Asymmetric synthesis of tetrahydrobenzodiazepines was achieved by transfer hydrogenation of dihydrobenzodiazepines with benzothiazoline having a hydrogen-bonding donor substituent by means of a newly synthesized chiral phosphoric acid. This method was applicable to various racemic dihydrobenzodiazepines to give the corresponding products in good yields with excellent diastereoselectivities and enantioselectivities taking advantage of the dynamic kinetic resolution. Furthermore, the effect of bulky substituent at 3,3'-position on the catalyst and hydrogen-bonding donor substituent on benzothiazoline was fully elucidated by the theoretical study.

Chiral phosphoric acid catalyzed transfer hydrogenation of ketimines derived from propiophenone derivatives and reductive amination of alkyl ethyl ketone derivatives were extensively examined in the presence of two representative hydrogen donors. The excellent enantioselective transfer hydrogenation was achieved by use of benzothiazoline as a hydrogen donor. The theoretical studies elucidated that the unsymmetrical structure of benzothiazoline plays an important role in high enantioselective hydrogenation.

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Dihydrobenzodiazepines or benzodiazepines bearing aryl substituents at the 2‐ and 4‐position of the heterocyclic part are transformed to the chiral title compounds in the presence of BNPA using different amounts of the hydrogen transfer reagent BTA.

Acid. -(SAKAMOTO, T.; HORIGUCHI, K.; SAITO, K.; MORI, K.; AKIYAMA*, T.; Asian J. Org. Chem. 2 (2013) 11, 943-946, http://dx.