Abstract: Nucleophilic substitution reactions constitute a fundamental component of undergraduate organic chemistry education, where the classical S_N1 and S_N2 mechanisms serve as the cornerstone for understanding reaction patterns. Nevertheless, the reactivity of certain systems, particularly sterically hindered α-haloamides, cannot be adequately explained within this conventional framework. This article presents a novel nucleophilic substitution mechanism mediated by zwitterionic intermediates. Through detailed examination of key intermediates such as aza-2-oxyallyl cations, we demonstrate that the reversal of electronic properties in deprotonated amides (from electron-withdrawing to electron-donating character) serves as the pivotal driver for this process. Additionally, this work surveys contemporary applications of these zwitterions in advanced research domains, including enantioselective synthesis and cycloaddition reactions. Incorporating these concepts into undergraduate curricula can significantly enhance students’ mechanistic understanding, bridge foundational theories with cutting-edge research, and foster investigative skills and innovative thinking.

Key words: Nucleophilic substitution reaction, Undergraduate teaching, Teaching expansion, Zwitterionic intermediates, Reaction mechanism