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

Gang Liao; Qi-Jun Yao; Zhuo-Zhuo Zhang; Yong-Jie Wu; Dan-Ying Huang; Bing-Feng Shi

doi:10.1002/anie.201713106

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.

Authors

Gang Liao¹, Qi-Jun Yao¹, Zhuo-Zhuo Zhang¹, Yong-Jie Wu¹, Dan-Ying Huang², Bing-Feng Shi^{1

3}

Affiliations

¹ Department of Chemistry, Zhejiang University, Hangzhou, 310027, China.
² School of Chemical and Environmental Engineering, Wuyi University, Jiangmen, 529020, China.
³ State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin, 300071, China.

PMID: 29388296
DOI: 10.1002/anie.201713106

Abstract

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