Dynamic kinetic resolution catalyzed by Ir axially chiral phosphine catalyst: Asymmetric synthesis of anti aromatic β-hydroxy-α-amino acid esters

Article abstract of DOI:10.1021/ja0432113

The anti selective hydrogenation of α-amino-β-keto esters via dynamic kinetic resolution was achieved for the first time by using the iridium-MeOBIPHEP catalyst in asymmetric synthesis of anti aromatic β-hydroxy-α-amino acid esters with excellent diastereo- and enantioslectivities. Acetic acid as a solvent and sodium acetate as an additive affected dramatically the yield and the enantioselectivity, respectively. The product anti aromatic β-hydroxy-α-amino acid esters are useful for synthesis of pharmaceuticals and natural products. Copyright

Full text of DOI:10.1021/ja0432113

Published on Web 03/31/2005
Dynamic Kinetic Resolution Catalyzed by Ir Axially Chiral Phosphine
Catalyst: Asymmetric Synthesis of anti Aromatic â-Hydroxy-r-amino Acid
Esters
Kazuishi Makino, Yasuhiro Hiroki, and Yasumasa Hamada*
Graduate School of Pharmaceutical Sciences, Chiba UniVersity, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Received November 11, 2004; E-mail: hamada@p.chiba-u.ac.jp
Scheme 1. Ru-BINAP-Catalyzed anti Selective Hydrogenation
Dynamic kinetic resolution (DKR) is one of several powerful
tools for efficient synthesis of one enantiomer from racemic starting
materials without any loss.1 The ruthenium-catalyzed DKR in
combination with axially chiral phosphines was originally developed
by Noyori et al.2 for asymmetric synthesis of 2-substituted
â-hydroxyesters including syn-â-hydroxy-R-amino esters from
chirally labile 2-substituted â-keto esters.3 This epoch-making
methodology has attracted considerable attention in the organic
chemistry community and has been successfully applied to produc-
tion of â-lactam antibiotic intermediate.3a Recently, we have
demonstrated4 for the first time that R-amino-â-keto ester hydro-
chlorides have been directly hydrogenated in an anti selective
manner through DKR with the Ru-BINAP catalyst to produce anti-
â-hydroxy-R-amino esters with high diastereo- and enantioselec-
tivities.5 This method has revealed that alkyl substrates are the most
suitable for the hydrogenation; however, aromatic substrates are
poor for the enantioselectivity (Scheme 1). The anti aromatic
â-hydroxy-R-amino acids are of importance and are incorporated
into the backbone of a wide range of antibiotics and cyclopeptides
such as vancomycins and papuamides. Therefore, stereoselective
synthesis of the anti aromatic â-hydroxy-R-amino acids still remains
a formidable challenge.6 Herein we describe the first successful
dynamic kinetic resolution catalyzed by in situ generated Ir axially
chiral phosphine catalyst in asymmetric synthesis of anti aromatic
â-hydroxy-R-amino esters from the corresponding R-amino-â-keto
esters.
Table 1. Optimization of Asymmetric Hydrogenation Using Ir
Catalysta
Initially, we briefly surveyed transition metals for the hydrogena-
tion of the R-amino-â-keto ester, as shown in Table 1. Interestingly,
in addition to the known ruthenium catalyst, the rhodium and
iridium catalysts also underwent highly anti selective hydrogenation
but with low enantioselectivities (entries 1-3). However, we were
pleased to find for the first time that the iridium complex derived
from [Ir(cod)Cl]2 and BINAP is a promising catalyst for DKR in
asymmetric hydrogenation of R-amino-â-keto ester (entry 3). The
procedure for preparation of the catalyst was critical for its catalytic
activities. The most active catalyst was made prior to hydrogenation
by mixing the iridium complex with BINAP in methylene chloride
at 23 °C for 10 min (entries 3 and 4). Acetic acid was the solvent
of choice for the diastereoselectivity (entry 5). The presence of
sodium acetate affected the enantioselectivity dramatically (entry
6). Next, we examined the ability of several chiral phosphines.
