Chiral phosphine catalyzed asymmetric michael addition of oxindoles

Article abstract of DOI:10.1002/anie.201208285

Bifunctional phosphines derived from amino acids mediate the asymmetric Michael addition of 3-substituted oxindoles to activated alkenes (see scheme). Biologically relevant chiral 3,3-disubstituted oxindoles were thus prepared in high yields and with exce

Full text of DOI:10.1002/anie.201208285

Angewandte
Chemie
DOI: 10.1002/anie.201208285
Asymmetric Catalysis
Chiral Phosphine Catalyzed Asymmetric Michael Addition of
Oxindoles**
Fangrui Zhong, Xiaowei Dou, Xiaoyu Han, Weijun Yao, Qiang Zhu, Yuezhong Meng, and
Yixin Lu*
Asymmetric synthesis through catalysis by nucleophilic
phosphines has advanced rapidly in recent years as a powerful
and versatile tool for the preparation of chiral organic
molecules.[1] Despite the broad scope of reactions that can
Scheme 1. Phosphine-catalyzed asymmetric Michael addition.
EWG=electron-withdrawing group.
be catalyzed by nucleophilic phosphines, asymmetric reac-
tions mediated by chiral phosphines are very limited. In
a general mode of activation, a tertiary phosphine adds to
activated alkenes, allenes, or alkynes to form a zwitterion,
which then gets trapped by a suitable electrophile. The (aza)-
Morita–Baylis–Hillman (MBH) reaction[2] and various annu-
lations belong to this category. Notably, the 1,3-dipolar nature
of the zwitterions derived from allenes and alkynes, in
combination with a variety of potential 1,3-dipolarophiles,
such as activated alkenes and imines, make annulations highly
divergent and synthetically valuable.[3] Kinetic resolution of
alcohols is another phosphine-promoted asymmetric reaction
that has been relatively well studied.[4] More recently, MBH
adducts have been intensively investigated as a reaction
partner in the allylic alkylations and cycloadditions.[5] On the
other hand, the above-mentioned zwitterion intermediates
can also behave as organic bases for the deprotonation of
pronucleophiles. In fact, employment of such an in situ
generated zwitterion as a base in the Michael addition of 2-
nitropropane to electron-deficient olefins was first reported
by White and Baizer almost four decades ago.[6] Recently, the
utilization of Brønsted basicity of the zwitterionic intermedi-
ates in mechanistically relevant g-additions has drawn much
attention.[7] In sharp contrast, very little attention was paid to
the conceptually simple Michael addition; only a few sporadic
examples were reported,[8] despite the fact that such trans-
formations are synthetically extremely useful.[9] To the best of
our knowledge, there is no report on an asymmetric Michael
addition mediated by a chiral phosphine (Scheme 1). Herein,
we document the first highly enantioselective Michael
additions that were mediated by chiral phosphine catalysts
derived from amino acids.
