Facile and efficient enantioselective hydroxyamination reaction: Synthesis of 3-hydroxyamino-2-oxindoles using nitrosoarenes

Article abstract of DOI:10.1002/anie.201100758

Sc takes action: The highly enantioselective hydroxyamination reaction of N-unprotected 2-oxindoles with nitrosoarenes has been realized using the Sc(OTf)₃/L1 complex. The catalyst system exhibited remarkably broad substrate scope and high effi

Full text of DOI:10.1002/anie.201100758

Communications
DOI: 10.1002/anie.201100758
Asymmetric Catalysis
Facile and Efficient Enantioselective Hydroxyamination Reaction:
Synthesis of 3-Hydroxyamino-2-Oxindoles Using Nitrosoarenes**
Ke Shen, Xiaohua Liu, Gang Wang, Lili Lin, and Xiaoming Feng*
Nitroso compounds are interesting reagents that are used in
synthetic organic chemistry mainly because of their applica-
tion in functional group transformations.[1–2] Nitrosoarenes
have been widely recognized as an attractive electrophile in
catalytic asymmetric nitroso aldol reactions. Organocatalysts
having hydrogen-bond donors such as amide or hydroxy
groups were used to control the regioselectivity of the nitroso
aldol reaction through hydrogen bonding to nitrogen or
oxygen atoms of the nitrosoarene.[2] Usually, the amino-
xylation reaction of carbonyl compounds proceeds to give a-
oxygenated compounds as the major products because of the
higher basicity of the hydrogen bond between the nitrogen
and the hydrogen atoms compared with that between the
oxygen and hydrogen atoms.[3] In contrast, only a few
contributions on the enantioselective hydroxyamination reac-
tion through the electrophilic attack on the nitrogen group of
the nitrosoarene have been reported to give a-amino com-
pounds; the reports focused on a-branched aliphatic alde-
hydes,[4] enolates,[5a] cyclic ketones,[5b] and a-cyanopropio-
nates.[6] However, it is still a challenge to control the chemo-
and enantioselectivity of the products by other methods,
owing to the high reactivity of nitrosoarene.
Oxindoles constitute an important structural motif in the
library of natural products and biologically active drugs.
Recently, Barbas and co-workers developed an asymmetric
aminoxylation reaction of N-protected 3-substituted-2-oxin-
doles, thus delivering the desired O adducts (Figure 1a).[3b]
The hydroxyamination reaction of oxindoles would provide
access to optically active 3-amino oxindole derivatives,[7–8]
which present common structural motifs in a variety of
bioactive molecules such as NITD609 and SSR-149415, the
drug candidates for the treatment of malaria and stress-
related disorders, respectively.[9] In view of this, a highly
enantioselective synthesis of 3-hydroxyamino-2-oxindole is
therefore considered to be in high demand. Such a reaction
has been recently reported as being promoted by a cinchona
Figure 1. Projected synthesis of chiral hydroxyamino oxindoles. The
aminoxylation (a) versus the hydroxyamination (b) reaction of 2-
oxindoles. RE=rare-earth metal, PG=protecting group, TS=transition
state.
alkaloid catalyst, but there is room for improvement in terms
of enantioselectivity and efficiency.[7]
Given our long-standing work in the development of
catalysts derived from rare-earth metal/N,N’-dioxide com-
plexes,[10] we envisioned that a rare-earth metal might
coordinate with the oxygen atom of a nitrosoarene as a
result of its strong oxygen affinity. The enolate would then
preferentially attack the nitrogen atom of the nitroso group to
provide direct access to enantioenriched hydroxyamino
oxindoles (Figure 1b). Herein, we address these issues and
describe a general, practical, and highly enantioselective
hydroxyamination of N-unprotected 3-substituted-2-oxin-
doles with nitrosoarenes in up to 98% yield with 98% ee
using a ScIII/N,N’-dioxide complex.
