Rapid Identification of a Scalable Catalyst for the Asymmetric Hydrogenation of a Sterically Demanding Aryl Enamide

• Published in: Organic process research & development 2010-05, Vol.14 (3), p.568-573
• Main Authors: Lefort, Laurent, Boogers, Jeroen A. F, Kuilman, Thijs, Vijn, Robert Jan, Janssen, John, Straatman, Harrie, de Vries, Johannes G, de Vries, André H. M
• Format: Article
• Language: English
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/op100011y

High throughput screening was used to find a cost-effective and scalable catalyst for the asymmetric hydrogenation of a sterically demanding enamide as an intermediate towards a new potent melanocortin receptor agonist useful in the treatment of obesity. Lessons drawn from the testing of a first library of 96 chiral monodentate phosphoramidites led to the design of a second focused library of 16 chiral ligands, allowing the discovery of a new efficient catalyst. This catalyst was based on rhodium and a bulky monodentate phosphite ligand. The catalyst was scaled up and used in the kilogram production of the desired bulky chiral amide.