Diastereo- and Enantioselective Catalytic Kinetic Resolution of 2-Substituted 3-Nitro-2H-chromenes.

An unprecedented catalytic kinetic resolution of 2-substituted 3-nitro-2H-chromenes via Rh-catalyzed asymmetric hydrogenation has been developed to simultaneously produce a variety of syn-chiral 2-substituted 3-nitro-2H-chromanes containing vicinal stereogenic centers with excellent diastero- and enantioselectivities [diastereomeric ratio (dr) of >99:1 and up to 99.9% enantiomeric excess (ee)] and recovered chiral 2-substituted 3-nitro-2H-chromenes with 90-99.9% ee in high yields, respectively, achieving excellent kinetic selectivity factors of up to 1057. Moreover, in addition to syn-chiral 2-substituted 3-nitro-2H-chromanes, this new approach provides concise, atom-economical, and straightforward access to anti-chiral 2-substituted 3-nitro-2H-chromanes and a mammalian target of rapamycin (mTOR) inhibitor, (R)-DHM25.