Organic Letters
Letter
Wang, Q. J. Org. Chem. 2013, 78, 2775. (e) Zheng, Y.; Liu, Y.; Wang,
Q. J. Org. Chem. 2014, 79, 3348.
(13) (a) Han, G.; Liu, Y.; Wang, Q. Org. Lett. 2013, 15, 5334.
(b) Chang, C.-F.; Li, C.-F.; Tsai, C.-C.; Chuang, T.-H. Org. Lett.
2016, 18, 638.
(14) Recently, we developed a synthetic protocol for piperidine-
containing natural products using the pyridine ring as a precursor for
the piperidine ring. See: Park, E.; Cheon, C.-H. Org. Biomol. Chem.
2017, 15, 10265.
ACKNOWLEDGMENTS
■
This work was supported by National Research Foundation of
Korea (NRF) grants funded by the Korean Government
(NRF-2018R1D1A1A02086110 and NRF-2014-011165, Cen-
ter for New Directions in Organic Synthesis), and by a grant
from the National Institutes of Health, U.S.A. (NIH
GM118185) to M.D.B.
(15) There has been only one report on the synthesis of
phenanthroindolizidines by B-ring formation through the connection
between C- and D-rings. See: Niphakis, M. J.; Georg, G. I. Org. Lett.
2011, 13, 196.
(16) Pyridyl bromide 10b was prepared according to the procedure
reported in literature. See: Zhang, B.; Chen, R.; Jiang, H.; Zhou, Q.;
Qiu, F.; Han, D.; Li, R.; Tang, W.; Zhong, A.; Zhang, J.; Yu, X.
Tetrahedron 2016, 72, 2813.
(17) The structures of products 10 were confirmed by the
conversion of 10 to 2-(3-hydroxypropyl)pyridine via the full
reduction of the triple bond and bromine with hydrogen using a Pd
(18) (a) Knapp, D. M.; Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc.
2009, 131, 6961. (b) Gonzalez, J. A.; Ogba, O.; Morehouse, G. F.;
Rosson, N.; Houk, K. N.; Leach, A. G.; Cheong, P. H.-Y.; Burke, M.
D.; Lloyd-Jones, G. C. Nat. Chem. 2016, 8, 1067.
(19) ortho-Aza-terphenyls 7 should be subjected to a workup prior to
hydrogenation although we did not need to completely isolate 7.
(20) Because compounds 7 were difficult to separate from the
reaction mixture, 7 were further transformed into compounds 13 by
hydrogenation. Fortunately, 13 were more easily isolable from the
reaction mixture than 7.
(21) We speculated that the poor efficiency of this transformation
might be due to the lower electrophilicity of the resulting pyridinium
salts. For the electrophilicity of pyridinium salts, see: Mayr, H.; Patz,
M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938.
REFERENCES
■
(1) Lehmann, J. W.; Blair, D. J.; Burke, M. D. Nat. Rev. Chem. 2018,
2, 0115.
(2) For highlights on the iterative Suzuki−Miyaura coupling
reaction, see: (a) Tobisu, M.; Chatani, N. Angew. Chem., Int. Ed.
2009, 48, 3565. (b) Wang, C.; Glorius, F. Angew. Chem., Int. Ed. 2009,
48, 5240. For reviews: (c) Xu, L.; Zhang, S.; Li, P. Chem. Soc. Rev.
2015, 44, 8848. (d) Trobe, M.; Burke, M. D. Angew. Chem., Int. Ed.
2018, 57, 4192.
(3) The Suginome group developed a 1,8-diaminonaphthalene
(DAN) boronate as a protecting group for boronic acid. See:
(a) Noguchi, H.; Hojo, K.; Suginome, M. J. Am. Chem. Soc. 2007, 129,
758. (b) Noguchi, H.; Shioda, T.; Chou, C.-M.; Suginome, M. Org.
Lett. 2008, 10, 377. (c) Iwadate, N.; Suginome, M. J. Organomet.
Chem. 2009, 694. (d) Iwadate, N.; Suginome, M. Org. Lett. 2009, 11,
1899.
(4) MIDA boronate has also been used as a boron-protecting group.
For selected examples, see: (a) Knapp, D. M.; Gillis, E. P.; Burke, M.
