Direct asymmetric aminoxylation reaction catalyzed by axially chiral amino acids

Article abstract of DOI:10.1246/cl.2008.250

Binaphthyl-based amino acids were prepared and applied for the direct asymmetric aminoxylation of aldehydes with nitrosobenzene. The reaction catalyzed by (S)-1e proceeded smoothly to give the aminoxylated product in good yield and enantioselectivity. Thi

Full text of DOI:10.1246/cl.2008.250

250
Chemistry Letters Vol.37, No.3 (2008)
Direct Asymmetric Aminoxylation Reaction Catalyzed by Axially Chiral Amino Acids
Taichi Kano, Akihiro Yamamoto, Haruka Mii, Jun Takai, Seiji Shirakawa, and Keiji MaruokaÃ
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502
(Received November 27, 2007; CL-071314; E-mail: maruoka@kuchem.kyoto-u.ac.jp)
Binaphthyl-based amino acids were prepared and applied
OTf
CO2Me
for the direct asymmetric aminoxylation of aldehydes with nitro-
sobenzene. The reaction catalyzed by (S)-1e proceeded smoothly
to give the aminoxylated product in good yield and enantioselec-
tivity. This method represents a rare example of the direct asym-
metric aminoxylation by a non-proline-type catalyst.
1. ArB(OH)2, Pd(OAc)2, PPh3
K3PO4, THF or dioxane
Me
Me
Me
Me
2. Pd(OAc)2, dppp, i-Pr2NEt
DMSO, MeOH, CO
OTf
Ar
(S)-2
CO2Me
1. N,N-Dimethylbarbituric
Nitroso compounds are frequently utilized as a nitrogen
and/or an oxygen source in synthetic organic chemistry,1 and
various catalytic asymmetric reactions, such as aminoxyla-
tion,2–5 hydroxyamination,4–6 and nitroso Diels–Alder reaction,7
have recently been developed by exploiting their unique proper-
ties. In this area, highly enantioselective aminoxylation reactions
using simple aldehydes and ketones were realized by organoca-
talysts through the in situ generation of the reactive enamine.3
To the best of our knowledge, however, most of the reported or-
ganocatalysts for the aminoxylation reaction are proline and its
derivatives, and structurally different catalysts have not yet been
studied. Accordingly, we have been interested in the possibility
of utilizing a binaphthyl-based amino acid catalyst (S)-1a,8
which is an effective catalyst for the direct asymmetric aldol re-
action, in the direct asymmetric aminoxylation of aldehydes.
Herein, we wish to report a direct asymmetric aminoxylation re-
action of aldehydes with nitrosobenzene by using binaphthyl-
based amino acid catalysts (Figure 1).
1. NBS, AIBN
benzene
acid, Pd(OAc)2
PPh3, CH2Cl2
N
(S)-1b–1e
2. Allylamine
CH3CN
2. 1M NaOH
MeOH–THF
Ar
Scheme 1. Synthesis of binaphthyl-based amino acid catalysts.
Table 1. Direct asymmetric aminoxylation of propanal with
nitrosobenzene catalyzed by (S)-1a
O
OH
cat (5 mol %)
NaBH4
EtOH
O
N
O
+
PhHN
CHCl3 (2.0 M)
0 °C, 1 h
Ph
Me
Me
Entry Cat Yield/%b ee/%c Entry Cat Yield/%b ee/%c
1
2
3
(S)-1a
(S)-1b
(S)-1c
82
99
82
49
64
60
4
5
(S)-1d
(S)-1e
88
87
62
79
We first attempted to use (S)-1a as a catalyst for the direct
asymmetric aminoxylation reaction. Thus, treatment of propanal
with nitrosobenzene in the presence of 5 mol % of (S)-1a in
CHCl3 at 0 ꢀC and subsequent reduction with NaBH4 in
CHCl3/EtOH furnished the corresponding 2-aminoxy alcohol
in good yield with moderate enantioselectivity (Table 1,
Entry 1). We then designed and synthesized new binaphthyl-
based amino acids (S)-1b–1e having an aromatic substituent
at 3-position to improve the enantioselectivity. The requisite
binaphthyl-based amino acids (S)-1b–1e were synthesized in
a 6-step sequence from bistriflate (S)-2,9 which was prepared
from (S)-BINOL, as shown in Scheme 1.
With catalysts (S)-1b–1e in hand, the direct asymmetric
aminoxylation of propanal with nitrosobenzene was carried
out, and the results were summarized in Table 1. Introduction
of an aromatic substituent at 3-position of the catalyst led to in-
creases in enantioselectivity in all cases examined (Entries 2–5),
and (S)-1e having 3,4,5-trifluorophenyl group was found to be
aThe reaction of propanal (3 equiv.) with nitrosobenzene was
carried out in CHCl3 in the presence of catalyst (S)-1 at 0 ꢀC.
bIsolated yield. cDetermined by HPLC analysis using chiral
column (Chiralpak AD-H, Daicel Chemical Industries, Ltd.).
the catalyst of choice (Entry 5).
We then examined the effects of solvents on the yield and
enantioselectivity. The results of the reaction using various sol-
vents are shown in Table 2. When other halogenated solvents
were used instead of CHCl3, similar results were obtained
(Entries 2 and 3). Switching the solvent to acetonitrile resulted
in no improvement (Entry 4). In the case of amide solvents