Initially, owing to the importance of protecting-group-free
synthetic strategies,[9d,11] we probed the optimal reaction
conditions using commercially available 3-methyl-2-oxindole
(1a) and nitrosobenzene as model substrates. The hydrox-
yamination reaction was effectively promoted by a 1:1
Sc(OTf)3/L1 complex in CH3CCl3 at 308C, thus giving the
N-nitroso aldol product 2aa in 88% yield with 90% ee and
trace amounts of the O-adduct 3 (Table 1, entry 1).[12] The
absolute configuration of 2aa was unambiguously determined
to be R by comparision of the optical rotation with that of the
known compound (Scheme 1). Ligands L2 and L3, which
have less sterically hindered substituents at the phenyl ring,
afforded less satisfactory results (Table 1, entries 2 and 3).
Other rare-earth-metal sources, such as La(OTf)3, Lu(OTf)3,
and Sm(OTf)3 only resulted in trace amounts of products. This
phenomenon could be attributed to the smallest ionic radius
and strongest Lewis acidity that ScIII possesses among the
rare-earth metals. When N,N’-dioxide L4 (derived from l-
proline) and L5 (derived from l-ramipril) were used instead
of L1 (l-pipecolic acid derived), the enantioselectivities
[*] K. Shen, Dr. X. H. Liu, G. Wang, Dr. L. L. Lin, Prof. Dr. X. M. Feng
Key Laboratory of Green Chemistry & Technology
Ministry of Education, College of Chemistry
Sichuan University, Chengdu 610064 (China)
Fax: (+86)28-8541-8249
E-mail: xmfeng@scu.edu.cn
[**] We acknowledge the National Natural Science Foundation of China
(Nos. 2073 2003 and 21021001 and 20872096) and the National
Basic Research Program of China (973 Program: No.
2010CB833300) for financial support, and Sichuan University
Analytical & Testing Centre for NMR analysis.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201100758.
4684
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 4684 –4688

Table 1: Optimization of the reaction conditions.[a]
decreased to 50% and 62% ee, respectively (Table 1, entries 4
and 5 versus entry 1).
The molar ratio of ligand L1 to the central metal ion ScIII
was found to be another important factor for reactivity
(Table 1, entries 6–10). To our delight, the reaction was
completed in 20 minutes when a small excess of L1 was
employed (Table 1, entry 6). The optimal ratio of Sc(OTf)3 to
L1 was determined to be 1:1.5 to meet the requirements of
atom economy and efficiency (Table 1, entry 7). In contrast,
2aa was not detected in the absence of L1 (Table 1, entry 10).
Thus, according to the remarkable enhancement on reactivity,
the enantioselective addition in the presence of Sc(OTf)3/L1
should be a ligand-accelerated process.[13] Excess Sc(OTf)3
significantly reduced the ee value of 2aa (Table 1, entry 9).
Surprisingly, even without stirring, the corresponding product
was isolated in good yield with an excellent ee value (Table 1,
entry 8). Lowering the temperature resulted in a longer
reaction time and diminished enantiocontrol (Table 1,
entry 11 versus 7). However, lowering the reaction temper-
ature and diluting the reaction mixture caused a slight
improvement in enantioselectivity (Table 1, entry 12 versus
11). Judging from these phenomena, the actual source N
should be the nitrosobenzene monomer, which was dissoci-
ated from the azodioxy dimer.[1b] Combined with the ligand-
acceleration catalysis, the introduction of an excess of L1
might suppress the coordination between scandium and the
azodioxy dimer. Notably, the reaction process could be
monitored by the naked eye since the reaction mixture
quickly changed from clear green solution to yellowish
suspension upon completion.
Entry
Ligand Ratio of Sc(OTf)3/L t [h]
Yield [%][b] ee [%][c]
1
2
3
4
5
6
L1
L2
L3
L4
L5
L1
L1
L1
L1
–
1:1
1:1
1:1
1:1
1:1
2:1
1:1.5
1:1.5
1.5:1
1:0
24
24
24
24
24
88
65
44
90
82
90 (R)
67
54
50
62
94
95
94
30
–
0.2 93
0.3 92
7[d]
8[d,e]
9
3
36
72
24
24
88
61
trace
95
10[f]
11[d,g]
L1
1:1.5
1:1.5
85
90
12[d,g,h] L1
92
[a] Reaction conditions (unless noted otherwise): 0.1 mmol scale with
respect to 1, catalyst (5 mol%), CH3CCl3 (1.0 mL). [b] Yield of isolated
2aa. [c] Determined by HPLC on a chiral stationary phase. [d] Used
3.3 mol% catalyst. [e] The reaction mixture was not stirred. [f] The
reaction was performed without L1. [g] At 08C. [h] In 3.0 mL CH3CCl3.
