Preliminary investigation into the reactivity differences between alkyl and allylic leaving groups

Transformation of one leaving group to another is fundamental in organic synthesis. Tosylates, acetates, and methanesulfonates are commonly employed due to their exceptional ability to behave as a leaving group. Nucleophilic substitution reactions may proceed by more than one mechanism depending on several factors. For instance, carboxylate esters and sulfonate esters are two broad classes of leaving groups that follow different mechanisms when subjected to nucleophilic displacement reactions. Transformation of primary and secondary alkyl alcohols to other leaving groups can be achieved with minimal complications. In contrast, allylic alcohols do not provide the same feasibility. As demonstrated from previous experiments conducted by our group, synthesis of tosylates from allylic alcohols is problematic. Moving away from tosylates, trifluoroacetates were alternatively explored. 3-phenyl-1-propanol was used to establish the synthetic methodology that was later applied to the allylic substrates cinnamyl alcohol and isophorol. Additionally, the synthesis and reactivity of methanesulfonates were explored using the same substrates. Once synthesized, the trifluoroacetate and methanesulfonate derivatives were subjected to a series of nucleophilic substitution reactions involving strong nucleophiles. Substitution at the carbon bearing the leaving group was desired, opposed to substitution occurring at an alternativecarbon. Compounds possessing the tosylate group were susceptible to elimination. The reactivity of the trifluoroacetate compounds seemed to follow a typical carboxylate mechanism, with the nucleophile attacking the carbonyl carbon. On the other hand, the reactivity of alkyl methanesulfonates yielded the unrearranged alkyl halide product with each nucleophile, with substitution occurring at the carbon bearing the leaving group. It is of future interest to compare the reactivity of allylic methanesulfonates with the reactivity of alkyl methanesulfonates. Cinnamyl methanesulfonate and 3-phenylpropyl methanesulfonate differ only by the double bond present in the cinnamyl analog. Additionally, the reactivity of isophoryl methanesulfonate can be explored to determine the influence of the ring structure over the reaction mechanism.