A new class of acetophenone-based cinchona alkaloids as phase-transfer catalysts: Application to the enantioselective synthesis of α-amino acids

Article abstract of DOI:10.1246/cl.2007.1354

A new class of acetophenone-based cinchona alkaloid-de-rived quaternary ammonium salts were prepared and evaluated as phase-transfer catalysts in the enantioselective alkylation of glycine imine ester. ⁺R ₃N-CH₂COAr and el

Full text of DOI:10.1246/cl.2007.1354

1
354
Chemistry Letters Vol.36, No.11 (2007)
A New Class of Acetophenone-based Cinchona Alkaloids as Phase-transfer Catalysts:
Application to the Enantioselective Synthesis of ꢀ-Amino Acids
ꢀ
Jian Lv, Liping Zhang, Lei Liu, and Yongmei Wang
Department of Chemistry and State Key Laboratory of Elemento-Organic Chemistry,
Nankai University, Tianjin 300071, P. R. China
(Received August 22, 2007; CL-070895; E-mail: ymw@nankai.edu.cn)
A new class of acetophenone-based cinchona alkaloid-de- purity of the products was found to be highly dependent on the
1
0a,10b
rived quaternary ammonium salts were prepared and evaluated
as phase-transfer catalysts in the enantioselective alkylation of
electron-withdrawing groups by Park et al.
and Shioiri et
1
0c
al. Hence, we synthesized a series of acetophenone-based cin-
chona ammonium salts and catalyzed the asymmetric alkylation
of glycine imine ester. We expected that electron-withdrawing
group (–COAr) and various functional groups on the phenyl ring
might increase the enantioselectivity by the formation of a tight-
er binding ion pair, which would lead to a more rigid conforma-
tion.
þ
glycine imine ester. R3N-CH2COAr and electron-withdrawing
0
4 -NO2 moieties may play an important role leading to high
enantioselectivity (85–>99% ee).
Since the application of chiral PTCs to the asymmetric al-
kylation of glycine imine ester, which was first reported by
First, a new class of acetophenone-based cinchona alkaloid-
11
1
O’Donnell et al. in 1989, catalytic asymmetric alkylation has
2
derived quaternary ammonium salts were prepared from cin-
been one of the most important asymmetric methodologies. A
number of methods have been developed for the asymmetric al-
chonidine (for 1–10), O9-benzylcinchonidine (11) or cinchonine
(for 13) (Chart 1), and the corresponding phenacyl bromide de-
rivatives were stirred in refluxing ethanol for 1 h in 86%–96%
yields, followed by O9 and C10-alkylation of 7 with benzyl bro-
mide and aqueous KOH (50%) for 24 h to give quaternary am-
monium salt 12 in 20% yield. Their catalytic efficiencies were
evaluated by enantioselective phase-transfer alkylation, using
10 mol % catalyst, N-(diphenylmethylene)glycine tert-butyl es-
ter 14, benzyl bromide, and 50% aqueous KOH in toluene/
3
kylation of glycine imine ester. Amongst them, a method utiliz-
ing chiral PTCs occupies a unique place, featuring many clear
synthetic advantages for large-scale procedures including easily
available and re-usable chiral catalysts and environmental bene-
4
fits. Recently, catalytic asymmetric PTCs alkylations by using
cinchona alkaloids-derived quaternary ammonium salts as chiral
5
PTC catalysts have been reported by several research groups.
6
7
ꢁ
Especially, the Lygo and Corey groups independently reported
the excellent phase-transfer catalysts, respectively, by the intro-
duction of the bulkier anthracenyl moiety instead of the phenyl
group. Moreover, our group and others have anchored Cincho-
na alkaloids to cross-linked polystyrene or chemically modified
PEG for the asymmetric alkylation of glycine imine ester.
Despite their practical potential, the high enantio-selectivity
was due to the steric bulkiness of N -arylmethyl group in cin-
chona-derived catalysts. But we can not ignore that an electronic
effect may be also another significant factor. The enantiomeric
chloroform (volume ratio = 7:3) at 25 C.
Table 1. Catalytic enantioselective phase-transfer alkylationa
8
9
Chiral catalyst
O
O
PhCH Br, 50% aq.KOH
2
Ph
N
*
Ph
N
Ot-Bu
Ot-Bu
PhCH /CHCl (7:3), temp.
3
3
Ph
Ph
þ
Ph
14
15a
Yieldb
/%
c
Temp
ꢁ
Time
/h
ee /%
(conf.)