Among them, MeOBIPHEP was most efficient for the enantiose-
lectivity (entry 7). Moreover, the addition of an iodide anion source,7
especially sodium iodide, led to maximized enantioselectivity
(entries 8 and 9). The absolute stereochemistry of the thus-obtained
amino acid was unambiguously determined as the known N-acetyl
derivative.8
a The reaction was carried out by using Ir-(S)-BINAP (prepared from
[IrCl(cod)]2 and BINAP prior to the hydrogenation) additive(s) in solvent.
b RuCl2[(S)-binap](dmf)n was used instead of Ir-(S)-BINAP. c The catalyst
derived from [Rh(cod)Cl]2 and (S)-BINAP and 50 atm of hydrogen was
used instead of Ir-(S)-BINAP and 100 atm of hydrogen. d 50 atm of
hydrogen was used. e The in situ generated catalyst from [IrCl(cod)]2 and
(S)-BINAP in the hydrogenation was used. f Not determined. g (S)-MeO-
BIPHEP was used as a chiral ligand instead of (S)-BINAP.
easily prepared by the known methods.4,9,10 The anti selective
hydrogenation via dynamic kinetic resolution using 3 mol % of
the Ir-(S)-MeOBIPHEP catalyst proceeded with almost complete
diastereoselectivities under 100 atm of hydrogen in the presence
of sodium acetate (1 equiv) and sodium iodide (0.06 equiv) in acetic
acid at 27-30 °C to afford the anti aromatic â-hydroxy-R-amino
esters with high enantioselectivities in excellent yields. The products
were protected without purification as the N-benzolyl derivatives
for their isolation and HPLC analysis. The diastereoselection in
this reaction was surprisingly high despite the substituent on the
aromatic nucleus, and the 1H NMR analysis of the crude products
revealed almost no presence of the syn-â-hydroxy-R-amino esters.
The halogeno substrates are compatible under the hydrogenation
This method was then applied to various aromatic substrates to
clarify the generality of the hydrogenation, and the results are shown
in Table 2. The starting R-amino-â-keto ester hydrochlorides were
9
5784
J. AM. CHEM. SOC. 2005, 127, 5784-5785
10.1021/ja0432113 CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Asymmetric anti Selective Hydrogenationa
In conclusion, we have developed an efficient asymmetric
synthesis of anti aromatic â-hydroxy-R-amino acid esters from the
readily available R-amino-â-keto esters using the Ir-MeOBIPHEP
catalyst for the first time. Our hydrogenation is the first example
of dynamic kinetic resolution using the Ir axially chiral phosphine
catalyst and can be carried out in an environmentally friendly
solvent using commercially available chiral phosphines. The product
anti aromatic â-hydroxy-R-amino acids are useful as building blocks
for the synthesis of various pharmaceuticals and natural products.
Further studies on the mechanism and the expansion of the scope
and applicability are now in progress.
Acknowledgment. Dedicated with great appreciation to Profes-
sor Takayuki Shioiri of Meijo University on the occasion of his
70th birthday (Koki).
Supporting Information Available: Experimental procedures and
spectral data for all new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
References
(1) For reviews on dynamic kinetic resolution, see: (a) Noyori, R.; Tokunaga,
M.; Kitamura, M. Bull. Chem. Soc. Jpn. 1995, 68, 36-56. (b) Ward, R.
S. Tetrahedron: Asymmetry 1995, 6, 1475-1490. (c) Ohkuma, T.;
Kitamura, M.; Noyori, R. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; pp 1-110. (d) Pellissier,
H. Tetrahedron 2003, 59, 8291-8327.
(2) Noyori, R.; Ikeda, T.; Ohkuma, T.; Widhalm, M.; Kitamura, M.; Takaya,
H.; Akutagawa, S.; Sayo, N.; Saito, T.; Taketomi, T.; Kumobayashi, H.
J. Am. Chem. Soc. 1989, 111, 9134-9135.
(3) (a) Mashima, K.; Matsumura, Y.; Kusano, K.; Kumobayashi, H.; Sayo,
N.; Hori, Y.; Ishizaki, T.; Akutagawa, S.; Takaya, H. J. Chem. Soc., Chem.
Commun. 1991, 609. (b) Geneˆt, J.-P.; Pinel, C.; Mallart, S.; Juge, S.;
Thorimbert, S.; Laffitte, J. A. Tetrahedron: Asymmetry 1991, 2, 555-
567. (c) Kitamura, M.; Tokunaga, M.; Noyori, R. J. Am. Chem. Soc. 1993,
115, 144-152. (d) Mashima, K.; Kusano, K.; Sato, N.; Matsumura, Y.;
Nozaki, K.; Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.; Akutagawa,
S.; Takaya, H. J. Org. Chem. 1994, 59, 3064-3076. (e) Geneˆt, J.-P.; de
Andrade, M. C. C.; Ratovelomanana-Vidal, V. Tetrahedron Lett. 1995,
36, 2063-2066. (f) Coulon, E.; de Andrade, M. C. C.; Ratovelomanana-
Vidal, V.; Geneˆt, J.-P. Tetrahedron Lett. 1998, 39, 6467-6470. (g)
Makino, K.; Okamoto, N.; Hara, O.; Hamada, Y. Tetrahedron: Asymmetry
2001, 12, 1757-1762. (h) Mohar, B.; Valleix, A.; Desmurs, J.-R.; Felemez,
M.; Wagner, A.; Mioskowski, C. Chem. Commun. 2001, 2572-2573.
