Chemical Kinetic Resolution of Unprotected β-Substituted β-Amino Acids Using Recyclable Chiral Ligands

The first chemical method for resolution of N, C-unprotected beta-amino acids was developed through enantioselective formation and disassembly of nickel(II) complexes under operationally convenient conditions. The specially designed chiral ligands are inexpensive and can be quantitatively recycled along with isolation of the target beta-substituted-beta-amino acids in good yields and excellent enantioselectivity. The method features a broad synthetic generality including beta-aryl, beta-heteroaryl, and beta-alkyl-derived beta-amino acids. The procedure is easily scaled up, and was used for the synthetically and economically advanced preparation of the anti-diabetic drug sitagliptin.