Encouraged by these initial results, we further explored
the scope of the transformations with a series of N-unpro-
tected oxindoles under the same reaction conditions. In each
case, the reaction was complete in only 20 to 60 minutes.
Evaluation of the substrate scope revealed that a high level of
regio- and enantioselectivity could be achieved (Table 2).[14]
The length of a linear saturated alkyl group at C3 of the
oxindoles had little effect upon the enantioselectivity
(Table 2, entries 1–4). With the 3-allyl-substituted oxindole
1e, the enantiomeric excess of the desired N adduct was still
excellent (Table 2, entry 5); this result is meaningful as the
unsaturated alkyl group is a useful handle for additional
functional group manipulation. 3-Benzyloxindole could be
consumed rapidly to deliver the corresponding adduct 2 fa
with 95% ee (Table 2, entry 6). The aromatic ring of R1 with
both electron-donating groups (Table 2, entries 7–10) and
electron-withdrawing groups (Table 2, entries 11–14)
afforded products in 90–94% yield with 90–97% ee. The
oxindole 1o bearing a bulky naphthylmethyl group reacted
quickly with nitrosobenzene, thus giving the desired products
with excellent enantioselectivity (up to 98% ee; Table 2,
entry 15). Remarkably, more challenging heterocyclic groups
containing 1p and 1q were also tolerated (Table 2, entries 16–
17). In addition, this method was compatible with the
modification of the benzo moiety of oxindole core (Table 2,
entries 18–20).
Scheme 1. Synthetic utility of this hydroxyamination reaction. Reagents
and conditions: a) 1a (1.47 g, 10 mmol), Sc(OTf)3/L1 (3.3 mol%),
PhNO (1.18 g, 11 mmol), CH3CCl3 (40 mL), 308C, 1.5 h, 82% yield,
94% ee; b) 2aa (2.08 g, 8.2 mmol) 10% Pd/C (0.2 g), NaBH4 (0.912 g,
24 mmol), H2, MeOH (20 mL), RT, 3 h, 95% yield, 94% ee; c) (R)-6
(0.49 g, 3 mmol) Cu2O (0.014 g, 0.1 mmol), NMP (2 mL), PhI (0.61 g,
3 mmol), 1408C, 72 h, 10% yield, 85% ee,; d) 2ah (28.4 g, 0.1 mmol)
10% Pd/C (3 mg), NaBH4 (11.3 g, 0.3 mmol), H2, MeOH (5 mL), RT,
3 h; e) CAN (164 mg, 0.3 mmol), aq. CH3CN (3 mL), 08C, 10 min,
64% yield in two steps from 2ah, 92% ee. CAN=ammonium cerium
nitrate, DMF=N,N’-dimethylformamaide, NMP=N-methylpyrrolidi-
none, PMP=p-methoxyphenyl.
A broad spectrum of nitrosoarenes could be employed in
the reaction to afford the desired N-addition products in
excellent yields and high enantioselectivities (Table 3) with
Angew. Chem. Int. Ed. 2011, 50, 4684 –4688
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 4685

Communications
Table 2: Catalytic asymmetric hydroxyamination reaction of oxindoles 1
with nitrosobenzene 4a.[a]
Table 3: Catalytic asymmetric hydroxyamination reaction of 3-methyl-2-
oxindole (1a) with nitrosoarenes 4.[a]
Entry
4
Product
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4 f
2aa
2ab
2ac
2ad
2ae
2af
0.3
0.5
1
0.5
0.5
1
92
88
92
90
66
90
85
95
95
90
94
92
92
88
89
92
Entry
1
Product
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1 f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
2aa
2ba
2ca
2da
2ea
2 fa
2ga
2ha
2ia
0.3
1
0.5
0.5
0.5
1
1
1
1
1
0.5
0.5
0.5
0.5
1
1
1
0.5
0.3
0.3
92
91
92
89
98
97
94
93
95
90
92
93
91
93
95
89
93
98
92
90
95
92
90
92
94
95
97
94
95
90
90
94
95
97
98
92
92
90
91
91
4g
4h
2ag
2ah
1
3
[a] For details, see the Supporting Information. [b] Yield of the isolated
product. [c] Determined by HPLC on a chiral stationary phase.