DMF and NMP as well as THF, significant decreases in yield
were observed, although the enantioselectivities were increased
to >90% ee (Entries 5–7). Aromatic solvents benzene, toluene,
and mesitylene were found to be effective both in terms of the
yield and enantioselectivity (Entries 8, 9, and 12). It should be
noted that the reaction performed at lower concentration afford-
ed the aminoxylated product with good enantioselectivity, albeit
with moderate yield (Entries 11, 13, and 14). Toluene proved to
be optimal for the present reaction due to the ease of handling
and was selected for further studies.
CO2H
(S)-1a : R = H
(S)-1b : R = Ph
(S)-1c : R = 3,5-Ph2C6H3
(S)-1d : R = 3,5-(CF3)2C6H3
(S)-1e : R = 3,4,5-F3C6H2
NH
The reactions using other aldehydes were then carried out
under optimized conditions and some selected examples are
summarized in Table 3. Similar high levels of yield and enantio-
selectivity were obtained when hexanal was used (Entry 2). In
R
Figure 1. Binaphthyl-based amino acid catalysts.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.3 (2008)
251
Table 2. Solvent effects in direct asymmetric aminoxylation of
propanal with nitrosobenzene catalyzed by (S)-1ea
F
F
O
OH
(S)-1e (5 mol %) NaBH4
Solvent, 0 °C
O
N
O
N
H
F
R
O
+
Ph
PhHN
EtOH
Ph
O
N
Me
Me
O
Entry
Solvent
Conc/M Time/h Yield/%b ee/%c
Figure 2. A transition state model for the direct asymmetric
aminoxylation reaction catalyzed by (S)-1e.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
CHCl3
2.0
2.0
2.0
1.0
2.0
2.0
2.0
1.0
2.0
1.0
0.5
1.0
0.5
0.2
1
1
1
1
1
2
2
1
1
1
1
1.5
1.5
5
87
86
88
81
<10
30
40
85
86
89
70
94
62
64
79
77
76
77
90
92
90
85
83
86
89
86
91
91
CH2Cl2
ClCH2CH2Cl
CH3CN
DMF
NMP
THF
Benzene
Toluene
Toluene
Toluene
Mesitylene
Mesitylene
Mesitylene
development of other enantioselective reactions using this
catalyst are in progress.
This work was partially supported by a Grant-in-Aid for
Scientific Research on Priority Areas ‘‘Advanced Molecular
Transformation of Carbon Resources’’ from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
References and Notes
1
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aThe reaction of propanal (3 equiv.) with nitrosobenzene was
carried out in the solvent mentioned above in the presence of
catalyst (S)-1e at 0 ꢀC. Isolated yield. Determined by HPLC
analysis using chiral column (Chiralpak AD-H, Daicel Chemi-
cal Industries, Ltd.).
b
c
2
3
N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2003, 125,
6038.
Representative papers: a) G. Zhong, Angew. Chem., Int. Ed.
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O
OH
´
´
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(S)-1e (5 mol %) NaBH4
O
N
O
+
PhHN
Toluene (1.0 M)
EtOH
Ph
R
R
0 °C
Entry
R
Time/h
Yield/%b
ee/%c
1
2
3
Me
Bu
i-Pr
1
2
1.5
89
81
69
86
88
86
aThe reaction of an aldehyde (3 equiv.) with nitrosobenzene
was carried out in toluene in the presence of catalyst (S)-1e at
0 ꢀC. bIsolated yield. cDetermined by HPLC analysis using
chiral column (Chiralpak AD-H, Daicel Chemical Industries,
Ltd.).
`
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4
5
6
the case of less reactive 3-methylbutanal, the corresponding
aminoxylated product was obtained in slightly lower yield with
good enantioselectivity (Entry 3).
In all cases examined in this study, the absolute configura-
tion of the aminoxylated products was determined to be R. On
the basis of the observed stereochemistry, a plausible transition
state is proposed (Figure 2). The activated and directed nitroso-
benzene by carboxyl group on (S)-1e would approach the Re face
of the enamine. Hence, the reaction of an aldehyde with nitroso-
benzene catalyzed by (S)-1e provides R isomer predominantly,
while at present we have no clear rationale for increases in enan-
tioselectivity by the aromatic substituent at 3-position.
´
C. Palomo, S. Vera, I. Velilla, A. Mielgo, E. Gomez-Bengoa,
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7
In summary, we have shown that the binaphthyl-based
amino acid (S)-1e prepared from (S)-BINOL can be utilized
as an organocatalyst in the direct asymmetric aminoxylation
reaction of aldehydes. Further investigations to clarify the role
of the aromatic substituent on the catalyst and efforts toward
8
9
a) T. Kano, J. Takai, O. Tokuda, K. Maruoka, Angew. Chem.,
Int. Ed. 2005, 44, 3055. b) T. Kano, O. Tokuda, J. Takai, K.
Maruoka, Chem. Asian J. 2006, 1, 210.
T. Ooi, M. Kameda, K. Maruoka, J. Am. Chem. Soc. 2003, 125,
5139.
Published on the web (Advance View) February 2, 2008; doi:10.1246/cl.2008.250