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Tremorgenic Indole Alkaloids. 10. An Improved Asymmetric Synthesis of a Tricyclic Common Intermediate
Author(s) -
Smith Amos B.,
Hartz Richard A.,
Spoors P. Grant,
Rainier Jon D.
Publication year - 1997
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1002/ijch.199700009
Subject(s) - chemistry , cyclopropanation , indole test , vicinal , moiety , ring (chemistry) , tricyclic , total synthesis , stereochemistry , enantioselective synthesis , yield (engineering) , lactone , combinatorial chemistry , organic chemistry , catalysis , materials science , metallurgy
An efficient third‐generation asymmetric synthesis of tricyclic lactone (+)‐1, designed to serve as the common intermediate for construction of the indole tremorgens, has been developed. The major challenge was stereocontrolled introduction of the vicinal quaternary methyl groups. Our initial approaches employed enolate chemistry to install the second methyl moiety; herein we exploit instead a hydroxyl‐directed Simmons‐Smith cyclopropanation followed by reductive opening of the three‐membered ring. The new 15‐step synthesis proceeds in 8.3% overall yield, nearly an eightfold increase over the second‐generation route, and is amenable to large‐scale production of (+)‐ 1.