A Facile Approach to Tetracyclic Indolines: Highly Diastereoselective [4+2] Annulation of Indoles with Bicyclic N-Substituted Cyclobutanes

Peng-Juan Li; Xiao-Kang Kuang; Jun Zhu; Yong Tang; Lijia Wang

doi:10.1021/acs.joc.4c02509

A Facile Approach to Tetracyclic Indolines: Highly Diastereoselective [4+2] Annulation of Indoles with Bicyclic N-Substituted Cyclobutanes

J Org Chem. 2025 Jan 10;90(1):899-907. doi: 10.1021/acs.joc.4c02509. Epub 2024 Dec 30.

Authors

Peng-Juan Li^{1

2}, Xiao-Kang Kuang³, Jun Zhu², Yong Tang^{1

2

3}, Lijia Wang^{1

2}

Affiliations

¹ Chang-Kung Chuang Institute, Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
² State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.
³ Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, P. R. China.

PMID: 39791131
DOI: 10.1021/acs.joc.4c02509

Abstract

A new stereoselective [4+2] annulation method for constructing tetracyclic indolines by reacting indoles with bicyclic N-substituted cyclobutanes has been developed. Using Sc(OTf)₃ as a catalyst, a series of tetracyclic indolines with four continued stereogenic carbon centers have been obtained in ≤86% yields as single diastereomers. This reaction offers an accessible way for the rapid construction of the core structures of biologically active natural products like paucidirinine, deethylibophyllidine, and ibophyllidine.