Date of Award

12-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Chemistry

Committee Member

Dr. R. Karl Dieter, Advisor and Department Chair

Committee Member

Dr. Bill Pennington

Committee Member

Dr. Dev Priya Arya

Committee Member

Dr. Daniel C. Whitehead

Abstract

This dissertation encompasses 4 independent projects in the field of Methodology Development in Organic Synthesis. Chapter 1 summarizes our efforts in the regio- and stereocontrol of copper mediated allylic substitutions with rearrangement of the double bond (SN2') in (Z)-α-halo-β,γ-unsaturated esters, (Z)-α-phosphate-β,γ-unsaturated esters, (Z)-α-mesylate-β,γ-unsaturated esters, (Z)-α-pentafluorobenzoate-β,γ-unsaturated esters, (E)-α-chloro-β,γ-unsaturated esters and allylic cyanophosphates. Different organocopper compounds bearing alkyl or aryl substituents were prepared from organolithium and Grignard reagents, and then added to these unsaturated substrates. When lithium cuprates were employed in combination with (Z)-α-nucleofuge-substituted-β,γ-enoates, exclusive formation of the SN2' products (e.g., γ-substituted-α,β-unsaturated esters) were obtained in good yields and with complete stereoselectivity (E:Z =100:0). The best yields and regio- and stereoselectivities were obtained with the use of (Z)-α-chloro-β,γ-enoate. With use of magnesium cuprates, more complex mixture of E:Z SN2' and SN2 products were obtained, especially when (E)-α-chloro-β,γ-enoate was used. Chapter 2 reports of the serendipitous synthesis of bis-heterocyclic spiro 3(2H)-furanones from the reaction of several lithiated cabanions (e.g., α-lithio-N-Boc pyrrolidine, α-lithio-N-Boc dimethylamine, α-lithio-N-Boc piperidine and 2-lithio-1,3-dithiane) with phenol triflates and enol triflates. Spiro 3(2H)-furanone compounds were obtained in moderate to good yields (38−81%) and the experimental results suggest that they are formed by a sequence of reactions involving nucleophilic acyl substitution, enolate formation, trifluoromethyl transfer, sulfenium ion formation, and subsequent ring closure to form the 3(2H)-furanone. In Chaper 3, the catalytic bromofunctionalization of electron rich alkenes with N-bromosuccinimide (NBS) as a source of bromide and different nucleophiles such as HOAc, PhCOOH and MeOH is shown. Enantioenriched and racemic imines, diimines, imidazolium and imidazolinium salts were prepared and examined as catalysts for these reactions. It was found, that the counter ion plays a major role with the imidazolium and imidazolinium salts, where salts with a Cl- counterion allow conversions of 90% over 1 h, while salts with BF4- or PF6- as the counterion did not catalyze the reactions. These halofunctionalization reactions are highly regioselective (>90%) in the case of β-methylstyrenes and cinnamyl alcohol with yields of over 70%. No enantioselectivity was induced with any of the catalyst employed. Chapter 4 describes the synthesis of new aryl difluorovinyl ether (DFVE) compounds, which were prepared in moderate to good yields (53-90%) from known trifluorovinyl ethers (TFVE). The studied reaction is the Suzuki-Miyaura coupling of aryl boronic acids with TFVE catalyzed by Pd(Ph3)4. The coupling of the boronic acids with TFVE is regioselective, yielding exclusively geminal difluorovinyl ethers.

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