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Gelder, J. H. Van Maarseveen and H. Hiemstra, Eur. J. Org.
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(f) B. Jiang, C.-G. Yang and X.-H. Gu, Tetrahedron Lett., 2001,
42, 2545; (g) F. Lei, Y.-J. Chen, Y. Sui, L. Liu and D. Wang,
Synlett, 2003, 1160; (h) B. Jiang and Z.-G. Huang, Synthesis, 2005,
2198; (i) M. Abid, L. Teixeira and B. Torok, Org. Lett., 2008, 10,
¨
¨
933; (j) T. Andreassen, L.-K. Hansen and O. R. Gautun, Eur. J.
Org. Chem., 2008, 4871; (k) J. Hang, H. Li and L. Deng, Org. Lett.,
2002, 4, 3321.
Fig. 2 Mechanistic proposals for stereocontrol.
to the higher reactivity of pyrroles that the reactions took
place rapidly and went to completion in several minutes to give
the desired a-(2-pyrrolyl)glycines 5a and 5b in 48% and 67%
yield, along with 2,5-dialkylation products in 51% and 22%
yield, respectively. The diastereomeric excesses of 5a and 5b
proved to be high (88% and 97% de).
4 For selected examples of racemic a-(3-indolyl)glycine syntheses,
see: (a) J. Hao, S. Taktak, K. Aikawa, Y. Yusa, M. Hatano and
K. Mikami, Synlett, 2001, 1443; (b) J.-L. Zhao, L. Liu,
H.-B. Zhang, Y.-C. Wu, D. Wang and Y.-J. Chen, Synlett, 2006,
96; (c) N. Sakai, J. Asano, Y. Shimano and T. Konakahara,
Tetrahedron, 2008, 64, 9208; (d) C. D. Hupp and J. J. Tepe, Org.
Lett., 2008, 10, 3737; (e) E. Angelini, C. Balsamini and
F. Bartoccini, J. Org. Chem., 2008, 73, 5654.
5 (a) G.-Q. Lin, M.-H. Xu, Y.-W. Zhong and X.-W. Sun, Acc. Chem.
Res., 2008, 41, 831; (b) Y.-W. Zhong, M.-H. Xu and G.-Q. Lin,
Org. Lett., 2004, 6, 3953; (c) Y.-W. Zhong, K. Isumi, M.-H. Xu
and G.-Q. Lin, Org. Lett., 2004, 6, 4747; (d) Y.-W. Zhong,
Y.-Z. Dong, K. Fang, K. Izumi, M.-H. Xu and G.-Q. Lin,
J. Am. Chem. Soc., 2005, 127, 11956; (e) M. Liu, X.-W. Sun,
M.-H. Xu and G.-Q. Lin, Chem.–Eur. J., 2009, 15, 10217;
(f) X.-W. Sun, M.-H. Xu and G.-Q. Lin, Org. Lett., 2006, 8,
4979; (g) X.-W. Sun, M. Liu, M.-H. Xu and G.-Q. Lin, Org. Lett.,
2008, 10, 1259.
On the basis of the observed diastereofacial selectivity, a
plausible transition state model for this asymmetric Friedel–
Crafts alkylation is illustrated in Fig. 2. In comparison with
the chelation of Lewis acid with the imine nitrogen and
sulfinyl oxygen (TS-2), activation of the imino ester by the
coordination of the Lewis acidic metal to the imine nitrogen
and carbonyl oxygen is more favorable (TS-1), in which the
uncoordinated N-sulfinyl group adopts an approximately
synperiplanar configuration.13 With the (S)-N-tert-butane-
sulfinyl substrate, to avoid the steric repulsion with the
bulky tert-butyl group, indole attacks preferentially from the
sterically non-blocked bottom face (Si-face) of the CQN bond
to give the corresponding (S)-product.
6 For recent reviews on the chemistry of N-tert-butanesulfinimines,
see: (a) J. A. Ellman, T. D. Owens and T. P. Tang, Acc. Chem.
Res., 2002, 35, 984; (b) J. A. Ellman, Pure Appl. Chem., 2003, 75,
39; (c) C. H. Senanayake, D. Krishnamurthy, Z.-H. Lu, Z. Han
and E. Gallon, Aldrichimica Acta, 2005, 38, 93; (d) F. Ferreira,
C. Botuha, F. Chemla and A. Pe
38, 1162.
