Organic Letters
Letter
Sivappa, R.; Yousufuddin, M.; Lovely, C. J. J. Org. Chem. 2014, 79, 2481.
(m) Koswatta, P. B.; Kasiri, S.; Das, J. K.; Bhan, A.; Lima, H. M.; Garcia-
Barboza, B. J.; Khatibi, N. N.; Yousufuddin, M.; Mandal, S. S.; Lovely, C.
J. Bioorg. Med. Chem. 2017, 25, 1608.
(2) (a) Koswatta, P. B.; Lovely, C. J. Nat. Prod. Rep. 2011, 28, 511.
(b) Lovely, C. J. Strategies and Tactics in Organic Synthesis; Academic
Press, 2012; Vol. 8, pp 199−224. (c) Sullivan, J. D.; Giles, R. L.; Looper,
R. E. Curr. Bioact. Compd. 2009, 5, 39. (d) Roue, M.; Quevrain, E.;
Domart-Coulon, I.; Bourguet-Kondracki, M. L. Nat. Prod. Rep. 2012, 29,
739.
(3) Edrada, R. A.; Stessman, C. C.; Crews, P. J. Nat. Prod. 2003, 66, 939.
(4) (a) Roche, S. P.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50,
4068. (b) Sannigrahi, M. Tetrahedron 1999, 55, 9007. (c) Sun, W.; Li,
G.; Hong, L.; Wang, R. Org. Biomol. Chem. 2016, 14, 2164.
(5) (a) Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2005, 127, 12230.
(b) Zhang, X.; Sarkar, S.; Larock, R. C. J. Org. Chem. 2006, 71, 236.
(c) Tang, B.; Tang, D.; Tang, S.; Yu, Q.; Zhang, Y.; Liang, Y.; Zhong, P.;
Li, J. Org. Lett. 2008, 10, 1063. (d) Clarke, A. K.; James, M. J.; O’Brien,
P.; Taylor, R. J. K.; Unsworth, W. P. Angew. Chem., Int. Ed. 2016, 55,
13798. (e) James, M. J.; Cuthbertson, J. D.; O’Brien, P.; Taylor, R. J. K.;
Unsworth, W. P. Angew. Chem., Int. Ed. 2015, 54, 7640.
(6) (a) Koswatta, P. B.; Das, J.; Yousufuddin, M.; Lovely, C. J. Eur. J.
Org. Chem. 2015, 2015, 2603. (b) Singh, R. P.; Spears, J. A.; Dalipe, A.;
Yousufuddin, M.; Lovely, C. J. Tetrahedron Lett. 2016, 57, 3096.
(7) (a) Reddy, C. R.; Prajapti, S. K.; Warudikar, K.; Ranjan, R.; Rao, B.
B. Org. Biomol. Chem. 2017, 15, 3130. (b) Quideau, S.; Pouysegu, L.;
Deffieux, D. Synlett 2008, 2008, 467. (c) Ding, Q.; Ye, Y.; Fan, R.
Synthesis 2013, 45, 1.
While not definitive, these results are suggestive of a possible
biosynthetic link between the spirocalcaridines and the
kealiinines (e.g., kealiinine A (50), Scheme 5)1i,6a,13b,15,18 and
it is thought that the kealiinines serve as biosynthetic precursors
to kealiiquinone/2-deoxy-2-aminokealiiquinone.1k,18 Treatment
of this mixture with TFA led to removal of the BOC group and
complete oxidation to deliver naphthimidazole 49. The
deprotection−oxidation sequence could be performed more
efficiently through the reaction of 14 with TFA in air over a
longer period, which resulted in the direct formation of 49 in a
few hours (Scheme 5).
In summary, we have developed a tandem alkyne amination−
dearomatization strategy for the rapid construction of complex
spiro heterocyclic frameworks. These derivatives may serve as
precursors to a variety of natural products belonging to the
Leucetta family of alkaloids including the spirocalcaridines, the
kealiinines, and the kealiiquinones. Efforts toward these ends are
underway and will be reported in due course.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental procedures and characterization data for all
new compounds (1H and 13C NMR) (PDF)
X-ray data for compound 14 (CIF)
X-ray data for compound 16 (CIF)
X-ray data for compound 31 (CIF)
X-ray data for compound 47 (CIF)
(8) Harned, A. M. Tetrahedron Lett. 2014, 55, 4681.
