Title : Propylene carbonate in Suzuki-Miyaura reaction
Abstract:
Several efforts were taken to carry out cross-coupling reaction under green and sustainable conditions. The Pd-catalysed cross-coupling of three iodo-heterocyclic compounds with different boronic acids will be discussed under Suzuki-Miyaura reaction conditions, in a green solvent. The propylene carbonate (PC) is a polar, aprotic solvent synthesized by addition of propylene oxide to carbon dioxide. It has a high boiling point and is more or less stable at elevated temperatures. This property of PC allows the Suzuki-Miyaura reaction to be carried out at higher temperatures, but under a shorter reaction time.
In the presence of base, PC suffers ring-opening and the formed propylene-glycol is able to alkylate the nucleophilic N-heteroatom giving byproducts with 2-hydroxypropyl side-chain besides the expected coupled products. We compared the yield of products obtained by traditional oil-heating with those obtained under similar reaction conditions under microwave irradiation as well. In some cases, the reactions were performed under flow conditions too. Based on the results, we assume that there are two possibilities: alkylation takes place first and then cross coupling happens or vice-versa. The first option was verified according to our investigation.
In sum, a green procedure was developed not only for the Suzuki-Miyaura cross-coupling reaction, but N-alkylation was carried out under sustainable conditions providing compounds not known in the literature, which possess a free OH-group and which may lead to the synthesis of drug candidates after further transformations.
