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Updated: May 15, 2026

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy
Published on: November 9, 2019
Diastereoselective one-pot Knoevenagel condensation/Corey-Chaykovsky cyclopropanation
Jeremy J Clemens1, Juliana L Asgian, Brett B Busch
1Department of Drug Innovation, Vertex Pharmaceuticals, 11010 Torreyana Road, San Diego, California 92121, USA. jeremy_clemens@sd.vrtx.com
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.
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