Bridge-Chlorinated Bicyclo[1.1.1]pentane-1,3-dicarboxylic Acids

Abstract

Radical chlorination of bicyclo[1.1.1]­pentane-1,3-dicarboxylic acid is highly selective, and up to four chlorine atoms can be introduced relatively easily without damage to the strained bicyclic cage. Combined with hydrodechlorination with TMS3SiH, direct chlorination provides access to five of the 15 possible chlorinated diacids. Their configuration has been established by X-ray diffraction. Their pK a values have been measured by capillary electrophoresis and calculated at the B3LYP-D3BJ/6-311+G­(d,p)-level. The results are in good agreement and reflect the expected trend, from 2.78 ± 0.08 and 4.14 ± 0.10 in the parent to 1.07 ± 0.03 and 2.31 ± 0.03 in the tetrachlorinated diacid. Strain energy relative to the parent diacid was calculated for all 15 chlorinated diacids and shows a dramatic increase with successive chlorination, due to nonbonded Cl–Cl repulsions.

Electrochemical Cleavage of Carbon‐Chlorine Bonds in Multiply Bridge‐Chlorinated Bicyclo[1.1.1]pentane‐1,3‐dicarboxylic Acids

“…The reduction of 4 to final products is accompanied by the opening of strained bicyclic system, which results in a mixture of final products. The same observation was made during a chemical reduction performed by tris (trimethylsilyl)silane in the presence of azobisisobutyronitrile and was confirmed by 1 H NMR spectroscopy [23] …”

“…Experiments of Savéant benefited from the addition of equimolar amounts (with respect to the reactant) of acetic acid as a source of protons. Reductions described in our communication profit from the availability of H + provided by the dissociation of dicarboxylic groups [23] …”

“…Preparation and identification of chlorinated compounds studied here was described previously [23] . Anhydrous acetonitrile was dried over molecular sieves.…”

“…Chemical structures are in Figure 1. The synthesis of halogen derivatives was described previously [23] . Compounds used in this study are expected to cleave Cl atom upon electrochemical reduction.…”

Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives

“…More recently, the same group has also accessed tri‐ and tetrachlorinated BCP derivatives through direct chlorination (Scheme 8 B). [43b] Elevated temperatures and gaseous Cl 2 were required for effective trichlorination, while elevated temperatures and pressurised liquid Cl 2 were required for tetrachlorination. The regio‐ and stereoselectivity of polychlorination was also rationalised.…”