Direct Synthesis of Bicyclic Acetals via Visible Light Catalysis

Fengjin Wu; Leifeng Wang; Ying Ji; Ge Zou; Hong Shen; David A Nicewicz; Jiean Chen; Yong Huang

doi:10.1016/j.isci.2020.101395

Direct Synthesis of Bicyclic Acetals via Visible Light Catalysis

iScience. 2020 Aug 21;23(8):101395. doi: 10.1016/j.isci.2020.101395. Epub 2020 Jul 24.

Authors

Fengjin Wu¹, Leifeng Wang², Ying Ji³, Ge Zou³, Hong Shen³, David A Nicewicz⁴, Jiean Chen⁵, Yong Huang⁶

Affiliations

¹ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, Shenzhen 518055, China.
² State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, Shenzhen 518055, China; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
³ Roche R&D Center (China) Ltd, 720 Cai Lun Road, Building 5, Shanghai 201203, China.
⁴ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, Shenzhen 518055, China; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA. Electronic address: nicewicz@unc.edu.
⁵ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, Shenzhen 518055, China; Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, China. Electronic address: chenja@pkusz.edu.cn.
⁶ State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University, Shenzhen Graduate School, Shenzhen 518055, China; Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518055, China. Electronic address: huangyong@pkusz.edu.cn.

Abstract

Polysubstituted bicyclic acetals are a class of privileged pharmacophores with a unique 3D structure and an adjacent pair of hydrogen bond acceptors. The key, fused acetal functionality is often assembled, via intramolecular cyclization, from linear substrates that are not readily available. Herein, we report a formal cycloaddition between cinnamyl alcohols and cyclic enol ethers under ambient photoredox catalysis conditions. Polysubstituted bicyclic acetals can be prepared in one step from readily available building blocks. Employment of sugar-derived enol ethers allows easy access to a library of scaffolds with intriguing conformation and medicinal chemistry potential.

Keywords: Catalysis; Chemistry; Organic Synthesis.