Racemization Catalyst for the DKR of Amines

The first example of racemization catalyst applied to the DKR of amines was described by Reetz and Schimossek, contemporary to the report of first cases of scc-alcohol DKRs [96]. Nevertheless, reported racemization catalysts for amines are not so numerous, due to the severe conditions required for ttie racemization, which frequently are not compatible with the activity of the enzyme. That pioneering work reported the use of 5% Pd/C as heterogeneous racemization catalyst and combined its action with CALB activity in the DKR of 1-phenylethylamine (rac-91). Although just moderate yields could be achieved after Sdays, palladium was, since then, considered a very attractive catalyst in the racemization of primary amines. 

Park and coworkers have developed a palladiinn nanocatalyst, applicable to the DKR of primary amines as well as amino acid amides [97]. This nanocatalyst, Pd/ AIO(OH), prepared as palladium nanoparticles entrapped in aluminum hydroxide required 70 °C for the racemization of benzylic amines and higher temperature (100 °C) in the case of aliphatic amines. For that reason, DKR processes were developed in combination with thermostable immobilized CALB. In fact, these authors have described the coupling of this catalyst with the activity of P. stutzeri lipase in the DKR of p-amino acid amides being necessary to perform the enzymatic resolution and the racemization at different temperatures and to add fresh lipase after the racemization due to the thermal enzyme deactivation [98]. 

More recently, Backvall and coworkers have described a very effective catalyst for the racemization of amines highly dispersed Pd nanoparticles supported in the large pores of silica-based mesocellular foam (MCF) [104]. This catalyst proved to be a more robust catalyst in amine racemization than any other catalysts reported before and is completely compatible with CALB activity. 

14 DYNAMIC KINETIC RESOLUTION VIA HYDROLASE-METAL COMBO CATALYSIS 

Ruthenium-based catalyst employed in the racemization of amines. 

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Raney Ni and Co were also tested as the racemization catalysts for the DKR of amines [57]. Raney Ni displayed better activity and selectivity (Scheme 5.34). Specifically, Raney Ni displayed good performance in the DKR of aliphatic amines (Chart 5.32). The DKR of 1-phenylethylamine with Raney Ni did not proceed to completion even after 5 days, whereas the DKR of 2-hexylamine was complete within 4 days to provide 98% yield and 97% ee. On tire other hand, the DKR of 1-phenylethyl-amine was performed in a two-pot process for higher )deld, in which the reaction medium was altematingly shuttled between two separate vessels containing the racemization catalysts and the enz5mies, respectively. After four cycles, the yield reached 94% 3ueld with 91% ee. 

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