[RuCl(p-cymene)-(S)-BINAP]Cl Catalyzed Asymmetric Preparation of trans-3-Amino-bicyclo[2.2.2]octane-2-carboxylic Acid Ethyl Ester

trans-3-Amino-bicyclo[2.2.2]octane-2-carboxylic acid ester is the key common chiral fragment of some novel antiviral drugs (like Pimodivir and ZSP1273), which targets the PB2 subunit of RNA polymerase. Now, the market demand of this molecule is at level of hundreds kilograms to tons, and there are several related innovative drugs in clinical study. Here a asymmetric transfer hydrogenation strategy to directly construct trans-3-amino-bicyclo[2.2.2]octane-2-carboxylic acid ethyl ester using [RuCl(p-cymene)-(S)-BINAP]Cl as catalyst with excellent enantioselectivity (over 98% ee) and without tautomerization and protecting/de-protecting process is developed, which holds the potential of scale up production and commercial value.

Automated summary

This paper presents an asymmetric transfer hydrogenation strategy to directly construct a key chiral fragment with excellent enantioselectivity and without protecting/de-protecting process, showing the potential for large-scale production and commercial value.