selective product. Removal of the OH group of 2ah and
removal of the p-methoxyphenyl (PMP) group[17] were
carried out under conventional conditions to give 3-amino-
3-methyloxindole (R)-6 in good yield without loss of enan-
tioselectivity (Scheme 1).
9
10
11
12
13
14
15
16
17
18
19
20
2ja
2ka
2la
2ma
2na
2oa
2pa
2qa
2ra
2sa
2ta
Recently, Sibi and Hasegawa,[18a] and Maruoka and co-
workers[18b] reported the asymmetric a-aminoxylation of
aldehydes using the stable radical 2,2,6,6-tetramethylpiper-
idine 1-oxyl free radical (TEMPO). To the best of our
knowledge, there have been no reports of the addition
reaction of TEMPO involving amides such as 2-oxindole. As a
special nitroso reagent in the preparation of a-hydroxy
carbonyl compounds, we did some preliminary investigations.
Pleasingly, the Sc(OTf)3/L4 complex was effective for this
reaction, thus delivering 3-hydroxy-3-methyl-2-oxindole with
a moderate ee value (Scheme 2). The reason for the cleavage
1s
1t
[a] For details, see the Supporting Information. [b] Yield of isolated
product. [c] Determined by HPLC on a chiral stationary phase.
the exception of 2-methyl-nitrosobenzene (Table 3, entry 5),
wherein by-products were observed. A prolonged reaction
time was required for consumption of 4-methoxyl-2-nitro-
sobenzene to deliver the stable nitrogen-selective product
2ah (Table 3, entry 8).
To further evaluate the synthetic potential of the catalytic
system, the reaction was conducted on a gram scale with no
loss in the ee value (Scheme 1). The oxindole 1a reacted with
dibenzyl azodicarboxylate in the presence of Sc(OTf)3/L1
with the subsequent sequential reduction using Pd/C and
raney nickel under a hydrogen atmosphere to generate (R)-6
in a 30% yield with 85% ee.[8e] The known compound (R)-6
was transformed into (R)-5 by the reported method[15] (not
optimized). In contrast, product 2aa (94% ee) could be
readily transformed into the corresponding amine (R)-5 in
95% yield with retention of enantiopurity using 10% Pd/C
and three equivalents of sodium borohydride under mild
ꢀ
of the N O bond was uncertain, but might be ascribed to the
bulky quaternary carbon center at the 3 position of 8. The
absolute configuration of 8 was unambiguously determined to
be R by comparision of the optical rotation with that that was
previously described.[19]
Scheme 2. Catalytic asymmetric synthesis of 3-hydroxy-3-methyl-2-oxin-
dole 8 using TEMPO as the O source.
While a detailed mechanism for this transformation is
unknown, we propose that the Sc(OTf)3/N,N’-dioxide com-
plex[10b] allows activation of both the nucleophile and electro-
phile simultaneously, as shown in Scheme 3. The in-situ
formed catalyst (real active species), which was generated
from L1 and Sc(OTf)3, deprotonated the a position of 1a to
ꢀ
reaction conditions (Scheme 1). The N O cleavage proce-
dure[16] was a modification to the existing reduction methods,
ꢀ
and was more convenient than the direct C N coupling
method to deliver 3-arylamino-2-oxindole. Moreover, this
transformation further validated the formation of the N-
4686 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 4684 –4688

Experimental Section
A mixture of L1 (5 mol%), Sc(OTf)3 (3.3 mol%), and oxindole 1a
(0.1 mmol) was stirred in CH3CCl3 (0.5 mL) at 358C for 1 h.
