C(sp3)–H arylation to construct all-syn cyclobutane-based heterobicyclic systems: a novel fragment collection

Abstract

All-syn fused cyclobutanes remain an elusive chemotype and thus present an interesting synthetic challenge. Herein, we report the successful application of Pd-catalysed C(sp³)–H arylation of cyclobutane compounds to generate all-syn heterobicyclic fragments using an innovative ‘inside-out’ approach. Through this strategy we generate a virtual collection of 90 fragments, which we demonstrate to have enhanced three-dimensionality and superior fragment-like properties compared to existing collections.