´
rez-Luna, Chem. Soc. Rev., 2009,
In summary, we have developed a highly diastereoselective
Friedel–Crafts alkylation of unprotected indoles with an
N-tert-butanesulfinylimino ester. The reaction could be
accomplished with ease in the presence of a catalytic amount
of Cu(OTf)2 at room temperature. It enables fast, efficient
and general access to various enantiomerically enriched
a-(3-indolyl)glycines. Moreover, the method provides
opportunities for extensive future applications of optically
active a-(3-indolyl)glycines in medicinal chemistry and organic
synthesis. Further exploration of this methodology is currently
under study in our laboratory.
7 A TMSOTf-promoted diastereoselective addition of aromatic
heterocycles to N-tert-butanesulfinylimino ester to afford hetero-
aromatic glycine derivatives has recently been reported, see ref. 3j.
In the case of an indole substrate, a mixture of isomers was obtained.
8 Reaction conducted in the absence of Lewis acid catalysts gave no
results in 24 h.
9 For a report of bisindolylalkane preparation by AMBERLYST,
iodine or KHSO4-catalyzed addition of indole to N-tert-butane-
sulfinyl aldimine, see: B. Ke, Y. Qin, Q. He, Z. Huang and
F. Wang, Tetrahedron Lett., 2005, 46, 1751.
10 Cu(OTf)2 (98%) from Alfa was used without further purification.
11 For recycling of the tert-butanesulfinyl, see: (a) M. Wakayama and
J. A. Ellman, J. Org. Chem., 2009, 74, 2646; (b) V. K. Aggarwal,
N. Barbero, E. M. McGarrigle, G. Mickle, R. Navas, J. R. Suarez,
M. G. Unthank and M. Yar, Tetrahedron Lett., 2009, 50, 3482.
12 Crystal data for 3e (C22H25BrN2O3S): T = 293(2) K; wavelength:
0.71073 A; crystal system: orthorhombic, P212121; unit cell
dimensions: a = 10.7973(14) A, b = 14.2880(18) A, c =
15.311(2) A, a = 901, b = 901, g = 901; V = 2362.0(5) A3;
Z = 4; rc = 1.343 Mg mÀ3; F(000) = 984; final R indices
[I 4 2s(I)]: R1 = 0.0710, wR2 = 0.1940; R indices (all data),
R1 = 0.1533, wR2 = 0.2290; 12 471 reflections measured, 4407
were unique (R(int) = 0.0569). CCDC 740797. Crystal data for 3l
(C16H21BrN2O3S): T = 293(2) K; wavelength: 0.71073 A; crystal
system: monoclinic, P21; unit cell dimensions: a = 9.3558(14) A,
b = 9.4206(14) A, c = 10.6930(16) A, a = 901, b = 99.473(3)1,
g = 901; V = 929.6(2) A3; Z = 2; rc = 1.434 Mg mÀ3; F(000) =
412; final R indices [I 4 2s(I)]: R1 = 0.0478, wR2 = 0.1071;
R indices (all data), R1 = 0.0595, wR2 = 0.1110; 5119 reflections
measured, 3425 were unique (R(int) = 0.0425). CCDC 740822.
13 For related crystal structures and theoretical calculations:
(a) T. D. Owens, F. J. Hollander, A. G. Oliver and J. A. Ellman,
J. Am. Chem. Soc., 2001, 123, 1539; (b) T. D. Owens, A. J. Souers
and J. A. Ellman, J. Org. Chem., 2003, 68, 3; (c) L. B. Schenkel and
J. A. Ellman, Org. Lett., 2003, 5, 545; (d) L. F. Tietze and
A. Schuffenhauer, Eur. J. Org. Chem., 1998, 1629;
(e) P. V. Bharatam, P. Uppal, A. Kaur and D. Kaur, J. Chem.
Soc., Perkin Trans. 2, 2000, 43.
This work was generously supported by the NSFC
(20721003), the Shanghai Rising-Star Program (08QH14027),
the Chinese Academy of Sciences, State Key Laboratory
of Drug Research, SIMM and National Science & Technology
Major Project (2009ZX09301-001).
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ꢀc
This journal is The Royal Society of Chemistry 2010
1552 | Chem. Commun., 2010, 46, 1550–1552