Highly Efficient Formal [2+2+2] Strategy for the Rapid Construction of Polycyclic Spiroindolines: A Concise Synthesis of 11-Demethoxy-16-epi-myrtoidine.
A novel formal [2+2+2] strategy for the stereoselective elaboration of polycyclic indole alkaloids is described. Upon treatment with the catalyst InCl3 (5 mol %), tryptamine-derived enamides reacted readily with methylene malonate, thus enabling rapid and gram-scale access to versatile tetracyclic spiroindolines with excellent diastereoselectivity (21 examples, up to 95 % yield, up to d.r.>95:5). This strategy provides a concise approach to alkaloids isolated from Strychnos myrtoides, as demonstrated by a short synthesis of 11-demethoxy-16-epi-myrtoidine.
State Key Laboratory of Organometallic Chemistry, Shanghai, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Jun
J
Zhu
State Key Laboratory of Organometallic Chemistry, Shanghai, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Yu-Jing
YJ
Cheng
State Key Laboratory of Organometallic Chemistry, Shanghai, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Xiao-Kang
XK
Kuang
State Key Laboratory of Organometallic Chemistry, Shanghai, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. wanglijia@sioc.ac.cn.
Lijia
L
Wang
State Key Laboratory of Organometallic Chemistry, Shanghai, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
Zhong-Bo
ZB
Zheng
State Key Laboratory of Organometallic Chemistry, Shanghai, Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China. tangy@sioc.ac.cn.|Collaborative Innovation Center of Chemical Science and Engineering, Tianjin, 300072, China. tangy@sioc.ac.cn.
Yong
Y
Tang
D003500:Cyclization; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013331:Strychnine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
C000628149:11-demethoxy-16-epi-myrtoidine; D026121:Indole Alkaloids; D011083:Polycyclic Compounds; D013141:Spiro Compounds; D013331:Strychnine
diastereoselectivity; indole alkaloids; polycyclic indolines; tandem reactions; tryptamine derivatives