Regiodivergent kinetic resolution of terminal and internal rac -aziridines with malonates under dinuclear schiff base catalysis

Article abstract of DOI:10.1021/ja5039165

Regiodivergent parallel kinetic resolution of aziridines with malonates was achieved under dinuclear Schiff base catalysis. The regiodivergent reaction proceeded under catalyst-control irrespective of the substituents on the aziridines, and 2.5-10 mol % of a Y(OTf)₃/La(OiPr)₃/a dinucleating Schiff base = 1:1:1 mixture gave versatile γ-amino acid derivatives in 96 → >99.5% ee. Not only terminal but also internal racemic aziridines reacted smoothly under suitably combined Lewis acid/Br?nsted base catalysis.

Full text of DOI:10.1021/ja5039165

Article
pubs.acs.org/JACS
Regiodivergent Kinetic Resolution of Terminal and Internal rac-
Aziridines with Malonates under Dinuclear Schiff Base Catalysis
Yingjie Xu,† Keiichi Kaneko,† Motomu Kanai,† Masakatsu Shibasaki,*,‡ and Shigeki Matsunaga*,†,§
†Graduate School of Pharmaceutical Sciences, the University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033, Japan
‡Institute of Microbial Chemistry, Tokyo, Kamiosaki 3-14-23, Shinagawa-ku, Tokyo 141-0021, Japan
§ACT-C, Japan Science and Technology Agency, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
S
* Supporting Information
ABSTRACT: Regiodivergent parallel kinetic resolution of azir-
idines with malonates was achieved under dinuclear Schiff base
catalysis. The regiodivergent reaction proceeded under catalyst-
control irrespective of the substituents on the aziridines, and 2.5−10
mol % of a Y(OTf)3/La(OiPr)3/a dinucleating Schiff base = 1:1:1
mixture gave versatile γ-amino acid derivatives in 96 → >99.5% ee.
Not only terminal but also internal racemic aziridines reacted
smoothly under suitably combined Lewis acid/Brønsted base
catalysis.
Scheme 1. Classification of Enantioselective Aziridine Ring-
Opening Reactions
1. INTRODUCTION
Enantioselective aziridine ring-opening reactions are powerful
tools for developing nitrogen-containing chiral building blocks
useful for the synthesis of biologically active molecules.1
Tremendous efforts, therefore, have been devoted to the
development of these reactions over the past decade, leading to
a variety of chiral metal- and organo-catalyzed desymmetriza-
tion reactions of meso aziridines with nitrogen,2 halogen,3
sulfur,4 phosphorus,5 carbon,6 and other nucleophiles7 (Scheme
1a).
More recently, Ooi8a,b and Morgan8c reported a couple of
elegant methods for kinetic resolution of racemic aziridines via
ring-opening reactions.8 For efficient kinetic resolution of
racemic aziridines, however, sufficiently large steric and/or
electronic differences between two possible reacting sites are
needed (Scheme 1b). Thus, high selectivity in kinetic resolution
is achieved mostly with terminal racemic aziridines, and
moderate selectivity is observed with internal racemic aziridines
when two substituents are sterically and electronically similar
but not identical (R ≈ R′).
Divergent parallel kinetic resolution9−11 can be a good
alternative for such racemic aziridines (Scheme 1c), where each
enantiomer is transformed into a different enantiomerically
enriched product at a similar reaction rate. Divergent kinetic
resolution is, in principle, advantageous over conventional
kinetic resolution for achieving high enantioselectivity (>98%
ee) even using substrates with similar reacting sites.
Regiodivergent parallel kinetic resolution of racemic aziridines,
however, is rare. In 2009, RajanBabu, Parquette and co-workers
for the first time realized regiodivergent ring-opening of
terminal racemic aziridines with an azide nucleophile,10 but
this is currently the only successful example of parallel kinetic
resolution of racemic aziridines. Thus, it is highly desirable to
expand the scope of both aziridines and nucleophiles to
broaden the synthetic utility of the process.
