Lonza biotin process

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

Fig. 3.24 Lonza s biotin process using Rh-Xyliphos-type ligands.

Fig. 5. Synthetic pathway for (/-biotin (Lonza synthesis). An improved process uses the chiral ferrocenyldisphoshine (36) to introduce stereospecificity...

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. 

As Lonza had complete freedom to modify its own process for (d)-(+)-biotin, and selective introduction of substituents at N-l (through choice of starting material) and N-3 (through functionalization of 2) was simple, the effect of substituents on the hydrogenation was briefly studied. The results for a selection of the N-l- and N-3-substituted analogues investigated in Fig. 6 are summarized in Tab. 2 and Tab. 3, respectively. 

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