Enantioselective Biocatalytic\nReduction of 2<i>H</i>‑1,4-Benzoxazines Using Imine\nReductases

A biocatalytic\nreduction of 2<i>H</i>-1,4-benzoxazines\nusing imine reductases is reported. This process enables a smooth\nand enantioselective synthesis of the resulting cyclic amines under\nmild conditions in aqueous media by means of a catalytic amount of\nthe cofactor NADPH as hydride source as well as glucose as the reducing\nagent used in stoichiometric amounts for in situ cofactor recycling.\nSeveral substrates were studied, and the 3,4-dihydro-2<i>H</i>-1,4-benzoxazines were obtained with up to 99% ee. In addition, the\nefficiency of this reduction process based on imine reductases as\ncatalysts has been demonstrated for one 2<i>H</i>-1,4-benzoxazine\non an elevated laboratory scale running at a substrate loading of\n10 g L<sup>–1</sup> in the presence of a tailor-made whole-cell\ncatalyst.