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A Concise Enantioselective Total Synthesis of (−)‐Virosaine A
Author(s) -
Hughes Jonathan M. E.,
Gleason James L.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201706273
Subject(s) - enantioselective synthesis , cycloaddition , chemistry , epoxide , nitrone , intramolecular force , total synthesis , combinatorial chemistry , furan , halogenation , surface modification , organic chemistry , stereochemistry , catalysis
The total synthesis of (−)‐virosaine A ( 1 ) was achieved in ten steps starting from furan and 2‐bromoacrolein. A one‐pot Diels–Alder cycloaddition/organolithium addition initiated an efficient sequence to access a key oxime/epoxide intermediate. Heating this intermediate in acetic acid resulted in an intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct the caged core of 1 in a single step. Several methods of C−H functionalization were assessed on the cascade product, and ultimately, a directed lithiation/bromination effected selective C14 functionalization, enabling the synthesis of 1 .