Nitrosobenzene (1.1 equiv) and additional CH3CCl3 (0.5 mL) were
added to the reaction mixture at 08C. Then the reaction was stirred at
308C for 20 min. The crude reaction mixture was dissolved in 0.3 mL
of THF to get a clear solution before purification by chromatography
on silica gel (petroleum ether/EtOAc 2:1) to afford product 2aa in
20
92% yield with 95% ee. ½aꢁD ¼ꢀ60.2 (c = 0.28, in THF). 1H NMR
(400 MHz, DMSO): d = 10.27 (s, 1H), 8.93 (s, 1H), 7.14 (dt, J = 12.3,
7.9 Hz, 3H), 7.10–7.04 (m, 3H), 6.99 (t, J = 7.1 Hz, 1H), 6.87 (t, J =
7.5 Hz, 1H), 6.69 (d, J = 7.7 Hz, 1H), 1.48 ppm (s, 3H). 13C NMR
(100 MHz, DMSO): d = 185.10, 150.44, 141.88, 130.95, 128.85, 127.96,
125.24, 124.54, 122.71, 121.49, 109.74, 70.72, 23.69 ppm. IR nmax (KBr,
film): n = 3197, 3088, 1715, 1332, 1211 cmꢀ1. HRMS (ESI): calcd for
~
C15H14N2O2 [M+Na+] 277.0947, found 277.0954.
Received: January 29, 2011
Revised: March 14, 2011
Published online: April 14, 2011
Keywords: amination · asymmetric catalysis · nitrosoarenes ·
.
oxindoles · scandium
Scheme 3. Proposed catalytic process.
[1] For early reviews on nitroso compounds, see: a) P. Zuman, B.
Shah, Chem. Rev. 1994, 94, 1621 – 1641; b) J. Lee, L. Chen, A. H.
West, G. B. Richter-Addo, Chem. Rev. 2002, 102, 1019 – 1065.
[2] For reviews, see: a) J. M. Janey, Angew. Chem. 2005, 117, 4364 –
4372; Angew. Chem. Int. Ed. 2005, 44, 4292 – 4300; b) H.
Yamamoto, N. Momiyama, Chem. Commun. 2005, 3514 – 3525;
c) G. Guillena, D. J. Ramꢀn, Tetrahedron: Asymmetry 2006, 17,
1465 – 1492; d) H. Yamamoto, M. Kawasaki, Bull. Chem. Soc.
Jpn. 2007, 80, 595 – 607; e) F. L. S. Da Machado, Synlett 2008,
3075 – 3076; f) H. Yamamoto, S. Saito, N. Momiyama, J. Synth.
Org. Chem. Jpn. 2008, 66, 774 – 784; g) A. Yanagisawa, T. Arai,
Chem. Commun. 2008, 1165 – 1172; h) T. Vilaivan, W. Bhan-
thumnavin, Molecules 2010, 15, 917 – 958.
[3] For previous work, see Ref. [2] and references cited therein; for
the most recent work, see: a) A. Yanagisawa, S. Takeshita, Y.
Izumi, K. Yoshida, J. Am. Chem. Soc. 2010, 132, 5328 – 5329;
b) T. Bui, N. R. Candeias, C. F. Barbas III, J. Am. Chem. Soc.
2010, 132, 5574 – 5575; c) M. Lu, Y. P. Lu, D. Zhu, X. F. Zeng,
X. S. Li, G. F. Zhong, Angew. Chem. 2010, 122, 8770 – 8774;
Angew. Chem. Int. Ed. 2010, 49, 8588 – 8592; d) A. Mielgo, I.
Velilla, E. Gꢀmez-Bengoa, C. Palomo, Chem. Eur. J. 2010, 16,
7496 – 7502; e) X. Ding, W. Tang, C. Zhu, Y. Cheng, Adv. Synth.
Catal. 2010, 352, 108 – 112.
give chiral scandium enolate T1.[10g] T1 coordinates with the
oxygen atom of nitrosobenzene monomer because of the
oxygen affinity characteristic of scandium to form intermedi-
ate T2. The coordination between the chiral Sc(OTf)3/N,N’-
dioxide complex and the oxygen atoms of both the oxindole
and nitrosobenzene serve not only to activate both the
nucleophile and electrophile at the same time, but also force
the two substrates to be in closer proximity to one another.
