Methyl on the Bridge: 2‐Methyl Propellane as Precursor for 1,3‐Substituted 2‐Methylated Bicyclo[1.1.1]Pentanes
Year: 2025
Type: article
Abstract: Bicyclo[1.1.1]pentanes (BCPs) have emerged as isosteric replacements for mono- and para-substituted benzene rings in medicinal and materials applications, involving substitution at the BCP bridgehead (1,3-positions). BCP functionalization at the 2-position is much less straightforward and currently under intense investigation. Herein, we report a synthetic route to 2-methyl BCPs allowing for functionalization at the 1,3-positions, with the novel 2-methyl[1.1.1]propellane as a key intermediate. Next to an optimization for the synthesis of 2-Me-propellane, this work contains an investigation of its reactivity leading to 1,2-disubstituted and 1,2,3-trisubstituted BCP derivatives. Compared to nonsubstituted propellane, the synthesis of 2-methyl propellane was lower-yielding, and its ring-opening reactions proceeded in similar or lower yields, with radical-based reactions generally giving the best results. A preliminary study of selected physicochemical properties was conducted to assess the impact of the introduction of a bridge-methyl group, showing an expected increase of about 0.5 logP units and featuring lower melting points.
Source: Chemistry - A European Journal
Institutions: Ghent University, University of Southampton
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
Awards: Magnetic resonance equipment for advanced material research: molecular characterisation of solid, soft, homogeneous and heterogeneous matter for the development of advanced functional materials and chemical catalysis, Harvesting the potential of fluorine labels and NMR spectroscopy to study the conformation of polyproline sequences and their interaction with biomolecular targets, G2492948467, Synthesis and property studies of fluorinated bicyclo[1.1.1]pentanes, Fluorinations with implications: enhancing the potential of biologically and medicinally interesting molecules through targeted fluorine introduction, G6244568949, G7875997330, Core Capability for Chemistry Research in Southampton
OpenAlex ID: W4415219416