Dynamic Kinetic Resolution Of Arylamines Catalyzed By Lipase-Palladium Complexes

The dynamic kinetic resolution (DKR) of arylamines has been studied in this paper. In the research, we designed and developed the rac-catalysts, chose acyl donors, studied the chemical enzymatic coupling. Later an enzyme-metal combo reaction has been successfully developed for the dynamic kinetic resolution of arylamines in which racemic substrates are transformed by Novozym435and Pd/LDH-DS or Pd/MWCNTs. The new prepared Pd/LDH-DS and Pd/MWCNTs have excellent racemization activity and good biocompatibility. The two catalysts were efficient in the racemization reaction. And an excellent eep value (>99%) at high yield (>99%) was achieved in the DKR of arylamines.Based on the mechanism of racemization catalyzed by palladium complex catalysts, we firstly prepared Pd/LDH-DS and Pd/MWCNTs. The two catalysts were very efficient in the racemization reaction, and it had the advantages of low reaction temperature, which was55℃and fast reaction rate for15h.The effects of lipases, solvents, acyl donors, substrate concentration and temperature on the reaction were investigated. And to improve the biocompatibility with chemical catalyst, an efficient reaction system of1-phenylethylamine was constructed. There was the non-selective amidation reaction catalyzed by amine with most acyl donors, which was the main reason for the decrease in eep of DKR. And through changing alcohol and acid moiety of the acyl donors, it was found that as the acyl donor, long carbon-chain esters could effectively inhibit the non-selective amidation reaction. When the number of acyl carbon atoms was more than five, the KR result could reach the optimal performance as that of4-Chlorophenyl valerate. The reaction had been successfully developed for the kinetic resolution of arylamines.Later we studied the chemical enzymatic coupling. A new and efficient dynamic kinetic resolution (DKR) process of1-phenylethylamine by using long carbon-chain esters as acyl donors was developed. During the process, the non-selective amidation reaction with different acyl donors was found effectively suppressed while the structures of acyl donors were made complex. According to this law, we found that when the number of acyl carbon atoms was more than five, the DKR result could reach the optimal performance as that of4-Chlorophenyl valerate. And excellent eep value (>99%) at high yield (>99%) can be achieved.When4-chlorophenyl valerate was used as the acyl donor, the DKR of most arylamines with Pd/LDH-DS or Pd/MWCNTs as racemization catalyst were achieved successfully. It was also found that the type and position of substituting group took effect on the result of DKR. In the reseach, the selectivity of enzyme and the non-selective amidation reaction catalyzed by amine with most acyl donors were two factors for the decrease in eep of DKR.The DKR of1-phenylethylamine catalyzed by Pd/LDH-DS or Pd/MWCNTs has excellent operational stability. The two systems can be reused more than30times without a loss of yield (>99%) and eep value(>99%).