Coupled with the possible hydrogen-bonding interactions
ꢀ
between the N H group of the oxindole and the carbonyl
moiety of the ligand, the observed unprecedented enantiose-
lectivity can be rationalized. The zwitterionic enolate pro-
posed by Barbas and co-workers might react with nitro-
sobezene in an O-selective fashion, presumably as a result of
the directing effect of the hydroxy group of the catalyst that
makes the oxygen atom more electrophilic (Figure 1a).[3b]
As revealed in Scheme 3, in this Sc(OTf)3/L1 catalyst
system, the nucleophile attacks the Re face through a
plausible six-membered cyclic transition state predominantly
to give the R-configured N-addition intermediate T3, which
was in accordance with the experimental results. Subsequent
protonation by HOTf afforded the N-adduct 2aa, and
regenerated the catalyst.
[4] a) T. Kano, M. Ueda, J. Takai, K. Maruoka, J. Am. Chem. Soc.
2006, 128, 6046 – 6047; b) H. M. Guo, L. Cheng, L. F. Cun, L. Z.
Gong, A. Q. Mi, Y. Z. Jiang, Chem. Commun. 2006, 429 – 431;
c) C. Palomo, S. Vera, I. Velilla, A. Mielgo, E. Gꢀmez-Bengoa,
Angew. Chem. 2007, 119, 8200 – 8202; Angew. Chem. Int. Ed.
2007, 46, 8054 – 8056.
In conclusion, we report a highly efficient enantioselective
hydroxyamination of N-unprotected 3-substituted-2-oxin-
doles catalyzed by a chiral Sc(OTf)3/N,N’-dioxide complex.
This transformation utilizes readily available nitrosoarenes as
nitrogen sources. A series of N-selective products are
obtained in good to excellent yields with excellent enantio-
selectivities within a very short reaction time. We are
currently working on the improvement of the synthesis of
chiral 3-hydroxy-2-oxindole using TEMPO, and ascertaining
the mechanistic details of the hydroxyamination reaction of
oxindoles as well.
[5] a) N. Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2004, 126,
5360 – 5361; b) N. Momiyama, H. Yamamoto, J. Am. Chem. Soc.
2005, 127, 1080 – 1081.
[6] J. Lꢀpez-Cantarero, M. B. Cid, T. B. Poulsen, M. Bella, J. L. G.
Ruano, K. A. Jøgensen, J. Org. Chem. 2007, 72, 7062 – 7065.
[7] T. Zhang, L. Cheng, L. Liu, D. Wang, Y. J. Chen, Tetrahedron:
Asymmetry 2010, 21, 2800 – 2806 (In this reference there are nine
examples of obtaining products with ee values of around 60–
70%).
[8] For intensive studies on amination reaction of oxindoles with
azodicarboxylate esters, see: a) L. Cheng, L. Liu, D. Wang, Y. J.
Chen, Org. Lett. 2009, 11, 3874 – 3877; b) Z. Q. Qian, F. Zhou,
Angew. Chem. Int. Ed. 2011, 50, 4684 –4688
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 4687

Communications
T. P. Du, B. L. Wang, M. Ding, X. L. Zhao, J. Zhou, Chem.
2010, 122, 6296 – 6300; Angew. Chem. Int. Ed. 2010, 49, 6160 –
6164; f) W. Li, J. Wang, X. L. Hu, K. Shen, W. T. Wang, Y. Y.
Chu, L. L. Lin, X. H. Liu, X. M. Feng, J. Am. Chem. Soc. 2010,
132, 8532 – 8533; g) K. Shen, X. H. Liu, W. T. Wang, G. Wang,
W. D. Cao, W. Li, X. L. Hu, L. L. Lin, X. M. Feng, Chem. Sci.
2010, 1, 590 – 595.
Commun. 2009, 6753 – 6755; c) T. Bui, M. Borregan, C. F.
Barbas III, J. Org. Chem. 2009, 74, 8935 – 8938; d) S. Mouri,
Z. H. Chen, H. Mitsunuma, M. Furutachi, S. Matsunaga, M.
Shibasaki, J. Am. Chem. Soc. 2010, 132, 1255 – 1257; e) Z. G.
