Modified BINAPO ligands for Rh-catalysed enantioselective hydrogenation of acetamidoacrylic acids and esters

Article abstract of DOI:10.1016/S0957-4166(02)00650-X

(S)- and (R)-2,2′-Bis[bis(3,5-dimethylphenyl)phosphinoyl]-5,5′,6, 6′,7,7′,8,8′-octahydro-1,1′-binaphthyl (Xyl-H₈-BINAPO) were synthesised by reacting chlorobis(3,5-dimethylphenyl)phosphine with (S)- and (R)-2,2′-dihydroxyl-5,5′,6,6′,7,7′,8,8′-

Full text of DOI:10.1016/S0957-4166(02)00650-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2519–2522
Modified BINAPO ligands for Rh-catalysed enantioselective
hydrogenation of acetamidoacrylic acids and esters
Rongwei Guo, Terry T.-L. Au-Yeung, Jing Wu, Michael C. K. Choi* and Albert S. C. Chan*
Open Laboratory of Chirotechnology of the Institute of Molecular Technology for Drug Discovery and Synthesis† and
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
Received 30 August 2002; accepted 9 October 2002
Abstract—(S)-
and
(R)-2,2%-Bis[bis(3,5-dimethylphenyl)phosphinoyl]-5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaphthyl
(Xyl-H8-
BINAPO) were synthesised by reacting chlorobis(3,5-dimethylphenyl)phosphine with (S)- and (R)-2,2%-dihydroxyl-
5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaphthyl, respectively. The applications of these ligands and their corresponding parent
analogues in the Rh-catalysed asymmetric hydrogenation of a variety of acetamidoacrylic acids and esters provided chiral amino
acid derivatives with good to excellent ee’s (up to 97%). © 2002 Published by Elsevier Science Ltd.
1. Introduction
than the unmodified 2,2%-bis(diphenylphosphinoyl)-
1,1%-binaphthyl (BINAPO).7a
The diphenylphosphinyl group (PPh2) is an important
functional moiety in chiral ligands for catalytic asym-
metric reactions.1 The stereochemical influence is usu-
ally conferred from the backbone chirality to PPh2 by
inducing face–edge interactions between the two
phenyl groups.2 However, these interactions do not
always give the desired results. Ligand optimisation,
without altering the backbone structure, by introduc-
ing various substituents onto the phenyl rings (espe-
cially at the meta-positions) may perturb the original
face–edge interactions of the parent moiety to create
a more rigid chiral pocket and lead to interesting
and/or improved results. Reports in the literature
espouse this special ‘3,5-dialkyl meta effect’, for
instance, in asymmetric Heck reactions,3 hydrogena-
tions,3,4 hydrocyanations5 and hydroborations.6
In this study, we were interested in enhancing the
performance of the BINAPO ligand series in the
enantioselective hydrogenation of acetamidoacrylic
acids and esters by dual modulations in the binaph-
thylene structure and the diarylphosphinyl groups.
2. Results and discussion
2.1. Synthesis of ligands
The ligands (3 and 4) to be examined were synthe-
sised by reacting the chlorobis(3,5-dimethylphenyl)-
phosphine with (S)-BINOL or (S)-H8-BINOL in the
presence of catalytic amount of 4-N,N-dimethyl-
As a result of the steric and electronic modulation in
the H8-binaphthyl skeleton, some chiral ligands
derived from it exhibit higher efficiency and enan-
tioselectivity in asymmetric catalytic reactions than
those shown by their parent counterparts.7 For exam-
aminopyridine
and
dry
triethylamine
in
dichloromethane under a nitrogen atmosphere at 0°C
(Scheme 1). Chromatographic purifications afforded
the diphosphinites in analytically pure forms. Both
antipodal forms can be obtained via this method by
starting from the corresponding BINOL and H8-
BINOL.8
ple,
2,2%-bis(diphenylphosphinoyl)-5,5%,6,6%,7,7%,8,8%-
octahydro-1,1%-binaphthyl (H8-BINAPO) provided
greater enantioselectivities in the Rh-catalysed asym-
metric hydrogenation of amidoacrylic acids and esters
2.2. Rh-catalysed enantioselective hydrogenation
of prochiral acetamidoacrylic acids and esters
* Corresponding author. Tel.: 852-27665607; fax: 852-23649932;
e-mail: bcachan@polyu.edu.hk
The cationic rhodium catalysts (A: [Rh(S)-
3(COD)]BF4, B: [Rh(S)-4(COD)]BF4) were prepared
in situ by reacting the appropriate ligand with
† A University Grants Committee Areas of Excellence Scheme in
Hong Kong.
0957-4166/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0957-4166(02)00650-X

