The stereoselective synthesis of chiral heterocyclic building blocks and optically pure complex molecular structures has been one of the major challenges for synthetic organic chemists. In this framework, asymmetric organocatalysis has emerged as a reliable and efficient approach to this aim. Additionally, among the extensive realm of organocatalytic methodologies, multicomponent reactions, sequential catalysis, domino/cascade, and one-pot reactions represent undoubtedly a breakthrough in the total synthesis of enantioenriched molecules. Key features are certainly the increased atom- and step-economy of these practical and efficient procedures, which dramatically decrease the cost and environmental impact of the syntheses, reducing the purification and isolation steps of the various intermediates. This project will focus on this interesting and challenging topic, with the aim to enlarge the scope of complex heterocyclic molecular architectures, which could be obtained in a practically simple and affordable way. In fact, the concept of sustainable chemistry and low environmental impact is of outmost importance nowadays. Considering the high importance of oxindoles and their derivatives as biologically relevant compounds, the target of this research project is to prepare large libraries of highly functionalized spiro-polycyclic oxindoles.
The envisaged detailed study on the reactivity of each employed substrate and the fine-tuning of these reactivities to direct the mechanistic pathway as needed by changing also the experimental conditions, either one-pot or domino, could not only widen the knowledge on these cascade organocatalytic reaction sequences, but could also yield to a large variety of structurally different and potentially bioactive chiral oxindole derivatives with multiple adjacent stereocenters. Simultaneously, with this project we aim at increasing the potential applications of asymmetric organocatalysis to a more industrially attractive synthetic organic chemistry, since constant efforts are addressed to the search of innovative procedures to obviate unnecessary time-, energy-, atom- and cost-consuming processes.
The results of this project could also potentially be applied to long-term future research opportunities, focusing on exciting new approaches in asymmetric organocatalysis such as flow organocatalysis, extremely hot topic in the field of asymmetric synthesis and sustainable chemistry. In fact, the combination of this approach to multi-step multicomponent reactions could result in a plethora of applications in both industrial and pharmaceutical chemistry. Additionally, the various libraries of enantioenriched chiral oxindoles could potentially be tested in the future for their biological activity and open up new exciting collaborations within multidisciplinary projects in the field of agro- and pharmaceutical chemistry.