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Eight‐Step Enantioselective Total Synthesis of (−)‐Cycloclavine
Author(s) -
McCabe Stephanie R.,
Wipf Peter
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201608820
Subject(s) - enantioselective synthesis , cycloaddition , allene , intramolecular force , total synthesis , chemistry , cyclopropanation , enone , carbanion , furan , stereochemistry , michael reaction , catalysis , organic chemistry
The first enantioselective total synthesis of (−)‐cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh 2 (S‐TBPTTL) 4 , and the enone 1,2‐addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain‐promoted Diels–Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (−)‐ 1 was completed by a late‐stage intramolecular Diels–Alder furan (IMDAF) cycloaddition to install the indole.