Scalable, Stereocontrolled Formal Syntheses of (+)-Isoschizandrin and (+)-Steganone: Development and Applications of Palladium(II)-Catalyzed Atroposelective C-H Alkynylation

Angew Chem Int Ed Engl. 2018 Mar 26;57(14):3661-3665. doi: 10.1002/anie.201713106. Epub 2018 Feb 28.


Dibenzocyclooctadiene lignans are an interesting class of molecules because of their unique structure based on an axially chiral biaryl moiety as well as their significant biological activity. Herein, we describe the development of a palladium-catalyzed atroposelective C-H alkynylation and its application in gram-scale, stereocontrolled formal syntheses of (+)-isoschizandrin and (+)-steganone. tert-Leucine was identified as an efficient, catalytic transient chiral auxiliary. A wide range of enantiomerically enriched biaryl compounds were prepared by this approach in good yields (up to 99 %) with excellent enantioselectivity (up to >99 % ee).

Keywords: C−H alkynylation; atroposelectivity; formal synthesis; homogeneous catalysis; natural products.

Publication types

  • Research Support, Non-U.S. Gov't