The counterion effect in the phase-transfer catalyzed asymmetric synthesis of α-amino acids promoted by anthryl-derived dimeric Cinchona ammonium salts

Article abstract of DOI:10.1016/j.tetasy.2004.07.025

Dimeric ammonium salts derived from cinchonidine or cinchonine and a bridging (anthracen-9,10-yl)dimethyl moiety bearing different counter-anions are used as chiral phase-transfer catalysts in the asymmetric alkylation reaction of a benzophenone-imine ter

Full text of DOI:10.1016/j.tetasy.2004.07.025

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 2603–2607
The counterion effect in the phase-transfer catalyzed
asymmetric synthesis of a-amino acids promoted by anthryl-derived
dimeric Cinchona ammonium salts
*
Rafael Chinchilla, Patricia Maz o´ n, Carmen N a´ jera and Francisco J. Ortega
Departamento de Qu ı´ mica Org a´ nica and Instituto de S ı´ ntesis Org a´ nica (ISO), Universidad de Alicante,
Apdo 99, 03080 Alicante, Spain
Received 13July 2004; accepted 16 July 2004
Available online 21 August 2004
Dedicated to the memory of Dr. Juan C. del Amo
Abstract—Dimeric ammonium salts derived from cinchonidine or cinchonine and a bridging (anthracen-9,10-yl)dimethyl moiety
bearing different counter-anions are used as chiral phase-transfer catalysts in the asymmetric alkylation reaction of a benzophen-
one-imine tert-butyl glycinate. The counterion generally has a great influence on the final enantioselectivity, the tetrafluoroborate
or hexafluorophosphate anion giving place to higher eeÕs compared to the chloride or bromide anions. The more noticeable differ-
ences are generally observed when the hexafluorophosphate salts of O-allylated dimeric catalysts are employed.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
Cl-
X-
Optically active a-amino acids are well-known interest-
ing compounds, their synthesis being an important syn-
thetic challenge, which has boosted the development of
N
N
+
+
OH
OR
1
many methodologies. Amongst all of them, the phase-
2
transfer catalysis (PTC) applied to the asymmetric alkyl-
N
N
1
r
ation of glycine and alanine Schiff bases is probably
the most simple and easy to scale-up. Thus, the enantio-
selective alkylation of amino acid imines under PTC
conditions catalyzed by quaternized Cinchona alka-
1
2a, R = H, X = Cl
b, R = Allyl, X = Br
2
3
loids, such as the cinchonidine-derived ammonium salts
4
of the type 1 and 2, pioneered by OÕDonnell 1 and im-
proved by Lygo 2a and Corey 2b, has allowed high de-
The counter-anion present in these ammonium salts is
usually a halogenide, a logical consequence of the com-
mon use of a halogenated compound for the N-quater-
nization, this anion always being considered irrelevant.
However, in a recently reported synthesis of the tetra-
peptide aeruginosin 298-A, the influence of the coun-
ter-anion in an asymmetric PTC alkylation reaction of
tert-butyl N-(diphenylmethylene)glycinate using
homochiral two-center tartrate-derived bis-ammonium
salt was observed. Thus, by changing the iodide counter-
anion to a tetrafluoroborate, the enantioselectivity was
improved from 74% to 81% ee, this effect being the first
example of such an influence in PTC reactions. In-
spired by this observation, we decided to study the coun-
terion effect in the asymmetric PTC alkylation reaction
5
6
grees of enantioselection using a very simple procedure
8
7
to be obtained. In addition, dimeric, trimeric, dendri-
9
meric Cinchona alkaloid-derived catalysts, and even
polymer-supported Cinchona-derived species have been
16
1
0
employed. Moreover, catalysts such as spiro ammo-
1
1
12
13a,b
nium and phosphonium salts, TADDOL
and
13e
guanidinium salts,
a
1
3c,d
other tartaric derivatives,
1
3b,14
binaphthyl-derived amines
1
plexes have also been used.
