Molecular design of a C2-symmetric chiral phase-transfer catalyst for practical asymmetric synthesis of α-amino acids [12]

Full text of DOI:10.1021/ja991062w

J. Am. Chem. Soc. 1999, 121, 6519-6520
6519
We employed a binaphthyl structure as a basic chiral unit and
first synthesized C2-symmetric chiral quaternary ammonium salts
of type 3 from commercially available (S)-binaphthol in a six-
step sequence as shown in Scheme 1.8 Evaluation of the potential
of the catalyst in the asymmetric phase-transfer alkylation of 1
using 1 mol % of 3a, benzyl bromide (1.2 equiv), and 50%
aqueous KOH/toluene (volume ratio ) 1:3.25) at 0 °C for 6 h
resulted in a disappointingly small induction (21% ee) with 34%
yield of 2 (R ) CH2Ph). Changing the aryl group of the catalyst
to R-naphthyl (3b) brought only a slight increase of the enantio-
Molecular Design of a C2-Symmetric Chiral
Phase-Transfer Catalyst for Practical Asymmetric
Synthesis of r-Amino Acids
Takashi Ooi, Minoru Kameda, and Keiji Maruoka*
Department of Chemistry
Graduate School of Science, Hokkaido UniVersity
Sapporo 060-0810, Japan
ReceiVed April 5, 1999
Despite the increasing importance and usefulness of phase
transfer catalysis (PTC) in synthetic organic reactions,1 catalytic
asymmetric synthesis utilizing chiral phase-transfer catalysts
remains poorly studied.2-4 Yet, since the pioneering work of
O’Donnell et al. in 1989, asymmetric synthesis of R-amino acids
by phase-transfer enantioselective alkylation of a prochiral
protected glycine derivative 1 using a chiral catalyst has provided
an attractive method for the preparation of both natural and
unnatural amino acids.5 Recently, the Corey6 and Lygo groups7
independently reported an impressive departure from the previous
results in terms of enantioselectivity and general applicability.
However, almost all of the elaborated chiral phase-transfer
catalysts reported so far have been restricted to cinchona alkaloid
derivatives, which unfortunately constitutes a major difficulty in
rationally designing and fine-tuning catalysts to attain sufficient
reactivity and selectivity for various chemical transformations
under phase-transfer catalyzed conditions.3,4 In this paper, we wish
to describe a new, rational approach to this subject, i.e., the
molecular design of a C2-symmetric chiral quaternary ammonium
salt and its successful application to the highly efficient, catalytic
enantioselective alkylation of tert-butyl glycinate-benzophenone
Schiff base 1 under mild phase-transfer conditions.
meric excess (29% ee). These results prompted us to design
structurally more rigid chiral spiro ammonium salts of type 4
which can be readily assembled, also illustrated in Scheme 1.8 In
the presence of 1 mol % of 4a under otherwise similar reaction
conditions, the benzylation of 1 proceeded smoothly at 0 °C to
furnish product 2 (R ) CH2Ph) in 73% yield after 6 h and the
enantiomeric excess was dramatically improved (79% ee).
Noteworthy is the fact that the beneficial effect of 3,3′-bisaryl
substituents (R′) of the catalysts on the reactivity as well as on
the enantioselectivity was greatly appreciated in this case. For
instance, the benzylation of 1 under the influence of 4b (1 mol
%) was completed within 30 min at 0 °C, producing the alkylation
product 2 (R ) CH2Ph) in 81% yield, whose enantiomeric purity
was determined to be 89% ee. Use of 4c as catalyst further
increased the enantioselectivity to 96% ee (95% yield) for the
benzylation.
Table 1 summarizes the results obtained for the alkylation of
1 with various alkyl halides using 1 mol % of catalyst 4c.
Enantioselectivities observed herein generally exceeded 90% ee,
indicating the remarkable potential and generality of the present
asymmetric system. It should be noted that none of the double
alkylation products was obtained under the reaction conditions.
The use of 50% NaOH as an aqueous phase brought a decrease
of reactivity with similar enantioselectivity (52%, 95% ee for the
benzylation at 0 °C for 6 h).
(1) (a) Makosza, M.; Ludwikow, M. Rocz. Chem. 1965, 39, 1223. (b)
Makosza, M.; Serafinowa, B. Rocz. Chem. 1965, 39, 1401, 1595, 1647, 1799,
1805. (c) Makosza, M. Pure Appl. Chem. 1975, 43, 439. (d) Dehmlow, E.
V.; Dehmlow, S. S. Phase Transfer Catalysis, 3rd ed.; VCH: Weinheim, 1993.
(2) Dolling, U.-H.; Davis, P.; Grabowski, E. J. J. J. Am. Chem. Soc. 1984,
106, 446. (b) Hughes, D. L.; Dolling, U.-H.; Ryan, K. M.; Schoenewaldt, E.
F.; Grabowski, E. J. J. J. Org. Chem. 1987, 52, 4745.
(3) For reviews of chiral PTC, 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) Ebrahim, S.; Wills, M. Tetrahedron Asymmetry 1997, 8, 3163.
(4) Quite recently, Shioiri reported successful results for PTC-catalyzed
asymmetric reactions, see: (a) Arai, S.; Shioiri, T. Tetrahedron Lett. 1998,
39, 2145. (b) Arai, S.; Hamaguchi, S.; Shioiri, T. ibid. 1998, 39, 2997. (c)
Arai, S.; Tsuge, H.; Shioiri, T. ibid. 1998, 39, 7653. (d) Arai, S.; Shirai, Y.;
Ishida, T.; Shioiri, T. Chem. Commun. 1999, 49.
(5) O’Donnell, M. J.; Benett, W. D.; Wu, S. J. Am. Chem. Soc. 1989, 111,
2353. See also: (a) O’Donnell, M. J.; Wu, S.; Huffman, J. C. Tetrahedron
1994, 50, 4507. (b) Lipkowitz, K. B.; Cavanaugh, M. W.; Baker, B.;
O’Donnell, M. J. J. Org. Chem. 1991, 56, 5181. (c) O’Donnell, M. J.; Esikova,
I. A.; Mi, A.; Shullenberger, D. F.; Wu, S. In Phase-Transfer Catalysis;
Halpern, M. E., Ed.; ACS Symposium Series 659; American Chemical
Society: Washington, DC, 1997; Chapter 10.
(6) (a) Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc. 1997, 119,
12414. (b) Corey, E. J.; Noe, M. C.; Xu, F. Tetrahedron Lett. 1998, 39, 5347.
(c) Corey, E. J.; Bo, Y.; Busch-Petersen, J. J. Am. Chem. Soc. 1998, 120,
13000.
The primary structure of the parent chiral spiro quaternary
ammonium salt 4a was successfully verified by single-crystal
X-ray diffraction analysis as shown in Figure 1.9
On the basis of the experimental findings as well as X-ray
structure of the catalyst 4a, the transition state in the catalytic
enantioselective alkylation can be visualized as shown in Figure
2. The space-filling model of the catalyst 4c is derived from the
structure of 4a. The conformation of the E-enolate of tert-butyl
glycinate-benzophenone Schiff base 1 makes a good match for
the molecular pocket of the chiral catalyst 4c, and the si-face of
the enolate can be effectively shielded by the binaphthyl and the
â-naphthyl moieties. Consequently, alkyl halides could only
approach the re-face of the enolate, producing the R isomer 2 in
accord with the experimental finding.
In conclusion, we introduced a new axis by designing a phase
transfer catalyst based on the C2-symmetric chiral unit and
(8) For the spectroscopic characterization of the catalysts, see Supporting
Information.
(7) (a) Lygo, B.; Wainwright, P. G. Tetrahedron Lett. 1997, 38, 8595. (b)
Lygo, B.; Crosby, J.; Peterson, J. A. ibid. 1999, 40, 1385. (c) Lygo, B. ibid.
1999, 40, 1389. For a recent impressive application to PTC-catalyzed
asymmetric epoxidation, see: Lygo, B.; Wainwright, G. P. Tetrahedron Lett.
1998, 39, 1599.
(9) The single-crystal of 4a was obtained by recrystallization from
acetonitrile/dichloromethane solvents. Crystal structure data for 4a: C48H32N3-
Br, Mw ) 730.70, orthorhombic, space group I212121, a ) 14.6723(9) Å, b )
25.127(1) Å, c ) 10.8390(5) Å, V ) 3996.1(4) Å3, Z ) 4, Dcalcd ) 1.214
gcm-3, R1 ) 0.077.
10.1021/ja991062w CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/14/1999