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R. Guo et al. / Tetrahedron: Asymmetry 13 (2002) 2519–2522
Scheme 1.
[Rh(COD)2]BF4 in dichloromethane at room tempera-
ture. Catalysts A and B were used in the asymmetric
hydrogenation of methyl acetamidocinnamate under
various conditions, and the results are summarised in
Table 1. In protic solvents such as methanol and etha-
nol (entries 1 and 2) both catalysts gave satisfactory
enantioselectivities. Further improvement was attained
on using dichloromethane as the reaction solvent (entry
4). Excellent enantioselectivities were observed at lower
temperatures (entries 5 and 6). A ten-fold reduction in
the amount of the catalyst did not affect the stereoselec-
tivity of the reaction (entry 4 versus entry 7) although
the time required for complete conversion had to be
extended. It is worth noting that for a given set of
conditions catalyst B always showed better enantiose-
lectivity over catalyst A. Thus, the incorporation of
bis(3,5-dimethylphenyl)phosphinyl groups in 3 and 4
outperformed their parent ligands by a substantial mar-
gin (entry 4).
under 50 psi H2 pressure, and the results are shown in
Table 2. It was discovered that electron-donating sub-
stituents had no influence on the enantioselectivity
(entries 2 and 3 versus 1) whilst the catalysts were
slightly less effective when the substrates contained
electron-withdrawing groups at the para-position
(entries 4–6). The sterically more hindered ortho-substi-
tuted substrate (entry 7) and a heteroaromatic substrate
(entry 8) could also be hydrogenated with comparable
enantioselectivities. Unsubstituted acetamidoacrylic
ester showed the best result (entry 9); however, the
corresponding acid gave somewhat lower enantioselec-
tivity. In all cases, catalyst B was again more effective
than catalyst A, giving further credence to the beneficial
effect of the 5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaphthyl
backbone. In addition, catalyst B was also found to
exceed the performance of its parent ligand (entries 3, 5
and 7–9).
The general applicability of catalysts A and B in the
hydrogenation of other (Z)-2-acetamido-3-aryl acrylic
esters and acids was also examined. The reactions were
carried out at room temperature in 10 min with a
substrate concentration of 0.25 M in dichloromethane
3. Conclusion
In summary, we have demonstrated that by simulta-
neously modifying the phosphinyl and binaphthalene
moieties of the parent BINAPO ligand, it is possible to
Table 1. The enantioselective hydrogenation of methyl acetamidocinnamate using catalysts A and Ba
Entry
Solvent
Substrate/cat.
Temp. (°C)
ee% with catalyst A
ee% with catalyst B
1
2
3
4
5
6
7c
Methanol
Ethanol
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
500
500
500
500
500
500
5000
rt
rt
rt
rt
83
85
87
89
88
89
92 (64)b
94
94 (84)b
96
0
−25
rt
94
92
97
94
a All reactions were performed at a substrate concentration of 0.25 M and under a hydrogen pressure of 50 psi and were completed within 10 min
unless otherwise stated. Over >99% conversion were noted in all cases. Enantioselectivities and conversions were determined by GC with a
CHROMPACK Chirasil-L-Val (25 m×0.25 mm) column. The S-product was obtained in all instances.
b Data in parentheses were obtained using corresponding catalysts with BINAPO and H8-BINAPO ligands, respectively, under otherwise identical
conditions.
c Quantitative yield was obtained within 30 min.

