Ruthenium-catalysed synthesis of chiral exocyclic allylic alcohols via chemoselective transfer hydrogenation of 2-arylidene cycloalkanones

An exclusive asymmetric reduction of C = O bonds of 2-arylidene four-, five-, six-, and seven-membered cycloalkanones has been studied systematically. The asymmetric transfer hydrogenation was performed using a robust and commercially available chiral diamine-derived ruthenium complex as a catalyst and HCOOH/Et3N as a hydrogen source under mild conditions, giving 51 examples of chiral exocyclic allylic alcohols in up to 96% yield and 99% ee. This method was also applicable to the gram-scale synthesis of the active intermediates of the anti-inflammatory loxoprofen and natural product (-)-goniomitine.

Automated summary

The asymmetric reduction of C = O bonds of 2-arylidene cycloalkanones using a chiral ruthenium complex as a catalyst and HCOOH/Et3N as a hydrogen source resulted in high yields and high enantiomeric excess. This method is not only suitable for small-scale synthesis, but also applicable for the gram-scale synthesis of pharmaceutically important compounds.