Yang, Z. Wang, S. Bai, K. Shen, D. H. Chen, X. H. Liu, L. L. Lin,
X. M. Feng, Chem. Eur. J. 2010, 16, 6632 – 6637; f) T. Bui, G.
Hernꢁndez-Torres, C. Milite, C. F. Barbas III, Org. Lett. 2010, 12,
5696 – 5699.
[11] For a recent review, see: I. S. Young, P. S. Baran, Nat. Chem.
2009, 1, 193 – 205.
[12] For detailed solvent screening, see the Supporting Information.
[13] For reviews on ligand-acceleration catalysis, see: a) D. J. Berris-
ford, C. Bolm, K. B. Sharpless, Angew. Chem. 1995, 107, 1159 –
1171; Angew. Chem. Int. Ed. Engl. 1995, 34, 1059 – 1070; b) J. W.
Faller, A. R. Lavioe, J. Parr, Chem. Rev. 2003, 103, 3345 – 3367.
[14] When using 3-phenyl-2-oxindole as a substrate, the N-adduct
slightly decomposed into the starting material during the
purification by flash chromatography on silica gel. No desired
N-adducts were obtained using N-Boc-3-methyl-2-oxindole and
N-methyl-3-methyl-2-oxindole as substrates.
[9] For selected reviews and examples, see: a) R. M. Williams, R. J.
Cox, Acc. Chem. Res. 2003, 36, 127 – 139; b) A. K. Franz, P. D.
Dreyfuss, S. L. Schreiber, J. Am. Chem. Soc. 2007, 129, 1020 –
1021; c) J. T. Mohr, M. R. Krout, B. M. Stoltz, Nature 2008, 455,
323 – 332; d) F. Zhou, Y. L. Liu, J. Zhou, Adv. Synth. Catal. 2010,
352, 1381 – 1407.
[10] For selected examples of studies on rare-earth metal/N,N’-
dioxide complexes, see: a) Z. P. Yu, X. H. Liu, Z. H. Dong, M. S.
Xie, X. M. Feng, Angew. Chem. 2008, 120, 1328 – 1331; Angew.
Chem. Int. Ed. 2008, 47, 1308 – 1311; b) Y. L. Liu, D. J. Shang, X.
Zhou, X. H. Liu and X. M. Feng, Chem. Eur. J. 2009, 15, 2055 –
2058; c) M. S. Xie, X. H. Chen, Y. Zhu, B. Gao, L. L. Lin, X. H.
Liu, X. M. Feng, Angew. Chem. 2010, 122, 3887 – 3890; Angew.
Chem. Int. Ed. 2010, 49, 3799 – 3802; d) Y. H. Hui, J. Jiang, W. T.
Wang, W. L. Chen, Y. F. Cai, L. L. Lin, X. H. Liu, X. M. Feng,
Angew. Chem. 2010, 122, 4386 – 4389; Angew. Chem. Int. Ed.
2010, 49, 4290 – 4293; e) Y. F. Cai, X. H. Liu, Y. H. Hui, J. Jiang,
W. T. Wang, W. L. Chen, L. L. Lin, X. M. Feng, Angew. Chem.
[15] H. H. Xu, C. Wolf, Chem. Commun. 2009, 1715 – 1717.
[16] The use of Pd/C only as reducing reagent caused cleavage of the
ꢀ
C N bond at the 3 position of 2aa.
[17] T. Nishikawa, S. Kajii, M. Isobe, Chem. Lett. 2004, 33, 440 – 441.
[18] a) M. P. Sibi, M. Hasegawa, J. Am. Chem. Soc. 2007, 129, 4124 –
4125; b) T. Kano, H. Mii, K. Maruoka, Angew. Chem. 2010, 122,
6788 – 6791; Angew. Chem. Int. Ed. 2010, 49, 6638 – 6641.
[19] T. Ishimaru, N. Shibata, J. Nagai, S. Nakamura, T. Toru, S.
Kanemasa, J. Am. Chem. Soc. 2006, 128, 16488 – 16489.
4688 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 4684 –4688