Influence of halogen atoms and the reactivity of nucleophiles on reactions of tetrahydropyran and tetrahydrofuran acetals with C-Nucleophiles: hyperconjugation and inductive effects

Abstract

Tetrahydropyran acetals bearing a fluorine atom adjacent to the acetal carbon atom can undergo highly stereoselective substitution reactions with nucleophilic alkenes to give the 1,2-cis products. By contrast, the chlorine- and bromine-substituted acetals give the 1,2-trans products. These results can be understood by considering oxocarbenium ion intermediates and their conformational preferences, which are dictated by hyperconjugative effects from axial substituents, with F << H < Cl < Br. Reactions of the corresponding five-membered-ring acetals are also 1,2-cis selective in the case of fluorine and 1,2-trans selective with chlorine- and bromine-substituted acetals, but selectivities showed different trends of reactivity vs selectivity. The reactions with the five-membered-ring acetal were interpreted as requiring anomeric halides as reactive intermediates because of the conditions required to obtain substitution products.