Substituted isoquinolines by Noyori transfer hydrogenation: Enantioselective synthesis of chiral diamines containing an aniline subunit

Transfer hydrogenation using the Noyori catalyst 5-Ts is effective for the enantioselective hydrogenation of imines containing fully substituted nitro gen groups (12 or 13). Analogues such as Ile could not be reduced in practi cal yield, apparently due to product inhibition of the catalyst. Asymmetric transfer hydrogenation of the aniline imine 8a was possible, but required. impractical purity levels for the substrate, and the nitro analogue 7 coul d not be reduced efficiently. The best results were Obtained with the bromo phenyl imine 20, In the case of 20b, the product 21b was formed with 98.7% ee, and the material could be upgraded to >99% ee by crystallization of the hydrochloride salt. Reaction of 21b with NH3 or MeNH2 in the presence of C u/CuCl gave the chiral anilines 10b or 23b. The latter substance is compara ble to the commercially available 1 as a chiral proton donor fog amide enol ates and provides access to the hitherto unavailable enantiomeric series.