A. Nakazaki et al. / Tetrahedron Letters 53 (2012) 7131–7134
7133
Table 2
Removal of p-(benzyloxy)aryl moiety
R2
N
R1
R2
R1
1) deprotection of
Bn group
O
O
2) PhI(OCOCF3)2
CH3CN-H2O, 0 °C
N
H
MeO
5a,
2
7
or
8
,
OBn
Entry
Substrate
R1
R2
Deprotection methoda
Yield
Removal of aryl moiety
Yield (%)
1
2
3
4
5
2a
2b
2c
2d
5a
Me
Et
Ph
Allyl
Me
OH
OH
OH
OH
A
A
B
B
A
Quant.
Quant.
70%b
8a
8b
8c
8d
8e
83
83
50
55
59
94%b
CH2CO2Me
83%
MeO2C
6
7
A
Quant.
8f
80c
a
b
c
Method A: H2 (1 atm), Pd/C, MeOH, rt; Method B: A1C13, N,N0-dimethylaniline, CH2C12, rt.
Combined yield of the corresponding phenol and isopropenylphenol derivatives.
dr = >95:<5, determined by 1H NMR analysis.
Acknowledgments
Bn
CO2Me
N
N
MeO2C
MeO
MeO2C
MeO
1) MeO2CCl, quant.
Financial support for this research from the Uehara Memorial
Foundation and the Ministry of Education, Culture, Sports, Science
and Technology of Japan (MEXT, No. 21790026 and 23780115) is
gratefully acknowledged. We thank Dr. Kenji Yoza (Bruker AXS)
for the X-ray crystallographic analysis.
O
O
2) H2 (1 atm), Pd/C
93%
N
N
OBn
OH
6a
9
Supplementary data
CO2Me
N
Supplementary data associated with this article can be found, in
PhI(OCOCF3)2
MeO2C
MeCN/H2O, 0 °C
94%
O
N
H
References and notes
8g
(dr = 90:10)
1. (a) Toyota, M.; Ihara, M. Nat. Prod. Rep. 1998, 15, 327; (b) Marti, C.; Carreira, E.
M. Eur. J. Org. Chem. 2003, 2209; (c) Trost, B. M.; Brennan, M. K. Synlett 2009,
3003–3025; (d) Klein, J. E. M. N.; Taylor, R. J. K. Eur. J. Org. Chem. 2011, 6821–
6841.
Diastereomeric ratio was determined by 1H NMR analysis.
Scheme 3. Removal of aryl moiety in 6a.
2. For
a recent review of enantioselective synthesis of 3,3-disubstituted
oxindoles, see: (a) Ball-Jones, N. R.; Badillo, J. J.; Franz, A. K. Org. Biomol.
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moiety in pyrrolidine derivative 6a was smoothly removed in the
same manner after conversion of the N-benzyl group into a
methoxycarbonyl group (Scheme 3).17 Thus, the sequential trans-
formation could be performed under mild conditions to remove
the p-(benzyloxy)phenyl group bearing a hindered ortho-substitu-
ent, even though it was introduced in the axially twisted amide
system. To the best of our knowledge, this is the first example of
the effective removal of an aryl moiety from the core amide after
atroposelective transformation,18 and this procedure would be
applicable to the oxidative cleavage of the aryl group in other
acid-labile N-aryl amides as well.
In summary, we have developed a method for the diastereose-
lective synthesis of 3,3-disubstituted oxindoles that incorporate a
stereogenic center at C3, from newly designed chiral N-aryl
oxindoles. Since a variety of reagents can be used in a highly
stereoselective manner, various oxindole derivatives, which would
be useful building blocks for alkaloid synthesis, can be obtained
from a common N-aryl oxindole intermediate. Removal of the
p-(benzyloxy)aryl moiety is possible even under mild conditions,
which implies that this protocol is applicable to other amide sys-
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doles and application to the synthesis of oxindole alkaloids will
be reported in due course.
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