Liu, Chang, Li, Wenyuan, Li, Renzhe, Marchant, Rohan, Kanda, Yuzuru and Qin, Tian (2026) Propellane-Free Access to Bicyclo[1.1.1]pentanes. Nature communications.

Abstract

Bicyclo[1.1.1]pentane (BCP) has emerged as a valuable three-dimensional bioisostere of benzene, attracting considerable interest from the pharmaceutical industry due to its potential to enhance drug-like properties. While [1.1.1]propellane has traditionally served as the key precursor to mono- and 1,3-di-substituted BCPs, the rising demand for multisubstituted and bridge-functionalized BCP derivatives has driven the development of alternative, propellane-free synthetic strategies. To access such strain and hindered system, recent advances in this area can be broadly classified into three mechanistic categories: (1) intramolecular diradical couplings, (2) carbene-mediated ring expansions, and (3) 2-electron polar disconnections. This perspective highlights these emerging methodologies, critically examining their scope and limitations, and provides an outlook on the synthetic challenges and their potential impact in medicinal chemistry.

Item Type:	Article
Date Deposited:	24 Jan 2026 00:45
Last Modified:	24 Jan 2026 00:45
URI:	https://oak.novartis.com/id/eprint/57966