Synthesis of 1,3-disubstituted bicyclo-[1.1.1]-pentane (BCP) salts: arylsulfonium, arylpyridinium and arylammonium isosteres

Herein, we describe the synthesis of pyridinium, sulfonium and ammonium bicyclo-[1.1.1]-pentane salts as potential aryl isosteres. Arylsulfonium, ammonium and pyridinium salts are central motifs in several natural products, pharmaceuticals, and high value commodities within the industrial chemical sector. The reaction proceeds by a nucleophilic substitution on a bench stable precursor 1,3-diodobicyclo-[1.1.1]-pentane (DIBCP). The transformation displays broad substrate scope, good to excellent yield profile, with several of the BCP products being fully characterised by single crystal X-ray crystallography, highlighting the unique 3-dimensional structure of these potential isosteres. Finally, the pyridinium and quinolinium BCP salts can be cleanly converted into piperidinone and quinolone BCP analogues.