(9) Wardrop, D. J.; Bowen, E. G. Synthetic Applications of Nitrenium
Ions. In Nitrenes and Nitrenium Ions; Falvey, D. E., Gudmundsdottir, A.
D., Eds.; John Wiley and Sons, Inc., 2013; Chapter 10, pp 347−449.
(10) (a) Huang, J.; He, Y.; Wang, Y.-G.; Zhu, Q. Chem. - Eur. J. 2012,
18, 13964. (b) Saito, A.; Matsumoto, A.; Hanzawa, Y. Tetrahedron Lett.
2010, 51, 2247.
(11) (a) Pelter, A.; Ward, R. S. Tetrahedron 2001, 57, 273.
(b) Pouysegu, L.; Deffieux, D.; Quideau, S. Tetrahedron 2010, 66,
2235. (c) Silva, L. F., Jr.; Olofsson, B. Nat. Prod. Rep. 2011, 28, 1722.
(12) Andrez, J.-C.; Giroux, M.-A.; Lucien, J.; Canesi, S. Org. Lett. 2010,
12, 4368.
(13) (a) Gainer, M. J.; Bennett, N. R.; Takahashi, Y.; Looper, R. E.
Angew. Chem., Int. Ed. 2011, 50, 684. (b) Gibbons, J. B.; Gligorich, K. M.;
Welm, B. E.; Looper, R. E. Org. Lett. 2012, 14, 4734. (c) Gibbons, J. B.;
Salvant, J. M.; Vaden, R. M.; Kwon, K.-H.; Welm, B. E.; Looper, R. E. J.
Org. Chem. 2015, 80, 10076.
(14) Ermolat’ev, D. S.; Bariwal, J. B.; Steenackers, H. P. L.; De
Keersmaecker, S. C. J.; Van der Eycken, E. V. Angew. Chem., Int. Ed.
2010, 49, 9465.
(15) Tian, G.; Fedoseev, P.; Van der Eycken, E. V. Chem. - Eur. J. 2017,
23, 5224. This paper appeared while this manuscript was in review.
(16) The dihydronaphthoxazole was isolated, which suggests that
either spirocyclization is disfavored in this solvent or spirocyclization
and rearrangement occur prior to demethylation.
AUTHOR INFORMATION
■
Corresponding Author
ORCID
Present Address
†(M. Y.) Department of Chemistry, University of North Texas at
Dallas, Dallas, TX 75241.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported through the Robert A. Welch
Foundation (Y-1362) and instrument grants from the NSF
(CHE-0234811 and CHE-0840509).
REFERENCES
■
(1) (a) Koswatta, P. B.; Sivappa, R.; Dias, H. V. R.; Lovely, C. J. Org.
Lett. 2008, 10, 5055. (b) Bhandari, M. R.; Sivappa, R.; Lovely, C. J. Org.
Lett. 2009, 11, 1535. (c) Koswatta, P. B.; Lovely, C. J. Tetrahedron Lett.
2009, 50, 4998. (d) Koswatta, P. B.; Sivappa, R.; Dias, H. V. R.; Lovely,
C. J. Synthesis 2009, 2009, 2970. (e) Koswatta, P. B.; Lovely, C. J. Chem.
Commun. 2010, 46, 2148. (f) Koswatta, P. B.; Lovely, C. J. Tetrahedron
Lett. 2010, 51, 164. (g) Mukherjee, S.; Sivappa, R.; Yousufuddin, M.;
Lovely, C. J. Org. Lett. 2010, 12, 4940. (h) Lima, H. M.; Garcia-Barboza,
B. J.; Khatibi, N. N.; Lovely, C. J. Tetrahedron Lett. 2011, 52, 5725.
(i) Das, J.; Koswatta, P. B.; Yousufuddin, M.; Jones, J. D.; Lovely, C. J.
Org. Lett. 2012, 14, 6210. (j) Lima, H. M.; Sivappa, R.; Yousufuddin, M.;
Lovely, C. J. Org. Lett. 2012, 14, 2274. (k) Das, J.; Bhan, A.; Mandal, S.;
Lovely, C. J. Bioorg. Med. Chem. Lett. 2013, 23, 6183. (l) Lima, H. M.;
(17) The intermediacy of a discrete guanidine or urea nitrenium ion
cannot be ruled out.
(18) Hassan, W.; Edrada, R.; Ebel, R.; Wray, V.; Berg, A.; Van Soest, R.;
Wiryowidagdo, S.; Proksch, P. J. Nat. Prod. 2004, 67, 817.
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