To demonstrate the value of chiral phosphines in promot-
ing asymmetric Michael addition, we chose 3-substituted
oxindoles[10] as pronucleophiles, as the Michael products of
such reactions, 3,3-disubstituted oxindoles, are molecules of
great biological importance.[11] To our delight, the reaction
between oxindole 1a and methyl vinyl ketone (MVK) 2a
proceeded smoothly in the presence of methyl diphenylphos-
phine (10 mol%), and the Michael adduct 3a was obtained
quantitatively within five minutes (Table 1, entry 1). The
reaction was found to be applicable to a wide range of 3-aryl-
and 3-alkyl-substituted oxindoles (Table 1, entries 2–11). The
Table 1: Michael addition of 3-substitued oxindoles to activated alke-
nes.[a]
Entry R1, R2
EWG (2)
3
t
Yield [%][b]
1
2
3
4
5
6
7
8
C6H5, H
COMe
COMe
COMe
COMe
3a
3b
3c
3d
3e
3 f
3g
3h
3i
5 min
5 min
5 min
5 min
5 min
5 min
12 h
5 min
5 min
5 min
5 min
5 min
98
97
93
90
93
96
98
93
92
95
94
93
92
88
71
63
85
4-F-C6H4, H
4-Ph-C6H4, H
3-Me-C6H4, H
3,5-Me2-C6H3, H COMe
[*] F. Zhong, X. Dou, X. Han, W. Yao, Q. Zhu, Prof. Dr. Y. Lu
Department of Chemistry & Medicinal Chemistry Program
Life Sciences Institute, National University of Singapore
3 Science Drive 3, Singapore 117543 (Singapore)
E-mail: chmlyx@nus.edu.sg
2-naphthyl, H
benzyl, H
C6H5, 5-Me
C6H5, 5-F
C6H5, 7-Cl
C6H5, 5,7-Me2
C6H5, H
C6H5, H
C6H5, H
C6H5, H
C6H5, H
COMe
COMe
COMe
COMe
COMe
COMe
COEt
COPh
CHO
CO2Et
CN
9
10
11
12
13
14
15[c]
16[c]
17
3j
3k
3l
Prof. Dr. Y. Meng
State Key Laboratory of Optoelectronic Materials and Technologies
and the Key Laboratory of Low-Carbon Chemistry & Energy
Conservation of Guangdong Province, Sun Yat-Sen University
Guangzhou 510275 (China)
3m 10 min
3n
3o
3p
5 min
5 h
12 h
6 h
[**] We thank the National University of Singapore and the Ministry of
Education (MOE) of Singapore (R-143-000-362-112), the Singapore-
Peking-Oxford Research Enterprise (COY-15-EWI-RCFSA/N197-1),
and GSK-EDB (R-143-000-491-592) for generous financial support.
=
C6H5, H
(BocN NBoc) 3q
[a] Reactions were performed with 1 (0.1 mmol), 2 (0.3 mmol), and
MePPh2 (0.01 mmol) in CHCl3 (1.0 mL). [b] Yields of isolated products.
[c] Reaction was performed with PPh3 (0.01 mmol) in CH3CN (1 mL)
under reflux. Boc=tert-butoxycarbonyl.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201208285.
Angew. Chem. Int. Ed. 2013, 52, 943 –947
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
943

.
Angewandte
Communications
catalytic system also worked well for other activated terminal
alkenes, including ethyl vinyl ketone, phenyl vinyl ketone, and
acrolein (Table 1, entries 12–14). It is noteworthy that acry-
late and acrylonitrile, which are substrates with lower
reactivity in Michael addition,[12] were also found to be
suitable electrophiles (Table 1, entries 15 and 16). Moreover,
amination of oxindole 3a could be realized with the employ-
ment of di-tert-butyl azodicarboxylate (DBAD; Table 1,
entry 17).
With such a design principle in mind, we investigated the
Michael addition of 3-phenyl oxindole 1a to MVK 2a
mediated by a chiral phosphine (Table 2). A set of bifunc-
tional phosphines derived from amino acids[14] were selected,
which have been shown previously to be high effective,
Table 2: Asymmetric Michael addition of oxindole 1a to MVK 2a
catalyzed by phosphines derived from amino acids.[a]
Our next goal was to develop an enantioselective process
for the above reaction. A plausible mechanism for a phos-
phine-mediated Michael addition is illustrated in Scheme 2.
Entry
Cat.
t
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
5
6a
6b
6c
6d
7
5 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
5 min
95
94
96
97
93
93
91
98
95
89
95
94
95
96
33
20
5
59
30
32
55
27
35
7
9
10
11
12
13[d]
14[e]
Scheme 2. Phosphine-mediated Michael addition.
