Piperidine rings are privileged scaffolds incorporated in medicinal and natural products. Given the chemical simplicity of this nitrogenous heterocycle, there are many challenges associated with its construction. In this research endeavor, the piperidine moiety was accessed by the intramolecular cyclization of a sulfonamide-protected vinylogous homoallylic carbamate catalyzed by an exogenous acid. It is proposed that the “push-pull” electronic nature of the vinylogous sulfonamide will be sufficiently basic to be activated by acids to generate an N-sulfonyliminium ion which will then trigger the intramolecular cyclization. In this presentation, the results of this research will be discussed including the protic acids screened to probe the required pK<sub>a</sub> for the reaction to take place. Acids such as formic acid, trifluoromethanesulfonic acid, and bistriflamide worked well to initiate the cyclization with subsequent addition of the conjugate base to the incipient carbocation. Acids such as phosphoric acid, camphor sulfonic acid, and Meldrum’s acid however failed to trigger the iminium ion formation. In addition to the acid screen, the inclusion of exogenous nitriles was studied to affect a Ritter reaction after the aza-Prins cyclization. The nitrile screen was found to be robust with many different substrates tolerated in the cascade process.

Synthesis of piperidines using the aza-Prins cyclization of n-aryl vinylogous Sulfonamides

ACS Spring Meeting 2021

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