The use of new carboranylphosphite ligands in the asymmetric Rh-catalyzed hydrogenation

Article abstract of DOI:10.1016/j.catcom.2009.11.012

A series of new monodentate phosphite ligands based on carboranes have been synthesized and used for asymmetric Rh-catalyzed hydrogenation of prochiral olefins in CH₂Cl₂ with the result of up to 99.5% ee. High reactivities (100% conv

Full text of DOI:10.1016/j.catcom.2009.11.012

Catalysis Communications 11 (2010) 419–421
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
The use of new carboranylphosphite ligands in the asymmetric
Rh-catalyzed hydrogenation
b
a
a
a
Sergey E. Lyubimov a, , Ilya V. Kuchurov , Andrey A. Tyutyunov , Pavel V. Petrovskii , Valery N. Kalinin ,
*
Sergei G. Zlotin b, Vadim A. Davankov a, Evamarie Hey-Hawkins c
a A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov Street 28, 119991 Moscow, Russia
b N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prosp. 47, 119991 Moscow, Russia
c Institut für Anorganische Chemie, Johannisallee 29, 04103 Leipzig, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 3 August 2009
Received in revised form 11 November 2009
Accepted 12 November 2009
Available online 5 December 2009
A series of new monodentate phosphite ligands based on carboranes have been synthesized and used for
asymmetric Rh-catalyzed hydrogenation of prochiral olefins in CH2Cl2 with the result of up to 99.5% ee.
High reactivities (100% conversion in 45–60 min) and enantioselectivities (up to 92%) were obtained in
the hydrogenation of dimethyl itaconate in supercritical CO2. In this case the catalytic performance is
affected greatly by hydrogen and total pressures.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Asymmetric hydrogenation
Rhodium
Supercritical carbon dioxide
Carboranylphosphite ligands
1. Introduction
we have prepared novel sterically congested carborane-containing
monodentate ligands for application in Rh-catalyzed hydrogena-
Sterically bulky ligands play an important role in organometal-
lic chemistry [1–9]. Carboranes are attractive synthons for the
preparation of sterically congested ligands due to their significant
steric bulk, stability to oxidative destruction and sufficiently sim-
ple functionalization [10,11]. Furthermore, isomeric carboranes
(ortho-, meta and para-) have unusual electronic properties. For
example, ortho-carboran-9-yl substituent is a powerful electron-
donating group (di = ꢀ0.23), unlike ortho-carboran-1-yl which is a
powerful electron acceptor (di = +0.39), while steric properties of
the both units are equal [11]. Recently, we designed first examples
of chiral mono- and bidentate phosphite-type ligands containing
sterically congested carborane fragments and showed their high
efficiency for the Rh-catalyzed asymmetric hydrogenation of func-
tionalized olefins (up to 99.8% ee) [12,13]. Further examination of
the catalytic activity and selectivity of the ligands shows that
monodentate ligands are more effective compared to bidentate
carboranylphosphite-type ligands, and electron-donating carbora-
nyl substituents are essential for obtaining high levels of enantio-
discrimination and conversion [13–15]. Encouraged by the
excellent enantioselectivities in the asymmetric hydrogenation
processes and motivated by our continuing efforts in the design
of novel highly modular chiral carboranylphosphite-type ligands,
tion of prochiral olefins.
2. Experimental
2-Chloro-dinaphtho[2,1-d:10,20-f][1,2,3]dioxaphosphepine (1)
[16] and 2-Chloro-5,50,6,60,7,70,8,80-octahydro-dinaphtho[2,1-d:10,
20-f][1,2,3]dioxaphosphepine (2) [17], 9-hydroxy-1,2-dimethylcar-
borane 3 and 9-hydroxy-ortho-carborane 4 [18] were prepared as
published. Ligands 5, 6 were synthesised analogously to the known
procedures [12,14].
(S)-2-(1,2-dimethyl-ortho-carboran-9-yloxy)-dinaphtho[2,1-d:10,
20-f][1–3]dioxaphosphepine (5). 31P{H} NMR (121.5 MHz, CDCl3): =
146.72 (q, JP,B = 14.5 Hz). 11B NMR (128.38 MHz, CDCl3): ꢀ14.59 to
10.75 (m, 8B), ꢀ6.28 (d, J = 147.8 Hz, 1B), 10.76 (s, 1B). 13C {H}
NMR (100.6 MHz, CDCl3): 20.65 (s, CH3), 23.44 (s, CH3), 59.45 (s,
carb), 68.83 (s, carb), 121.93, 122.35, 122.91, 124.36 (d, J = 4.6 Hz),
124.48, 124.71, 125.71, 125.92, 126.80, 126.89, 128.06, 128.16,
129.24, 129.87, 130.98, 131.28, 132.49, 132.72, 147.55, 147.69 (d,
J = 4.2 Hz) aryl all. Anal. Calc. for C24H27B10O3P: C, 57.36; H, 5.42; B,
21.51. Found: C, 57.42; H, 5.51; B, 21.47.
(R)-2-(ortho-carboran-9-yloxy)-5,50,6,60,7,70,8,80-octahydro-dinaph-
tho [2,1-d:10,20-f][1–3]dioxaphosphepine (6). 31P{H} NMR (121.5 MHz,
CDCl3): = 138.01 (q, JP,B = 15.0 Hz). 11B NMR (128.38 MHz, CDCl3):
ꢀ19.91 to 13.13 (m, 6B), ꢀ10.35 (d, J = 147.8 Hz, 2B), ꢀ3.69 (d,
* Corresponding author. Tel.: +7 499 1352548; fax: +7 499 1356471.
E-mail address: lssp452@mail.ru (S.E. Lyubimov).
1566-7367/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2009.11.012