5
8
4d
4d
19
76
94
10 min
24 h
The conjugate addition of phosphine to electron-deficient
alkenes generates zwitterion A, which deprotonates the
incoming nucleophile, resulting in the formation of an ion
pair that consists of the anionic form of the nucleophile (B)
and phosphonium intermediate C. Subsequently, addition of
B to the alkene substrate leads to enolate D, which abstracts
a proton from the nucleophile to afford the final Michael
adduct E and complete the catalytic cycle. In order to develop
an asymmetric version of this reaction, stereochemical control
has to be in place during the addition of B to the activated
alkene. Apparently, efficient chirality transfer from phospho-
[a] Reactions were performed with 1a (0.05 mmol), 2a (0.15 mmol), and
the catalyst (0.005 mmol) in CHCl3 (0.75 mL). [b] Yields of isolated
products. [c] Determined by HPLC analysis on a chiral stationary phase.
[d] The reaction was performed at 08C. [e] The reaction was performed at
À558C. TBDPS=tert-butyldiphenylsilyl, TBS=tert-butyldimethylsilyl,
TMS=trimethylsilyl, Ts=4-toluenesulfonyl.
À
nium C to the addition product in the C C bond-forming step
through ion-pairing interactions is not trivial, which partly
explains why there was no literature precedent on phosphine-
catalyzed asymmetric Michael addition.[13] We reasoned that
bifunctional phosphines may provide a solution to this long-
standing problem. We hypothesized that employment of
phosphine catalysts that contains an appropriately arranged
hydrogen-bond-donating motif may provide constraint to the
nucleophile–phosphonium ion pair through hydrogen-bond-
ing interaction with the nucleophile, and such a structurally
well-defined ion pair may likely have better stereochemical
interactions with the incoming activated alkene (Scheme 3).
tunable, and versatile in a range of enantioselective organic
transformations.[15] We were pleased to discover that valine-
based catalysts were effective, the reactions were completed
in five minutes and some asymmetric induction was achieved
(Table 2, entries 1–5). In particular, phosphine amide 4d,
which bears a 3,5-bistrifluoromethylbenzoyl group, turned
out to be a promising catalyst, furnishing the desired product
with 59% ee (Table 2, entry 4). However, introduction of
a sterically more-hindered threonine core[16] into the catalyst
structure (6a–c) did not lead to further improvement, nor did
the employment of less-hindered alanine-based compound 5
or compound 6d, which contains a free hydroxy group
Scheme 3. Induction of asymmetry in Michael additions through
bifunctional chiral phosphines.
944
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 943 –947

Angewandte
Chemie
(Table 2, entries 6–10). The dipeptide backbone[3i] also turned
out to be ineffective (Table 2, entries 11–12). Solvent screen-
ing showed that CHCl3 was the best reaction medium (see the
Supporting Information for details). When the reaction was
performed at À558C, the desired Michael adduct was isolated
in 96% yield and with 94% ee (Table 2, entry 14).
Table 4: Michael addition of various 3-alkyl-substituted oxindoles 1 to
different alkenes 2.[a]
The generality of the reaction was next evaluated by
employing various 3-substituted oxindoles (Table 3). Differ-
ent 3-aryl-substituted oxindoles were well tolerated, and high
yields and excellent enantioselectivities were attained
(Table 3, entries 1–7). Moreover, the substituents on the
oxindole core could also be varied, and high yields and ee
values were obtained (Table 3, entries 8–12). The absolute
configurations of the Michael adducts were determined by
comparing the optical rotation of 3a with the reported
value.[10b]
Entry Product
1
Cat. t [h]
3
Yield [%][b] ee [%][c]
6a
6a
72
72
3g
87
75
90
89
2
3u
3
4
6a
4d
72
72
3v
81
78
91
79
Table 3: Michael addition of 3-aryl-substituted oxindoles 1 to 2a.[a]
3w
Entry
Ar, R
3
Yield [%][b]
ee [%][c]
5
6
7
4d
4d
6d
72
24
24
3x
3l
73
92
93
83
88
82
1
2
3
4
5
6
7
8
C6H5, H
3a
3b
3r
3c
3d
3s
3 f
3h
3i
96
93
89
93
91
97
94
95
91
94
90
90
94
92
95
94
89
94
90
95
86
96
86
91
4-F-C6H4, H
4-tBu-C6H4, H
4-Ph-C6H4, H
3-Me-C6H4, H
4-OMe-C6H4, H
2-naphthyl, H
C6H5, 5-Me
C6H5, 5-F
3m
9
10
11
12
C6H5, 7-F
C6H5, 7-Cl
C6H5, 5,7-Me
3t
3j
3k
8
6a
24
3y
83
71
[a] Reactions were performed with 1 (0.05 mmol), 2a (0.15 mmol), and
4d (0.005 mmol) in CHCl3 (0.75 mL). [b] Yields of isolated products.
