Bicyclo[1.1.1]pentane is highly strained, but relatively stable. Bridgehead- or 1,3-substituted derivatives of this compound are fairly easy to access. Bridge-substituted derivatives (example pictured), in contrast, are more challenging to prepare.

Jiří Kaleta, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic, and University of Colorado, Boulder, USA, and colleagues have developed a selective radical chlorination of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid. The team converted the diacid to the corresponding acid dichloride using SOCl₂.

This compound was then chlorinated in CCl₄ that was saturated with Cl₂ under irradiation with visible light at 0–5 °C and quenched with methanol to give bridge-substituted di- and trichlorides. The same reaction at 60–65 °C gives predominantly bridge-substituted tri- and tetrachlorides. Chlorination with liquid chlorine at 50 °C provides selective access to the tetrachloride.

In addition, the obtained di- and trichlorides can be reduced using tris(trimethylsilyl)silane (TMS₃SiH) to give the corresponding mono- and dichlorides, respectively. Overall, the reaction provides selective access to five of 15 possible chlorinated isomers of bicyclo[1.1.1]pentane-1,3-dicarboxylic acid. The strain in the bicyclo[1.1.1]pentane cage increases with the number of chlorine substituents.

• Bridge-Chlorinated Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acids,
  Jiří Kaleta, Igor Rončević, Ivana Císařová, Martin Dračínský, Veronika Šolínová, Václav Kašička, Josef Michl,
  J. Org. Chem. 2019.
  https://doi.org/10.1021/acs.joc.8b02780