Single electron studies of acylammonium intermediates, zinc-mediated carboxylations in flow, and the total synthesis of (–)-inthomycin C.
For the past two decades, the synthetic utility of chiral ⍺,𝛽-unsaturated acylammonium salts has led to the development and disclosure of unique, multibond forming, organocascade reactions, all of which have proceed through two-electron, polar pathways. This has led our group to begin exploring the potential for unique forms of reactivity through single-electron radical pathways, utilizing acylammonium intermediates. Herein, we describe our studies implementing three synthetic techniques used for generating radical intermediates and their compatibility with unsaturated acylammonium salts. We began with hopes of utilizing electrochemistry as a synthesis method for forming carbon radicals, specifically executing a heterogenous reduction of an acylammonium intermediate, giving rise to a ⍺,𝛽-radical, acylammonium enolate; however, we quickly discovered the acylammonium intermediate's incompatibility under this type of reductive conditions, leading us to abandon this idea. From here, we shifted our attention to developing a novel rearrangement transformation, facilitated by a dual Lewis-base, photoredox catalysis system, proceeding through an unsaturated acylammonium intermediate. Tragedy struck when a simplified variation of our idea was published, lowering the level of novelty we were originally hoping for. This ultimately led us to forgo pursuing this photoredox idea for the time being and investigate a third method of carbonradical formation, being traditional chemically initiated techniques. This led to the development of a method for the construction of optically active 𝛿-lactones via an enantioselective radical conjugate addition of an unsaturated acylammonium intermediate, diastereoselective keck allylation, and lactamization to furnish the desired ring. Compared to the recent publications using the photoredox method, our method takes advantage of the ⍺-radical's inherent reactivity through both an intermolecular and intramolecular capturing reaction, leading to high levels of stereochemical enrichment. Also reported herein is our work conducting zinc-mediated carboxylations of allylic and propargylic halides in a flow-chemical module, leading to a streamlined, indirect approach of forming -lactones; as well as our unpublished total synthesis of the oxazole triene natural product, inthomycin C, a feat achieved during our group's on-going studies towards the bioactive peptide-polyketide natural products: oxazolomycin B and curromycin A.
Organic chemistry., Methodology., Asymmetric organocatalysis., Total synthesis.
Networked Digital Library of Theses and Dissertations