The emerging role of radical chemistry in the amination transformation of highly strained [1.1.1]propellane: Bicyclo[1.1.1]pentylamine as bioisosteres of anilines

Qiwen Pang; Yang Li; Xin Xie; Jie Tang; Qian Liu; Cheng Peng; Xiang Li; Bo Han

doi:10.3389/fchem.2022.997944

The emerging role of radical chemistry in the amination transformation of highly strained [1.1.1]propellane: Bicyclo[1.1.1]pentylamine as bioisosteres of anilines

Front Chem. 2022 Oct 21:10:997944. doi: 10.3389/fchem.2022.997944. eCollection 2022.

Authors

Qiwen Pang¹, Yang Li¹, Xin Xie¹, Jie Tang¹, Qian Liu¹, Cheng Peng¹, Xiang Li¹, Bo Han¹

Affiliation

¹ State Key Laboratory of Southwestern Chinese Medicine Resources, Hospital of Chengdu University of Traditional Chinese Medicine, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Abstract

Bicyclo[1.1.1]pentylamines (BPCAs), emerging as sp³-rich surrogates for aniline and its derivatives, demonstrate unique structural features and physicochemical profiles in medicinal and synthetic chemistry. In recent years, compared with conventional synthetic approaches, the rapid development of radical chemistry enables the assembly of valuable bicyclo[1.1.1]pentylamines scaffold directly through the amination transformation of highly strained [1.1.1]propellane. In this review, we concisely summarize the emerging role of radical chemistry in the construction of BCPAs motif, highlighting two different and powerful radical-involved strategies including C-centered and N-centered radical pathways under appropriate conditions. The future direction concerning BCPAs is also discussed at the end of this review, which aims to provide some inspiration for the research of this promising project.

Keywords: [1.1.1]propellane; amination; bicyclo[1.1.1]pentylamine; bioisosteres; radical chemistry.

Publication types

Review