Orellana, ArturoShi, Jiaqi2024-03-182024-03-182024-03-16https://hdl.handle.net/10315/41881Pyridines are widely used and extensively studied heterocyclic compounds in industry and academia. Developing mild and selective methods for functionalizing pyridines would facilitate the synthesis of more structurally diverse pyridine derivatives, which could aid the development of potential drug candidates and streamline the drug discovery process. Through a “soft-enolization” logic, 4-alkylpyridines can be readily converted to corresponding alkylidene dihydropyridines (ADHPs), enabling mild and selective palladium-catalyzed allylation and dehydrogenation, as previously shown by our group. During the mechanistic study of the allylation reaction, prompted by the low enantioselectivity of pyridine allylation using optically active ligands, our group demonstrated that ADHPs are “soft” nucleophiles towards the allylpalladium(II) complex. We thus began employing this class of intermediates as soft nucleophiles in other reactions. Here I will first discuss the work towards enantioselective allylation of 4-alkylpyridines. Then I will describe the conjugate addition of ADHPs to a,b-unsaturated ketones that are activated by triethylsilyl triflate. Finally, I will introduce the approach to unite piperidine and pyridine with a carbon atom through addition of ADHPs to protonated pyridines with subsequent transfer hydrogenation reaction.Author owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.Organic chemistryElectronic Thesis or Dissertation2024-03-16Alkylidene dihydropyridineADHPPyridineAlkylpyridineAlkyl pyridinePyridine functionalizationPiperidineAllylationPalladium catalysisPyridylic allylationDihydropyridineDHPLewis acidUnsaturated ketoneConjugate additionRegioselective conjugate additionMichael additionFunctional group toleranceSoft nucleophileHard nucleophilePyridinium cationPyridine activationTriethysilyl triflateEnantioselective allylationLigand screen4-alkylpyridine4-pyridylic position4-pyridylic site4-pyridylic functionalizationPyridine hydrochloridePyridinium chlorideTrans-dearomatizationTransfer hydrogenation