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Approach to Fully Substituted Cyclic Nitrones from N ‐Hydroxylactam Derivatives: Development and Application to the Total Synthesis of Cylindricine C
Author(s) -
Hiraoka Shobu,
Matsumoto Tsutomu,
Matsuzaka Koki,
Sato Takaaki,
Chida Noritaka
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201901049
Subject(s) - nitrone , trimethylsilyl , reagent , nucleophilic addition , chemistry , nucleophile , combinatorial chemistry , total synthesis , chiral auxiliary , organic chemistry , stereochemistry , enantioselective synthesis , catalysis , cycloaddition
Abstract An approach to cyclic nitrones from N ‐hydroxylactam derivatives is documented. The nucleophilic addition of an organolithium reagent to an N ‐OSEM [SEM=2‐(trimethylsilyl)ethoxymethyl] lactam forms a five‐membered chelated intermediate, which undergoes both elimination and deprotection to give a fully substituted nitrone in a one‐pot process. When combined with the N ‐oxidation of easily available chiral lactams, this method becomes especially useful for the quick synthesis of chiral nitrones in enantio‐pure form, enabling the concise total synthesis of cylindricine C.