An Unexpected Michael-Aldol-Smiles Rearrangement Sequence for the Synthesis of Versatile Optically Active Bicyclic Structures by Using Asymmetric Organocatalysis

• Published in: Chemistry : a European journal 2010-04, Vol.16 (14), p.4337-4346
• Main Authors: Holub, Nicole, Jiang, Hao, Paixão, Marcio W., Tiberi, Caterina, Jørgensen, Karl A.
• Format: Article
• Language: English
• Subjects: Aldehydes; asymmetric catalysis; Asymmetry; Bicycles; Chemistry; enones; Ketones; Ligands; Optical activity; organocatalysis; Radicals; Smiles rearrangement; Synthesis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200903274

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. Bicycle race: A facile organocatalytic route to optically active 6‐substituted bicyclo[2.2.2]oct‐5‐en‐2‐ones is presented. The key step is the enantioselective 1,4‐addition of β‐keto benzothiazoylsulfones to α,β‐unsaturated cyclic ketones. Subsequent intramolecular aldol reaction and Smiles rearrangement gives rise to the optically active bicyclic compounds (see scheme).