Harnessing radical relay strategies for the difunctionalization of unsaturated hydrocarbons using FGTRs
BORIS DOI
Abstract
This thesis centers on the development and application of functional group transfer reagents (FGTRs) for the radical-mediated difunctionalization of alkenes, utilizing either radical-polar crossover (RPC) or radical ligand transfer (RLT) mechanisms. To promote green and sustainable synthesis, techniques such as photoredox catalysis, electrochemistry, and mechanochemistry are employed to generate reactive radical species under mild conditions. Here’s a concise overview of each chapter’s content in the thesis:
Chapter 1 introduces alkene reactivity, functionalization, and key synthetic strategies, highlighting mechanisms such as Markovnikov and anti-Markovnikov addition, as well as the importance of functional group transfer reagents (FGTRs). The chapter also outlines foundational tools for transformations, including photochemistry, electrochemistry, and mechanochemistry.
Chapter 2 narrows in on organic nitrating reagents, discussing their properties, reactivity, and applications for targeted functionalization in synthesis.
Chapter 3 details a dual photoredox-cobalt catalyst system for difunctionalizing unsaturated hydrocarbons, focusing on the challenging synthesis of 1,2-halonitroalkanes using N-nitrosuccinimide as a nitryl radical source in radical ligand transfer (RLT) reactions. A cobalt-free, net-neutral radical/polar crossover approach further broadens nucleophile compatibility.
Chapter 4 builds on the previous chapter, introducing a strategy for carbo-heterofunctionalizing alkenes via radical-polar crossover, using geminal bromonitroalkanes with O-centered nucleophiles to synthesize a variety of 1,3-nitro-functionalized products.
Chapter 5 presents an efficient anti-Markovnikov hydronitration approach for synthesizing terminal nitroalkanes. Using N-nitrosuccinimide and a hydrogen atom transfer (HAT) mediator, this photoredox method achieves regioselective addition, also enabling chain extension using bromonitroalkanes.
Chapter 6 introduces an electrochemical method for generating nitryl radicals from ferric nitrate using simple, cost-effective electrodes, facilitating broad nitration protocols compatible with various substrates. This scalable, electricity-driven approach underscores its sustainable synthesis potential.
Chapter 7 builds on electron catalysis from Chapter 6 by introducing a mechanochemical protocol for alkene difunctionalization using ferric nitrate and catalytic TEMPO. This method achieves selective 1,2-nitronitrooxylation of alkenes under solvent-free conditions, highlighting mechanochemistry’s role in radical-driven transformations.
Chapter 8 utilizes ball-milling for solvent-free synthesis of halogenated compounds. Through iron-mediated RLT catalysis, it enables selective dihalogenation of alkenes, producing vicinal dihalides with high selectivity and substrate compatibility, demonstrating mechanochemistry’s utility in functionalizing unsaturated hydrocarbons. This compressed summary captures each chapter’s focus, emphasizing advancements in sustainable, radical-based methodologies for alkene functionalization.
Chapter 1 introduces alkene reactivity, functionalization, and key synthetic strategies, highlighting mechanisms such as Markovnikov and anti-Markovnikov addition, as well as the importance of functional group transfer reagents (FGTRs). The chapter also outlines foundational tools for transformations, including photochemistry, electrochemistry, and mechanochemistry.
Chapter 2 narrows in on organic nitrating reagents, discussing their properties, reactivity, and applications for targeted functionalization in synthesis.
Chapter 3 details a dual photoredox-cobalt catalyst system for difunctionalizing unsaturated hydrocarbons, focusing on the challenging synthesis of 1,2-halonitroalkanes using N-nitrosuccinimide as a nitryl radical source in radical ligand transfer (RLT) reactions. A cobalt-free, net-neutral radical/polar crossover approach further broadens nucleophile compatibility.
Chapter 4 builds on the previous chapter, introducing a strategy for carbo-heterofunctionalizing alkenes via radical-polar crossover, using geminal bromonitroalkanes with O-centered nucleophiles to synthesize a variety of 1,3-nitro-functionalized products.
Chapter 5 presents an efficient anti-Markovnikov hydronitration approach for synthesizing terminal nitroalkanes. Using N-nitrosuccinimide and a hydrogen atom transfer (HAT) mediator, this photoredox method achieves regioselective addition, also enabling chain extension using bromonitroalkanes.
Chapter 6 introduces an electrochemical method for generating nitryl radicals from ferric nitrate using simple, cost-effective electrodes, facilitating broad nitration protocols compatible with various substrates. This scalable, electricity-driven approach underscores its sustainable synthesis potential.
Chapter 7 builds on electron catalysis from Chapter 6 by introducing a mechanochemical protocol for alkene difunctionalization using ferric nitrate and catalytic TEMPO. This method achieves selective 1,2-nitronitrooxylation of alkenes under solvent-free conditions, highlighting mechanochemistry’s role in radical-driven transformations.
Chapter 8 utilizes ball-milling for solvent-free synthesis of halogenated compounds. Through iron-mediated RLT catalysis, it enables selective dihalogenation of alkenes, producing vicinal dihalides with high selectivity and substrate compatibility, demonstrating mechanochemistry’s utility in functionalizing unsaturated hydrocarbons. This compressed summary captures each chapter’s focus, emphasizing advancements in sustainable, radical-based methodologies for alkene functionalization.
Date of Publication
2024
Year of graduation
2024
Theses Type
dissertation
Subject(s)
Language(s)
en
Author(s)
Faculty/Graduate School
Access(Rights)
open.access
Primary OA Publication
true