Entry
Catalyst
/ C
1
2
3
4
5
6
7
8
9
10
11
12
13
4
5
6
1
2
3
4
5
6
7
8
9
10
11
12
13
13
13
13
13
25
25
25
25
25
25
25
25
25
25
25
25
25
0
ꢂ20
ꢂ20
ꢂ20
1.0
0.8
0.8
0.9
1.3
0.4
0.2
0.4
0.3
1.2
0.4
2.0
0.05
0.4
1.0
2.0
4.0
88
90
92
93
85
95
96
89
91
90
95
91
96
95
93
94
90
60 (S)
71 (S)
73 (S)
70 (S)
48 (S)
83 (S)
84 (S)
81 (S)
83 (S)
63 (S)
83 (S)
60 (S)
85 (R)
87 (R)
90 (R)
92 (R)
88 (R)
Br
9
Br
N
N
O
O
1
OH
0
1
'
OH
2
'
N
N
3
'
X
4
'
1
0
1
2
3
4
5
X = H
6 X = 4'-CF3
7 X = 4'-NO2
8 X = 3'-NO2
X = 4'-F
X = 2'-Fl
X = 4'-Cl
9 X = 2'-NO2
X = 4'-OMe
1
1
1
d
e
OH
Br
17
N
O
N
O
a
Reaction was carried out with 5.0 equiv. of benzyl bromide and 13.0 equiv.
Y'
N
OY
Bn
of 50% aqueous KOH in the presence of 10 mol % 1–13 in toluene/chloro-
form (volume ratio = 7:3) under the given conditions. bIsolated yields.
Br
N
cEnantiopurity was determined by HPLC analysis of benzylated imine
NO2
13
1
1 Y = Y' = H
NO2
15a using a chiral colume (DAICEl Chiralcel OD-H) with hexanes/2-prop-
anol (volume ratio = 99.5:0.5) as a solvent. dThe presence of 5 mol % 13.
1
2 Y = Y' = Bn
eThe presence of 1 mol % 13.
Chart 1.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.11 (2007)
1355
Table 2. Catalytic enantioselective phase-transfer alkylation using cata-
a
mides afforded higher enantioselective than allylic bromide and
methyl iodide.
lysts 13
O
In conclusion, we prepared a series of new cinchona alkaloid
ammonium salt catalysts 1–13 by the introduction of the N-aro-
matic acyl group instead of the N-arylmethyl group to enhance
catalytic efficiency. Among the PTC catalysts, the catalyst 13
showed the higher catalytic activity (85–>99% ee) in the alkyl-
ation of 14.
O
13 (5 mol%)
RX, 50% aq.KOH
Ph
N
Ph
N
Ot-Bu
Ot-Bu
PhCH /CHCl (7:3), −20°C
3
3
Ph
R
15
Ph
1
4
b
c
Entry
RX
Time/h
Yield /%
ee /% (conf.)
a
b
c
d
e
f
g
h
i
PhCH2Br
2
3
3
3
2
2
2
3
3
4
94
89
92
90
87
93
95
91
90
80
92 (R)
95 (R)
95 (R)
99 (R)
94 (R)
>99 (R)
90 (R)
92 (R)
90 (R)
85 (R)
p-ClC6H4CH2Br
References and Notes
m-ClC6H4CH2Br
o-ClC6H4CH2Br
p-CH3C6H4CH2Br
m-CH3C6H4CH2Br
o-CH3C6H4CH2Br
m-BrC6H4CH2Br
p-NO2C6H4CH2Br
CH3I
1
2
M. J. O’Donnell, W. D. Bennett, S. Wu, J. Am. Chem. Soc. 1989, 111, 2353.
a) C. H. Stammer, Tetrahedron 1990, 46, 2231. b) H. Heimartner, Angew.
Chem., Int. Ed. Engl. 1991, 30, 238. c) R. M. Williams, J. A. Hendrix,
Chem. Rev. 1992, 92, 889. d) R. O. Duthaler, Tetrahedron 1994, 50,
1
2
539. e) C. Cativiela, M. D. Diaz-de-Villegas, Tetrahedron: Asymmetry
000, 11, 645. f) C. N a´ jera, Synlett 2002, 1388.
3
4
5
a) R. M. Williams, in Organic Chemistry Series, ed. by J. E. Baldwin, P. D.
Magnus, Pergamon Press, Oxford, 1989, Vol. 7. b) I. Wagner, H. Musso,
Angew. Chem., Int. Ed. Engl. 1983, 22, 816.