As a part of our ongoing studies on dinuclear Schiff base
catalysis,12,13 we previously reported desymmetrization of meso
aziridines with malonates using a heterodinuclear rare earth
Received: April 19, 2014
© XXXX American Chemical Society
A
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Journal of the American Chemical Society
Article
metals/Schiff base 1 complex (Figure 1). Suitable selection of a
Brønsted basic rare earth metal alkoxide and a Lewis acidic rare
2. RESULTS AND DISCUSSION
Optimization studies of regiodivergent parallel kinetic reso-
lution of racemic aziridines are summarized in Table 1. Because
a racemic terminal aziridine bearing a 3,5-dinitrobenzoyl
protecting group was unstable, racemic aziridine 2a bearing a
4-nitrobenzoyl group and malonate 3a were initially selected as
model substrates. We first applied the reaction conditions,
previously optimized for meso aziridines, for 2a and 3a (Table
1, entries 1−3). Although the enantioselectivity was promising
in the presence of Et3N additive (entries 2−3, 95−98% ee), the
reactivity was poor, giving products 4aa and 5aa in <10% yield.
Thus, we fully optimized the reaction conditions toward a
regiodivergent ring-opening of racemic aziridines. Among the
various solvents screened, toluene/Et2O = 1:2 mixture was the
best (entry 4, 4aa: 14% yield, 99% ee, 5aa: 11% yield, 98% ee).
N-Acyl protecting groups affected the reactivity (entries 4−6)
and aziridine 2c bearing a 3,5-ditrifluoromethyl-benzoyl group
showed the best reactivity (entry 6). An amine additive was also
important to obtain the desired ring-opening adducts, while
suppressing undesired Lewis acid-promoted rearrangement into
oxazolines.15 Among amine additives, DMAP was the best, and
the yield of 4ca and 5ca improved to 30% and 29%, respectively
(entry 10). Rare earth metal effects are summarized in entries
10−18. Among Brønsted basic rare earth metal alkoxides
screened (entries 10−14), the most Brønsted basic La(OiPr)3
gave the highest yield. The yield of products was also well
correlated with the Lewis acidity of rare earth metal triflates
[Y(OTf)3 > Yb(OTf)3 > Gd(OTf)3 > Sm(OTf)3 > La(OTf)3]
Figure 1. Dinucleating Schiff base 1 and postulated structures of
heterobimetallic rare earth (RE) catalysts bearing acid/base moieties.
earth metal triflate was important to achieve good reactivity and
enantioselectivity, and a La(OiPr)3/Yb(OTf)3/Schiff base 1
was the optimum one, giving ring-opened products in 97 →
>99.5% ee (Scheme 1a, PG = 3,5-dinitrobenzoyl; Nu =
malonate).14 On the basis of high enantio-discriminating ability
of the heterodinuclear rare earth metals/Schiff base 1 complex
for meso aziridines, we hypothesized that the same catalyst
would be applicable even for racemic aziridines bearing two
sterically and electronically similar but not identical substituents
(Scheme 1c, bottom). In this article, we describe trials to
expand the utility of our dinuclear Schiff base catalysis to
regiodivergent parallel kinetic resolution of racemic aziridines.
Table 1. Optimization Studies of Regiodivergent Resolution of Aziridine with Malonate
a
b
a
b
temp
(°C)
time
(h)
% yield
of 4
% ee
% yield
of 5
% ee
entry RE1 source
RE2 source
solvent
additives
PG:Ar
2
of 4
of 5
1
2
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
Nd(OiPr)3
Sm(OiPr)3
Gd(OPr)3
Er(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
La(OiPr)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
Yb(OTf)3
La(OTf)3
Sm(OTf)3
Gd(OTf)3
Y(OTf)3
THF
none
Et3N
4-NO2-C6H4
4-NO2-C6H4
2a
2a
2a
2a
2b
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
25
45
45
45
45
45
45
45
45
45
45
48
48
48
48
48
48
48
48
48
trace
5
ND
97
trace
5
ND
ND
98
THF
3
toluene
Et3N
4-NO2-C6H4
9
95
7
4
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
toluene/Et2O
Et3N
4-NO2-C6H4
14
99
11
98
5
Et3N
4-CF3-C6H4
trace
22
ND
99
trace
20
ND
98
6
Et3N
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
3,5-(CF3)2-C6H3
7
iPr2NEt
TMEDA
pyridine
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
DMAP
trace
trace
19
ND
ND
99
trace
trace
19
ND
ND
97
8
9
10
11
12
13
14
15
16
17
18
19
30
99
29
97
12
98
11
97
trace
trace
trace
5
ND
ND
ND
ND
99
trace
trace
trace
trace
14
ND
ND
ND
ND
99
12
20
99
22
99
33
>99.5
>99.5
36
>99.5
>99.5
Y(OTf)3
toluene/Et2O DMAP + MS 3,5-(CF3)2-C6H3
4 Å
40
47
c
d
c
d
20
La(OiPr)3
Y(OTf)3
toluene/Et2O DMAP + MS 3,5-(CF3)2-C6H3
4 Å
2c
35
38
45
>99.5
49
>99.5
a
b
c
1
Determined by H NMR analysis of the crude mixture. Determined by chiral HPLC analysis. Isolated yield after purification by column
d
chromatography. (S)-Schiff base 1 was used, giving ent-4ca and ent-5ca in major.