and salen–metal com-
13c
5
1
6
*
Corresponding author. Tel.: +34-96-5903728; fax: +34-96-
903549; e-mail: cnajera@ua.es
5
0
957-4166/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.07.025

2604
R. Chinchilla et al. / Tetrahedron: Asymmetry 15 (2004) 2603–2607
of iminic glycine esters when using our previously pre-
pared dimeric cinchonidinium and cinchoninium salts
mers of their cinchonidine counterparts, and hence being
4
a simple way of achieving an opposite enantioselection,
f
7
c
3
a and 4a, respectively. This type of ammonium salt
the cinchonine-derived series 4 was also prepared fol-
lowing the same methodology described in Scheme 1.
Thus, starting from chloride 4a, obtained from cincho-
has shown good eeÕs combined with the possibility of
catalyst recovering by simple precipitation. An improve-
ment in the enantioselectivity of the chiral PTC catalysts
achieved by just changing their accompanying counter-
ion would be more simple and straightforward than by
modifying their structural features.
7
c
nine similarly to 3a, the corresponding tetrafluorobo-
rate 4b and hexafluorophosphate 4c were obtained in
60% and 63% yield, respectively, whereas identical anion
exchange from the O-allylated bromide 4d gave place to
the corresponding salts 4e and 4f in 68% and 76% yield,
respectively. These anion exchanges were also confirmed
by IR spectroscopy.
2
. Results and discussion
Attending to different counter-anions for these types of
salts, the tetrafluoroborate and hexafluorophosphate
where considered promising, as they could form less
tight ionic pairs than chloride or bromide, thus allowing
a more easy and rapid complexation of the chiral ammo-
nium cation with the glycine-derived enolate, therefore
driving to a higher enantioselection. Thus, dimeric chlo-
ride salt 3a was obtained by the reaction of 9,10-di(chloro-
2
X-
N
+
RO
N+
N
OR
N
7
c
methyl)anthracene with cinchonidine as described, and
the chloride anion exchanged by the tetrafluoroborate
and the hexafluorophosphate anions after the reaction
of 3a with 2.5equiv of either sodium tetrafluoroborate
or potassium hexafluorophosphate, respectively, in
acetonitrile as the solvent for 1day at room temperature.
After the addition of ether and filtration, the resulting
solids were washed with water and dried to give the
corresponding salts 3b and 3c in 62% and 86% yield,
respectively (Scheme 1). Similarly were prepared the O(9)-
allylated tetrafluoroborate and hexafluorophosphate
cinchonidine-derived salts 3e and 3f in 50% and 61%
yield, respectively, now starting from the O-allylated di-
4
a, R = H, X = Cl
b, R = H, X = BF4
c, R = H, X = PF6
4d, R = Allyl, X = Br
4e, R = Allyl, X = BF4
4f, R = Allyl, X = PF6
4
4
These dimeric ammonium salts bearing different counter-
anions were employed as chiral PTC catalysts (5mol%)
in the model benzylation reaction of tert-butyl N-(diphe-
nylmethylene)glycinate 5 to give compound 6a (Table 1).
The aqueous base selected for these PTC reactions was
50% KOH whereas the solvent employed was a mixture
of toluene/chloroform (7/3v/v), these reaction conditions
were previously found as more appropriate when work-
7
c
ing with these dimeric PTC catalysts. The enantioselec-
tivity of the reaction was measured by chiral GLC
7
c
meric bromide 3d. These new tetrafluoroborates 3b
and 3e and hexafluorophosphates 3c and 3f showed
identical H and C NMR spectra than the correspond-
1
7
analysis of the corresponding N-trifluoroacetamide es-
18
1
13
ters from 6a, whereas the absolute configuration was
determined by the sign of the specific rotation of the
7
c
ing parent chloride 3a or bromide 3d. However, their
infrared spectra revealed new strong absorption bands
at 1066 cm for 3b and 3e and 842 cm for 3c and
phenylalanine, obtained by hydrolysis of 6a under reflux-
19
ꢀ
1
ꢀ1
ing 6M HCl and treatment with propylene oxide. The
catalysts could be recovered by precipitation with ether
ꢀ1
3
f cm , corresponding to the tetrafluoroborate and
hexafluorophosphate anions, respectively.
