Lonza asymmetric hydrogenation

Fig. 4 Structures of the Josiphos ligands used in the Lonza asymmetric hydrogenation programs.

Lonza has performed the asymmetric hydrogenation of a cyclic imine 64 with iridium catalysts that contain 4j to form dextromethorphan (65), an antitussive, in 90% ee (Scheme 12.20) at the multi-kilogram scale (>100 kg produced).87... 

Phosphines ligands that have chirality from ferrocenes have been implemented in the iridium-catalyzed asymmetric hydrogenation of imine with moderate enantioselectivities for Novartis s manufacture of metolachlor. Electronic modifications of these ferrocenyl ligands have increased the enantioselectivity and catalyst reactivity for Lonza s asymmetric hydrogenation processes of biotin and 2-substituted piperazines, intermediates for several pharmaceutical drugs. 

Since Lonza carried out its first homogeneous asymmetric hydrogenation on a 17 ton scale in 1994, the development and application of asymmetric hydrogenations has been a major strength in Lonza s technology portfolio. The applications in Lonza have varied from internally-generated projects, for end-products marketed by Lonza, to projects in the custom-manufacturing field, in which the Lonza Exclusive Synthesis department is active. This chapter will illustrate how process de-... 

Asymmetric Hydrogenation in the Lonza Biotin Process 287 Josiphos Ligands(R)- S)-R2PF-PR 2... 

---