Synthesis of substituted bicyclo[1.1.1]pentane scaffolds

Manso, Mariana, Gomes Goncalves Arelo (2021) Synthesis of substituted bicyclo[1.1.1]pentane scaffolds. University of Southampton, Doctoral Thesis, 193pp.

Record type: Thesis (Doctoral)

Abstract

Bicyclo[1.1.1]pentanes (BCPs) involving substitution at the bridgehead positions (C1 and C3) have emerged as isosteric replacements for mono- and para-substituted benzene rings in medicinal and materials applications. Based on limited precedence regarding functionalisation at the bridge positions, we describe the synthesis of 2-methyl[1.1.1]propellane from diethyl malonate, and explore its reactivity through a number of ring opening reactions leading to 1,2-disubstituted and 1,2,3-trisubstituted bicyclo[1.1.1]pentane derivatives. Additionally we explore the synthesis of possible suitable precursors for both 2-trifluoromethyl, 2-fluoro and 2,2- difluorobicyclo [1.1.1]pentanes. The introduction of bridge substituents in the bicyclo[1.1.1] pentane frame is expected to change physical properties and physicochemical parameters. This was studied by comparing 2-methyl[1.1.1] propellane derivatives with their corresponding aromatic and non-bridge substituted bicyclo[1.1.1]pentane analogues.

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