[c] Determined by HPLC analysis on a chiral stationary phase.
[a] Reactions were performed with 1 (0.05 mmol), 2 (0.15 mmol), and
the catalyst (0.005 mmol) in CHCl3 (0.75 mL). [b] Yields of isolated
products. [c] Determined by HPLC analysis on a chiral stationary phase.
3-Alkyl-substituted oxindoles exhibit much lower reac-
tivity than their aryl-substituted counterparts. Furthermore,
stereochemical controls for these two types of substrates may
be quite different. In fact, few catalytic systems can work well
for both aryl- and alkyl-substituted substrates. Given the
efficiency that our catalysts had displayed for 3-aryl-sub-
stitued oxindoles, and high tunability of our catalytic systems,
we decided to search for a solution by fine-tuning the catalyst
structures. For oxindoles with a benzyl-type substituent at the
3-position, a bulkier catalyst 6a with an OTMS group led to
the formation of adducts with excellent enantiomeric excesses
(Table 4, entries 1–3). For linear or branched 3-alkyl-substi-
tuted oxindole substrates, 4d was found to be the best
catalyst, affording the products with good ee values (Table 4,
entries 4 and 5). Moreover, other electron-deficient alkenes,
including ethyl vinyl ketone, phenyl vinyl ketone, and
acrolein, could also be employed, and good results were
attained (Table 4, entries 6–8).
The phosphorus species that were involved in the reaction
were investigated by 31P NMR spectroscopy.[17] Catalyst 4d
showed a resonance at À22.7 ppm. When 4d was mixed with
MVK, a new resonance at 32.7 ppm appeared, suggesting the
presence of a phosphonium enolate.[18] We also took 31P NMR
spectra during the reaction progress; two resonances at
À22.7 ppm and 32.7 ppm presented in the course of the
reaction. These results suggested that the resting state of the
catalyst is phosphonium ketone C,[19] and there is clearly an
equilibrium between the phosphine catalyst and the phos-
phonium enolate intermediate.
The Brønsted acid moiety of the chiral phosphines was
conceivably crucial for the asymmetric induction. Accord-
ingly, we prepared the N-methylated phosphine 9 and
compared its catalytic effects with those of catalyst 4d
(Table 5). The presence of the amide NH in 4d was shown
to be crucial for both reactivity and enantioselectivity of the
reaction; in the presence of N-methylated 9, the Michael
Angew. Chem. Int. Ed. 2013, 52, 943 –947
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
945

.
Angewandte
Communications
Table 5: Michael additions promoted by different phosphines and the
proposed transition-state model.[a]
[1] For reviews, see: a) X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res.
2001, 34, 535; b) J. L. Methot, W. R. Roush, Adv. Synth. Catal.
2004, 346, 1035; c) L.-W. Ye, J. Zhou, Y. Tang, Chem. Soc. Rev.
2008, 37, 1140; d) B. J. Cowen, S. J. Miller, Chem. Soc. Rev. 2009,
38, 3102; e) A. Marinetti, A. Voituriez, Synlett 2010, 174; f) S.-X.