B
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Journal of the American Chemical Society
Article
Table 2. Substrate Scope of Regiodivergent Resolution of Aziridines with Malonates
a
b
a
b
entry
R
R′
2
cat. (× mol %)
R″
3
time (h)
4
% yield of 4 % ee of 4
5
% yield of 5 % ee of 5
c
c
1
2
cyclo-hex
cyclo-hex
cyclo-hex
cyclo-pent
iPr
H
H
2c
2c
2c
2d
2e
2f
10
10
10
10
10
10
10
10
2.5
10
10
10
Me
Et
3a
3b
3c
3a
3a
3a
3a
3a
3a
3a
3a
3a
38
39
64
48
48
26
26
37
72
26
35
48
4ca
4cb
4cc
4da
4ea
4fa
45
46
29
36
36
49
45
49
36
43
42
47
>99.5
99
5ca
5cb
5cc
5da
5ea
5fa
49
46
40
48
49
46
46
49
44
44
49
47
>99.5
>99.5
99
3
H
Bn
99
4
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
>99.5
98
96
5
H
>99.5
>99.5
>99.5
>99.5
>99.5
96
6
nBu
H
>99.5
99
−
7
cyclo-hex-CH2
iBu
H
2g
2h
2h
2i
4ga
4ha
4ha
4ia
5ga
5ha
5ha
5ia
8
H
99
9
iBu
H
99
10
11
12
Et
Me
Me
Et
>99.5
99
nPr
2j
4ja
5ja
>99.5
98
nPr
2k
4ka
99
5ka
a
b
c
Isolated yield after purification by column chromatography. Determined by chiral HPLC analysis. (S)-Schiff base 1 was used, giving ent-4ca and
ent-5ca in major.
(entries 10, 15−18),16 and the best yield was achieved with a
a
Scheme 2. Transformation into γ-Amino Acid
combination of La(OiPr)3 and Y(OTf)3 (entry 18, 4ca: 33%
yield, 5ca: 36% yield). Finally, the addition of molecular sieves
4 Å further improved the yield, and ring-opening adducts were
obtained in 94% isolated yield (4aa: 45%, 5aa: 49%) with
>99.5% ee each at 35 °C (entry 20).
The substrate scope of aziridines and malonates as well as a
trial to reduce catalyst loading are summarized in Table 2. The
a
Reagents and reaction conditions: (a) LiCl, H2O, DMSO, 130 °C, 3.5
h, 85% yield; (b) Boc2O, Et3N, cat. DMAP, THF, rt, 2.5 h; (c)
NaOMe, MeOH, rt, 17 h, 87% yield (2 steps).
present regiodivergent reaction was rather sensitive to the steric
hindrance of nucleophiles. While the reaction proceeded
smoothly with dimethyl malonate (3a, entry 1) and diethyl
malonate (3b, entry 2), the reactivity of the bulkier dibenzyl
malonate (3c) decreased. The reaction pathway to produce 4,
in which an enolate should attack the sterically more hindered
site under catalyst-control, was significantly affected by a subtle
change in nucleophiles. In entry 3 using malonate 3c, product
4cc was obtained in only 29% yield (99% ee), while product
5cc was obtained in 40% yield (99% ee). The results with other
terminal racemic aziridines are summarized in entries 4−8.
