title: Diastereoselective one-pot Knoevenagel condensation/Corey-Chaykovsky cyclopropanation.
abstract: Efforts to substitute the cyclopropane ring in a series of aryl cyclopropylnitriles led to the discovery of an operationally simple one-pot method for Knoevenagel condensation and subsequent Corey-Chaykovsky cyclopropanation giving diastereomerically pure products as a racemic mixture of enantiomers. Method development and results for variably substituted aryl acetonitriles and aldehydes in the reaction are reported. A concise synthesis of (±)-bicifadine in two steps is provided to demonstrate the utility of the method.
authors.affiliation: Department of Drug Innovation, Vertex Pharmaceuticals, 11010 Torreyana Road, San Diego, California 92121, USA. jeremy_clemens@sd.vrtx.com
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Clemens
authors.forename: Juliana L
authors.initials: JL
authors.lastname: Asgian
authors.forename: Brett B
authors.initials: BB
authors.lastname: Busch
authors.forename: Timothy
authors.initials: T
authors.lastname: Coon
authors.forename: Justin
authors.initials: J
authors.lastname: Ernst
authors.forename: Leonard
authors.initials: L
authors.lastname: Kaljevic
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Krenitsky
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Neubert
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Schweiger
authors.forename: Andreas
authors.initials: A
authors.lastname: Termin
authors.forename: Dean
authors.initials: D
authors.lastname: Stamos
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D003521:Cyclopropanes / Q000737:chemistry*; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D003521:Cyclopropanes; D009570:Nitriles; C030797:cyclopropane