Rhodium-catalyzed Arylation of Electron-deficient Alkenes for the Synthesis of Oxindoles and Gem-Difluoroalkenes

Transition-metal catalyzed carbon-carbon bond forming functionalization of alkenes is a powerful tool in organic chemistry, as it allows for rapid introduction of molecular complexity from simple starting materials. Most commonly used metal catalysts include palladium, nickel and rhodium, and they have been shown to enable the functionalization of alkenes. Compared to palladium and nickel, rhodium exhibits enhanced affinity towards alkenes and alkynes, which allows for highly chemo- and stereoselective transformations of these reactive functionalities. The rhodium-catalyzed 1,4-conjugate addition, also known as the Hayashi-Miyaura reaction, is one of the robust and mild olefin functionalization reactions. The rhodium enolate generated from the initial addition has been shown to further react with suitable electrophiles to construct multiple carbon-carbon bonds in a single operation. To further broaden the synthetic utility of these domino reactions, we investigated the reactivity of the rhodium enolate towards intramolecular cyclization reactions. The first chapter describes a rhodium-catalyzed transformation of o-bromoaniline derived acrylamides to a diverse array of 3-monosubstituted oxindoles. Our findings provided rapid access to a library of oxindole scaffolds from simple acrylamides and commercially available boronic acids. Inspired by our previous study, we examined the development of an analogous enantioselective transformation using o-bromoaniline derived 1,1-disubstituted acrylamides. The second chapter details the studies pertaining to the discovery of a chiral rhodium-phosphine complex to catalyze the enantioselective intramolecular reductive arylation reaction. Using our methodology, a diverse array of 3,3-disubstitued oxindoles was synthesized and the challenging construction enantiomerically enriched quaternary stereocenter was made possible. In the third chapter, our findings on the rhodium-catalyzed enantioselective defluorinative α-arylation of β-trifluoromethyl substituted secondary acrylamides are presented. We successfully demonstrated that this methodology can serve as an alternative approach in functionalizing the α-position of secondary amides, providing an efficient route to a novel class of gem-difluoroolefins containing a stereo-labile tertiary stereocenter.Ph.D