Wang, X. Han, F. Zhong, Y. Lu, Synlett 2011, 2766; g) Q.-Y.
Zhao, Z. Lian, Y. Wei, M. Shi, Chem. Commun. 2012, 48, 1724;
for related examples, see: h) A. Sakakura, A. Ukai, K. Ishihara,
Nature 2007, 445, 900; i) A. Sakakura, M. Sakuma, K. Ishihara,
Org. Lett. 2011, 13, 3130.
Entry
Cat.
T
t
Yield [%][b]
ee [%][c]
1
2
3
9
9
4d
À558C
RT
RT
24 h
5 h
5 min
trace
94
97
–
13
59
[2] For reviews on (aza)-MBH reactions, see: a) D. Basavaiah, B. S.
Reddy, S. S. Badsara, Chem. Rev. 2010, 110, 5447; b) P. Langer,
Angew. Chem. 2000, 112, 3177; Angew. Chem. Int. Ed. 2000, 39,
3049; c) D. Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev.
2003, 103, 811; d) G. Masson, C. Housseman, J. Zhu, Angew.
Chem. 2007, 119, 4698; Angew. Chem. Int. Ed. 2007, 46, 4614;
e) D. Basavaiah, K. V. Rao, R. J. Reddy, Chem. Soc. Rev. 2007,
36, 1581; f) Y.-L. Shi, M. Shi, Eur. J. Org. Chem. 2007, 2905;
g) G.-N. Ma, J.-J. Jiang, M. Shi, Y. Wei, Chem. Commun. 2009,
5496; h) V. Declerck, J. Martinez, F. Lamaty, Chem. Rev. 2009,
109, 1; i) Y. Wei, M. Shi, Acc. Chem. Res. 2010, 43, 1005.
[3] For selected examples on phosphine-catalyzed annulation reac-
tions, see: a) C. Zhang, X. Lu, J. Org. Chem. 1995, 60, 2906; b) G.
Zhu, Z. Chen, Q. Jiang, D. Xiao, P. Cao, X. Zhang, J. Am. Chem.
Soc. 1997, 119, 3836; c) J. E. Wilson, G. C. Fu, Angew. Chem.
2006, 118, 1454; Angew. Chem. Int. Ed. 2006, 45, 1426; d) B. J.
Cowen, S. J. Miller, J. Am. Chem. Soc. 2007, 129, 10988; e) Y. Q.
Fang, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130, 5660; f) A.
Voituriez, A. Panossian, N. Fleury-Brꢀgeot, P. Retailleau, A.
Marinetti, J. Am. Chem. Soc. 2008, 130, 14030; g) M. Sampath,
T.-P. Loh, Chem. Sci. 2010, 1, 739; h) H. Xiao, Z. Chai, C.-W.
Zheng, Y.-Q. Yang, W. Liu, J.-K. Zhang, G. Zhao, Angew. Chem.
2010, 122, 4569; Angew. Chem. Int. Ed. 2010, 49, 4467; i) X. Han,
Y. Wang, F. Zhong, Y. Lu, J. Am. Chem. Soc. 2011, 133, 1726;
j) Y. Fujiwara, G. C. Fu, J. Am. Chem. Soc. 2011, 133, 12293;
k) H. Guo, Q. Xu, O. Kwon, J. Am. Chem. Soc. 2009, 131, 6318;
l) R. Na, C. Jing, Q. Xu, H. Jiang, X. Wu, J. Shi, J. Zhong, M.
Wang, D. Benitez, E. Tkatchouk, W. A. Goddard III, H. Guo, O.
Kwon, J. Am. Chem. Soc. 2011, 133, 13337; m) Q. Zhang, L.
Yang, X. Tong, J. Am. Chem. Soc. 2010, 132, 2550; n) X. Han, F.
Zhong, Y. Wang, Y. Lu, Angew. Chem. 2012, 124, 791; Angew.
