Development of a recyclable fluorous chiral phase-transfer catalyst: Application to the catalytic asymmetric synthesis of α-amino acids

Article abstract of DOI:10.1021/ol049724w

A recyclable fluorous chiral phase-transfer catalyst was synthesized and successfully applied for the catalytic asymmetric synthesis of both natural and unnatural α-amino acids. The reaction involves alkylation of a glycine derivative followed by extractive recovery of the chiral phase-transfer catalyst using fluorous solvent.

Full text of DOI:10.1021/ol049724w

ORGANIC
LETTERS
2004
Vol. 6, No. 9
1429-1431
Development of a Recyclable Fluorous
Chiral Phase-Transfer Catalyst:
Application to the Catalytic Asymmetric
Synthesis of r-Amino Acids
Seiji Shirakawa, Youhei Tanaka, and Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto UniVersity,
Kyoto 606-8502, Japan
maruoka@kuchem.kyoto-u.ac.jp
Received February 16, 2004
ABSTRACT
A recyclable fluorous chiral phase-transfer catalyst was synthesized and successfully applied for the catalytic asymmetric synthesis of both
natural and unnatural r-amino acids. The reaction involves alkylation of a glycine derivative followed by extractive recovery of the chiral
phase-transfer catalyst using fluorous solvent.
The development of chiral phase-transfer catalysts for the
synthesis of optically active natural and unnatural R-amino
acids by the enantioselective alkylation of prochiral protected
glycine derivatives is one of the recent exciting topics in
synthetic organic chemistry,1 and hence several efficient
catalysts for the system have been developed by our group2
and others.3 A further useful advance in the field of such
chiral phase-transfer catalysis would involve the design of
easily recyclable catalysts. Few examples of polymer-
supported chiral phase-transfer catalysts derived from cin-
chona alkaloid have been reported for this purpose;4 however,
unfortunately almost all of these systems seriously reduced
the enantioselection of the product compared with that of
nonsupported catalyst systems. In this context, we are
interested in the development of a fluorous chiral phase-
transfer catalyst as a recyclable catalyst, since fluorous phase
separation techniques for the recovery of fluorinated catalyst
have been found a most useful method in recently advanced
catalyst recovery techniques,5 and some fluorous chiral metal
catalysts for this method have been developed.6,7 Here we
wish to report the design and synthesis of easily recyclable
fluorous chiral phase-transfer catalyst and their successful
use in the asymmetric synthesis of R-amino acid derivatives
(Scheme 1). To the best of our knowledge, this is the first
example of a recyclable fluorous chiral phase-transfer
catalyst.
(1) For reviews, see: (a) O’Donnell, M. J. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; Verlag Chemie: New York, 1993; Chapter 8. (b)
Shioiri, T. In Handbook of Phase-Transfer Catalysis; Sasson, Y., Neumann,
R., Eds.; Blackie Academic & Professional: London, 1997; Chapter 14.
(c) O’Donnell, M. J. Phases-The Sachem Phase Transfer Catalysis ReView;
Sachem: Austin, TX, 1998; issue 4, p 5. (d) O’Donnell, M. J. Phases-
The Sachem Phase Transfer Catalysis ReView; Sachem: Austin, TX, 1999;
issue 5, p 5. (e) Shioiri, T.; Arai, S. In Stimulating Concepts in Chemistry;
Vogtle, F., Stoddart, J. F., Shibasaki, M., Eds.; Wiley-VCH: Weinheim,
2000; p 123. (f) O’Donnell, M. J. Aldrichim. Acta 2001, 34, 3. (g) Maruoka,
K.; Ooi, T. Chem. ReV. 2003, 103, 3013.
