Application of force field calculations to organic chemistry. Part 7. Steric interpretation of thermolysis, homoketonization, ring enlargement, and acid-catalysed rearrangement of strained cage molecules

Abstract

Empirical force field calculations are applied to elucidate various types of reaction mechanisms for strained cage molecules. Rates of novel thermal decarbonylation in homologous series of homocubanone derivatives (1; R = phenyl) increase with the calculated strain of the C(2)–C(3) bond, which in turn is strongly influenced by the length of alkylene bridge X, two bonds away from the C(2)–C(3) bond. The remarkable sensitivity of the rates on the calculated C(2)–C(3) bond strain is interpreted in terms of a reactant-like transition state. In contrast, thermolyses, homoketonizations, cationic ring enlargements, and anionic rearrangements of birdcage and homocubyl systems are shown to proceed through product-like transition states based on highly selective formation of the thermodynamically most stable product. The most favourable pathway is presented for a novel acid-catalysed multi-step rearrangement of a bisethanocubanedione derivative (29) to a bisnordiamantanedione derivative (30) based on enthalpy calculations of the intermediate carbonium ions. The failure to produce the ‘stabilomer’ upon acid treatment of (29) under ordinary conditions is attributed to the absence of a mechanistically acceptable path for further skeletal isomerization.