Part I: The Study Of 2-Aryl-1,3-Dithiane Derivatives As Pronucleophiles In Palladium-Catalyzed Allylic Alkylation And Propellylation Part Ii: Ligand-Free Palladium-Catalyzed Allylic Amintion Of Hydrazone Derivatives Part Iii: Synthesis Of Criegee Intermediate Precursors
Date of Award
Doctor of Philosophy (PhD)
Patrick J. Walsh
Chapter 1 and 2 detail studies of 2-aryl-1,3-dithianes as pronucleophiles in palladium-catalyzed allylic alkylation and propellylation to access skeletally diverse aryl alkyl ketone cores. Allylic carbonate and [1.1.1]propellane electrophiles successfully couple with in situ generated 2-sodio-1,3-dithiane nucleophiles to afford the corresponding products in good to excellent yields. Deprotection of these products leads to valuable aryl alkyl ketones. The palladium-catalyzed allylic alkylation of 2-aryl-1,3-dithianes is examined in chapter 1. A direct synthesis of unsaturated ketones via a one-pot allylation-oxidation protocol is also presented. Additionally, the utility of this method is demonstrated through a sequential one-pot allylation-Heck cyclization to produce asterogynin derivatives which are important bioactive compounds in medicinal chemistry.
Chapter 2 discloses a general method for the synthesis of bicyclo[1.1.1]pentane (BCP)-containing dithianes which, upon deprotection, provide access to BCP analogues of medicinally abundant diarylketones. Transformation of the dithiane part into a variety of functional groups such as BCP aryl difluoromethanes and BCP esteare demonstrated. A computational study indicates that the reaction of 2-aryl-1,3-dithianes and [1.1.1]propellane proceeds via a two-electron pathway.
Chapter 3 focuses on a protocol for ligand-free palladium catalyzed allylic amination of in situ generated hydrazone nucleophiles at room temperature. This method is effective and applicable for a variety of hydrazones in excellent yields and also economical due to low palladium loading and ligand-free conditions. In addition, we demonstrated an example of tandem allylation-Fischer indole cyclization to afford the core structure of antifungal drug.
In chapter 4, we introduce detailed on novel synthesis of (Z/E)-1,3-diiodobut-2-ene and (E)-1,3-diiodo-2-methylprop-1-ene which are considered as precursors of Criegee intermediates methyl vinyl ketone oxide (MVK-oxide) and methacrolein oxide (MARC-oxide) respectively.
Trongsiriwat, Nisalak, "Part I: The Study Of 2-Aryl-1,3-Dithiane Derivatives As Pronucleophiles In Palladium-Catalyzed Allylic Alkylation And Propellylation Part Ii: Ligand-Free Palladium-Catalyzed Allylic Amintion Of Hydrazone Derivatives Part Iii: Synthesis Of Criegee Intermediate Precursors" (2019). Publicly Accessible Penn Dissertations. 3502.