title: Scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene ligands.
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.
authors.affiliation: Process Research Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil, Switzerland. stefan.abele@actelion.com
authors.forename: Stefan
authors.initials: S
authors.lastname: Abele
authors.forename: Roman
authors.initials: R
authors.lastname: Inauen
authors.forename: Dirk
authors.initials: D
authors.lastname: Spielvogel
authors.forename: Christian
authors.initials: C
authors.lastname: Moessner
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D003512:Cyclohexanones / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: C574746:6-hydroxy-5-phenylbicyclo(2.2.2)octan-2-one; D001643:Bridged Bicyclo Compounds; D003512:Cyclohexanones; D008024:Ligands; C028215:2-cyclohexen-1-one; D000079:Acetaldehyde; C013192:phenylacetaldehyde