7
c
after the reaction.
Furthermore, by taking into account the consideration
of cinchonine-derived ammonium salts as pseudoenantio-
When the cinchonidine-derived OH-free chloride 3a was
employed as the PTC catalyst, the reaction showed a
Cl
2 X-
N
+
NaBF4
or KPF6
MeCN
N
OH
OR
+
N
3b, R = H, X = BF4
3c, R = H, X = PF
2
+
N
6
N
RO
Cl
N
3
a, R = H, X = Cl
Br
5
0% KOH
NaBF4 or KPF6
MeCN
3
e, R = Allyl, X = BF4
3
d, R = Allyl, X = Br
3f, R = Allyl, X = PF6
Scheme 1. Preparation of chiral dimeric PTC catalysts 3.

R. Chinchilla et al. / Tetrahedron: Asymmetry 15 (2004) 2603–2607
Table 1. Enantioselective PTC benzylation of 5
2605
Ph
N
CO2tBu
Ph
N
CO2tBu
Ph
N
CO2tBu
PhCH2Br, 4 (5 mol%)
PhCH2Br, 3 (5 mol%)
Ph
R)-6a
Ph
5
0% aq KOH
Ph
50% aq KOH
PhMe/CHCl3
Ph
Ph
PhMe/CHCl3
(
5
(S)-6a
a
b
Entry
Catalyst
R
Temp. (°C)
Time (h)
Yield (%)
S/R ratio
Ee (%)
No.
X
1
2
3
4
5
6
7
8
9
3a
3a
3a
3b
3b
3c
3c
3d
3d
3e
3e
3f
H
Cl
Cl
Cl
25
0
395
87/1 73 4
H
6
12
88
75
87
87
80
93/7
93/7
91/9
94/6
89/11
86
86
82
88
78
H
ꢀ20
25
0
H
BF
BF
4
2
20
H
4
H
PF
PF
Br
6
25
0
2
16 /7
H
6
639386
98
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
Allyl
H
25
0
1
1
80/20
85/15
87/1374
91/9
91/9
84
60
70
Br
84
94
10
11
12
13
14
15
16
17
18
19
20
21
BF
BF
4
25
0
2
4
5
78
91
82
82
PF
PF
PF
PF
Cl
6
6
6
6
25
0
2
3f
362
5
92/8
3f
ꢀ20
ꢀ50
0
98
76
93/7
96/4
82
86
92
3f
48
376
379
4
4a
4b
4c
4d
4e
4f
9/91
8/92
H
BF
4
0
84
H
PF
Br
6
0
80
85
90
10/90
14/86
19/81
88
80
72
62
Allyl
Allyl
Allyl
0
4
BF
PF
4
0
8
391
6
0
6/94
a
1
Crude yield determined by H NMR (300MHz).
b
Determined by chiral GLC from the corresponding trifluoroacetamides (see text).
higher ee of the benzylated product (S)-6a when the
reaction temperature was lowered from 25 to 0°C (Table
15), although with longer reaction times, especially in
the second case.
7c
1
, entries 1 and 2). No increment in the ee was ob-
served when the reaction was performed at ꢀ20°C
When the pseudoenantiomeric cinchonine-derived salts 4
were used as PTC catalysts in the benzylation reaction,
the expected enantiomer (R)-6 was obtained. In accord-
ance with the previous results, the reaction was now per-
formed at 0°C, a temperature, which combined good
enantioselectivities and yields with not very long reac-
tion times. Almost no effect in the ee was achieved by
changing the counter-anion when the OH-free cincho-
nine-derived system was used, with catalysts 4a–c giving
similar results (Table 1, compare entries 16–18). How-
ever, the O-allylated counterpart shown a counter-anion
influence, and up to 88% ee was reached when using the
hexafluorophosphate catalyst 4f, compared to the 72%
ee obtained when bromide 4d was employed (Table 1,
entries 19 and 21), whereas only a 62% ee was achieved
using tetrafluoroborate 4e (Table 1, entry 20).
