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We present, to the best of our knowledge, the first parametric study of the asymmetric transfer hydrogenation of imines catalyzed by a Noyori-type catalytic complex based on ruthenium. A model imine for this study was 1-methyl-3,4-dihydroisoquinoline, and a well-known complex RuCl(η 6 - p -cymene)((1 S ,2 S )- N - p -toluenesulfonyl-1,2-diphenylethylenediamine) was chosen as the model catalyst. The reactions were performed in the presence of a formic acid–triethylamine mixture as the source of hydrogen. The parameters examined include general parameters, for example, concentration, temperature, and substrate-to-catalyst molar ratio, as well as parameters specific to this particular reaction, such as the amount of the hydrogenation mixture used, the ratio of its components, or the inhibitive effect of carbon dioxide. During this study, several unexpected parameters worth further investigation have emerged.

A chiral precursor of Mivacurium chloride, (R)-5′-methoxylaudanosine, was prepared using two different methods. The chiral resolution of racemic 5′-methoxylaudanosine, typically used in industry, was carried out in parallel with a procedure consisting of asymmetric transfer hydrogenation (ATH) and reductive methylation. A novel one-pot synthetic step was developed for the synthesis of racemic 5′-methoxylaudanosine. In both routes, the enantioselectivity was high but further purification was necessary to reach the level of a pharmaceutical standard. The individual synthetic steps reported herein can also be used for the synthesis of analogous bistetrahydroisoquinoline-based skeletal muscle relaxants.