D. J. Am. Chem. Soc. 2009, 131, 6961. (b) Dick, G. R.; Knapp, D. M.;
Gillis, E. P.; Burke, M. D. Org. Lett. 2010, 12, 2314. (c) Dick, G. R.;
Woerly, E. M.; Burke, M. D. Angew. Chem., Int. Ed. 2012, 51, 2667.
(5) (a) Gillis, E. P.; Burke, M. D. J. Am. Chem. Soc. 2007, 129, 6716.
(b) Mohamed, Y. M. A.; Hansen, T. V. Tetrahedron Lett. 2011, 52,
1057. (c) Fujita, K.; Matsui, R.; Suzuki, T.; Kobayashi, S. Angew.
̈
Chem., Int. Ed. 2012, 51, 7271. (d) Weber, A.; Dehn, R.; Schlager, N.;
Dieter, B.; Kirschning, A. Org. Lett. 2014, 16, 568. (e) Woerly, E. M.;
Roy, J.; Burke, M. D. Nat. Chem. 2014, 6, 484. (f) Li, J.; Ballmer, S.
G.; Gillis, E. P.; Fujii, S.; Schmidt, M. J.; Palazzolo, A. M. E.;
Lehmann, J. W.; Morehouse, G. F.; Burke, M. D. Science 2015, 347,
1221. (g) Brun, E.; Bellosta, V.; Cossy, J. J. Org. Chem. 2016, 81,
8206. (h) Go, E. B.; Wetzler, S. P.; Kim, L. J.; Chang, A. Y.; Vosburg,
D. A. Tetrahedron 2016, 72, 3790. (i) Nishioka, Y.; Yano, Y.; Kinashi,
N.; Oku, N.; Toriyama, Y.; Katsumura, S.; Shinada, T.; Sakaguchi, K.
Synlett 2017, 28, 327. (j) Haley, H. M. S.; Hill, A. G.; Greenwood, A.
I.; Woerly, E. M.; Rienstra, C. M.; Burke, M. D. J. Am. Chem. Soc.
2018, 140, 15227.
(6) (a) Ishiyama, T.; Murata, M.; Miyaura, N. J. Org. Chem. 1995,
60, 7508. (b) Baron, O.; Knochel, P. Angew. Chem., Int. Ed. 2005, 44,
3133. (c) Jiang, Q.; Ryan, M.; Zhichkin, P. J. Org. Chem. 2007, 72,
6618.
(7) For reviews on MIDA boronates, see: (a) Gillis, E. P.; Burke, M.
D. Aldrichimica Acta 2009, 42, 17. (b) Li, J.; Grillo, A. S.; Burke, M.
D. Acc. Chem. Res. 2015, 48, 2297.
(8) For our original reports on the use of a boronic acid moiety as a
blocking group in electrophilic aromatic substitution reactions, see:
(a) Lee, C.-Y.; Ahn, S.-J.; Cheon, C.-H. J. Org. Chem. 2013, 78 (23),
12154. (b) Ahn, S.-J.; Lee, C.-Y.; Kim, N.-K.; Cheon, C.-H. J. Org.
Chem. 2014, 79, 7277.
(9) Lee, C.-Y.; Cheon, C.-H. Adv. Synth. Catal. 2017, 359, 3831.
(10) Chemler, S. R. Curr. Bioact. Compd. 2009, 5, 2.
(11) For a review on the synthesis of phenanthroindolizidine
alkaloids, see: Burtoloso, A. C. B.; Bertonha, A. F.; Rosset, I. G. Curr.
Top. Med. Chem. 2013, 14, 191.
(12) Most previously reported syntheses have been designed for a
specific phenanthroindolizidine target molecule via a different
synthetic route. For selected examples, see: (a) Kim, S.; Lee, J.;
Lee, T.; Park, H.-g.; Kim, D. Org. Lett. 2003, 5, 2703. (b) Camacho-
Davila, A.; Herndon, J. W. J. Org. Chem. 2006, 71, 6682. (c) Niphakis,
M. J.; Georg, G. I. J. Org. Chem. 2010, 75, 6019. (d) Su, B.; Chen, F.;
D
Org. Lett. XXXX, XXX, XXX−XXX