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An Unexpected Michael–Aldol–Smiles Rearrangement Sequence for the Synthesis of Versatile Optically Active Bicyclic Structures by Using Asymmetric Organocatalysis
Author(s) -
Holub Nicole,
Jiang Hao,
Paixão Marcio W.,
Tiberi Caterina,
Jørgensen Karl A.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903274
Subject(s) - bicyclic molecule , aldol reaction , trifluoroacetic acid , organocatalysis , chemistry , intramolecular force , metathesis , stereochemistry , combinatorial chemistry , enantioselective synthesis , catalysis , organic chemistry , polymer , polymerization
A facile and simple organocatalytic procedure to generate optically active 6‐alkyl‐ and 6‐aryl‐substituted bicyclo[2.2.2]oct‐5‐en‐2‐ones is presented. The reaction is catalysed by a 9‐amino‐9‐deoxyepiquinine trifluoroacetic acid salt, which activates α,β‐unsaturated cyclic ketones for the 1,4‐addition of β‐keto benzothiazoyl sulfones in a stereoselective fashion. Subsequent intramolecular aldol reaction and Smiles rearrangement gives rise to important optically active bicycles, which are a common motif in natural products, ligands in asymmetric catalysis and substrates for Cope rearrangements, photochemical reactions, radical cyclisations and metathesis. Different bicyclic structures were obtained by utilisation of various cyclic enones or by performing ring‐expanding reactions. Furthermore, two possible mechanistic pathways are outlined and discussed.