Amines CALB effect

Similarly, CALB has been used in combination with a palladium/alkaline earth metal-based racemization catalyst to effect a DKR on the benzylic amine 56e (Scheme 2.27). The (R)-amide 57e was obtained in very good yield and excellent optical purity. Several other substrates also underwent the reaction [29],... 

Similarly, (R)-acetamides and (S)-amines were produced by the lipase-catalyzed resolution of l-(heteroaryl)ethanamines (Scheme 4.10) [17] in a study that assessed the effect of different solvents and lipases on the effectiveness of the resolution. The best results were obtained with CALB in the presence of tert-butyl methyl ether (TBME) or tetrahydrofuran (THF) depending on starting material solubility. 

Similarly, trans-cycloalkane 1,2-diamines and boron containing amines and amides have been resolved very effectively (E> 200) using CALB [18,19]. 

Figure 9.10 The effect of (a) pressure and temperature on the CaLB N435-catalyzed KR of an alcohol rac-llh and (b) the mode of immobilization of CaLB and temperature on the CaLB-catalyzed KR of an amine rac-lA in continuous-flow PBRs and the structures of the products ...

The DKR procedure described above was improved by Meijer and coworkers in 2007 [87]. The protocol was improved both in terms of reaction time (26 h instead of 72 h) and the required amount of acyl donor (the excess acyl donor could be reduced to 1.1 equiv). This was accomplished using a more effective acyl donor isopropyl 2-methoxyacetate for the enzymatic acylation. CALB was used for the kinetic resolution, and the para-methoxyphenyl derivative of the Shvo catalyst was used for racemization (22). All the DKR reactions were performed under reduced pressure (750 mbar) to eliminate the isopropyl alcohol from the reaction mixture. The isopropyl alcohol can be oxidized to acetone, and the latter can in subsequent reaction steps form unwanted condensation products with the amine substrates. The revised protocol afforded the products with excellent selectivity (96-99% ee). The yields were slightly lower (56-80%) than those obtained with the Backvall protocol [86], mainly due to problems with purification. 

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. 

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