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Title: Development of axially chiral 2-aryl-4-dialkylaminopyridine-N-oxide based catalysts for the sulfonylative kinetic resolution of amines
Author: Bob-Egbe, Opetoritse
ISNI:       0000 0004 2724 3272
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Lewis base catalysis has been studied extensively in recent years as a powerful tool for introducing asymmetry into a variety of reactions, avoiding the use of expensive and potentially toxic metal catalysts. There is however still ample scope for the development of procedures for the non-enzymatic catalytic kinetic resolution (KR) of amines. Unlike alcohols, the intrinsic high reactivity of amines towards acyl and sulfonyl donors makes their KR highly challenging. As a result, there are relatively few publications on non-enzymatic catalytic KR of amines via acylation1-8 and none via sulfonylation. This thesis describes the development of a new class of chiral 2-aryl-(4-dialkylamino)pyridine-N-oxides (2-Ar-(4-DAAP)-N-oxides) (A), which are chiral by virtue of atropisomerism around the biaryl axis, and their application as catalysts for the KR of amines via sulfonylation. [molecular structure diagram] The use of C-H activation was explored for the development of a concise and modular synthetic procedure to the target catalyst structure. As a result, the key step in our final synthesis is a microwave (MW) assisted C-H halogenation procedure.(9) This reaction provides facile access to a di-ortho functionalised late stage intermediate from which a subsequent Pd catalysed cross coupling with a range of activated aryl partners provides access to an array of chiral catalyst structures. [molecular structure diagram] These catalysts were synthesised for assessment in the kinetic resolution of the axially chiral amine NOBIN, a synthetically useful chiral ligand which suffers from a difficult enantioselective synthesis. [molecular structure diagram] This thesis will provide a description of the synthetic route developed to achiral and chiral catalysts, the dependence of sulfonylation rates on the electronics of the catalyst and the key role of C-H activation in achieving a successful efficient synthesis of the target chiral catalyst structures. *For molecular structure diagrams, please see the PDF of the thesis.
Supervisor: Spivey, Allan Sponsor: Engineering and Physical Sciences Research Council ; Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral