<i>S</i>‐Aryl Substitution Enhances Acidity of the 1,2,4‐Triazolium Scaffold

Abstract The 1,2,4‐triazolium scaffold in asymmetric organocatalysis results in remarkable rate accelerations, with reactions typically occurring via N ‐heterocyclic carbene (NHC) intermediates. Although the most acidic NHC pre‐catalyst class, there remains scope for further increases in acidity particularly for aqueous organocatalysis applications. The acidity‐enhancing effects of thio‐substituents on carbon acidity are well‐documented but not explored in the 1,2,4‐triazolium scaffold. Herein, we report the synthesis of a large series of N , N ‐dialkyl‐C(3)‐ S ‐aryltriazolium ions and quantitative kinetic evaluation of C(5)‐H acidity. The direct attachment of S ‐aryl substituents to the triazolium heterocycle results in substantial increases in protofugalities (kinetic acidities) with second order rate constants ( k DO ) for C(5)‐H deprotonation by DO − base that are 2.9–60.3 fold higher than for reference 1,4‐dimethyl‐1,2,4‐triazolium iodide in D 2 O solution. Protofugalities for the N , N ‐dialkyl‐C(3)‐ S ‐aryltriazolium series are similar to commonly used bicyclic N ‐aryl‐1,2,4‐triazolium organocatalysts despite having two electron donating N ‐alkyl substituents. This highlights the future potential of this NHC design which could enable the introduction of two chiral alkyl substituents close to the C(5) carbenic position with pre‐catalyst acidity controlled by distal C(3)‐ S ‐aryl substitution. Detailed X‐ray structural data‐protofugality correlations enabled evaluation of the S ‐aryl substituent effect origins. C(5)‐H p K a values (16.9–18.6) were calculated by utilisation of experimental protofugalities.