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COMMUNICATION
Journal Name
reaction would be more convenient in potential industrial
applications.
National Natural Science Foundation of China (Grant No.
21272024).
DOI: 10.1039/C6CC00705H
Boc
Boc
O
N
O
Ph
O
O
Ph3P
Boc
N
Boc
Notes and references
5
CH2Cl2
rt, 20 h
1b
N
Boc
+
O
1
For reviews on biologically active oxindole‐containing
compounds, see: (a) K. B. V. S. Suneel, L. Narasu, R. Gundla, R.
Dayam and J. A. R. P. Sarma, Curr. Pharm. Des., 2013, 19, 687;
(b) C. R. Prakash, P. Theivendren and S. Raja, Pharmacol.
5 mol% VI, 10 h
N
PhCHO
O
4
Boc
6
3b
54% yield, 89:11 dr, 96% ee
Pharm., 2012, 3, 62; (c) A. D. Huters, E. D. Styduhar and N. K.
Scheme 4 One‐pot four‐component reaction.
Me
Garg, Angew. Chem. Int. Ed., 2012, 51, 3758; (d) M. E. Sobhia,
S. Paul, R. Shinde, M. Potluri, V. Gundam, A. Kaur and T.
Haokip, Expert Opin. Ther. Pat., 2012, 22, 125.
Boc
O
H
N
O
O
N
N
O
O
O
Boc
Boc
Boc
CF3CO2H
MeI, K2CO3, DMF
2
3
(a) Z. Bian, C. C. Marvin and S. F. Martin, J. Am. Chem. Soc.,
Ph
O
Ph
O
Ph
O
0
oC to rt, 12 h
94% yield
2013, 135, 10886 and references therein; (b) T. Mugishima,
CH2Cl2, rt, 4 h
92% yield
N
Me
N
N
M. Tsuda, Y. Kasai, H. Ishiyama, E. Fukushi, J. Kawabata, M.
H
Boc
8
>99% ee
Watanabe, K. Akao and J. Kobayashi, J. Org. Chem., 2005, 70
,
7
93% ee
3b 93% ee
9430; (c) B. M. Trost D. A. Bringley, T. Zhang and N. Cramer, J.
Am. Chem. Soc., 2013, 135, 16720.
Me
N
Me
N
COCl
O
O
HO
(a) M. Bella, S. Kobbelgaard and K. A. Jørgensen, J. Am. Chem.
Soc., 2005, 127, 3670; (b) X.‐H. Chen, Q. Wei, S.‐W. Luo, H.
Xiao and L.‐Z. Gong, J. Am. Chem. Soc., 2009, 131, 13819; (c)
, Et3N
LiAlH4, THF
Ph
CH2Cl2, 0 oC to rt, 5 h
83% yield
Ph
reflux, 20 h
67% yield
N
N
M.‐N. Cheng, H. Wang and L.‐Z. Gong, Org. Lett., 2011, 13
,
Me
10 96% ee
Me
2418; (d) L. Wang, X.‐M. Shi, W.‐P. Dong, L.‐P. Zhu and R.
Wang, Chem. Commun., 2013, 49, 3458; (e) T. Arai, H. Ogawa,
A. Awata, M. Sato, M. Watabe and M. Yamanaka, Angew.
Chem. Int. Ed., 2015, 54, 1595.
9
Scheme 5 Synthetic transformation of adduct 3b
.
To further extend the potential of this protocol a facile route
to obtain enantiomerically pure analogue of spirooxindole for
potential clinical application, the derivatization of the major
diastereomer of 3b was also investigated (Scheme 5). The N‐
Boc protecting group in 3b can be removed smoothly using
4
(a) M. Monari, E. Montroni, A. Nitti, M. Lombardo, C.
Trombini and A. Quintavalla, Chem. Eur. J., 2015, 21, 11038;
(b) J. Stiller, D. Kowalczyk, H. Jiang, K. A. Jørgensen and Ł.
Albrecht, Chem. Eur. J., 2014, 20, 13108; (c) J. Zhou, Q.‐L.
Wang, L. Peng, F. Tian, X.‐Y. Xu and L.‐X. Wang, Chem.
Commun., 2014, 50, 14601; (d) W. Sun, L. Hong, G. Zhu, Z.