Chem. Int. Ed. 2012, 51, 767.
[a] Reactions were performed with 1a (0.05 mmol), 2a (0.15 mmol), and
the catalyst (0.005 mmol) in CHCl3 (0.75 mL). [b] Yields of isolated
products. [c] Determined by HPLC analysis on a chiral stationary phase.
addition did not proceed at À558C (entry 1), and furnished
the addition product with only 13% ee at room temperature
(entry 2). In comparison, 59% ee was attained when 4d was
used as the catalyst under otherwise identical conditions
(Table 5, entry 3). On the basis of these experimental results,
a plausible transition-state model was presented. We propose
that the hydrogen-bonding interaction between the amide
NH and the enolate oxygen atom of the nucleophile facilitates
formation of the nucleophile–phosphonium ion pair,[20] and
makes the latter more structurally defined. The presence of
the 3,5-CF3-substituted phenyl ring blocks the Re face and
makes the approach of the incoming electrophile from the
Si face more favorable.
[4] a) E. Vedejs, O. Daugulis, S. T. Diver, J. Org. Chem. 1996, 61,
430; b) E. Vedejs, O. Daugulis, J. Am. Chem. Soc. 1999, 121,
5813; c) E. Vedejs, O. Daugulis, J. A. MacKay, E. Rozners,
Synlett 2001, 1499; d) E. Vedejs, O. Daugulis, N. Tuttle, J. Org.
Chem. 2004, 69, 1389.
In summary, we have reported the first highly enantiose-
lective Michael addition of oxindoles catalyzed by chiral
phosphines. It is noteworthy that the asymmetry induced by
the nucleophilic bifunctional phosphine in the Michael
addition is unprecedented, and we believe that this novel
mode of asymmetric induction will extend the scope of
phosphine-mediated asymmetric catalysis and open up new
avenues to the design of enantioselective organic processes.
Currently, we are extending the concept demonstrated in this
report to other important organic transformations, and
theoretical studies to fully understand the origin of the
observed enantioselectivity are also in progress.
[5] For a review, see: a) T.-Y. Liu, M. Xie, Y.-C. Chen, Chem. Soc.
Rev. 2012, 41, 4101; for selected examples with phosphine
catalysis, see: b) Y.-Q. Jiang, Y.-L. Shi, M. Shi, J. Am. Chem. Soc.
2008, 130, 7202; c) C.-W. Cho, J.-R. Kong, M. J. Krische, Org.
Lett. 2004, 6, 1337; d) Q.-G. Wang, S.-F. Zhu, L.-W. Ye, C.-Y.
Zhou, X.-L. Sun, Y. Tang, Q.-L. Zhou, Adv. Synth. Catal. 2010,
352, 1914; e) B. Tan, N. R. Candeias, C. F. Barbas III, J. Am.
Chem. Soc. 2011, 133, 4672; f) F. Zhong, X. Han, Y. Wang, Y. Lu,
Angew. Chem. 2011, 123, 7983; Angew. Chem. Int. Ed. 2011, 50,
7837; g) H.-P. Deng, Y. Wei, M. Shi, Adv. Synth. Catal. 2012, 354,
783; h) F. Zhong, G.-Y. Chen, X. Han, W. Yao, Y. Lu, Org. Lett.
2012, 14, 3764; i) F. Zhong, J. Luo, G.-Y. Chen, X. Dou, Y. Lu, J.
Am. Chem. Soc. 2012, 134, 10222.
Received: October 15, 2012
Published online: December 7, 2012
[6] D. A. White, M. M. Baizer, Tetrahedron Lett. 1973, 14, 3597.
[7] a) B. M. Trost, C.-J. Li, J. Am. Chem. Soc. 1994, 116, 3167; b) C.
Zhang, X. Lu, Synlett 1995, 645; c) B. M. Trost, G. R. Dake, J.
Org. Chem. 1997, 62, 5670; d) B. M. Trost, C.-J. Li, J. Am. Chem.
