The Use of High-Throughput Experimentation to Accelerate the Development of Methods for Complex Amine Synthesis
type: CreativeWork
description: Technological innovations are crucial to advancing the chemical communities’ ability to develop new synthetic methodologies. To continue developing new reactions for the construction of important but increasingly complex molecules, modern chemists need to create faster and more environmentally sustainable methods for reaction discovery. The field of high-throughput experimentation (HTE) is vital to achieving these goals. HTE platforms exploit improvements in reaction dosing technology, parallelised reactors and analytical techniques to explore large numbers of reactions simultaneously in a materially conservative format. While HTE workflows have proven effective in developing new reactions and optimising production routes to drug molecules, the uptake of these techniques is slow across the chemical community. The slow uptake can be partially attributed to the prohibitive infrastructure costs associated with HTE. However, the lack of cohesive information of which reactions are compatible with HTE makes chemists hesitant to make infrastructure investments. One important molecular scaffold that still requires new general synthetic methods to access is ⍺-branched amines. The ability of the α-branched amine motifs to modulate key biological interactions and regulate the physicochemical properties of molecules has led them to become ubiquitous structural features in pharmaceutical agents. Despite many effective reactions being developed to synthesise this important motif, the assembly of α-branched amines commonly relies on a small number of reactions, such as reductive aminations. One of the most effective ways of assembling an α-branched amine motif is the 1,2-addition of a nucleophile to an in-situ formed iminium ion. However, most current reactions that exploit this approach are limited in the scaffolds they can produce. This thesis details the contributions to the development of a new carbonyl alkylative amination reaction for the synthesis of α-branched amine scaffo…
abstract: Technological innovations are crucial to advancing the chemical communities’ ability to develop new synthetic methodologies. To continue developing new reactions for the construction of important but increasingly complex molecules, modern chemists need to create faster and more environmentally sustainable methods for reaction discovery. The field of high-throughput experimentation (HTE) is vital to achieving these goals. HTE platforms exploit improvements in reaction dosing technology, parallelised reactors and analytical techniques to explore large numbers of reactions simultaneously in a materially conservative format. While HTE workflows have proven effective in developing new reactions and optimising production routes to drug molecules, the uptake of these techniques is slow across the chemical community. The slow uptake can be partially attributed to the prohibitive infrastructure costs associated with HTE. However, the lack of cohesive information of which reactions are compatible with HTE makes chemists hesitant to make infrastructure investments. One important molecular scaffold that still requires new general synthetic methods to access is ⍺-branched amines. The ability of the α-branched amine motifs to modulate key biological interactions and regulate the physicochemical properties of molecules has led them to become ubiquitous structural features in pharmaceutical agents. Despite many effective reactions being developed to synthesise this important motif, the assembly of α-branched amines commonly relies on a small number of reactions, such as reductive aminations. One of the most effective ways of assembling an α-branched amine motif is the 1,2-addition of a nucleophile to an in-situ formed iminium ion. However, most current reactions that exploit this approach are limited in the scaffolds they can produce. This thesis details the contributions to the development of a new carbonyl alkylative amination reaction for the synthesis of α-branched amine scaffo…
author: Phelps, Joseph
language: eng
keywords: high throughput experimentation, organic synthesis, organometallics, synthetic methodology
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/dc63b1f5-a54d-4258-b005-87f3839eb08f/download
license: http://purl.org/NET/rdflicense/allrightsreserved
date published: 2024-09-04
date modified: 2026-07-22T22:24:11Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.115806