Journal of the American Chemical Society
Communication
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(5) Intermolecular additionof β-aminoalkyl radicals to alkenes has
been demonstrated: Maria, E. J.; Da Silva, A. D.; Fourrey, J.-L.;
Machado, A. S.; Robert-Gero, M. Tetrahedron Lett. 1994, 35, 3301.
(6) Intramolecular Heck-type coupling of β-aminoalkyl intermediates
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K.-T.; Zhu, N.-Y.; Yang, D. Org. Lett. 2009, 11, 5626. (c) Fuller, P. H.;
Chemler, S. R. Org. Lett. 2007, 9, 5477.
the 5-HT7 receptor antagonist 9. This synthesis was accom-
plished in 4 steps from commercially available reagents without the
aid of protecting groups and is several steps shorter than its original
synthesis.14
In conclusion, we have developed an efficient and
enantioselective alkyl Heck-type coupling cascade for the
formation of functionalized chiral indolines, pyrrolidines
and an isoquinoline from the respective acyclic γ- and δ-
alkenylsulfonamides. The concise synthesis of a 5-HT7 receptor
antagonist was accomplished to demonstrate the utility of the
method. Sulfonamides and sultams are common moieties found
in bioactive compounds.14,15 This method accesses such targets
directly, enantioselectively and without the use of protecting
groups. Removal of the N-sulfonyl groups can further provide
valuable chiral amines. Further investigation into the hetero-
cycle and alkene scope and application in the total synthesis of
bioactive alkaloids is ongoing.
(7) Cu-catalyzed doubly intramolecular carboamination: (a) Zeng,
W.; Chemler, S. R. J. Am. Chem. Soc. 2007, 129, 12948. (b) Miao, L.;
Haque, I.; Manzoni, M. R.; Tham, W. S.; Chemler, S. R. Org. Lett.
2010, 12, 4739.
(8) Cu-catalyzed aminooxygenation: (a) Fuller, P. H.; Kim, J.-W.;
Chemler, S. R. J. Am. Chem. Soc. 2008, 130, 17638. (b) Paderes, M. C.;
Chemler, S. R. Eur. J. Org. Chem. 2011, 3679.
(9) Cu-catalyzeddiamination: Sequeira, F. C.; Turnpenny, B. W.;
Chemler, S. R. Angew. Chem., Int. Ed. 2010, 49, 6365.
(10) (a) Sherman, E. S.; Fuller, S. R.; Kasi, D.; Chemler, S. R. J. Org.
Chem. 2007, 72, 3896. (b) Paderes, M. C.; Belding, L.; Fanovic, B.;
Dudding, T.; Keister, J. B.; Chemler, S. R. Chem.Eur. J. 2012,
DOI: 10.1002/chem.201101703.
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures, spectroscopic data, and crystallog-
raphy data of 2a (CIF). This material is available free of charge
■
S
AUTHOR INFORMATION
Corresponding Author
■
(11) Chemler, S. R. J. Organomet. Chem. 2011, 696, 150.
(12) Selected Pd-catalyzed intermolecular carboamination/cycliza-
tion of alkenes with unfunctionalized arenes and functionalized alkenes
and arenes: (a) Rosewall, C. F.; Sibbald, P. A.; Liskin, D. V.; Michael,
F. E. J. Am. Chem. Soc. 2009, 131, 9488. (b) Mai, D. N.; Wolfe, J. P.
J. Am. Chem. Soc. 2010, 132, 12157. (c) Houlden, C. E.; Bailey, C. D.;
Ford, J. G.; Gagne, M. R.; Lloyd-Jones, G. C.; Booker-Milburn, K. I.
J. Am. Chem. Soc. 2008, 130, 10066. Au-catalyzed intermolecular
carboamination/cyclization of alkenes with functionalized arenes:
(d) Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010,
132, 1474. (e) Brenzovich, W. E.; Benitez, D.; Lackner, A. D.;
Shunatona, H. P.; Tkatchouk, E.; Goddard, W. A.; Toste, F. D. Angew.
Chem., Int. Ed. 2010, 49, 5519.
(13) (a) Choi, J.; Tang, L.; Norton, J. R. J. Am. Chem. Soc. 2007, 129,
234. (b) Fischer, H.; Radom, L. Angew. Chem., Int. Ed. 2001, 40, 1340.
(14) Lovell, P. J.; Bromidge, S. M.; Dabbs, S.; Duckworth, D. M.;
Forbes, I. T.; Jennings, A. J.; King, F. D.; Middlemiss, D. N.; Rahman,
S. K.; Saunders, D. V.; Collin, L. L.; Hagan, J. J.; Riley, G. J.; Thomas,
D. R. J. Med. Chem. 2000, 43, 342.
(15) (a) Rotella, D. P.; Sun, Z.; Zhu, Y.; Krupinski, J.; Pongrac, R.;
Seliger, L.; Normandin, D.; Macor, J. E. J. Med. Chem. 2000, 43, 5037.
(b) Lee, D.; Long, S. A.; Murray, J. H.; Adams, J. L.; Nuttall, M. E.;
Nadeau, D. P.; Kikly, K.; Winkler, J. D.; Sung, C.-M.; Ryan, M. D.;
Levy, M. A.; Keller, P. M.; DeWolf, W. E. J. Med. Chem. 2001, 44,
2015. (c) Cole, D. C.; Lennox, W. J.; Lombardi, S.; Ellingboe, J. W.;
Bernotas, R. C.; Tawa, G. J.; Mazandarani, H.; Smith, D. L.; Zhang, G.;
Coupet, J.; Schechter, L. E. J. Med. Chem. 2005, 48, 353.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the National Institutes of Health (NIGMS 078383)
for support of this work. We thank William W. Brennessel and
the X-ray Crystallographic Facility at the University of
Rochester for the X-ray structure of 2a.
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