Computational Study of SmI₂-Catalyzed Intermolecular Couplings of Cyclopropyl Ketones: Links between the Structure and Reactivity

SmI₂-catalyzed intermolecular coupling reactions of cyclopropyl ketones with alkenes or alkynes offer an efficient strategy for furnishing diverse five-membered ring-containing molecular architectures. This study presents a systematic computational investigation to reveal the structure-reactivity relationships in these reactions. The reactivity of aryl cyclopropyl ketones is enhanced by the stabilized ketyl radical and cyclopropyl fragmentation, arising from the conjugation effect of the aryl ring, despite an obstacle emerging from the <i>gauche</i> styrene intermediate that elevates the energy barrier for radical trapping. By contrast, alkyl cyclopropyl ketones lack conjugation and exhibit high barriers for reduction and fragmentation but undergo facile radical trapping due to the minimal steric hindrance. Interestingly, <i>ortho</i>-substituted phenyl cyclopropyl ketones exhibit superior reactivity due to a balance between the moderate conjugation, promoting cyclopropyl fragmentation, and the pretwisted nature of the <i>ortho</i>-substituted phenyl that circumvents the hindrance posed by the <i>gauche</i> intermediate and facilitates the radical trapping. The markedly enhanced reactivity of bicyclo[1.1.0]butyl (BCB) ketones arises from facile fragmentation of the strained BCB motif. Bicyclo[2.1.0]pentyl (BCP) ketones, less strained than BCB ketones, are computationally verified to undergo efficient couplings with various partners, and this can be attributed to their stable fragmentation intermediates that facilitate radical trapping. Our findings provide insights that can aid in designing related reactions.