Both branched- and linear-alkyl substituted aziridines 2d−2h
gave products 4 and 5 in good yield (4: 36−49%, 5: 46−49%)
and excellent enantioselectivity (96 → >99.5% ee). Catalyst
loading was successfully reduced to 2.5 mol %, and products
4ha and 5ha were obtained in 36% and 44%, respectively (entry
9). Internal cis-aziridines 2i−2k bearing sterically and electroni-
cally similar substituents were also applicable without problems,
and products 4 and 5 were obtained in good yield (42−49%)
and high enantioselectivity (entries 10−12, 96 → >99.5% ee).
On the other hand, trans-aziridines did not produce any desired
products under the present heterodinuclear Schiff base catalysis.
The products in the present reaction are useful precursors for
γ-amino acids. Decarboxylation of 4ha gave 6ha in 81% yield.
Protection of 6ha with Boc-group, followed by treatment with
NaOMe at rt gave Boc-protected γ-amino ester 7ha in 87%
yield (2 steps, Scheme 2). The absolute stereochemistry of
product 4ha was determined to be (R) by comparing the
optical rotation of 7ha with reported data.17 The absolute
stereochemistry of products 4ka and 5ka was also unequiv-
ocally determined by X-ray crystallographic analysis (Figure 2).
Figure 2. ORTEP drawings of 4ka and 5ka.
The exceptionally high enantioselectivity observed in the
present regiodivergent ring-opening reaction represents the
power of dinuclear Schiff base catalysis. The chiral catalyst
strictly distinguished enantiomers of starting aziridines, and
(2R,3S)-2i−2k selectively gave 4 while (2S,3R)-2i−2k gave 5
under chiral catalyst-control irrespective of the substituents on
the aziridines (Figure 3). The results in Table 1, entries 10−18
implied that both Lewis acidity and Brønsted basicity of the
catalyst are important. In the precedent regiodivergent ring-
opening of aziridine, RajanBabu and Parquette utilized a
dimeric Y/Schiff base 1 = 1:1 complex, and cooperative
mechanism of two Y-metal centers was proposed.10,18 By
analogy, the Lewis acid/Brønsted base intramolecular cooper-
ative mechanism would also be key in the present reaction to
C
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Journal of the American Chemical Society
Article
3330. (c) Larson, S. E.; Baso, J. C.; Li, G.; Antilla, J. C. Org. Lett. 2009,
11, 5186. (d) Zhang, Y.; Kee, C. W.; Lee, R.; Fu, X.; Soh, J. Y. T.; Loh,
E. M. F.; Huang, K.-W.; Tan, C.-H. Chem. Commun. 2011, 47, 3897.
(e) Cao, Y.-M.; Zhang, F.-T.; Shen, F.-F.; Wang, R. Chem.Eur. J.
2013, 19, 9476.
(5) Hayashi, M.; Shiomi, N.; Funahashi, Y.; Nakamura, S. J. Am.
Chem. Soc. 2012, 134, 19366.
(6) With cyanide: (a) Mita, T.; Fujimori, I.; Wada, R.; Wen, J.; Kanai,
M.; Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 11252. (b) Wu, B.;
Gallucci, J. C.; Parquette, J. R.; RajanBabu, T. V. Angew. Chem., Int. Ed.
2009, 48, 1126. With other carbon nucleophiles: (c) Muller, P.; Nury,
̈
Figure 3. Reaction pathway of the regiodivergent ring-opening
reaction under dinuclear Schiff base catalysis.
P. Org. Lett. 1999, 1, 439. See also ref 14.
(7) (a) Senatore, M.; Lattanzi, A.; Santoro, S.; Santi, C.; Della Salla,
G. Org. Biomol. Chem. 2011, 9, 6205. (b) Della Salla, G. Tetrahedron
2013, 69, 50. For other examples, see reviews in ref 1.
producing ring-opening adducts efficiently via proper activation
(8) For leading highly selective examples, see: (a) Ohmatsu, K.;
Ando, Y.; Ooi, T. J. Am. Chem. Soc. 2013, 135, 18706. (b) Ohmatsu,
K.; Hamajima, Y.; Ooi, T. J. Am. Chem. Soc. 2012, 134, 8794.
(c) Cockrell, J.; Wilhelmsen, C.; Rubin, H.; Martin, A.; Morgan, J. B.
