Synthesis of ketones through aerobic transition metal-catalyzed cross-coupling of thioesters.

Abstract

Asymmetric diaryl ketones are an important class of compounds in organic chemistry due to their presence in natural products, synthesis, cosmetics as well as in biological active compounds. The aim of this project was to expand the scope of thiophilic metal carboxylates catalysts that can be applied to the aerobic Liebeskind-Srogl cross coupling reaction between various thioesters and phenylboronic acids. Thioesters bearing electron neutral, withdrawing and donating groups were successfully synthesized in yields ranging from 35 to 54%Xcv. The electron neutral thioester was used in the optimization of the aerobic Liebeskind-Srogl reaction and CuMeSal proved to be the most effective catalyst in this protocol. CuMeSal was applied in the aerobic synthesis of the asymmetric diaryl ketones bearing a wide range of functional groups including CF3, SMe, OMe and F yielding up to 65% in 24hrs. Aerobic Liebeskind-Srogl cross-coupling reaction was applied in the successful synthesis of chalcones, through the coupling of commercially available phenylboronic acids with previously synthesised thioesters catalysed by CuMeSal in DMF for 24hrs,furnishing desired products in poor to excellent yields 26-89%.