Organic Letters
Letter
Wright, L. Bioorg. Med. Chem. Lett. 2004, 14, 5689. (c) Enz, A.;
unexpected formation of product 14 in 52% conversion from the
indole 13 (Scheme 2, eq 2) further underpins the formation of
the N-iodoammonium intermediate such as 7 on the piperidine
ring, which can be sequestered by the proximal indole in this
instance.
Feuerbach, D.; Frederiksen, M. U.; Gentsch, C.; Hurth, K.; Muller, W.;
̈
Nozulak, J.; Roy, B. L. Bioorg. Med. Chem. Lett. 2009, 19, 1287.
(d) Shorvon, S. Lancet 2001, 358, 1885.
(4) Hari, Y.; Osawa, T.; Kotobuki, Y.; Yahara, A.; Shrestha, A. R.;
Obika, S. Bioorg. Med. Chem. 2013, 21, 4405.
In summary, we have developed a mild, late-stage strategy for
the chemoselective oxidation of cyclic amines to the correspond-
ing lactams under mild conditions. We envisage that this
approach could be generalized by medicinal chemists to create a
diverse range of compounds from a small subset of molecular
scaffolds, providing synthetic access to drug metabolites,1e,16
potentially accelerating the hit-to-lead process of drug discovery
compared to more traditional linear routes.
(5) Bailey, P. D.; Collier, I. D.; Morgan, K. M. In Comprehensive Organic
Functional Group Transformations; Moody, C. J., Ed.; Pergamon: Oxford,
1995; pp 257.
(6) (a) Naota, T.; Murahashi, S.-I. Synlett 1991, 1991, 693.
(b) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317, 790.
(7) (a) Al-Subu, M. M.; Jondi, W. J.; Amer, A. A.; Hannoun, M.;
Musmar, M. J. Chem. Heterocycl. Compd. 2003, 39, 478. (b) Wenkert, E.;
Angell, E. C. Synth. Commun. 1988, 18, 1331. (c) Wei, Y.; Ding, H.; Lin,
S.; Liang, F. Org. Lett. 2011, 13, 1674. (d) Rao, G.; Periasamy, M. Synlett
2015, 26, 2231. (e) Yan, X.; Fang, K.; Liu, H.; Xi, C. Chem. Commun.
2013, 49, 10650. (f) Tanaka, K.-I.; Yoshifuji, S.; Nitta, Y. Chem. Pharm.
Bull. 1988, 36, 3125. (g) Sheehan, J. C.; Tulis, R. W. J. Org. Chem. 1974,
39, 2264. (h) Breault, G.; Eyermann, C. J.; Geng, B.; Morningstar, M.;
Reck, F. Compounds for the Treatment of Multi-Drug Resistant
Bacterial Infections. WO2006134378 (A1), 2006.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental details and characterization data (PDF)
(8) Khusnutdinova, J. R.; Ben-David, Y.; Milstein, D. J. Am. Chem. Soc.
2014, 136, 2998.
(9) Legacy, C. J.; Wang, A.; O’Day, B. J.; Emmert, M. H. Angew. Chem.,
Int. Ed. 2015, 54, 14907.
(10) Jin, X.; Kataoka, K.; Yatabe, T.; Yamaguchi, K.; Mizuno, N. Angew.
Chem. 2016, 128, 7328.
AUTHOR INFORMATION
Corresponding Authors
■
ORCID
(11) (a) Yusubov, M. S.; Zhdankin, V. V. Resour. Technol. 2015, 1, 49.
(b) Li, J.; Lear, M. J.; Kawamoto, Y.; Umemiya, S.; Wong, A. R.; Kwon,
E.; Sato, I.; Hayashi, Y. Angew. Chem., Int. Ed. 2015, 54, 12986. (c) Li, J.;
Lear, M. J.; Kwon, E.; Hayashi, Y. Chem. - Eur. J. 2016, 22, 5538.
(d) Liang, Y.-F.; Li, X.; Wang, X.; Zou, M.; Tang, C.; Liang, Y.; Song, S.;
Jiao, N. J. Am. Chem. Soc. 2016, 138, 12271.
(12) (a) Kutney, J. P.; Balsevich, J.; Honda, T.; Liao, P.-H.; Thieelier,
H. P. M.; Worth, B. R. Can. J. Chem. 1978, 56, 2560. (b) Langlois, N.;
Andriamialisoa, R. Z.; Neuss, N. Helv. Chim. Acta 1980, 63, 793.
(c) Zhao, G.; Xie, X.; Sun, H.; Yuan, Z.; Zhong, Z.; Tang, S.; She, X. Org.
Lett. 2016, 18, 2447. (d) Bartlett, M. F.; Dickel, D. F.; Taylor, W. I. J. Am.
Chem. Soc. 1958, 80, 126. (e) Lee, B. H.; Clothier, M. F. Tetrahedron Lett.