(
Table 1, entry 3). When the reaction was carried out
using the corresponding tetrafluoroborate 3b at 25°C,
the enantioselectivity increased to 82% ee compared to
the result obtained employing 3a (74% ee) (Table 1, en-
try 4). Furthermore, only a small difference in ee was ob-
served when working at 0°C (Table 1, compare entries 2
and 5). The improvement in the enantioselectivity of the
catalyst was less noticeable when using the OH-free
cinchonidine-derived hexafluorophosphate 3c when
compared to 3a (Table 1, compare entries 1 and 2 with
entries 6 and 7).
When the O-allylated cinchonidine-derived bromide cat-
alyst 3d was employed at 25 and 0°C, the resulting eeÕs
were modest (60% and 70%, respectively) (Table 1, en-
7
c
tries 8 and 9).
In order to determine the extension of this counterion
effect, we performed the alkylation of 5 with the cincho-
nidine-derived salts 3d and 3f as PTC catalysts although
now using other activated electrophiles such as allyl bro-
mide and tert-butyl bromoacetate, as well as a nonacti-
vated electrophile such as n-butyl iodide, at 0°C (Table
2). We compared the behavior of these precise dimeric
salts because the counterion effect seemed to be more
remarkable when using O-allylated dimeric species (see
above). In general, hexafluorophosphate salt 4f gave
However, in this case the counter-anion effect was con-
siderable, and the analogous tetrafluoroborate 3e gave
ee values of 74% and 82% working at these temperatures
(
Table 1, entries 10 and 11). These differences compared
to 3d were even higher when the hexafluorophosphate 3f
was employed (82% ee at 25°C and 84% ee at 0°C)
(
Table 1, entries 12 and 13). Using 3f at lower reaction
temperatures such as ꢀ20°C or even ꢀ50°C gave place
to higher enantioselectivities (Table 1, entries 14 and

2606
R. Chinchilla et al. / Tetrahedron: Asymmetry 15 (2004) 2603–2607
Table 2. Enantioselective PTC alkylations with O-allylated catalysts
RHal
3 or 4 (5 mol%)
Ph
N
CO2tBu
Ph
N
2
CO tBu
*
R
6
5
0% aq KOH
Ph
Ph
PhMe/CHCl3, 0 ºC
5
Entry
Catatyst
RHal
Time (h)
Product
a
Yield (%)
b
No.
X
No.
S/R ratio
Ee (%)
1
2
3
4
5
6
7
8
9
3d
3e
3f
Br
BF
CH
CH
CH
2
2
2
@CHCH
@CHCH
@CHCH
2
2
2
Br
Br
Br
8
8
(S)-6b
(S)-6b
S)-6b
(S)-6c
(S)-6c
(S)-6c
(S)-6d
S)-6d
S)-6d
98
96
90/10
89/11
95/5
80
78
90
44
4
PF
Br
6
3(
24
24
36
46
70
54
3d
3e
3f
BrCH
BrCH
BrCH
2
2
2
CO
CO
CO
2
2
2
tBu
tBu
tBu
72/28
87/1374
93/7
BF
4
56
PF
Br
6
67
72
86
64
3d
3e
3f
CH
CH
CH
CH
CH
CH
3
3
3
2
2
2
CH
CH
CH
2
2
2
CH
CH
CH
2
2
2
CH
CH
CH
2
I
2
I
2
I
82/18
84
93/7
BF
4
3
3
5
0
(
(
8392/8
72
PF
Br
6
86
70
10
11
12
4d
4e
4f
@CHCH
@CHCH
@CHCH
2
2
2
Br
Br
Br
8
8
6
(R)-6b
(R)/ -86 7b
(R)-6b
97
931374
74
15/85
BF
4
PF
6
7/9386
a
1
Crude yield determined by H NMR (300MHz).