For recent representative review, see: a) M. J. O’ Donnell, in Catalytic
Asymmetric Synthesis, ed. by I. Ojima, Verlag Chemie, 1993, Chap. 8. b)
M. J. Porter, J. Skidmore, Chem. Commun. 2000, 1215.
a) M. J. O’Donnell, Acc. Chem. Res. 2004, 37, 506. b) B. Lygo, B. I.
Andrews, Acc. Chem. Res. 2004, 37, 518. c) A. Siva, E. Murugan, J.
Mol. Catal. A: Chem. 2006, 248, 1. d) S. Elango, M. Venugopal, P. S.
Suresh, Eni, Tetrahedron 2005, 61, 1443. e) S. Kumar, U. Ramachandran,
Tetrahedron 2005, 61, 7022. f) N. Mase, T. Ohno, H. Morimoto, F. Nitta,
H. Yoda, K. Takabe, Tetrahedron Lett. 2005, 46, 3213. g) M. B. Andrus, Z.
Ye, J. Zhang, Tetrahedron Lett. 2005, 46, 3839. h) H.-G. Park, B.-S. Jeong,
M.-S. Yoo, J.-H. Lee, M.-J. Kim, S.-S. Jew, Angew. Chem., Int. Ed. 2002,
j
k
Br
4
91
86 (R)
aReaction was carried out with 5.0 equiv. of alkyl halides and 13.0 equiv.
of 50% aqueous KOH in the presence of 5 mol % 13 in toluene/chloroform
(
v/v = 7:3) under the given conditions.
As shown in Table 1, there are, depending on the position
substituted with different groups, quite dramatic variations in
the enantioselectivity. Generally, the electronic factor is critical
for enhancement of the induction, however, the steric factor is
not important (1, 60% ee; 10, 63% ee). The best results were ob-
tained with an electron-withdrawing –NO2 group on the 4 -posi-
tion (7, 84% ee; 13, 85% ee), however, an electron-donating me-
thoxy group on the 4 -position gave lower enantioselectivity (11,
48% ee). It indicated that the electron-withdrawing acetophe-
none and 4 -NO2 groups, caused by the overall electron deficien-
cy of the positive charge, helped to enhance the degree of the ion
pairing with enolate. The more tight ion pairing was formed, the
4
1, 3036. i) S.-S. Jew, B.-S. Jeong, M.-S. Yoo, H. Huh, H.-G. Park, Chem.
Commun. 2001, 1244. j) R. Chinchilla, P. Maz o´ n, C. N a´ jera, Tetrahedron:
Asymmetry 2002, 13, 927. k) H.-G. Park, B.-S. Jeong, M.-S. Yoo, H. Huh,
S.-S. Jew, Tetrahedron Lett. 2001, 42, 4645. l) P. Maz o´ n, R. Chinchilla,
C. N a´ jera, G. Guillena, R. Kreiter, R. J. M. K. Gebbink, G. van Koten,
Tetrahedron: Asymmetry 2002, 13, 2181.
0
0
6
a) B. Lygo, P. G. Wainwright, Tetrahedron Lett. 1997, 38, 8595. b) B.
Lygo, J. Crosby, J. A. Peterson, Tetrahedron Lett. 1999, 40, 1385. c) B.
Lygo, Tetrahedron Lett. 1999, 40, 1389. d) B. Lygo, J. Crosby, J. A.
Peterson, Tetrahedron Lett. 1999, 40, 8671. e) B. Lygo, J. Crosby, T. R.
Lowdon, J. A. Peterson, P. G. Wainwright, Tetrahedron 2001, 57, 2403.
f) B. Lygo, B. I. Andrews, J. Crosby, J. A. Peterson, Tetrahedron Lett.
0
7
a
higher enantioselective was obtained. Moreover, use of lower
temperature improved the enantioselectivity (13, 87% ee, at
2
002, 43, 8015. g) B. Lygo, B. Allbutt, Synlett 2004, 326.
7
8
9
a) E. J. Corey, F. Xu, M. C. Noe, J. Am. Chem. Soc. 1997, 119, 12414. b)
E. J. Corey, M. C. Noe, F. Xu. Tetrahedron Lett. 1998, 39, 5347. c) M.
Horikawa, J. Busch-Petersen, E. J. Corey, Tetrahedron Lett. 1999, 40,
ꢁ
ꢁ
0
C; 90% ee, at ꢂ20 C). Notably, 13 can conserve its high cat-
alytic efficiency in terms of both reactivity and enantioselectiv-
ity, even when present in a smaller quantity (1 mol %, 88% ee, at
3
843.
a) Y. Wang, Zh. P. Zhang, Zh. Wang, J. B. Meng, P. Hodge, Chin. J. Polym.
