ORGANIC
LETTERS
2006
Vol. 8, No. 10
2115-2118
Enantioselective Friedel−Crafts
Alkylation of Indoles with Nitroalkenes
Catalyzed by Bifunctional Tridentate
Bis(oxazoline)−Zn(II) Complex
Shao-Feng Lu, Da-Ming Du,* and Jiaxi Xu
Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of
Bioorganic Chemistry and Molecular Engineering, College of Chemistry and
Molecular Engineering, Peking UniVersity, Beijing 100871, P. R. China
Received March 10, 2006
ABSTRACT
A more practical and efficient catalytic asymmetric Friedel
(oxazoline) Zn(OTf)2 as catalyst has been developed. Various types of the nitroalkylated indoles were obtained in excellent yields (85
and high enantioselectivities (up to 98% ee).
−
Crafts alkylation of indoles with nitroalkenes using bifunctional tridentate bis-
−
−99%)
The Friedel-Crafts reaction is one of the most powerful
carbon-carbon bond-forming reactions in synthetic organic
chemistry.1 Recently, using nitroalkenes as substrates to
achieve asymmetric Friedel-Crafts alkylation of indoles has
been paid considerable attention.2 It is the result of chemists’
effort to develop new types of substrates for the enantiose-
lective version of the Friedel-Crafts reaction,3 which has
suffered from significant restrictions that R,â-unsaturated
carbonyl compounds were overwhelmingly investigated.4 In
addition, nitroalkenes are very active Michael acceptors,5 and
the easy transformation of the nitro group into a range of
different functionalities6 makes this methodology more
attractive. In fact, the products of alkylations of indoles with
nitroalkenes can be applied to the synthesis of many
biologically active compounds such as physostigmine,7 which
serves as a useful clinical anticholinergic drug.8
(3) For recent examples, see: (a) Jensen, K. B.; Thorhauge, J.; Mazell,
R.-G.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2001, 40, 160. (b) Zhuang,
W.; Gathergood, N.; Hazell, R. G. J. Org. Chem. 2001, 66, 1009. (c) Paras,
N. A.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 7894. (d) Zhou,
J.; Tang, Y. J. Am. Chem. Soc. 2002, 124, 9030. (e) Evans, D. A.; Scheidt,
K. A.; Frandrick, K. R.; Lam, H. W.; Wu, J. J. Am. Chem. Soc. 2003, 125,
10780. (f) Zhou, J.; Ye, M.-C.; Huang, Z.-Z.; Tang, Y. J. Org. Chem. 2004,
69, 1309. (g) Yuan, Y.; Wang, X.; Li, X.; Ding, K. J. Org. Chem. 2004,
69, 146. (h) Palomo, C.; Oiarbide, M.; Kardak, B. G.; Garcia, J. M.; Linden,
A. J. Am. Chem. Soc. 2005, 127, 4154. (i) Evans, D. A.; Fandrick, K. R.;
Song, H. J. J. Am. Chem. Soc. 2005, 127, 8942. (j) Yamazaki, S.; Iwata, Y.
J. Org. Chem. 2006, 71, 739.
(4) For reviews, see: (a) Bandini, M.; Melloni, A.; Umani-Ronchi, A.
Angew. Chem., Int. Ed. 2004, 43, 550. (b) Bandini, M.; Melloni, A.;
Tommasi, S.; Umani-Ronchi, A. Synlett 2005, 1199. (c) Wang Y.; Ding
K.-L. Chin. J. Org. Chem. 2001, 21, 763.
(5) Berner, O. M.; Tedeschi, L.; Enders, D. Eur. J. Org. Chem. 2002,
1877.
(1) (a) Olah, G. A.; Khrisnamurti, R.; Prakash, G. K. S. In ComprehensiVe
Organic Synthesis, 1st ed.; Trost, B. M., Fleming, I., Eds.; Pergamon:
Oxford, 1991; Vol. III, p 293. (b) Roberts, R. M.; Khalaf, A. A. Friedel-
Crafts Alkylation Chemistry. A Centry of DiscoVery; Marcel Dekker: New
York, 1984.
(2) (a) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Angew. Chem.,
Int. Ed. 2005, 44, 6576. (b) Zhuang, W.; Hazell, R. G.; Jørgensen, K. A.
Org. Biomol. Chem. 2005, 3, 2566. (c) Jia, Y.-X.; Zhu, S.-F.; Yang, Y.;
Zhou, Q.-L. J. Org. Chem. 2006, 71, 75. (d) Bandini, M.; Garelli, A.;
Rovinetti, M.; Tommasi, M.; Umani-Ronchi, A. Chirality 2005, 17, 1.
10.1021/ol060586f CCC: $33.50
© 2006 American Chemical Society
Published on Web 04/13/2006