Preparation of tricyclic imidazopyridines by asymmetric ketone hydrogenation in the presence of ruthenium phosphino-oxazoline catalyst

The asymmetric hydrogenation of the prochiral heterocyclic ketone 2 and its O-protected analogues 9 to 11 in the presence of the ruthenium POX catalyst RuCl2(PPh3)(Ph2P-Fc-oxaiPr) was studied. The reactivity of the substrate and the enantioselectivity of the reduction depended on the nature of the protecting group. The best results were achieved with the thexyldimethylsilyl protecting group: the corresponding alcohol 13 was obtained in 86% yield and 88% ee and constitutes a valuable intermediate for the synthesis of the potassium-competitive acid blocker BYK 311319 1.

Graphical abstractThe asymmetric reduction of O-protected ketones in the presence of Ru-POX catalyst constitutes a key step in the synthesis of drugs for the treatment of acid-related diseases.Figure optionsDownload full-size imageDownload as PowerPoint slide