Executive Summary : | (Hetero)arenes are crucial structural motifs in various bio-active molecules, including active pharmaceutical ingredients and agrochemicals. Synthetic methodologies for derivatization/modification of (hetero)arenes include metal-free SNAr, metal-catalyzed cross-coupling, C?H bond functionalization reactions, and recent photocatalytic methodologies. The outcome depends on the nature of the reagents added, which are usually soluble or miscible in the reaction solvent. However, when reactants or nucleophiles are gaseous, the reactivity of the catalytic system changes. Common problems associated with gaseous reactants include storage facilities, closed reactor systems, gas detection systems, pressure reactors, and cost. To minimize these problems and make it convenient for synthetic chemists to perform these processes, a methodology can be developed to generate reactive gases in-situ or ex-situ through thermal/chemical decomposition of reagents. This method allows for localized generation of hazardous gases, reaction under mild conditions, compatible catalytic reactions, and reactions performed under normal pressure. In-situ methods involve identifying molecules that provide localized MeSH gas readily for thiomethylation, while ex-situ methods involve a two-chamber gas reactor assembly that allows localized gas generation in one chamber and its utilization in the other. The developed methodology could be applied to the synthesis of small volume, high-cost molecules, including deuterated drugs or APIs. |