R. Guo et al. / Tetrahedron: Asymmetry 13 (2002) 2519–2522
2521
Table 2. The rhodium-catalysed enantioselective hydrogenation of dehydroamino acid derivatives using Xyl-BINAPO and
Xyl-H8-BINAPO as ligandsa
Entry
Substrate
Catalyst A, ee%
Catalyst B, ee%b
Product configuration
1
2
3
4
5
6
7
8
R=Me, R%=Ph
92
91
92
90
91
89
90
89
94
86
94
94
94 (84)
93
93 (81)
91
93 (85)
92 (64)
97 (81c)
90
S
S
S
S
S
S
S
S
S
S
R=Me, R%=4-MeO-Ph
R=Me, R%=4-Me-Ph
R=Me, R%=4-AcO-Ph
R=Me, R%=4-Cl-Ph
R=Me, R%=4-NO2-Ph
R=Me, R%=2-Cl-Ph
R=Me, R%=2-furanyl
R=Me, R%=H
9d
10e
R=H, R%=H
a Quantitative conversion was obtained within 10 min at ambient temperature in CH2Cl2. Sub./cat.=500, [sub.]=0.25 M. The enantioselectivities
and conversions were determined by GC with a CHROMPACK Chirasil-L-Val (25 m×0.25 mm) column. These conditions were applied in all
cases unless otherwise stated.
b Data in parentheses were obtained using corresponding catalysts with H8-BINAPO ligand.
c Only 49% conversion.
d The ee value and conversion were determined by GC with a CP-Chirasil-Dex (25 m×0.25 mm) column.
e Methanol was used as solvent for the reaction. The determination of ee and conversion was accomplished by transforming the acid product to
the corresponding methyl ester followed by GC analysis with a CP-Chirasil-Dex CB (25 m×0.25 mm) column.
improve greatly the enantioselective hydrogenation of
(Z)-acetamido-3-substituted acrylic esters. Continuing
efforts will be focused on the use of these new ligands
in reactions where BINAPO failed to work effectively
as a catalyst.
2,2%-dihydroxy-5,5%-6,6%7,7%,8,8%-octahydro-1,1%-binaph-
thyl (292 mg, 1.0 mmol) and 4-N,N%-dimethylaminopy-
ridine (15 mg, 0.1 mmol) in dichloromethane (30 ml) at
0°C. The reaction mixture was vigorously stirred for 3
h at the same temperature before removing the solvent
under reduced pressure. The residue was dissolved in
toluene (15 ml) and purified by flash column chro-
matography (silica gel, eluent: toluene) to afford the
title compound as white solids (645 mg, 85%): decomp.
temp. 213°C; [h]D20 −66.2 (c 1.25, CHCl3); 1H NMR
(CDCl3): l 1.52–1.68 (m, 8H), 2.21 (s, 12H), 2.19 (s,
12H), 2.14–2.23 (m, 2H), 2.38–2.42 (m, 2H), 2.60–2.64
(m, 2H), 2.69–2.75 (m, 2H). 13C NMR (CDCl3): l
21.39, 21.48, 23.22, 23.30, 27.80, 29.76, 115.28, 115.41,
127.36, 127.54, 127.65, 127.84, 129.09, 130.85, 131.01,
131.33, 137.03, 137.59, 142.11, 142.26. 31P NMR
(CDCl3): l 109.7. Anal. calcd for C52H56O2P2: C, 80.59;
H, 7.28; O, 4.13; P, 7.99. Found: C, 80.67; H, 7.22, O,
4.20; P, 7.89%.
4. Experimental
4.1. General
All experiments were carried out under a nitrogen
atmosphere using standard Schlenk techniques or in a
glovebox. Flash column chromatography was per-
formed on silica gel (Merck Kieselgel 60, particle size
0.032–0.063 mm). Hexane, toluene, tetrahydrofuran
and diethyl ether were distilled from sodium or sodium
benzophenone ketyl before use. Methanol and ethanol
were distilled from magnesium/iodine. Dichloro-
methane was distilled from CaH2. 1H, 31P and 13C
NMR were recorded on a Varian AS 500 at rt using
CDCl3 as solvent. Enantiomeric excesses were deter-
mined by gas chromatographic analyses conducted on a
HP 4890A or HP 5890 series II system. Bis(3,5-
dimethylphenyl)phosphine chloride was prepared
according to a literature procedure.4a
Spectral data of (R)-4 were identical to those of the
(S)-isomer but the former decomposes at 214°C and
shows an optical rotation of [h]2D0 +66.4 (c 1.38,
CHCl3).9
4.3. Typical procedures for the Rh-catalysed asymmet-
ric hydrogenation of amidoacrylic acids and esters
In a glovebox, [Rh(COD)2]BF4 (0.01 mmol), the phos-
phinite ligand (0.01 mmol) and dried CH2Cl2 (1 ml)
were placed in a 4 ml glass bottle and stirred at rt for
1 h to prepare a stock solution of the catalyst. In a
typical experiment, the catalyst solution (10 ml, 0.0001
mmol) was added in a 50 ml autoclave, which was
charged with the substrate (0.05 mmol) and solvent
(190 ml). The autoclave was purged with hydrogen gas
4.2. (S)- and (R)-2,2%-Bis[bis(3,5-dimethylphenyl)-
phosphinoyl]-5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaphthyl,
(S)-4 and (R)-4
Bis(3,5-dimethylphenyl)phosphine chloride (691 mg, 2.5
mmol) was added over a period of 20 min to a cooled
solution of dry triethylamine (0.8 ml, 6.1 mmol), (S)-

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R. Guo et al. / Tetrahedron: Asymmetry 13 (2002) 2519–2522
three times before finally being pressurised with 50 psi
H2. The mixture was stirred at rt for 10 min after which
the H2 was released. The enantiomeric excesses and
conversion were determined by GC analysis. The
hydrogenation product of acetamidoacrylic acid was
converted to its methyl ester before GC analysis with a
capillary chiral column (CHROMPACK CP Chirasil-
DEX CB, 25 m×0.25 mm column or CHROMPACK
Chirasil-L-Val, 25 m×0.25 mm column).
Pregosin, P. S.; Tschoerner, M. J. Am. Chem. Soc. 1997,
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G. A.; You, K. K.; Calabrese, J. C. J. Org. Chem. 1997,
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Acknowledgements
We thank The Hong Kong Research Grants Council
Central Allocation Fund (Project ERB003), The Uni-
versity Grants Committee Areas of Excellence Scheme
in Hong Kong (AoE P/10-01) and The Hong Kong
Polytechnic University ASD Fund for financial support
of this study.
5. (a) Casalnuovo, A. L.; RajanBabu, T. V.; Ayers, T. A.;
Warren, T. H. J. Am. Chem. Soc. 1994, 116, 9869–9882;
(b) RajanBabu, T. V.; Casalnuovo, A. L. J. Am. Chem.
Soc. 1996, 118, 6325–6326.
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