Soc. 1994, 116, 10819; e) Y. K. Chung, G. C. Fu, Angew. Chem.
2009, 121, 2259; Angew. Chem. Int. Ed. 2009, 48, 2225; f) S. W.
Keywords: alkenes · amino acids · bifunctional phosphines ·
Michael addition · oxindoles
.
946
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 943 –947

Angewandte
Chemie
Smith, G. C. Fu, J. Am. Chem. Soc. 2009, 131, 14231; g) J. Sun,
G. C. Fu, J. Am. Chem. Soc. 2010, 132, 4568; h) R. Sinisi, J. Sun,
G. C. Fu, Proc. Natl. Acad. Sci. USA 2010, 107, 20652; i) Y.
Fujiwara, J. Sun, G. C. Fu, Chem. Sci. 2011, 2, 2196.
Int. Ed. 2010, 49, 7753; h) F. Zhong, G.-Y. Chen, Y. Lu, Org. Lett.
2011, 13, 82; i) F. Zhong, X. Han, Y. Wang, Y. Lu, Chem. Sci.
2012, 3, 1231; j) X. Dou, X. Han, Y. Lu, Chem. Eur. J. 2012, 18,
85.
[8] a) T. Yoshida, S. Saito, Chem. Lett. 1982, 1587; b) R. B. Gross-
man, D. S. Pendharkar, B. O. Patrick, J. Org. Chem. 1999, 64,
7178; c) I. C. Stewart, R. G. Bergman, F. D. Toste, J. Am. Chem.
Soc. 2003, 125, 8696; d) G.-L. Zhao, M. Shi, Tetrahedron 2005,
61, 7277; e) C. Gimbert, M. Lumbierres, C. Marchi, M. Moreno-
MaÇas, R. M. Sebastiꢁn, A. Vallribera, Tetrahedron 2005, 61,
8598; f) V. Sriramurthy, G. A. Barcan, O. Kwon, J. Am. Chem.
Soc. 2007, 129, 12928; g) X. Wang, F. Fang, C. Zhao, S.-K. Tian,
Tetrahedron Lett. 2008, 49, 6442; h) D. Bhuniya, S. Mohan, S.
Narayanan, Synthesis 2003, 1018; i) O. Baslꢀ, S. Porcel, S.
Ladeira, G. Bouhadir, D. Bourissou, Chem. Commun. 2012, 48,
4495.
[12] Michael additions of 3-substituted oxindoles to acrylates and
acrylonitrile are unknown; employment of one equivalent of
DIPEA or DBU did not give the desired adduct.
[13] R. B. Grossman, S. Comesse, R. M. Rasne, K. Hattori, M. N.
Delong, J. Org. Chem. 2003, 68, 871.
[14] For reviews on asymmetric catalysis mediated by amino acids
and peptides, see: a) L.-W. Xu, J. Luo, Y. Lu, Chem. Commun.
2009, 1807; b) L.-W. Xu, Y. Lu, Org. Biomol. Chem. 2008, 6,
2047; c) E. A. C. Davie, S. M. Mennen, Y. Xu, S. J. Miller, Chem.
Rev. 2007, 107, 5759.
[15] For our recent account, see reference [1f]; for examples reported
by us, see: a) F. Zhong, Y. Wang, X. Han, K.-W. Huang, Y. Lu,
Org. Lett. 2011, 13, 1310; b) X. Han, Y. Wang, F. Zhong, Y. Lu,
Org. Biomol. Chem. 2011, 9, 6734; c) X. Han, S.-X. Wang, F.
Zhong, Y. Lu, Synthesis 2011, 1859; d) Q. Zhao, X. Han, Y. Wei,
M. Shi, Y. Lu, Chem. Commun. 2012, 48, 970; also see references
[3i,n, 5f,h,i, 11i]; for other examples, see: e) K. Ishihara, Y.
