Synthesis of Benzene Isosteres

Bioisosteres of phenyl rings are prominent within pharmaceutical industry. Particularly 1,3-disubstitued bicyclo[1.1.1]pentane derivatives are excellent special isosteres of a para-substituted phenyl ring and have been shown to improve the pharmacological profile and 3-dimensionality of multiple lead drug candidates.1-3 However, methods towards the formation of 1,3-disubstituted bicyclo[1.1.1]pentane derivatives are currently limited in scope and functional group tolerance.
The main project aim in to develop a methodology for the easy incorporation of the bicyclo[1.1.1]pentane functionality as a late stage functionalisation of drug compounds. The methodology must therefore focus on a broad scope, mild conditions and good functional group tolerance.
1. J. Am. Chem. Soc., 2017, 139, 3209-3226. 2. J. Med. Chem., 2012, 55, 3414-3420. 3. ChemMedChem., 2017, 12, 590-598.