Organic Letters
Letter
(24) For the complete H- and 13C-NMR assignment of gephyrotoxin
287C, see: Edwards, M. W.; Bax, A. J. Am. Chem. Soc. 1986, 108, 918−
923.
1
(
7) Daly, J. W.; Witkop, B.; Tokuyama, T.; Nishikawa, t.; Karle, I. L.
Helv. Chim. Acta 1977, 60, 1128−1140.
8) The optical rotation was measured from a sample of gephyrotoxin
(
isolated from extracts of frogs collected in 1974. The gephyrotoxin used
for the X-ray analysis had been obtained from frogs collected in the same
area in 1971: see refs 4b, c, e.
(
9) (a) Mensah-Dwumah, M.; Daly, J. W. Toxicon 1978, 16, 189−194.
(
b) Souccar, C.; Varanda, W. A.; Daly, J. W.; Albuquerque, E. X. Mol.
Pharmacol. 1984, 25, 384−394. (c) Aronstam, R. S.; Daly, J. W.; Spande,
T. F.; Narayanan, T. K.; Albuquerque, E. X. Neurochem. Res. 1986, 11,
1
(
227−1240.
10) For the synthesis of (±)-perhydrogephyrotoxin, see: (a) Over-
man, L. E.; Fukaya, C. J. Am. Chem. Soc. 1980, 102, 1454−1456. For the
synthesis of (±)-gephyrotoxin 287C, see: (b) Fujimoto, R.; Kishi, Y.;
Blount, J. F. J. Am. Chem. Soc. 1980, 102, 7154−7156. (c) Hart, D. J.;
Kanai, K. J. Am. Chem. Soc. 1983, 105, 1255−1263. (d) Overman, L. E.;
Lesuisse, D.; Hashimoto, M. J. Am. Chem. Soc. 1983, 105, 5373−5379.
(
e) Shirokane, K.; Wada, T.; Yoritate, M.; Minamikawa, R.; Takayama,
N.; Sato, T.; Chida, N. Angew. Chem., Int. Ed. 2014, 53, 512−516.
f) Shirokane, K.; Tanaka, Y.; Yoritate, M.; Takayama, N.; Sato, T.;
Chida, N. Bull. Chem. Soc. Jpn. 2015, 88, 522−537.
11) (a) Fujimoto, R.; Kishi, Y. Tetrahedron Lett. 1981, 22, 4197−4198.
b) Chu, S.; Wallace, S.; Smith, M. D. Angew. Chem., Int. Ed. 2014, 53,
3826−13829. (c) Nemoto, T.; Yamaguchi, M.; Kakugawa, K.; Harada,
S.; Hamada, Y. Adv. Synth. Catal. 2015, 357, 2547−2555.
12) For formal enantioselective syntheses, see: (a) Wei, L.-L.; Hsung,
R. P.; Sklenicka, H. M.; Gerasyuto, A. I. Angew. Chem., Int. Ed. 2001, 403,
516−1518. (b) Santarem, M.; Vanucci-Bacque, C.; Lhommet, G. J.
(
(
(
1
(
1
́
Org. Chem. 2008, 73, 6466−6469. (c) Miao, L.; Shu, H.; Noble, A. R.;
Fournet, S. P.; Stevens, E. D.; Trudell, M. L. Arkivoc 2010, viii, 6−14.
(
7
d) Pichette, S.; Winter, D. K.; Lessard, J.; Spino, C. J. Org. Chem. 2013,
8, 12532−12544.
13) (a) Amat, M.; Fabregat, R.; Griera, R.; Florindo, P.; Molins, E.;
(
Bosch, J. J. Org. Chem. 2010, 75, 3797−3805. (b) Amat, M.; Ghirardi, E.;
Navío, L.; Griera, R.; Llor, N.; Molins, E.; Bosch, J. Chem. - Eur. J. 2013,
1
9, 16044−16049. (c) Amat, M.; Pinto, A.; Griera, R.; Bosch, J. Chem. -
Eur. J. 2015, 21, 12804−12808. (d) Pinto, A.; Griera, R.; Molins, E.;
Fernandez, I.; Bosch, J.; Amat, M. Org. Lett. 2017, 19, 1714−1717.
14) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Sato, M.;
Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314−321.
15) Amat, M.; Fabregat, R.; Griera, R.; Bosch, J. J. Org. Chem. 2009,
́
(
(
7
(
(
4, 1794−1797.
16) Jones, G. R. Tetrahedron 1996, 52, 7599−7662.
17) The absolute configuration of unsaturated and saturated tricyclic
lactams related to 4, 7, and 8 (methyl substituent instead of CH CH X
2
2
at the DHQ 5-position) was unambiguously determined by X-ray
13a
crystallography.
18) For the ruthenium tetroxide oxidation of N-acyl cyclic amines to
(
the corresponding N-acyl lactams, see: (a) Sheehan, J. C.; Tulis, R. W. J.
Org. Chem. 1974, 39, 2264−2267. (b) Moriyama, K.; Sakai, H.;
Kawabata, T. Org. Lett. 2008, 10, 3883−3886.
(
19) (a) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33,
6
2
299−6302. (b) Foti, C. J.; Comins, D. L. J. Org. Chem. 1995, 60, 2656−
657.
(
20) Deslongchamps, P. In Stereoelectronic Effects in Organic Chemistry;
Baldwin, J. E., Ed.; Pergamon: Oxford, 1983.
21) An alternative, more direct route involving a Pd-catalyzed Suzuki
coupling of triflate 11 with boronic acid 15 [Pd(dppf)Cl , Ag O,
(
2
2
K CO ], followed by NaBH CN−TFA reduction of the resulting
2
3
3
enecarbamate, provided DHQ 14 in only 26% yield.
(
(
22) Corey, E. J.; Ru
23) (a) Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Org. Chem. 1982, 47,
̈
cker, C. Tetrahedron Lett. 1982, 23, 719−722.
2
225−2227. (b) Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.;
Yamamoto, H. Bull. Chem. Soc. Jpn. 1984, 57, 2768−2776.
D
Org. Lett. XXXX, XXX, XXX−XXX