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Updated: May 22, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene ligands
Stefan Abele1, Roman Inauen, Dirk Spielvogel
1Process Research Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil, Switzerland. stefan.abele@actelion.com
Abstract:
An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition-aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product 4a (6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one) is transformed into phenylbicyclo[2.2.2]oct-5-en-2-one 2, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi's Ph-bod* ligand, as well as novel unsymmetrical chiral dienes.
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