1997, 38, 4009.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work was provided by GSK via the
GSK/University of Strathclyde Centre for Doctoral Training in
Synthetic and Medicinal Chemistry. We also thank Stephen
Richards and Sean Lynn (both GSK) for their assistance with
NMR analysis.
(13) (a) Moriarty, R. M.; Vaid, R. K.; Duncan, M. P.; Ochiai, M.;
Inenaga, M.; Nagao, Y. Tetrahedron Lett. 1988, 29, 6913. (b) de Graaff,
C.; Bensch, L.; van Lint, M. J.; Ruijter, E.; Orru, R. V. A. Org. Biomol.
Chem. 2015, 13, 10108. (c) Waghmode, N. A.; Kalbandhe, A. H.;
Thorat, P. B.; Karade, N. N. Tetrahedron Lett. 2016, 57, 680. (d) Castro-
REFERENCES
■
C., A.; Juar
Enríquez, R. G. Tetrahedron: Asymmetry 2005, 16, 949. (e) Juar
Castro, A.; Romero, O.; Teran, J. L.; Gnecco, D.; Orea, L.; Mendoza, A.
Heterocycles 2014, 89, 725.
́
ez-P., J.; Gnecco, D.; Teran
́
, J. L.; Galindo, A.; Bernes
̀
, S.;
(1) For recent reviews on late-stage C−H functionalization, see:
(a) Cernak, T.; Dykstra, K. D.; Tyagarajan, S.; Vachal, P.; Krska, S. W.
Chem. Soc. Rev. 2016, 45, 546. (b) Newhouse, T.; Baran, P. S. Angew.
Chem., Int. Ed. 2011, 50, 3362. For recent research on C−H oxidation,
see: (c) Osberger, T. J.; Rogness, D. C.; Kohrt, J. T.; Stepan, A. F.;
White, M. C. Nature 2016, 537, 214. (d) Howell, J. M.; Feng, K.; Clark, J.
R.; Trzepkowski, L. J.; White, M. C. J. J. Am. Chem. Soc. 2015, 137,
́
ez, J. R.;
́
(14) Morpholine substrates required the use of DMSO/H2O solvent
system to prevent reaction stalling. At present the reason for this
observation is unclear, and we are currently investigating further the
influence of solvent on the rates of iodination and oxidation.
(15) Nagakura, S. J. Am. Chem. Soc. 1958, 80, 520. (b) Yada, H.;
Tanaka, J.; Nagakura, S. Bull. Chem. Soc. Jpn. 1960, 33, 1660.
́
14590. (e) Genovino, J.; Lutz, S.; Sames, D.; Toure, B. B. J. J. Am. Chem.
̈
Soc. 2013, 135, 12346. (f) Mbofana, C. T.; Chong, E.; Lawniczak, J.;
Sanford, M. S. Org. Lett. 2016, 18, 4258. (g) Lee, M.; Sanford, M. S. J. J.
Am. Chem. Soc. 2015, 137, 12796. (h) Sun, S.-Z.; Shang, M.; Wang, H.-
L.; Lin, H.-X.; Dai, H.-X.; Yu, J.-Q. J. Org. Chem. 2015, 80, 8843.
(i) Zhang, Y. H.; Yu, J. Q. J. J. Am. Chem. Soc. 2009, 131, 14654. (j) See,
Y. Y.; Herrmann, A. T.; Aihara, Y.; Baran, P. S. J. J. Am. Chem. Soc. 2015,
137, 13776. (k) Horn, E. J.; Rosen, B. R.; Chen, Y.; Tang, J.; Chen, K.;
Eastgate, M. D.; Baran, P. S. Nature 2016, 533, 77. (l) McNeill, E.; Du
Bois, J. Chem. Sci. 2012, 3, 1810. (m) Adams, A. M.; Du Bois, J. Chem.
Sci. 2014, 5, 656.
(16) (a) Genovino, J.; Sames, D.; Toure,
56, 3066. (b) Genovino, J.; Sames, D.; Hamann, L. G.; Toure,
Angew. Chem., Int. Ed. 2016, 55, 14218.
́
B. B. Tetrahedron Lett. 2015,
́
B. B.
(2) (a) Toyooka, N.; Nemoto, H. In Studies in Natural Products
Chemistry; Atta-ur-Rahman, Ed.; Elsevier B.V., 2003; pp 419.
(b) Guntern, A.; Ioset, J.-R.; Queiroz, E. F.; San
́
dor, P.; Foggin, C.
M.; Hostettmann, K. J. Nat. Prod. 2003, 66, 1550.
(3) (a) Drawz, S. M.; Bonomo, R. A. Clin. Microbiol. Rev. 2010, 23, 160.
(b) Kazmierski, W. M.; Andrews, W.; Furfine, E.; Spaltenstein, A.;
D
Org. Lett. XXXX, XXX, XXX−XXX