The design of the fluorous chiral phase-transfer catalyst
originated from a series of our recently developed binaphthyl-
modified spiro-type catalysts.2 We focused on the very
recently reported symmetrical 4,4′,6,6′-tetra-substituted
catalysts2n to prepare a highly fluorinated catalyst of type 1
10.1021/ol049724w CCC: $27.50 © 2004 American Chemical Society
Published on Web 04/03/2004

Scheme 1. Catalytic Asymmetric Synthesis of R-Amino Acids
Scheme 3. Recovery of Fluorous Catalyst 1 by Extraction
with FC-72
with high efficiency. For introduction of several fluoroalkyl
chains on the 4,4′,6,6′ positions of catalyst 1, we used
commercially available C8F17CH2CH2SiMe2Cl. The requisite
catalyst 1 can be prepared from the known (R)-4,4′6,6′-
tetrabromobinaphthol 48 as outlined in Scheme 2.
asymmetric alkylation of protected glycine derivative 2. For
example, treatment of 2 with benzyl bromide (1.2 equiv) and
50% aqueous KOH/toluene (1:3 v/v) under the influence of
3 mol % of 1 at 0 °C for 96 h resulted in formation of
phenylalanine derivative 3 (R ) CH2Ph) in 82% yield with
90% ee. In the 50% aqueous KOH/toluene biphasic system,
catalyst 1 becomes heterogeneous as a result of its low
solubility in toluene solvent.9 Nevertheless, 1 was found to
promote the alkylation efficiently and gave the alkylated
product 3 with high enantioselectivity.10 After the reaction,
catalyst 1 could be easily recovered by the simple extraction
with FC-7211 as a fluorous solvent (Scheme 3)12 and could
Scheme 2. Synthesis of Fluorous Chiral Phase-Transfer
Catalyst 1a
(2) (a) Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc. 1999, 121,
1, 6519. (b) Ooi, T.; Takeuchi, M.; Kameda, M.; Maruoka, K. J. Am. Chem.
Soc. 2000, 122, 5228. (c) Ooi, T,; Kameda, M.; Tannai, H.; Maruoka, K.
Tetrahedron Lett. 2000, 41, 8339. (d) Ooi, T.; Takeuchi, M.; Maruoka, K.
Synthesis 2001, 1716. (e) Maruoka, K. J. Fluorine Chem. 2001, 112, 95.
(f) Ooi, T.; Takeuchi, M.; Ohara, D.; Maruoka, K. Synlett 2001, 1185. (g)
Ooi, T.; Uematsu, Y.; Maruoka, K. AdV. Synth. Catal. 2002, 344, 288. (h)
Ooi, T.; Uematsu, Y.; Kameda, M.; Maruoka, K. Angew. Chem., Int. Ed.
2002, 41, 1551. (i) Ooi, T.; Taniguchi, M.; Kameda, M.; Maruoka, K.
Angew. Chem., Int. Ed. 2002, 41, 4542. (j) Ooi, T.; Tayama, E.; Maruoka,
K. Angew. Chem., Int. Ed. 2003, 42, 579. (k) Ooi, T.; Sakai, T.; Takeuchi,
M.; Tayama, E.; Maruoka, K. Angew. Chem., Int. Ed. 2003, 42, 5868. (l)
Ooi, T.; Kubota, Y.; Maruoka, K. Synlett 2003, 1931. (m) Ooi, T.; Kameda,
M.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 5139. (n) Hashimoto, T.;
Tanaka, Y.; Maruoka, K. Tetrahedron: Asymmetry 2003, 14, 1599. (o)
Hashimoto, T.; Maruoka, K. Tetrahedron Lett. 2003, 44, 3313. (p) Ooi, T.;
Uematsu, Y.; Maruoka, K. Tetrahedron Lett. 2004, 45, 1675.
(3) For representative examples, see: (a) O’Donnell, M. J.; Bennett, W.
D.; Wu, S. J. Am. Chem. Soc. 1989, 111, 2353. (b) Corey, E. J.; Xu, F.;
Noe, M. C. J. Am. Chem. Soc. 1997, 119, 12414. (c) Lygo, B.; Wainwright,
P. G. Tetrahedron Lett. 1997, 38, 8595. (d) Park, H.-g.; Jeong, B.-S.; Yoo,
M.-S.; Lee, J.-H.; Park, M.-k.; Lee, Y.-J.; Kim, M.-J.; Jew, S.-s. Angew.
