrogenation of dimethyl itaconate.
Table 3
Hydrogenation of dimethyl itaconate (20 h, 5 atm H2, 20 ꢁC)
Entry
Catalyst
Solvent
ee, %
Conversion, %
1
2
3
4
5
5
6
6
CH2Cl2
EtOAc
CH2Cl2
EtOAc
83 (S)
80 (S)
70 (S)
61 (S)
100
100
30
3.3. (Sax)-2-(cymantrenylmethyloxy)-dinaphtho [2,1-
d:10,20-f] [1–3] dioxaphosphepine (3)
93
13C NMR (CDCl3): dC: 66.3, 82.0, 82.6, 83.1, 84,0,
100.7, 117.8–152.7 (arryl), 224.5 (broad (CO)). MS (EI),
m/z (I, %): 548 (2, [M]+), 365 (90), 286 (100), 217 (20),
120 (18). Anal. Calc. for C29H18O6PMn (%): C 63.52, H
3.31; Found: C 63.61, H 3.41%.
3. Experimental
IR spectra were recorded on a Specord M80 instrument.
31P, 13C and 1H NMR spectra were recorder with a Bruker
AMX 400 instrument (162.0 MHz for 31P, 100.6 MHz for
3.4. (Sax)-(2-(dinaphto [2,1-d:10,20-f] [1,3,2]
dioxaphosphepine) oxymethyl)cyclopentadienyl-
(dicarbonyl) (triphenylphosphine)manganese (4)
13C and 400.13 MHz for H). Complete assignment of all
1
the resonances in 13C NMR spectra was achieved by the
use of DEPT techniques. Chemical shifts (ppm) are given
relative to Me4Si (1H and 13C) and 85% H3PO4 (31P
NMR). Mass spectra were recorded with a Varian MAT
311 spectrometer (EI) and a Finnigan LCQ Advantage
spectrometer (electrospray ionization technique, ESI). Ele-
mental analyses were performed at the Laboratory of
Microanalysis (Institute of Organoelement Compounds,
Moscow). The photochemical substitution of a CO-ligand
by PPh3 was carried out for 1 using the immersed ultravi-
olet lamp NORMAG TQ 150.
13C NMR (CDCl3): dC, (JC,P
,
Hz): 61.57 (d,
2JC,P = 39.1), 82.7, 82.5, 83.7, 83.9, 95.6, 119.9–148.2
(arryl), 231.9, 231.6. MS (EI), m/z (I, %): 782 (1, [M]+),
396 (10), 262 (70), 183 (70), 83.0 (100). Anal. Calc. for
C46H33O5P2Mn (%): C 70.59, H 4.25; Found: C 70.67, H
4.36%.
3.5. Cationic rhodium complex
½RhðCODÞð3Þ2ꢁþBF4 (5). Yellow solid. MS (ESI), m/z
ꢀ
All reactions were carried out under a dry argon atmo-
sphere in freshly dried and distilled solvents; phosphorylat-
ing reagent (Sax)-2-chloro-dinaphtho[2,1-d:10,20-f][1,3,2]
dioxaphosphepine was prepared as published [18].
[Rh(COD)2]BF4 was synthesised using literature procedures
[19]. The syntheses of rhodium(I) complexes (5 and 6) were
performed by techniques similar to that reported [11–14].
(I, %): 1397 (10%, [MꢀBF4]+), 1202 (100%, [MꢀBF
,
ꢀ
4
ꢀCOD)]+. Anal. Calc. for C66H51BF4Mn2O 12P2Rh (%):
C 56.72, H 3.68; Found: C 56.84, H 3.79%.
½RhðCODÞð4Þ2ꢁþBF4 (6). Yellow solid. MS (ESI), m/z
ꢀ
(I, %): 1778 (5%, [MꢀBF4]+), 1670 (100%, [MꢀBF
,
ꢀ
4
ꢀCOD)]+. Anal. Calc. for C100H80BF4Mn2O10P4Rh (%):
C 64.39, H 4.32; Found: C 64.48, H 4.48%.
3.1. Hydroxymethylcyclopentadienyl(dicarbonyl)
(triphenylphosphine)manganese (2)
3.6. Hydrogenation procedure (general technique)
A solution of 0.7 g (3 mmol) of 1 and 0.84 g (3.2 mmol)
PPh3 in 250 ml dried benzene was irradiated at 5 ꢁC for
1.5 h in the Ar stream. Then the solvent was removed
A 25 ml stainless steel autoclave was charged open to air
with Rh-complexes 5 or 6 (0.006 mmol) and substrates 7 or
9 (0.6 mmol). Solvent was added (5 ml) and the system was

S.E. Lyubimov et al. / Journal of Organometallic Chemistry 691 (2006) 5980–5983
5983
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autoclave was pressurized with hydrogen (5 bar) and the
reactions were stirred at 20 ꢁC for 20 h. After the hydrogen
was released, the mixture was filtered through a shot silica
gel column to remove the catalyst; the filtrate was concen-
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determined using HPLC (Chiralcel OD-H column) accord-
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1
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Acknowledgements
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This work was supported by RFBR grant N 04-03-
39017. S.E.L. thanks the Russian Science Support Founda-
tion for a fellowship.
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