420
S.E. Lyubimov et al. / Catalysis Communications 11 (2010) 419–421
J = 149.6 Hz 1B), 11.93 (s, 1B). 13C {H} NMR (100.6 MHz, CDCl3): 22.30
(CH2), 22.34 (CH2), 22.48 (CH2), 22.57 (CH2), 27.58 (CH2), 27.67 (CH2),
28.99 (CH2), 29.10 (CH2), 40.59 (s, carb), 49.92 (s, carb), 118.85 (CH
ar), 119.10 (CH ar), 127.92 (C ar), 128.77 (CH ar), 129.04 (CH ar),
129.45 (d, J = 5.2 Hz, C ar), 133.53 (C ar), 134.46 (C ar), 137.00 (C ar),
138.13 (C ar), 145.44 (d, J = 3.8 Hz, C ar), 146.08 (C ar). Anal. Calc. for
C22H31B10O3P: C, 54.76; H, 6.48; B, 22.40. Found: C, 54.82; H, 6.55; B,
22.44.
Substrates 9, 10 were prepared according to the published pro-
cedures [19,20].
(Z)-Methyl 2-acetamido-3-(cymantrenyl)acrylate (13) was pre-
pared similarly to 9, 10 from corresponding azlactone [21]. 1H NMR
(CDCl3, 300 MHz) d 2.16 (s, 3H, CH3 Ac), 3.81 (s, 3H, CH3, O–Me),
4.78 (s, 2H, Cp), 5.05 (s, 2H, Cp), 6.95 (s, 1H, NH), 7.01 (s, 1H,
CH). Anal. Calc. for C14H12MnNO6: C, 48.71; H, 3.50; N, 4.06. Found:
C, 48.80; H, 3.59; N, 3.98.
Dimethyl itaconate 7 and methyl 2-acetamidoacrylate 8 were
obtained from Aldrich.
2.1. Hydrogenation of dimethyl itaconate in scCO2
The catalysts were prepared by adding the corresponding
monodentate ligand (0.012 mmol) to a solution of [Rh(COD)2]BF4
(2.4 mg, 0.006 mmol) in CH2Cl2 (0.5 ml). The solution was stirred
for 5 min before removing the solvent in vacuo. The pre-formed
catalysts (0.006 mmol) and substrate 7 (0.6 mmol) were placed
open to air into a 10 ml autoclave. The vessel was pressurized with
hydrogen and then filled with scCO2 by means of a syringe-press.
The mixture was allowed to equilibrate to the reaction tempera-
ture (15 min) and stirred for 45–60 min. After stirring, the vessel
was slowly depressurized. The reaction products were dissolved
in acetone (3 ml), the catalyst removed via a short silica gel col-
umn. The filtrate was concentrated in vacuo to afford the target
product 12.
Scheme 2. Asymmetric hydrogenation of dimethyl itaconate 7 and
amino acids esters 8–11.
a-dehydro
(S)-ligand 5 results in (R)-product 12. The (R)-phosphite 6 afforded
12 in opposite absolute configuration.
To expand the utility of these ligands, we also examined the Rh-
catalyzed enantioselective hydrogenation of a-dehydro amino acids
esters: methyl 2-acetamidoacrylate 8, (Z)-methyl 2-acetamido-3-
phenylacrylate 9, (Z)-methyl 2-acetamido-3-(4-chlorophenyl)acry-
late 10 and (Z)-methyl 2-acetamido-3-cymantrenylacrylate 10
(Scheme 2). In the hydrogenation of 8 the ligands 5 and 6 showed
complete conversion and ee up to 80% and 76%, respectively (Table
1, entries 3 and 4). Hydrogenation of more sterically hindered sub-
strate 9 gave complete conversion to the phenylalanine ester 14
after 16 h, but disappointingly low ee‘s (30–46%) were observed (Ta-
ble 1, entries 5 and 6). However, reduction of the substrate 10 with
electron-withdrawing Cl-substituent on the phenyl ring gave better
enantioselectivity (60% ee) in the case of ligand 5 (Table 1, entry 7).
Remarkable increase of enantioselectivity (up to 90% ee and 86% ee)
3. Results and discussion
The new monodentate phosphite 5 and 6 were synthesized by a
convenient one step phosphorylation of the corresponding 9-hy-
droxy-1,2-dimethylcarborane 3 and 9-hydroxy-ortho-carborane 4.
The products were characterized by 31P, 13C and 11B spectroscopy
and by elemental analysis (see Section 2). They are white solids
and are air stable under ambient conditions (Scheme 1).
Ligands 5 and 6 were first used in the Rh-catalyzed hydrogena-
tion of dimethyl itaconate 7 (Scheme 2). The catalysts were formed
in situ by mixing [Rh(COD)2]BF4 with 2 equiv. of the chiral ligand 5
or 6 in CH2Cl2 under argon. The catalysts exhibited excellent
enantioselectivities (98 and 99.5% ee) and complete conversion of
7 (Table 1, entries 1 and 2). It should be noted that the use of
Table 1
Asymmetric hydrogenation of dimethyl itaconate and
a-dehydro amino acids esters
(10 atm H2, 20 °C, CH2Cl2).a
Entry
Catalyst
Substrate
t (h)
Conversion (%)b
ee (%)c
1
2
3
4
5
6
7
8
9
10
[Rh(COD)2]BF4/5
[Rh(COD)2]BF4/6
[Rh(COD)2]BF4/5
[Rh(COD)2]BF4/6
[Rh(COD)2]BF4/5
[Rh(COD)2]BF4/6
[Rh(COD)2]BF4/5
[Rh(COD)2]BF4/6
[Rh(COD)2]BF4/5
[Rh(COD)2]BF4/6
7
7
8
8
9
9
10
10
11
11
16
16
16
16
16
16
18
18
18
18
100
100
100
100
100
100
100
100
100
100
98 (S)
99.5 (R)
80 (R)
76 (S)
30 (R)
46 (S)
60 (R)
47 (S)
86 (R)
90 (S)
a
b
c
Substrate/[Rh(COD)2]BF4/ligand = 1.0/0.01/0.02.
Determined by 1H NMR spectroscopy.
Determined by HPLC (KromasilÒ 5-AmyCoat, 250 ꢁ 4.6 mm column, 9/1 hex-
ane/i-PrOH, 1 ml/min, 219 nm) for products 13–16. Ee of 12 determined by HPLC
(Daicel Chiralcel OD-H) 98/2 hexane/i-PrOH, 0.8 ml/min, 219 nm.
Scheme 1. Synthesis of chiral carborane-containing phosphites.

