Nucleophilic Substitution of 1,3-Diiodobicyclo[1.1.1]pentane: Synthesis of Bicyclo[1.1.1]pentylpyridinium, Quinolinium, Isoquinolinium, and Pyrazolium Salts

In this study, we describe the synthesis of bicyclo[1.1.1]pentane salts by the nucleophilic reaction of 1,3-diodobicyclo[1.1.1]pentane (DIBCP) with several classes of nucleophiles. The bicyclo[1.1.1]pentane fragments are established isosteres for <i>^t</i>butyl, alkynyl, and 1,4-diaryl structural units, whose synthesis is typically achieved by addition to the unstable, cryogenically stored, [1.1.1]propellane precursor. In contrast, DIBCP is a stable crystalline solid, with the potential to be a feedstock in the synthesis of BCP fragments. This work provides a straightforward, practical synthetic route to bicyclo[1.1.1]pentylpyridinium, quinolinium, isoquinolinium and pyrazolium salts. This transformation displays a broad substrate scope, good yield profile, with several of the BCP products being fully characterized by single-crystal X-ray crystallography. The reaction proceeds by nucleophilic substitution on 1,3-diodobicyclo[1.1.1]pentane (DIBCP), and we provide detailed computational analysis, showing the role of two nucleophiles in stabilizing a key carbocation intermediate. The synthesized salts are isosteres of existing arylpyridinium and arylquinolinium salts used within pharmaceuticals and high-value commodity chemicals within the industrial chemical sector. Finally, the synthetic utility of these salts is examined, providing practical synthetic routes to <i>N</i>-pyridin-4-one and <i>N</i>-quinolin-4-one substituted bicyclo[1.1.1]pentanes.