Thiopyran route to polypropionates : proline catalyzed aldol reactions of tetrahydro-4H-thiopyran-4-one
Date
2007
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ORCID
Type
Degree Level
Doctoral
Abstract
The thiopyran route to polypropionates is an attractive strategy that involves a stepwise iterative aldol homologation of tetrahydro-4H-thiopyran-4-one (I) with thiopyran aldehyde (II) followed by desulfurization to rapidly assemble stereochemically complex polypropionate synthons. In chapter 1, the thesis is summarized in the context of relevant background research including; a) the basic principle of the thiopyran route; b) dynamic kinetic resolution of α-substituted aldehydes; c) previous syntheses of serricornin; iv) previous syntheses of membrenones. In chapter 2, proline-catalyzed enantioselective direct intermolecular aldol reactions of tetrahydro-4H-thiopyran-4-one with various achiral aldehydes were studied. The results provided insights on the behaviour and stereoselectivity profile of thiopyranone (a crucial starting block in the thiopyran design) in the proline-catalyzed aldol reaction.In chapter 3, inspired by the results of the aldol reaction of ketone (I) with achiral aldehydes, we next investigated the proline-catalyzed asymmetric aldol reactions of (I) with racemic thiopyran aldehyde (II) as a strategy to rapidly prepare enantiomerically pure tetrapropionate synthons without any requirement of enantioenriched aldehyde. The reaction occurred with high enantiotopic group selectivity and dynamic kinetic resolution.In chapter 4, a detailed study to ascertain the scope and limitations of the design strategy described in chapter 3 was extended towards other catalysts, aldehydes and ketones. Finally, applications of the above mentioned strategy towards the synthesis of serricornin and membrenones A and B are elaborated in chapters 5 and 6 respectively.
Description
Keywords
dynamic kinetic resolution, serricornin, membrenones, double stereodifferentiation, diastereotopic, tetrazole, enantiotopic, proline, aldol, organocatalysis, cyclic sulfides, mutual kinetic enantioselection
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Chemistry
Program
Chemistry