S.E. Lyubimov et al. / Catalysis Communications 11 (2010) 419–421
421
Table 2
sures. The use of the ligands in the Rh-catalyzed hydrogenation
of -dehydro amino acids esters showed from moderate to high
enantioselectivities (30–90% ee), in the last case electron-with-
drawing substituents in substrates are favorable for high
enantiodiscrimination.
Rh-catalyzed hydrogenation of 7 in scCO2, 40 °C.
a
b
Entry P, H2
Total pressure
(atm)
t
Conversion
(%)a
ee (%)
(atm)
(min)
1
2
3
25
25
80
200
125
200
60
60
45
100
100
100
60 (R)
80 (R)
92 (R)
Acknowledgement
a
Determined by 1H NMR spectroscopy.
Ee of 12 determined by HPLC (Daicel Chiralcel OD-H) 98/2 hexane/i-PrOH,
b
This work was supported by the Russian Foundation for Basic
Research (Grant No. 09-03-12104-ofi_m) and DFG-RFBR Grant
No. 09-03-91345.
0.8 ml/min, 219 nm.
was observed in the Rh-catalyzed hydrogenation of the substrate 11
bearing strong electron-withdrawing and bulky cymantrenyl group
(Table 1, entry 10), showing that in this case the electronic effect of
substituents in the enamides 8–11 played very important role in the
enantiocontrol. It should be noted, that in all the cases the (S)-BINOL
based phosphocycle induces (R)-absolute configuration of the prod-
ucts 13-16 (Table 1, entries 3, 5, 7, 9), while the (R)-H8-BINOL based
phosphorcycle gives the products with (S)-configuration (Table 1,
entries 4, 6, 8, 10).
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4. Conclusions
In summary, new modular chiral ligands containing different
carboranyl substituents and phosphorus centers have been synthe-
sized. The new ligands demonstrated high enantioselectivity in the
Rh-catalyzed hydrogenation of dimethyl itaconate (up to 99.8% ee
in CH2Cl2 and up to 92% ee in scCO2). In the case of scCO2 the cat-
alytic performance is affected greatly by hydrogen and total pres-
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