Enantioselective Synthesis of Chiral 1,5-Benzodiazepin-2-ones by Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination

The enantioselective synthesis of chiral 4-substituted 4,5-dihydro-1<i>H</i>-[1,5]benzodiazepin-2(3<i>H</i>)-ones via asymmetric hydrogenation catalyzed by the Pd/f-spiroPhos complex in the presence of hydrochloric acid as an additive has been developed, achieving excellent enantioselectivities and high turnover numbers, up to 99% ee and TON = 4600. More significantly, the asymmetric reductive amination of β-keto esters with 1,2-phenylenediamine has also been successfully realized to afford chiral 4-substituted 4,5-dihydro-1<i>H</i>-[1,5]benzodiazepin-2(3<i>H</i>)-ones with comparable enantioselectivities of up to 99% ee.