Approaches to the synthesis of (±)-strychnine via the cobalt-mediated [2+2+2] cycloaddition:: Rapid assembly of a classic framework

被引:103
作者
Eichberg, MJ
Dorta, RL
Grotjahn, DB
Lamottke, K
Schmidt, M
Vollhardt, KPC [1 ]
机构
[1] Univ Calif Berkeley, Dept Chem, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Chem Sci, Berkeley, CA 94720 USA
关键词
D O I
10.1021/ja016333t
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Five synthetic approaches to racemic strychnine (1), with the cobalt-mediated [2 + 2 + 2] cycloaddition of alkynes to indoles as the key step, are described. These include the generation and attempted cyclization of macrocycle 8 and the synthesis of dihydrocarbazoles 15, 22, and 26 and their elaboration to pentacyclic structures via a conjugate addition, dipolar cycloaddition, and propellane-to-spirofused skeletal rearrangement, respectively. Finally, the successful total synthesis of 1 is discussed. The development of a short, highly convergent route (14 steps in the longest linear sequence) is highlighted by the cyclization of enynoylindole 40 with acetylene and the formal intramolecular 1,8-conjugate addition of amine 49 to form pentacycle 50. Numerous attempts toward the formation of the piperidine ring of 1 from vinyl iodide 56 were made and its successful formation via palladium-, nickel-, and radical-mediated processes is described.
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页码:9324 / 9337
页数:14
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