Kosugi, M. Akakura, J. Am. Chem. Soc. 2004, 126, 12212; f) Y.
Kosugi, M. Akakura, K. Ishihara, Tetrahedron 2007, 63, 6191;
g) K. Ishihara, Y. Kosugi, S. Umemura, A. Sakakura, Org. Lett.
2008, 10, 3191; h) A. Sakakura, S. Umemura, K. Ishihara, Synlett
2009, 1647.
[16] a) L. Cheng, X. Han, H. Huang, M. W. Wong, Y. Lu, Chem.
Commun. 2007, 4143; b) L. Cheng, X. Wu, Y. Lu, Org. Biomol.
Chem. 2007, 5, 1018; c) X. Wu, Z. Jiang, H.-M. Shen, Y. Lu, Adv.
Synth. Catal. 2007, 349, 812; d) Q. Zhu, Y. Lu, Chem. Commun.
2010, 46, 2235; e) X. Dou, F. Zhong, Y. Lu, Chem. Eur. J. 2012,
18, 13945; also see references[3i,n, 5f,h,i, 11i,j, 15a – d].
[17] See the Supporting Information for 31P NMR spectra.
[18] H. G. Alt, H. I. Hayen, J. Organomet. Chem. 1986, 316, 301.
[19] This result is consistent with an observed phosphonium ketone
intermediate, see [8c].
[9] For reviews, see: a) D. Almas¸i, D. A. Alonso, C. Najera,
Tetrahedron: Asymmetry 2007, 18, 299; b) S. B. Tsogoeva, Eur.
J. Org. Chem. 2007, 1701.
[10] For selected examples on the Michael additions of 3-substituted
oxindoles, see: a) T. Bui, S. Syed, C. F. Barbas III, J. Am. Chem.
Soc. 2009, 131, 8758; b) R. He, C. Ding, K. Maruoka, Angew.
Chem. 2009, 121, 4629; Angew. Chem. Int. Ed. 2009, 48, 4559;
c) Y. Kato, M. Furutachi, Z. Chen, H. Mitsunuma, S. Matsunaga,
M. Shibasaki, J. Am. Chem. Soc. 2009, 131, 9168; d) R. He, S.
Shirakawa, K. Maruoka, J. Am. Chem. Soc. 2009, 131, 16620;
e) X. Li, B. Zhang, Z.-G. Xi, S. Luo, J.-P. Cheng, Adv. Synth.
Catal. 2010, 352, 416; f) T. Zhang, L. Cheng, S. Hameed, L. Liu,
D. Wang, Y.-J. Chen, Chem. Commun. 2011, 47, 6644; g) C.
Wang, X. Yang, D. Enders, Chem. Eur. J. 2012, 18, 4832.
[11] For reviews, see: a) C. Marti, E. M. Carreira, Eur. J. Org. Chem.
2003, 2209; b) R. M. Williams, R. J. Cox, Acc. Chem. Res. 2003,
36, 127; c) H. Lin, S. J. Danishefsky, Angew. Chem. 2003, 115, 38;
Angew. Chem. Int. Ed. 2003, 42, 36; d) C. V. Galliford, K. A.
Scheidt, Angew. Chem. 2007, 119, 8902; Angew. Chem. Int. Ed.
2007, 46, 8748; e) B. M. Trost, M. K. Brennan, Synthesis 2009,
3003; f) F. Zhou, Y.-L. Liu, J. Zhou, Adv. Synth. Catal. 2010, 352,
1381; for our work on constructing chiral oxindole cores, see:
g) Q. Zhu, Y. Lu, Angew. Chem. 2010, 122, 7919; Angew. Chem.
[20] A. Sakakura, R. Kondo, Y. Matsumura, M. Akakura, K.
Ishihara, J. Am. Chem. Soc. 2009, 131, 17762.
Angew. Chem. Int. Ed. 2013, 52, 943 –947
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
947