Asymmetric Hydrogenation of α-Substituted Acrylic Acids Catalyzed by a Ruthenocenyl Phosphino-oxazoline-Ruthenium Complex

Org Lett. 2016 May 6;18(9):2122-5. doi: 10.1021/acs.orglett.6b00748. Epub 2016 Apr 25.

Abstract

Asymmetric hydrogenation of various α-substituted acrylic acids was carried out using RuPHOX-Ru as a chiral catalyst under 5 bar H2, affording the corresponding chiral α-substituted propanic acids in up to 99% yield and 99.9% ee. The reaction could be performed on a gram-scale with a relatively low catalyst loading (up to 5000 S/C), and the resulting product (97%, 99.3% ee) can be used as a key intermediate to construct bioactive chiral molecules. The asymmetric protocol was successfully applied to an asymmetric synthesis of dihydroartemisinic acid, a key intermediate required for the industrial synthesis of the antimalarial drug artemisinin.

Publication types

  • Research Support, Non-U.S. Gov't