Sci. 1998, 16, 356. b) Z. Zhengpu, W. Yongmer, W. Zhen, P. Hodge, React.
Funct. Polym. 1999, 41, 37. c) X. Wang, L. Yin, T. Yang, Y. Wang, Tetra-
hedron: Asymmetry 2007, 18, 108.
a) R. Chinchilla, P. Maz o´ n, C. N a´ jera, Adv. Synth. Catal. 2004, 346, 1186.
b) R. Chinchilla, P. Maz o´ n, C. N a´ jera, Molecules 2004, 9, 349. c) B.
Thierry, J.-C. Plaguevent, D. Cahard, Tetrahedron: Asymmetry 2003, 14,
ꢁ
ꢂ20 C). Furthermore, catalytic efficiencies of 11 and 12 were
also evaluated. In agreement with our expectation, C(9)O-benzyl
ꢁ
(
11, 83% ee, at 25 C) derivative of 7 gave a little lower enantio-
ꢁ
selectivity than 7 with a free C(9)OH group (84% ee, at 25 C).
Catalyst 12 obtained by O9 and C10-alkylation of 7 with benzyl
bromide gave a notable decrease in the enantioselectivity (60%
1671. d) T. Danelli, R. Annunziata, M. Benaglis, M. Cinquini, F. Cozzi,
G. Tocco, Tetrahedron: Asymmetry 2003, 14, 461.
ꢁ
ee, at 25 C).
1
0
1
a) S.-S. Jew, M.-S. Yoo, B.-S. Jeong, I. Y. Park, H.-G. Park, Org. Lett.
2002, 4, 4245. b) M.-S. Yoo, B.-S. Jeong, J.-H. Lee, H.-G. Park, S.-S.
Jew, Org. Lett. 2005, 7, 1129. c) S. Arai, H. Tsuge, T. Shioiri, Tetetrahe-
dron Lett. 1998, 39, 7563.
After optimizing the reaction condition, we considered
whether the catalyst could be decomposed or not during the re-
action procedure. So we reclaimed the catalyst and investigated
its structure. The catalyst 13 could be separated from the reaction
mixture when we added diethyl ether to the reaction residue, be-
cause of the reaction product could dissolve in diethyl ether and
the catalyst was insoluble in it. We found that the catalyst was
not decomposed under the present conditions examined by
H NMR. It indicated that the catalyst is stable under the reac-
tion conditions.
The best enantioselectivity was obtained with catalyst 13,
which was chosen for further investigation with various alkyl
halides. Satisfactory enantioselectivities (85–>99% ee) and
yields were shown in Table 2. It is clear that different benzyl bro-
1
All new compouds gave satisfactory analytical and spectral data. Selected
ꢁ
20
data for 13: mp 210–212 C; [ꢀ]D = +63 (c ¼ 0:1, ethanol); IR (KBr)
ꢂ1
3
441, 3149, 2987, 1694, 1653, 1600, 1530, 1496, 1455, 1027, 759 cm
;
1
H NMR (300 MHz, DMSO-d6) ꢁ 9.00 (d, J ¼ 4:2 Hz, 1H), 8.44–8.37 (t,
3
H), 8.13–8.08 (t, 3H), 7.88–7.74 (m, 3H), 6.83 (d, J ¼ 3:3 Hz, 1H), 6.52
(s, 1H), 6.06–5.94 (m, 1H), 5.25–5.05 (m, 3H), 4.29–3.91 (m, 3H), 3.52–
3.45 (t,J ¼ 11:4 Hz, 1H), 2.99 (d, J ¼ 9:6 Hz, 1H), 2.61 (d, J ¼ 8:1 Hz,
1H), 2.48 (t, J ¼ 12:3 Hz, 1H), 1.87–1.74 (m, 3H), 1.08–0.82 (m, 2H);
1
12
1
3
C NMR (75 MHz, DMSO-d6) ꢁ: 191.9, 150.4, 147.6, 147.4, 141.2,
1
116.7, 64.9, 62.9, 61.0, 58.5, 56.8, 36.5, 26.6, 22.6, 20.8; MS(ESI): m=z
38.9, 136.1, 130.0, 129.8, 126.7, 124.5, 124.0, 123.6, 123.2, 118.7,
þ
þ
4
58 [M] ; HRMS (ESI) calcd for [C27H28N3O4] : m=z 458.2074, found:
4
58.2078.
20
1
2
The recovery date for 13: recovery yield 92%; [ꢀ]D = +62 (c ¼ 0:1,
ethanol).
Published on the web (Advance View) October 13, 2007; doi:10.1246/cl.2007.1354