(4) Makino, K.; Goto, T.; Hiroki, Y.; Hamada, Y. Angew. Chem., Int. Ed.
2004, 43, 882-884.
(5) (a) Lei, A.; Wu, S.; He, M.; Zhang, X. J. Am. Chem. Soc. 2004, 126,
1626-1627. (b) Mordant, C.; Dunkelmann, P.; Ratovelomanana-Vidal,
V.; Geneˆt, J. P. Chem. Commun. 2004, 1296-1297. (c) Mordant, C.;
Dunkelmann, P.; Ratovelomanana-Vidal, V.; Geneˆt, J.-P. Eur. J. Org.
Chem. 2004, 3017-3026.
(6) (a) Ooi, T.; Kameda, M.; Taniguchi, M.; Maruoka, K. J. Am. Chem. Soc.
2004, 126, 9685-9694. (b) Thayumanavan, R.; Tanaka, F.; Barbas, C.
F., III. Org. Lett. 2004, 6, 3541-3544. (c) Kobayashi, J.; Nakamura, M.;
Mori, Y.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126,
9192-9193.
a The reaction was carried out by using Ir-(S)-MeOBIPHEP (prepared
from [IrCl(cod)]2 (0.015 equiv), (S)-MeOBIPHEP (0.04 equiv), and NaI
(0.06 equiv) prior to the hydrogenation) and NaOAc (1 equiv) in AcOH.
b (R)-MeOBIPHEP was used instead of (S)-MeOBIPHEP. c As the N-Boc
protected derivative. d (2R,3R)-Isomer was obtained.
conditions (entries 8 and 11). The heteroaromatic substrates are
also suitable for the hydrogenation (entries 9 and 10).
The method opens up a new efficient access to 3-methoxytyrosine
with anti stereochemistry, a stereochemically undefined component
of papuamides.11 For instance, O-methylation of the obtained
benzyloxyphenyl derivative (entry 3) using trimethyloxonium
tetrafluoroborate in the presence of Proton Sponge and subsequent
hydrolysis furnished (2R,3R)-3-methoxytyrosine, a building block
for papuamides, in good overall yield and excellent stereoselection.
As part of our study on the potential of the Ir-MeOBIPHEP
catalyst, we carried out asymmetric hydrogenation of â-keto ester,
R-amino acetophenone, and N-benzoyl R-amino-â-keto ester, which,
surprisingly, gave apparently different results, namely, no or low
conversion, no diastereoselectivity, and poor enantioselectivity,
compared to those of the Ru-catalyzed hydrogenation.12 This failure
suggests that the Ir-catalyzed hydrogenation might proceed with a
different mechanism from that of the Ru-catalyzed hydrogenation.
(7) (a) Spindler, F.; Pugin, B.; Blaser, H.-U. Angew. Chem., Int. Ed. 1990,
29, 558-559. (b) Morimoto, T.; Nakajima, N.; Achiwa, K. Chem. Pharm.
Bull. 1994, 42, 1951-1953. (c) Xiao, D.; Zhang, X. Angew. Chem., Int.
Ed. 2001, 40, 3425-3428.
(8) Chenevert, R.; Letourneau, M.; Thiboutot, S. Can. J. Chem. 1990, 68,
960-963.
(9) Hara, O.; Ito, M.; Hamada, Y. Tetrahedron Lett. 1998, 39, 5537-5540.
(10) Singh, J.; Gordon, T. D.; Earley, W. G.; Morgan, B. A. Tetrahedron Lett.
1993, 34, 211-214.
(11) Okamoto, N.; Hara, O.; Makino, K.; Hamada, Y. J. Org. Chem. 2002,
67, 9210-9215 and references therein.
(12) See the Supporting Information.
JA0432113
9
J. AM. CHEM. SOC. VOL. 127, NO. 16, 2005 5785