Chem., Int. Ed. 2002, 41, 3036. (e) Kita, T.; Georgieva, A.; Hashimoto,
Y.; Nakata, T.; Nagasawa, K. Angew. Chem., Int. Ed. 2002, 41, 2832. (f)
Shibuguchi, T.; Fukuta, T.; Akachi, Y.; Sekine, A.; Oshima, T.; Shibasaki,
M. Tetrahedron Lett. 2002, 43, 9539. (g) Arai, S.; Tsuji, R.; Nisida, A.
Tetrahedron Lett. 2002, 43, 9535. (h) Jew, S.-s.; Yoo, M.-S.; Jeong, B.-S.;
Park, I. Y.; Park, H.-g. Org. Lett. 2002, 4, 4245. (i) Lygo, B.; Allbutt, B.;
James, S. R. Tetrahedron Lett. 2003, 44, 5629.
(4) (a) Zhengpu, Z.; Yongmer, W.; Zhen, W.; Hodge, P. React. Funct.
Polym. 1999, 41, 37. (b) Chinchilla, R.; Mazo´n, P.; Na´jera, C. Tetrahe-
dron: Asymmetry 2000, 11, 3277. (c) Thierry, B.; Plaquevent, J.-C.; Cahard,
D. Tetrahedron: Asymmetry 2001, 12, 983. (d) Thierry, B.; Perrard, T.;
Audouard, C.; Plaquevent, J.-C.; Cahard, D. Synthesis 2001, 1742. (e)
Danelli, T.; Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Tocco,
G. Tetrahedron: Asymmetry 2003, 14, 461. (f) Thierry, B.; Plaquevent,
J.-C.; Cahard, D. Tetrahedron: Asymmetry 2003, 14, 1671.
a Conditions: (a) MOMCl, NaH, THF, 0 °C to rt, 99%; (b) tBuLi,
THF, -78 °C, then C8F17CH2CH2SiMe2Cl, -78 °C to rt, 78%; (c)
TsOH, CH2Cl2/MeOH, 50 °C, 92%; (d) Tf2O, NEt3, CH2Cl2, 0 °C,
64%; (e) CO, Pd(OAc)2, DPPP, Pr2NEt, MeOH/DMSO, 100 °C,
15 atm, 80%; (f) LiAlH4, THF, 0 °C to rt, 95%; (g) CBr4, PPh3,
THF, 0 °C to rt, 95%; (h) 28% aq NH3, CH3CN, reflux, 90%.
i
(5) For reviews, see: (a) Horva´th, I. T. Acc. Chem. Res. 1998, 31, 641.
(b) Curran, D. P. Angew. Chem., Int. Ed. 1998, 37, 1175. (c) Wolf, E. d.;
Koten, E. d.; Deelman, B.-J. Chem. Soc. ReV. 1999, 28, 37. (d) Cavazzini,
M.; Montanari, F.; Pozzi, G.; Quici, S. J. Fluorine Chem. 1999, 94, 183.
(e) Fish, R. H. Chem. Eur. J. 1999, 5, 1677.
The chiral efficiency and reusability of the fluorinated
phase-transfer catalyst 1 was examined by carrying out
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Org. Lett., Vol. 6, No. 9, 2004

In conclusion, we have developed recyclable fluorous
chiral phase-transfer catalyst 1 and applied it to the catalytic
asymmetric synthesis of R-amino acids. Further application
of this catalyst to other asymmetric transformations is now
in progress.
Table 1. Chiral Efficiency and Reusability of Fluorous Chiral
Catalyst 1a
Acknowledgment. This work was supported by the Asahi
Glass Foundation and a Grant-in-Aid for Scientific Research
(13853003) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. S.S. thanks the Japan Society
for the Promotion of Science for Young Scientists for a
research fellowship.
Supporting Information Available: Experimental pro-
cedures and characterization for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL049724W
(6) (a) Pozzi, G.; Cinato, F.; Montanari, F.; Quici, S. Chem. Commun.
