Gold(I)-Catalyzed Synthesis of Highly Substituted 1,4-Dicarbonyl Derivatives via Sulfonium [3,3]-Sigmatropic Rearrangement

An efficient and straightforward gold-catalyzed protocol for the synthesis of 2-substituted 4-oxo-4-arylbutanal derivatives from commercially available or easily accessible alkynes and vinylsulfoxide substrates has been developed. Extension of the methodology to the use of 1-cycloalkenyl sulfoxides allowed the facile synthesis of five-, six-, and seven-membered-ring cycloalkyl-1-one backbone. Subsequently, the tetrahydrocycloalkyl[b]pyrrole derivatives, which are found in many active pharmaceutical ingredients, were isolated in good yields. Mechanistic investigation highlighted a [3,3]-sigmatropic rearrangement of a sulfonium intermediate in this process.

Automated summary

An efficient and straightforward gold-catalyzed protocol has been developed for the synthesis of 2-substituted 4-oxo-4-arylbutanal derivatives, allowing for the facile synthesis of cycloalkyl-1-one compounds of different ring sizes. The methodology was also extended to the synthesis of tetrahydrocycloalkyl[b]pyrrole derivatives found in active pharmaceutical ingredients, with a mechanistic investigation revealing a [3,3]-sigmatropic rearrangement of a sulfonium intermediate in the process.