ORGANIC
LETTERS
2013
Vol. 15, No. 22
5702–5705
Catalytic Intermolecular Haloamidation
of Simple Alkenes with N‑Halophthalimide
as Both Nitrogen and Halogen Source
Lu Song, Sanzhong Luo,* and Jin-Pei Cheng
Beijing National Laboratory for Molecule Sciences (BNLMS), CAS Key Laboratory
for Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of
Sciences, Beijing 100190, China
Received September 20, 2013
ABSTRACT
A simple, efficient, and highly atom economic haloamidation of simple alkenes has been developed, using AgBF4 or InBr3/AgBF4 (1:3) as catalyst
and N-halophthalimide as both nitrogen and halogen source. A broad range of olefins can be applied to afford vicinal haloamines in good yields
and with high regioselectivity and diastereoselectivity.
Haloamidation of olefins is a fundamental transforma-
tion to produce vicinal haloamines as versatile synthons in
organic synthesis.1 Hence, the reaction has been exten-
sively explored and remains a current research focus in
order to address the remaining issues such as limited
substrate scope and lack of enantiocontrol.2 Typically, a
haloamidation reaction occurs via nucleophilic attack to a
halogenium intermediate with an amide nucleophile. In
this step, the nucleophile is normally an externally added
amide (Scheme 1).3 The in situ generated amide anion
derived from the N-halogenic reagents after delivering the
halogenium ion may also participate in the nucleophilic
addition, and this process is highly atom economic since
both of the halogen and nitrogen moiety are preserved in
the haloamidation product. Unfortunately, successful ex-
amples on suchatom-economic processes are quite limited,
presumably due to the low nucleophilicity of the in situ
formed amide anion, a prerequisite for a high electrophilic
halogenium ion.
In the catalytic haloamidation reaction, both Lewis
acids4 and Lewis bases5 have been reported to facilitate
smooth transformation by promoting the halogenium
ion formation.6 In this regard, notable progress has been
achieved in intermolecular haloamidation of electron-
deficient alkenes by Li et al.7 Elegant catalytic asymmetric
(1) (a) Kemp, J. E. G. In Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7, pp 469ꢀ513. (b)
Pearson, W. H.; Lian, B. W.; Bergmeier, S. C. In Comprehensive
Heterocyclic Chemistry II; Padwa, A., Ed.; Pergamon Press: Oxford,
1996; Vol. 1A, pp 1ꢀ60. (c) Thomas, G. Medicinal Chemistry: An
Introduction; John Wiley & Sons: New Yok, 2000. (d) Qui, J.; Silverman,
R. B. J. Med. Chem. 2000, 43, 706. (e) Mukai, T.; Hagimori, M.;
Arimitsu, K.; Katoh, T.; Ukon, M.; Kajimoto, T.; Kimura, H.; Magata,
Y.; Miyoshi, E.; Taniguchi, N.; Node, M.; Saji, H. Bioorg. Med. Chem.
2011, 19, 4312. (f) Chemler, S. R.; Bovino, M. T. ACS Catal. 2013, 3,
1076. (g) Aberhart, D. J.; Gould, S. J.; Lin, H. J.; Thiruvengadam, T. K.;
Weiller, B. H. J. Am. Chem. Soc. 1983, 105, 5461.
(2) (a) Kharasch, M. S.; Priestley, H. M. J. Am. Chem. Soc. 1939, 61,
3425. (b) Shelton, J. R.; Cialdella, C. J. Org. Chem. 1958, 23, 1128. (c)
Zalkow, L. H.; Kennedy, C. D. J. Org. Chem. 1964, 29, 1290. (d) Seden,
T. P.; Turner, R. W. J. Chem. Soc. C 1968, 876. (e) Terauchi, H.;
Takemura, S.; Ueno, Y. Chem. Pharm. Bull. 1975, 23, 640. (f) Zawadzki,
S.; Zwierzak, A. Tetrahedron 1981, 37, 2675. (g) Griffith, D. A.;
Danishefsk, S. J. J. Am. Chem. Soc. 1990, 112, 5811. (h) Klepacz, A.;
Zwierzak, A. Tetrahedron Lett. 2001, 42, 4539.
(4) Yadav, J. S.; Reddy, B. V. S.; Chary, D. N.; Chandrakanth, D.
Tetrahedron Lett. 2009, 50, 1136.
(5) (a) Ji, X.; Mei, H.; Qian, Y.; Han, J.; Li, G.; Pan, Y. Synthesis
2011, 22, 3680. (b) Mei, H.; Han, J.; Li, G.; Pan, Y. RSC Adv. 2011, 1,
429. (c) Denmark, S. E.; Kalyani, D.; Collins, W. R. J. Am. Chem. Soc.
2010, 132, 15752. (d) Tay, D. W.; Tsoi, I. T.; Er, J. C.; Leung, G. Y. C.;
Yeung, Y.-Y. Org. Lett. 2013, 15, 1310.
(6) Wang, Z.; Zhang, Y.; Fu, H.; Jiang, Y.; Zhao, Y. Synlett 2008, 17,
2667.
(7) (a) Li, G.; Wei, H.-X.; Kim, S. H.; Neighbors, M. Org. Lett. 1999,
1, 395. (b) Li, G.; Wei, H.-X.; Kim, S. H. Org. Lett. 2000, 2, 2249. (c) Wei,
H.-X.; Kim, S. H.; Li, G. Tetrahedron 2001, 57, 3869. (d) Li, G.; Wei,
H.-X.; Kim, S. H. Tetrahedron 2001, 57, 8407. (e) Han, J.-L.; Zhi, S.-J.;
Wang, L.-Y.; Pan, Y.; Li, G. Eur. J. Org. Chem. 2007, 1332. (f) Sun, H.;
Han, J.; Kattamuri, P. V.; Pan, Y.; Li, G. J. Org. Chem. 2013, 78, 1171.
(3) (a) Wei, J.-F.; Zhang, L.-H.; Chen, Z.-G.; Shi, X.-Y.; Cao, J.-J.
Org. Biomol. Chem. 2009, 7, 3280. (b) Wei, J.-F.; Chen, Z.-G.; Lei, W.;
Zhang, L.-H.; Wang, M.-Z.; Shi, X.-Y.; Li, R.-T. Org. Lett. 2009, 11,
4216.
r
10.1021/ol402726d
Published on Web 10/24/2013
2013 American Chemical Society