Mitsuhisa Yamano

Asymmetric catalytic hydrogenation for large scale preparation of optically active 2-(N-benzoylamino)cyclohexanecarboxylic acid derivatives

Asymmetric catalytic hydrogenation methodology was applied to the synthesis of 2-[N-(4-difluoromethoxy)benzoylamino]cyclohexanecarboxylic acid derivatives. During the course of optimization, it was found that chiral Ru(II) dicarboxylate complexes worked efficiently with an acid additive, aqueous HBF4. Regarding chiral ligand, DTBM-BINAP showed the best result with full-conversion and the highest stereoselectivity. Practical conditions for the asymmetric hydrogenation were also established suppressing the amount of the catalyst and multi-kilogram scale synthesis was successfully achieved.

Novel Methods of Synthesizing Naphtho[1,2-c]furan-1,3-dione and Benzo[e]isoindole-1,3-dione

Convenient methods of synthesizing naphtho[1,2-c]furan-1,3-dione and benzo[e]isoindole-1,3-dione from phenylbutyric acid derivatives have been established. Naphtho[1,2-c]furan-1,3-dione and benzo[e]isoindole-1,3-dione were obtained respectively from 4,5-dihydronaphtho[1,2-c]furan-1,3-dione and 4,5-dihydrobenzo[e]isoindole-1,3-dione by aromatization with 10% Pd-C in AcOH under mild conditions. In addition, benzo[e]isoindole-1,3-dione derivatives were obtained from 4,5-dihydronaphtho[1,2-c]furan-1,3-dione by imidation and simultaneous aromatization with primary amine in AcOH in one pot.