Underutilized Dineophiles: Asymmetric Diels-Alder Reaction of Ynones and Ynoates with Oxygen-Functionalized Dienes

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Walley, Michael S

Issue Date

2020

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Dissertation

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BINOL , Diels-Alder reaction , Organic chemistry , Ynoate , Ynone

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Enantioselective Diels-Alder reactions are among the most powerful tools in the chemist’s toolbox. Over the long history of research into the Diels-Alder reaction, the use of alkynyl ketones and alkynyl esters has been limited. The 1,4-cyclohexadiene products are useful intermediates for the synthesis of biologically active small molecules. Biologically active molecules are not the only targets of the Diels-Alder reaction, other cases have used the cycloaddition to develop novel ligands, and create polymers. My research focus is on the use of oxygen-functionalized dienes in an enantioselective Diels-Alder reaction using ynones and ynoates (Figure A1).The proposal is to use electron-rich dienes, similar to Danishefsky’s diene, in order to generate 1,4-cyclohexadienes that have functional groups that can take part in further chemoselective transformations. The ability to construct six-membered rings with distinct functional groups adds utility to these small molecules. We want to develop a synthesis that can construct such molecules in an enantioselective manner. Ynones have been shown to be highly useful in the Diels-Alder reaction and recent research has been on going in the use of other alkyne dienophiles. Ynones being an underutilized dienophile in the DA reaction, ynoates are uses even less. Ynoates present their own unique challenges. We propose that a chiral Lewis acid can catalyze the reaction of ynoates and oxygen-functionalized dienes with excellent enantioselectivities. The products of the Diels-Alder reaction between ynoates and these electron-rich dienes will provide functionalized 1,4-cyclohexadienes that will lend to various post-synthetic pathways. Figure A1 Proposed Diels-Alder reaction between ynones/ynoates and oxygen-functionalized dienes.

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Creative Commons Attribution 4.0 United States

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