1998, 877. (b) Pozzi, G.; Cavazzini, M.; Cinato, F.; Montanari, F.; Quici,
S. Eur. J. Org. Chem. 1999, 1947. (c) Kleijn, H.; Rijnberg, E.; Jastrzebski,
J. T. B. H.; Koten, G. v. Org. Lett. 1999, 1, 853. (d) Tian, Y.; Chan, K. S.
Tetrahedron Lett. 2000, 41, 8813. (e) Nakamura, Y.; Takeuchi, S.; Ohgo,
Y.; Curran, D. P. Tetrahedron Lett. 2000, 41, 57. (f) Cavazzini, M.;
Manfredi, A.; Montanari, F.; Quici, S.; Pozzi, G. Chem. Commun. 2000,
2171. (g) Nakamura, Y.; Takeuchi, S.; Ohgo, Y.; Curran, D. P. Tetrahedron
2000, 56, 351. (h) Cavazzini, M.; Pozzi, G.; Quici, S.; Maillard, D.; Sinou,
D. Chem. Commun. 2001, 1220. (i) Nakamura, Y.; Takeuchi, S.; Okumura,
K.; Ohgo, Y. Tetrahedron 2001, 57, 5565. (j) Maillard, D.; Bayardon, J.;
Kurichiparambil, J. D.; Nguefack-Fournier, C.; Sinou, D. Tetrahedron:
Asymmetry 2002, 13, 1449. (k) Cavazzini, M.; Quici, S.; Pozzi, G.
Tetrahedron 2002, 58, 3943. (l) Tian, Y.; Yang, Q. C.; Mak, T. C. W.;
Chan, K. S. Tetrahedron 2002, 58, 3951. (m) Nakamura, Y.; Takeuchi, S.;
Okumura, K.; Ohgo, Y.; Curran, D. P. Tetrahedron 2002, 58, 3963. (n)
Maillard, D.; Pozzi, G.; Quici, S.; Sinou, D. Tetrahedron 2002, 58, 3971.
(7) Fluorous chiral base catalyst derived from cinchona alkaloid: Fache,
F.; Piva, O. Tetrahedron Lett. 2001, 42, 5655.
(8) Hu, Q.-S.; Pugh, V.; Sabat, M.; Pu, L. J. Org. Chem. 1999, 64, 7528.
(9) Catalyst 1 is soluble in CH2Cl2, CHCl3, Et2O, and perfluoro solvents
and less soluble in toluene, benzene, hexane, etc.
(10) The reaction in the toluene/50% aqueous KOH/FC-72 (as catalyst
phase) triphase system caused a slight decrease of the enantioselectivity in
the asymmetric alkylation of 2.
(11) FC-72 ) perfluorohexanes.
(12) In each run, >95% of the catalyst 1 was recovered by the fluorous
extraction.
a Unless otherwise specified, the reaction was carried out with 1.2 equiv
of alkyl halide (RX) in the presence of 3 mol % of 1 in 50% aq KOH/
toluene (v/v 1:3) at 0 °C under an argon atmosphere. b Isolated yield.
c Enatiopurity of 3 was determined by HPLC analysis of the alkylated imine
using a chiral column (DAICEL Chiralcel OD or OD-H) with hexane-2-
propanol as solvent. d Absolute configuration of 3 was determined by
comparison of the HPLC retention time with the authentic sample
independently prepared by the reported procedure.2m e Using the recovered
catalyst in entry 1. f Using the recovered catalyst in entry 2. g 10 equiv each
of RX and CsOH‚H2O (as a base), and R,R,R-trifluorotoluene (as a solvent)
were used, and the reaction was performed at -20 °C.
be utilized for the next run without any loss of reactivity
and selectivity (entries 1-3 in Table 1). Other selected
examples are also listed in Table 1. The chiral phase-transfer
catalysis of 1 found a broad scope, and good to high
asymmetric inductions were achieved with not only substi-
tuted benzyl bromides but also propargylic bromide (entries
4-6). In the reaction with a simple alkyl halide such as ethyl
iodide, excess alkyl halide and CsOH‚H2O were employed
to attain sufficient reactivity (entry 7).2m
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