Wang, X. Wei, J. Ni and R. Wang, Org. Lett., 2014, 16, 544; (e)
A. Noole, K. Ilmarinen, I. Järving, M. Lopp and T. Kanger, J.
Org. Chem., 2013, 78, 8117; (f) B. Tan, N. R. Candeias and C.
CF3CO2H at room temperature for 4 h, the corresponding
product
enantioselectivity (93% ee). The product
transformed into ‐methyl substituted product
using methyl iodide. A subsequent LiAlH4 reduction of
7
was obtained in 92% yield without erosion of
can be easily
in 94% yield
7
F. Barbas, III. Nat. Chem., 2011, 3, 473; (g) B. M. Trost, N.
N
8
Cramer and S. M. Silverman, J. Am. Chem. Soc., 2007, 129
,
12396.
compound
spiro[octahydrocyclopenta[
8
in refluxing THF for 20
h
afforded
9 in 67%
couldn’t be
led to the
5
6
N. R. Ball‐Jones, J. J. Badillo, N. T. Tran and A. K. Franz,
Angew. Chem. Int. Ed., 2014, 53, 9462.
c
]pyrrole‐3,3’‐indoline]
yield. Due to the fact that enantiomers of
separated by HPLC, further esterification of
For selected reviews on domino/cascade reactions, see: (a) C.
M. R. Volla, I. Atodiresei and M. Rueping, Chem. Rev., 2014,
114, 2390; (b) L.‐Q. Lu, J.‐R. Chen and W.‐J. Xiao, Acc. Chem.
Res., 2012, 45, 1278; (c) C. Grondal, M. Jeanty and D. Enders,
9
9
synthesis of ester 10 in 83% yield with 96% ee using naphthoyl
chloride. The enantiomers of 10 could be well separated by
HPLC. This methodology provides additional opportunities for
preparing this intriguing class of compounds and might be
useful in medicinal chemistry.
In summary, we have successfully developed an efficient
cascade Michael/Michael reaction catalyzed by a bifunctional
tertiary amine‐squaramide catalyst for the asymmetric
synthesis of five‐membered spirooxindoles containing five
contiguous stereocenters with a broad scope of substrates.
The corresponding products were obtained in good yields with
excellent diastereoselectivities and enantioselectivities (up to >
99:1 dr, 98% ee). Importantly, this cascade reaction could be
easily scaled up and one‐pot four‐component reaction was
also successfully applied to the synthesis of spirooxindole.
Specifically, an asymmetric synthesis of the core structure of
Nat. Chem., 2010, 2, 167; (d) K. C. Nicolaou and J. S. Chen,
Chem. Soc. Rev., 2009, 38, 2993; (e) B. B. Tour and D. G. Hall,
Chem. Rev., 2009, 109, 4439; (f) D. Enders, C. Grondal and M.
R. Huttl, Angew. Chem. Int. Ed., 2007, 46, 1570.
Q.‐S. Sun, H. Zhu, Y.‐J. Chen, X.‐D. Yang, X.‐W. Sun and G.‐Q.
Lin, Angew. Chem. Int. Ed., 2015, 54, 13253.
P. Chauhan, J. Kaur and S. S.Chimni, Chem. Asian J., 2013,
328.
7
8
9
8
,
X. Dou and Y. Lu, Chem. Eur. J., 2012, 18, 8315.
10 (a) Y. Liu and W. Zhang, Angew. Chem. Int. Ed., 2013, 52
,
2203; (b) W.‐L. Yang, Y.‐Z. Liu, S. Luo, X. Yu, J. S. Fossey and
W.‐P. Deng, Chem. Commun., 2015, 51, 9212.
11 (a) P. Chauhan, S. Mahajan, U. Kaya, D. Hack and D. Enders,
Adv. Synth. Catal., 2015, 357, 253; (b) R. I. Storer, C. Aciro
and L. H. Jones, Chem. Soc. Rev., 2011, 40, 2330; (c) J.
Alemán, A. Parra, H. Jiang and K. A. Jørgensen, Chem. Eur. J.
,
2011, 17, 6890.
12 Crystallographic data for compound‐3e (CCDC‐1446037) has
spiro[octahydrocyclopenta‐[c]pyrrole‐3,3’‐indoline] derivatives
has been efficiently achieved within several synthetic steps.
been provided as CIF file in supporting information.
4 | J.Name., 2016, 00, 1‐4
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