b
Determined by chiral GLC from the corresponding trifluoroacetamides (see text).
place to higher enantioselectivities. Thus, when the alkyl-
ation of 5 was carried out with allyl bromide using the
O-allylated bromide 3d as catalyst, an 80% ee was ob-
tained of the corresponding (S)-6b (Table 2, entry 1),
with this value remaining very similar when the corre-
sponding tetrafluoroborate 3e was used (Table 2, entry
Although the effect of changing the anion could be very
small, it seems worthwhile to investigate it when new
chiral quaternary ammonium salts are prepared, even
before of thinking in a modification of the catalyst struc-
ture. The improvement in enantioselectivities can be
very rewarding after performing such
transformation.
a simple
2
). However, when using hexafluorophosphate 3f an in-
creased ee of 90% was achieved in a lower reaction time
Table 2, entry 3). In addition, a remarkable increment
(
in the enantioselectivity to compound (S)-6c was ob-
served when catalyst 3d was changed by 3e or especially
by 3f in the case of using tert-butyl bromoacetate as
electrophile (Table 2, compare entry 4 with entries 5
and 6). When the alkylation of 5 was performed with
an unactivated electrophile such as n-butyl iodide, the
achieved ee of (S)-6d was considerably higher in shorter
reaction times when using 3e or 3f as catalysts when
compared to using bromide 3d (Table 2, compare entry
Acknowledgements
We thank the Spanish Ministerio de Ciencia y Tec-
nolog ´ı a (BQU2001-0724-C02-01), the Generalitat Val-
enciana (CTIDIB/2002/320) and the Universidad de
Alicante for financial support. F.J.O. thanks the Univer-
sidad de Alicante for a grant.
7
with entries 8 and 9). As expected, the O-allylated
References
cinchonine-derived bromide 4d gave the corresponding
enantiomer (R)-6b in 70% ee when using allyl bromide
as the electrophile (Table 2, entry 10), a slight increment
in the enantioselectivity being achieved when using their
tetrafluoroborate 4e (74% ee) (Table 2, entry 11)
whereas the use of the hexafluorophosphate 4f produced
a much higher ee value (86%) (Table 2, entry 12).
1
. (a) Williams, R. M. Synthesis of Optically Active Amino
Acids; Pergamon: Oxford, 1989; (b) Stammer, C. H.
Tetrahedron 1990, 46, 2231–2254; (c) Heimgartner, H.
Angew. Chem., Int. Ed. Engl. 1991, 30, 238–264; (d)
Williams, R. M.; Hendrix, J. A. Chem. Rev. 1992, 92,
889–917; (e) Duthaler, R. O. Tetrahedron 1994, 50,
1
540–1650; (f) Burgess, K.; Ho, K.-K.; Mye-Sherman,
D. Synlett 1994, 575–583; (g) Bailey, P. D.; Clayson, J.;
Boa, A. N. Contemp. Org. Synth. 1995, 173–187; (h)
North, M. Contemp. Org. Synth. 1996, 323–343; (i) Studer,
A. Synthesis 1996, 793–815; (j) Seebach, D.; Sting, A. R.;
Hoffmann, M. Angew. Chem., Int. Ed. 1996, 35,
3
. Conclusion
It can be concluded that the counterion accompanying
anthryl-derived Cinchona ammonium salts employed as
chiral PTC catalysts, can play an important role in the
enantioselectivity of the alkylation reaction of glycinate
imines. This effect of giving better eeÕs has been observed
more noticeably in the case of using O-allylated dimeric
catalysts carrying a hexafluorophosphate counter-anion.
