Tandem [3+1+1+1] Heterocyclization of α‐Acyl Ketene Dithioacetals with Ammonia and Methanol: Rapid Assembly of Polysubstituted Pyrimidines

Abstract

A straightforward copper‐catalyzed aerobic cyclocondensation reaction of α‐acyl ketene dithioacetals with ammonium acetate and methanol was developed for synthesizing highly functionalized pyrimidines. This domino conversion relied on the dual activities of CuCl2, namely Lewis acid and dehydrogenation, which began with single C−S ammonolysis directed by an in situ generated imine, followed by cyclocondensation with aldehyde produced from alcohol and concomitant oxidative dehydrogenation under an oxygen atmosphere. Notably, readily accessible and flexible substrates, common chemical feedstock nitrogen and C1 sources, good functional group tolerance and procedural simplicity exhibit the efficiency and potential application of the new method.

Acyl-Ethynylbenziodoxolone (acyl-EBX): Access to Ketene Dithioarylacetals

“…They are most often used as a 3-carbon synthon in the synthesis of heterocycles taking advantage of the electrophilicity of the β-carbon, the leaving group ability of the sulfur atom via an addition–elimination process, and the possibility of condensation on the carbonyl group. Accessible heterocycles include pyrazoles, isoxazoles, pyrimidines, benzofurans, and quinolines . Moreover, numerous C–H functionalization methods have been developed to transfer carbon substituents, halides, and chalcogens to the α-carbon, thereby allowing access to a large variety of building blocks.…”