Angew. Chem., Int. Ed. 2012, 51, 9842. For an early partially successful
example, see also (d) Leung, W.-H.; Mak, W.-L.; Chan, E. Y. Y.; Lam,
T. C. H.; Lee, W.-S.; Kwong, H.-L.; Yeung, L. L. Synlett 2002, 1688.
(9) Reviews: (a) Miller, L. C.; Sarpong, R. Chem. Soc. Rev. 2011, 40,
4550. (b) Kumar, R. R.; Kagan, H. B. Adv. Synth. Catal. 2010, 352,
231. (c) Vedejs, E.; Jure, M. Angew. Chem., Int. Ed. 2005, 44, 3974.
(10) Regiodivergent reaction of terminal rac-aziridines: (a) Wu, B.;
Parquette, J. R.; RajanBabu, T. V. Science 2009, 326, 1662. (b) Wu, B.;
Gallucci, J. C.; Parquette, J. R.; RajanBabu, T. V. Chem. Sci. 2014, 5,
1102.
(11) For representative examples of regio- and chemo-divergent
catalytic parallel kinetic resolution with other racemic substrates, see:
(a) Bertozzi, F.; Crotti, P.; Macchia, F.; Pineschi, M.; Feringa, B. L.
Angew. Chem., Int. Ed. 2001, 40, 930. (b) Chen, Y.; Deng, L. J. Am.
Chem. Soc. 2001, 123, 11302. (b) Tanaka, K.; Fu, G. C. J. Am. Chem.
Soc. 2003, 125, 8078. (c) Pineschi, M.; Moro, F. D.; Crotti, P.; Di
of both aziridine and malonate.
3. CONCLUSION
In summary, we demonstrated the utility of dinuclear Schiff
base catalysis for regiodivergent parallel kinetic resolution of
aziridines with malonates. Both terminal and internal racemic
aziridines reacted smoothly under suitably combined Lewis
acid/Brønsted base catalysis, giving versatile γ-amino acid
derivatives in 96 → 99.5% ee. Further studies are ongoing to
broaden the scope of the regiodivergent reaction,19 such as for
trans-aziridines and other nucleophiles.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimetal details, including procedures, syntheses and
characterization of new products, H and 13C NMR charts,
1
and cif. This material is available free of charge via the Internet
at http://pubs.acs.org.
Bussolo, V.; Macchia, F. J. Org. Chem. 2004, 69, 2099. (c) Gansauer,
̈
A.; Fan, C.-A.; Keller, F.; Keil, J. J. Am. Chem. Soc. 2007, 129, 3484.
(d) Jana, C. K.; Studer, A. Angew. Chem., Int. Ed. 2007, 46, 6542.
(e) Webster, P.; Boing, C.; Lautens, M. J. Am. Chem. Soc. 2009, 131,
444. (e) Miller, L. C.; Ndungu, M. J.; Sarpong, R. Angew. Chem., Int.
AUTHOR INFORMATION
■
Corresponding Authors
mshibasa@bikaken.go.jp
smatsuna@mol.f.u-tokyo.ac.jp
Ed. 2009, 48, 2398. (f) Gansauer, A.; Shi, L.; Otte, M. J. Am. Chem.
̈
Notes
Soc. 2010, 132, 11858. (g) Worthy, A. D.; Sun, X.; Tan, K. L. J. Am.
Chem. Soc. 2012, 134, 7321. (h) Rodrigo, J. M.; Zhao, Y.; Hoveyda, A.
H.; Snapper, M. L. Org. Lett. 2011, 13, 3778. (i) Katayev, D.;
The authors declare no competing financial interest.
Nakanishi, M.; Burgi, T.; Kundig, E. P. Chem. Sci. 2012, 3, 1422.
̈
̈
ACKNOWLEDGMENTS
■
(j) Mulzer, M.; Whiting, B. T.; Coates, G. W. J. Am. Chem. Soc. 2013,
135, 10930. (k) Mulzer, M.; Ellis, W. C.; Lobkovsky, E. B.; Coates, G.
W. Chem. Sci. 2014, 5, 1928. For other early examples, see reviews in
ref 9.
(12) Review: Matsunaga, S.; Shibasaki, M. Chem. Commun. 2014, 50,
1044.
We thank Dr. Sato at RIGAKU and Dr. T. Yoshino (ACT-C,
JST) for assistance in X-ray analysis. This work was supported
in part by ACT-C program from JST, Grant-in-Aid for
Scientific Research (B) from JSPS, and the Naito Foundation
(S.M.).