2
3
708–2748; (k) Wirth, T. Angew. Chem., Int. Ed. 1997,
6, 225–227; (l) Cativiela, C.; D ´ı az-de-Villegas, M. D.
Tetrahedron: Asymmetry 1998, 9, 3517–3599; (m) Cativi-
ela, C.; D ´ı az-de-Villegas, M. D. Tetrahedron: Asymmetry
2000, 11, 645–732; (n) Abell a´ n, T.; Chinchilla, R.;
Galindo, N.; Guillena, G.; N a´ jera, C.; Sansano, J. M.

R. Chinchilla et al. / Tetrahedron: Asymmetry 15 (2004) 2603–2607
2607
Eur. J. Org. Chem. 2000, 2689–2697; (o) N a´ jera, C. Synlett
002, 1388–1403.
Tetrahedron: Asymmetry 2001, 12, 983–986; (e) Thierry,
B.; Perrard, T.; Audouard, C.; Plaquevent, J.-C.; Cahard,
D. Synthesis 2001, 1742–1746; (f) Thierry, B.; Plaquevent,
J.-C.; Cahard, D. Tetrahedron: Asymmetry 2003, 14,
1671–1677; (g) Danelli, T.; Annunziata, R.; Benaglia,
M.; Cinquini, M.; Cozzi, F.; Tocco, G. Tetrahedron:
Asymmetry 2003, 14, 461–467; (h) Chinchilla, R.; Maz o´ n,
P.; N a´ jera, C. Molecules 2004, 9, 349–364; (i) Chinchilla,
R.; Maz o´ n, P.; N a´ jera, C. Adv. Synth. Catal., in press.
11. (a) Ooi, T.; Kameda, M.; Maruoka, K. J. Am. Chem. Soc.
1999, 121, 6519–6520; (b) Ooi, T.; Tayama, E.; Doda, K.;
Takeuchi, M.; Maruoka, K. Synlett 2000, 1500–1502; (c)
Ooi, T.; Takeuchi, M.; Kameda, M.; Maruoka, K. J. Am.
Chem. Soc. 2000, 122, 5228–5229; (d) Ooi, T.; Uematsu,
Y.; Maruoka, K. Adv. Synth. Catal. 2002, 344, 288–291;
(e) Ooi, T.; Uematsu, Y.; Maruoka, K. Tetrahedron Lett.
2004, 45, 1675–1678; (f) Jew, S.; Lee, Y.-J.; Lee, J.; Kang,
M. J.; Jeong, B.; Lee, J.-H.; Yoo, M.; Kim, M.; Choi, S.;
Ku, J.-M.; Park, H. Angew. Chem., Int. Ed. 2004, 43,
2382–2385.
2
2
. (a) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer
Catalysis, 3rd ed.; VCH: Weinheim, 1993; (b) Starks, C.
M.; Liotta, C. L.; Halpern, M. Phase-Transfer Catalysis;
Chapman & Hall: New York, 1994; (c) Handbook of
Phase-Transfer Catalysis; Sasson, Y., Neumann, R., Eds.;
Blackie Academic & Professional: London, 1997; (d)
Phase-Transfer Catalysis; Halpern, M. E., Ed.; ACS
Symposium Series 659; American Chemical Society:
Washington, DC, 1997; (e) Nelson, A. Angew. Chem.,
Int. Ed. 1999, 38, 1583–1585; (f) Makosza, M. Pure Appl.
Chem. 2000, 72, 1399–1403; (g) Maruoka, K.; Ooi, T.
Chem. Rev. 2003, 103, 3013–3028.
3
. For a review on synthetic uses of Cinchona alkaloids and
derivatives: Kacprzak, K.; Gawronski, J. Synthesis 2001,
9
61–998.
4
. (a) OÕDonnell, M. J.; Bennett, W. D.; Wu, S. J. Am. Chem.