6520 J. Am. Chem. Soc., Vol. 121, No. 27, 1999
Communications to the Editor
Scheme 1
b
c
a Tf2O, Et3N, CH2Cl2. MeMgI, NiCl2(PPh3)2, ether. NBS, benzoyl
peroxide, cyclohexane. dAllylamine, MeCN. eRhCl(PPh3)3, MeCN-H2O.
fK2CO3, MeOH. ArB(OH)2, Pd(OAc)2, PPh3, K3PO4, THF.
g
Table 1. Catalytic Enantioselective Phase-Transfer Alkylationa
Figure 1. ORTEP diagram of the catalyst 4a. The solvent molecules
(MeCN) and all hydrogen atoms are omitted for clarity.
Figure 2. The space-filling model of a plausible transition-state structure
of a chiral spiro ammonium E-enolate derived from 4c and 1.
of the catalyst should further enhance the reactivity and selectivity,
which obviously emphasizes the unequivocal advantage of our
approach for the development of new, yet practical phase-transfer
catalyzed enantioselective reaction systems.
a Unless otherwise specified, the reaction was carried out with 1.2
equiv of RX in the presence of 1 mol % of 4c in 50% aqueous KOH/
toluene (volume ratio ) 1:3.25) under the given reaction conditions.
bIsolated yield. cEnantiopurity of 2 was determined by HPLC analysis
of the alkylated imine using a chiral column [DAICEL Chiralcel OD
(entries 1-6, 8, and 9) and Chiralpak AD (entry 7)] with hexane-
isopropanol as solvent. dAbsolute configuration was determined by
comparison of the HPLC retention time with the authentic sample
independently synthesized by the reported procedure.5 eUse of 5 equiv
of alkyl halide.
Acknowledgment. We are grateful to Professor T. Inabe (Hokkaido
University) for the single-crystal X-ray analysis of the catalyst. This work
was partially supported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Science, Sports and Culture, Japan.
Supporting Information Available: Representative experimental
procedure as well as spectroscopic characterization of catalyst 4 and all
new compounds (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
demonstrated its potential in an application to asymmetric
synthesis of R-amino acids. Steric and/or electronic manipulation
JA991062W