Premium
A Concise Enantioselective Total Synthesis of (−)‐Virosaine A
Author(s) -
Hughes Jonathan M. E.,
Gleason James L.
Publication year - 2017
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.201706273
Subject(s) - cycloaddition , enantioselective synthesis , epoxide , intramolecular force , nitrone , chemistry , total synthesis , furan , halogenation , combinatorial chemistry , surface modification , organic chemistry , oxime , 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 .