Soc. 1989, 111, 2353–2355; (b) Lipkowitz, K. B.; Cava-
naugh, M. W.; Baker, B.; OÕDonnell, M. J. J. Org. Chem.
1
991, 56, 5181–5192; (c) OÕDonnell, M. J.; Wu, S.
12. (a) Manabe, K. Tetrahedron Lett. 1998, 39, 5807–5810; (b)
Manabe, K. Tetrahedron 1998, 54, 14456–14476.
Tetrahedron: Asymmetry 1992, 3, 591–594; (d) OÕDonnell,
M. J.; Wu, S.; Huffman, J. C. Tetrahedron 1994, 50,
13. (a) BelokonÕ, Y. N.; Kotchetkov, K. A.; Churkina, T. D.;
Ikonnikov, N. S.; Chesnokov, A. A.; Larionov, A. V.;
Parm a´ r, V. S.; Kumar, R.; Kagan, H. B. Tetrahedron:
Asymmetry 1998, 9, 851–857; (b) BelokonÕ, Y. N.;
Kotchetkov, K. A.; Churkina, T. D.; Ikonnikov, N. S.;
Chesnokov, A. A.; Larionov, A. V.; Singh, I.; Parm a´ r, V.
S.; Vyskocil, S.; Kagan, H. B. J. Org. Chem. 2000, 65,
7041–7048; (c) Shibuguchi, T.; Fukuta, Y.; Akachi, Y.;
Sekine, A.; Oshima, T.; Shibasaki, M. Tetrahedron Lett.
2002, 43, 9539–9543; (d) Arai, S.; Tsuji, R.; Nishida, A.
Tetrahedron Lett. 2002, 43, 9535–9537; (e) Kita, T.;
Georgieva, A.; Hashimoto, Y.; Nakata, T.; Nagasawa,
K. Angew. Chem., Int. Ed. 2002, 41, 2832–2834.
14. (a) BelokonÕ, Y. N.; Kotchetkov, K. A.; Churkina, T. D.;
Ikonnikov, N. S.; Vyskocil, S.; Kagan, H. B. Tetrahedron:
Asymmetry 1999, 10, 1723–1728; (b) BelokonÕ, Y. N.;
Kotchetkov, K. A.; Churkina, T. D.; Ikonnikov, N. S.;
Larionov, O. V.; Harutyunyan, S. R.; Vyskocil, S.; North,
M.; Kagan, H. B. Angew. Chem., Int. Ed. 2001, 40,
1948–1951; (c) Casas, J.; N a´ jera, C.; Sansano, J. M.;
Gonz a´ lez, J.; Sa a´ , J. M.; Vega, M. Tetrahedron: Asymme-
try 2001, 12, 699–702.
4
507–4518; (e) OÕDonnell, M. J.; Delgado, F.; Pottorf, R.
S. Tetrahedron 1999, 55, 6347–6362; (f) OÕDonnell, M. J.
Aldrichimica Acta 2001, 34, 3–15.
5
. (a) Lygo, B.; Wainwright, P. G. Tetrahedron Lett. 1997,
3
8, 8595–8598; (b) Lygo, B.; Crosby, J.; Peterson, J. A.
Tetrahedron Lett. 1999, 40, 1385–1388; (c) Lygo, B.
Tetrahedron Lett. 1999, 40, 1389–1392; (d) Lygo, B.;
Crosby, J.; Peterson, J. A. Tetrahedron Lett. 1999, 40,
8
671–8674; (e) Lygo, B.; Crosby, J.; Lowdon, T. R.;
Peterson, J. A.; Wainwright, P. G. Tetrahedron 2001, 57,
403–2409; (f) Lygo, B.; Andrews, B. I.; Crosby, J.;
2
Peterson, J. A. Tetrahedron Lett. 2002, 43, 8015–8018; (g)
Lygo, B.; Allbutt, B. Synlett 2004, 326–328.
