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Organocatalytic, Asymmetric Total Synthesis of (−)‐Haliclonin A
Author(s) -
Guo LianDong,
Huang XiongZhi,
Luo ShiPeng,
Cao WenSen,
Ruan YuanPing,
Ye JianLiang,
Huang PeiQiang
Publication year - 2016
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.201512005
Subject(s) - stereocenter , enone , chemistry , total synthesis , enantioselective synthesis , alkene , stereochemistry , nitromethane , quaternary carbon , cyclohexenone , organic chemistry , catalysis
The first total synthesis of the alkaloid (−)‐haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3‐alkenyl cyclohex‐2‐enone to set the stereochemistry of the all‐carbon quaternary stereogenic center. The synthesis also features a Pd‐promoted cyclization to form the 3‐azabicyclo[3,3,1]nonane core, a SmI 2 ‐mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring‐closing alkene and alkyne metathesis reactions to build the two aza‐macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.