Thiosemicarbazone organocatalysis: tetrahydropyranylation and 2-deoxygalactosylation reactions and kinetics-based mechanistic investigation

The first use of thiosemicarbazone-based organocatalysis was demonstrated on both tetrahydropyranylation and 2-deoxygalactosylation reactions. The organocatalysts were optimised using kinetics-based selection. The best catalyst outperformed previously reported thiourea catalysts for tetrahydropyranylation by 50-fold. Hammett investigations of both the organocatalyst and the substrate indicate an oxyanion hole-like reaction mechanism. Thiosemicarbazones are introduced as a new class of highly tunable and efficient organocatalysts. We showcase this by studies of the tetrahydropyranylation reaction, where insights to the mechanism was achieved by a double Hammett analysis of both the substrate and the catalyst.