. (a) Corey, E. J.; Xu, F.; Noe, M. C. J. Am. Chem. Soc.
6
1
997, 119, 12414–12415; (b) Corey, E. J.; Noe, M. C.; Xu,
F. Tetrahedron Lett. 1998, 39, 5347–5350; (c) Horikawa,
M.; Busch-Petersen, J.; Corey, E. J. Tetrahedron Lett.
1
999, 40, 3843–3846.
7
. (a) Jew, S.; Jeong, B.; Yoo, M.; Huh, H.; Park, H. Chem.
Commun. 2001, 1244–1245; (b) Park, H.; Jeong, B.; Yoo,
M.; Lee, J.; Park, M.; Lee, Y.; Kim, M.; Jew, S. Angew.
Chem. Int. Ed. 2002, 41, 3036–3038; (c) Chinchilla, R.;
Maz o´ n, P.; N a´ jera, C. Tetrahedron: Asymmetry 2002, 13,
15. (a) BelokonÕ, Y. N.; North, M.; Kublitski, V. S.;
Ikonnikov, N. S.; Krasik, P. E.; Maleev, V. L. Tetrahedron
Lett. 1999, 40, 6105–6108; (b) BelokonÕ, Y. N.; Davies, R.
G.; North, M. Tetrahedron Lett. 2000, 41, 7245–7248; (c)
BelokonÕ, Y. N.; Bhave, D.; DÕAddario, D.; Groaz, E.;
North, M.; Tagliazucca, V. Tetrahedron 2004, 60,
1849–1861.
9
27–931; (d) Park, H.; Jeong, B.; Yoo, M.; Lee, J.; Park,
B.; Kim, M.; Jew, S. Tetrahedron Lett. 2003, 44,
497–3500.
3
8
. Park, H.; Jeong, B.; Yoo, M.; Park, M.; Huh, H.; Jew, S.
Tetrahedron Lett. 2001, 42, 4645–4648.
9
. (a) Maz o´ n, P.; Chinchilla, R.; N a´ jera, C.; Guillena, G.;
Kreiter, R.; Klein Gebbink, R. J. M.; van Koten, G.
Tetrahedron: Asymmetry 2002, 13, 2181–2185; (b) Guil-
lena, G.; Kreiter, R.; van de Coevering, R.; Klein
Gebbink, R. J. M.; van Koten, G.; Maz o´ n, P.; Chinchilla,
R.; N a´ jera, C. Tetrahedron: Asymmetry 2003, 14,
16. Ohshima, T.; Gnanadesikan, V.; Shibuguchi, T.; Fukuta,
Y.; Nemoto, T.; Shibasaki, M. J. Am. Chem. Soc. 2003,
125, 11206–11207.
17. Chirasil-LVal (Chrompack). Reference racemic samples
were prepared using tetrabutylammonium bromide as
phase-transfer catalyst.
3
705–3712.
18. Obtained after 15% aq citric acid hydrolysis of the imine 6
and further reaction with trifluoroacetic anhydride
(Oppolzer, W.; Moretti, R.; Zhou, C. Helv. Chim. Acta
1994, 77, 2363–2380).20
1
0. (a) Yongmei, W.; Zhengpu, Z.; Zhen, W.; Jiben, M.;
Hodge, P. Chin. J. Polym. Sci. 1998, 16, 356–361; (b)
Zhengpu, Z.; Yongmei, W.; Zhen, W.; Hodge, P. React.
Funct. Polym. 1999, 41, 37–43; (c) Chinchilla, R.; Maz o´ n,
P.; N a´ jera, C. Tetrahedron: Asymmetry 2000, 11, 3277–
19. S-Phenylalanine: ½aŠ ¼ ꢀ34:5 (c, 1; H O) (Dic-
D
tionary of Organic Compounds; Chapman & Hall: New
2
3
281; (d) Thierry, B.; Plaquevent, J.-C.; Cahard, D.
York, 1982).