Mechanistic Study on Gold(I)-Catalyzed Unsaturated Spiroketalization Reaction

The mechanism of metal-catalyzed spiroketalization of propargyl acetonide is explored by employing DFT with the B3LYP/6-31+G(d) method. Acetonide is used as a regioselective regulator in the formation of monounsaturated spiroketal. The energies of transition states, intermediates, reactants and products are calculated to provide new insight into the mechanism of the reaction. The energetic features, validation of the observed trends in regioselectivity are conferred in terms of electronic indices via FMO analysis. The presence of acetonide facilitates a stepwise spiroketalization as it masks the competing nucleophile, and thus hydroxyl group present, exclusively acts as a nucleophile. The vinyl gold intermediate 3 is formed from 2 via activation barrier TS1. This is the first ring formation, which is 6-exo-dig cyclization. The intermediate 3 is converted into allenyl ether 4, which isomerizes to the intermediate oxocarbenium ion 5 via activation barrier TS2. The intermediate 5 cyclizes to 6 via TS3. This is the second ring formation. The intermediate 6 on protodeauration turns into 6,6-monounsaturated spiroketal 7. It is concluded that acetonide as a protecting group serves the purpose, and thus a wide range of spiroketals can be prepared, regioselectivity.

Novel Greener Microwave-Assisted Deprotection Methodology for the 1,3-Dioxolane Ketal of Isatin Using Calix[n]arenes

In this work, the combined use of p-sulfonic acid-calix[n]arene and microwave energy to hydrolyze the 1,3-dioxolane ketal of isatin was evaluated with excellent results. This is the first time that p-sulfonic acid-calix[n]arene has been used as the catalyst in a ketal hydrolysis reaction and the deprotection of the ketone carbonyl of isatin is reported. The presence of 2.5 mol% of p-sulfonic acid-calix[4,6]arene at 160 ºC resulted in over 96% conversion of this ketal in 10 min, with the additional advantage of using water as a solvent. This catalytic system (aqueous phase containing p-sulfonic acid-calix[4]arene) was reused for five consecutive cycles, with a conversion above 96% maintained. This reusable system is not practicable using p-toluenesulfonic acid and p-hydroxybenzenesulfonic acid as catalysts since both are extracted to the organic phase with the reaction product. The hydrolysis of 1,3-dioxolane ketal of isatins with different substituents (CH3, I, Br, Cl, F, NO2) in the aromatic ring was also evaluated. The protecting group of 5-methyl-isatin was removed with 73% conversion using 2.5 mol% of p-sulfonic acid-calix[4]arene at 160 ºC for 5 min. In contrast, the ketal of 5-nitro-isatin reached 80% conversion using the same conditions after 40 min.

Stepwise PEG synthesis featuring deprotection and coupling in one pot

The stepwise synthesis of monodisperse polyethylene glycols (PEGs) and their derivatives usually involves using an acid-labile protecting group such as DMTr and coupling the two PEG moieties together under basic Williamson ether formation conditions. Using this approach, each elongation of PEG is achieved in three steps – deprotection, deprotonation and coupling – in two pots. Here, we report a more convenient approach for PEG synthesis featuring the use of a base-labile protecting group such as the phenethyl group. Using this approach, each elongation of PEG can be achieved in two steps – deprotection and coupling – in only one pot. The deprotonation step, and the isolation and purification of the intermediate product after deprotection using existing approaches are no longer needed when the one-pot approach is used. Because the stepwise PEG synthesis usually requires multiple PEG elongation cycles, the new PEG synthesis method is expected to significantly lower PEG synthesis cost.