Mechanochemical Enzymatic Resolution Of N-Benzylated-Beta(3)-Amino Esters

The use of mechanochemistry to carry out enantioselective reactions has been explored in the last ten years with excellent results. Several chiral organocatalysts and even enzymes have proved to be resistant to milling conditions, which allows for rather efficient enantioselective transformations under ball-milling conditions. The present article reports the first example of a liquid-assisted grinding (LAG) mechanochemical enzymatic resolution of racemic beta(3)-amino esters employing Candida antarctica lipase B (CALB) to afford highly valuable enantioenriched N-benzylated-beta(3)-amino acids in good yields. Furthermore the present protocol is readily scalable.