Enantioselective desymmetrization via Heck-Matsuda reactions: development of new methodologies and applications

Abstract

This research project aims to develop new desymmetrization reactions of non-activated olefins because of the observation of the existence of electrostatic interaction between the substrate and the metallic center of the palladium complex. Therefore, this project is focused on the investigation of different functional groups that could be acting as directing groups in these systems and consequently leading to the formation of synthetic structural blocks in high diastereo and enantioselectivities. The specific objectives of this project are: (I) to study substrate-controlled enantioselective and diastereoselective Heck-Matsuda arylation reactions, through the evaluation of directing groups and the expansion of functional groups capable of performing efficient interactions with the metallic center; (II) optimization of reaction conditions such as palladium sources, different classes of N,N ligands, solvents, bases, and reaction temperatures; (III) with an established methodology, expand the reaction scope and demonstrate the applicability of the products as building blocks through the synthesis of molecules with biological and synthetic interest. Among the numerous benefits sought in this project are (I) the formation of high added value diastereo and enantioenriched building blocks whose skeleton can be found in several natural products with biological activity; (II) development of practical and effective methods that demonstrate the generality and robustness of the Heck Matsuda reactions; (III) the study of the interactions between the substrate and the metallic center during the Heck Matsuda reaction will bring important contributions not only to the research group but also for the organometallic chemistry and catalysis community. It is worth mentioning that this project started in the second half of 2018 as a FAPESP direct doctoral scholarship under process nº 2018/16916-8, and as expected, some of the objectives proposed herein have already been accomplished, but that several others remain to be accomplished. (AU)