Sintesi e caratterizzazione di catalizzatori squaramidici chirali e loro applicazione in una reazione aldolica enantioselettiva

Recently, the application of asymmetric organocatalysis on industrial scale is becoming more and more relevant because of its many advantages. One of the reported examples is the synthesis of Funapide, an oxindole with a chiral spirocycle, which has been tested as a drug candidate against the postherpetic neuralgia by Xenon Pharmaceuticals. The key step in its synthesis is an asymmetric aldol reaction between an oxindole and formaldehyde, catalyzed by a thioureidic bifunctional organocatalyst, which affords the product with a moderate enantiomeric excess. In this thesis, it was studied the possibility to improve the enantioselectivity of the aldol reaction by using catalysts of the same class but with squaramide groups instead of thioureas, because of their powerful catalytic properties. We synthesized eight different functionalized squaramide catalysts, and then we tested them in a preliminary screening on a substrate similar to the target. The one who showed the best results was then used to optimize the reaction parameters, and applied to the target substrate.