One-Pot Three-Component Cascade Strategy for the Site-Selective Synthesis of 5-Sulfenylated/Selenylated...

We describe an efficient synthesis of 5-sulfenylated/selenylated 2,4-disubstituted pyrimidines through the three-component cascade reaction of readily available enaminones, amidines, and thio/seleno-benzenesulfonates. This reaction simultaneously constructs two C-N bonds and one C-S/Se bond through a one-pot method without the need for any external catalysts, metals, oxidants, or bases. This protocol features good functional group tolerance, a broad substrate scope, a simple operation procedure, high site selectivity, and a green reaction process. The utility of this strategy is demonstrated by gram-scale experiments and late-stage structural modifications of structurally complex molecules. Mechanistic studies indicate that the reaction begins with the enaminones attacking the sulfur atom of the thiophenyl sulfonates, followed by intermolecular cyclization with benzamidines to yield 5-sulfenylated 2,4-disubstituted pyrimidines.