Development of novel bicyclopentanes (BCP) bioisosteres from bench stable (1.1.1)-propellane precursors

Bicyclo-[1.1.1]-pentanes (BCPs) are an exciting class of strained, sp3 rich carbon. While their initial use was in the materials sector, recent impact has been in medicinal chemistry, drug development and the agrochemical sector. Learn more atDevelopment of novel bicyclopentanes (BCP) bioisosteres from bench stable (1.1.1)-propellane precursors from theLoughborough University.

Key facts

Their appeal is due to a unique 3-D structure, a direct consequence of its high sp3 carbon content, and has led to its use as a bioisosteres for the tert-butyl group, internal alkynes and significantly, mono- and disubstituted arenes.

Their synthesis is accomplished using hetero- or homolytic cleavage and relies on the inherent strain in the central carbon-carbon bond of [1.1.1]-propellane. However, the practical isolation and storage of [1.1.1]-propellane is very problematic; it is isolated as a solution in ethereal solvents, it must be cryogenically stored, and should be used before its rapid degradation.This project Development of novel bicyclopentanes (BCP) bioisosteres from bench stable (1.1.1)-propellane precursors offered by Loughborough University will significantly increase the synthetic scope of BCPs compared to current strategies, as well as providing an excellent training platform to the prospective PhD candidate in our new state-of-the-art laboratories here at Loughborough.

Curriculum:

• In this project we will pioneer a stable crystalline alternatives of [1.1.1]-propellane. Functionalization will be explored using several nucleophiles, providing orthogonal 1,3-disubstituted-[1.1.1]-bicyclopentane (BCP) precursors amenable to subsequent cross-coupling reactions (e.g., transition metal and photoredox mediated).

• This methodology will provide a superior synthetic approach to 1,3-disubstituted BCPs, with far less waste, as well as delivering stable crystalline BCP precursors.