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

## TL;DR

This paper presents a new method to synthesize bicyclo[1.1.1]pentane salts using a stable precursor, enabling practical and efficient production of compounds used in pharmaceuticals and chemicals.

## Contribution

A practical and stable synthetic route for bicyclo[1.1.1]pentane salts using 1,3-diiodobicyclo[1.1.1]pentane as a feedstock.

## Key findings

- The reaction provides a broad substrate scope and good yields for various bicyclo[1.1.1]pentyl salts.
- Several products were fully characterized using single-crystal X-ray crystallography.
- Computational analysis reveals the role of nucleophiles in stabilizing a key carbocation intermediate.

## Abstract

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
t
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 N-pyridin-4-one and N-quinolin-4-one
substituted bicyclo[1.1.1]­pentanes.