(13) For selected examples of bifunctional heterobimetallic Schiff
base complexes in asymmetric catalysis, see: (a) Annamalai, V.;
DiMauro, E. F.; Carroll, P. J.; Kozlowski, M. C. J. Org. Chem. 2003, 68,
1973 and references therein. (b) Yang, M.; Zhu, C.; Yuan, F.; Huang,
Y.; Pan, Y. Org. Lett. 2005, 7, 1927. (c) Li, W.; Thakur, S. S.; Chen, S.-
W; Shin, C.-K.; Kawthekar, R. B.; Kim, G.-J. Tetrahedron Lett. 2006,
47, 3453. (d) Hirahata, W.; Thomas, R. M.; Lobkovsky, E. B.; Coates,
G. W. J. Am. Chem. Soc. 2008, 130, 17658. (e) Mazet, C.; Jacobsen, E.
N. Angew. Chem., Int. Ed. 2008, 47, 1762. (f) Mihara, H.; Xu, Y.;
Shepherd, N. E.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2009,
131, 8384.
REFERENCES
■
(1) Reviews: (a) Schneider, C. Angew. Chem., Int. Ed. 2009, 48, 2082.
(b) Wang, P.-A. Beilstein J. Org. Chem. 2013, 9, 1677.
(2) For leading examples with azide, see: (a) Li, Z.; Fernandez, M.;
́
Jacobsen. Org. Lett. 1999, 1, 1611. (b) Fukuta, Y.; Mita, T.; Fukuda,
N.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 6312.
(c) Rowland, E. B.; Rowland, G. B.; Rivera-Otero, E.; Antilla, J. C. J.
Am. Chem. Soc. 2007, 129, 12084. (d) Nakamura, S.; Hayashi, M.;
Kamada, Y.; Sasaki, R.; Hiramatsu, Y.; Shibata, N.; Toru, T.
Tetrahedron Lett. 2010, 51, 3820. With anilines (e) Arai, K.;
Lucarini, S.; Salter, M. M.; Ohta, K.; Yamashita, Y.; Kobayashi, S. J.
Am. Chem. Soc. 2007, 129, 8103. (f) Peruncheralathan, S.; Teller, H.;
Schneider, C. Angew. Chem., Int. Ed. 2009, 48, 4849. (g) Marti, A.;
Peruncheralathan, S.; Schneider, C. Synthesis 2012, 44, 27.
(14) Xu, Y.; Lin, L.; Kanai, M.; Matsunaga, S.; Shibasaki, M. J. Am.
Chem. Soc. 2011, 133, 5791.
(15) Rearrangement of N-acylaziridines to 2-aryloxazoline predom-
inantly proceeded in the absence of basic La(O-iPr)3. For Lewis acid-
promoted rearrangement of N-acylaziridines into oxazolines, see:
Ferraris, D.; Drury, W. J., III; Cox, C.; Lectka, T. J. Org. Chem. 1998,
63, 4568.
(3) Mita, T.; Jacobsen, E. N. Synlett 2009, 1680. See also ref 8b.
(4) (a) Hayashi, M.; Ohno, K.; Hoshimi, H.; Oguni, N. Tetrahedron
1996, 52, 7817. (b) Della Sala, G.; Lattanzi, A. Org. Lett. 2009, 11,
D
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(16) Evaluation of the relative Lewis acidity of rare earth metals:
Tsuruta, H.; Yamaguchi, K.; Imamoto, T. Chem. Commun. 1999, 1703.
(17) (a) Brenner, M.; Seebach, D. Helv. Chim. Acta 1999, 82, 2365.
(b) Seebach, D.; Brenner, M.; Rueping, M.; Jaun, B. Chem.Eur. J.
2002, 8, 573.
(18) For other related examples of bifunctional asymmetric catalysis
using dinucleating Schiff base 1, see refs 6b and 13f. See also:
(a) Yoshino, T.; Morimoto, H.; Lu, G.; Matsunaga, S.; Shibasaki, M. J.
Am. Chem. Soc. 2009, 131, 17082. (b) Lu, G.; Yoshino, T.; Morimoto,
H.; Matsunaga, S.; Shibasaki. Angew. Chem., Int. Ed. 2011, 50, 4382.
(19) Functional group compatibility of the present system also
remained problematic. For example, aziridines bearing an ether
functional group resulted in poor reactivity.
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