Date of Award

1-1-2018

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

Chemistry and Biochemistry

First Advisor

Bryan J. Cowen, Ph.D.

Second Advisor

Gareth Eaton

Third Advisor

Andrei Kutateladze

Fourth Advisor

Brian Michel

Fifth Advisor

Matthew Rutherford

Keywords

Allylsamarium bromide, Samarium iodide

Abstract

Three efficient methods for synthesis of five membered carbocycles, a highly understudied product motif in samarium(II) chemistry, were explored and optimized. These methods utilized simple starting materials to generate linear substrates with functional groups that are reactive towards samarium(II) iodide. The three methods explored were the Reformatsky-aldol, Reformatsky-alkylation, and pinacol cyclizations. The critical discovery for efficient formation of the Reformatsky-aldol and pinacol carbocycles products was the use of lithium bromide. This addition of lithium bromide facilitates easy in situ formation of samarium(II) bromide. The Reformatsky-alkylation cyclization was a newly realized reaction employing samarium enolates. Two of the three methods, the Reformatsky-aldol and pinacol, generated carbocycles with multiple functional groups attached. These reactions were able to proceed with exceptional diastereoselectivity. In addition to the new methods for five membered, a lead results towards asymmetric samarium (II) Reformatsky-aldol cyclization was explored. This provided the product with modest enantiomeric excess.

The mechanism of the alkylation reaction was studied with the use of spin trapped products and electron paramagnetic resonance spectroscopy (EPR). By analyzing the spectra of the resulting spin trapped products the initial site of reduction being the carbon-bromine bond was supported. This was supported by simulated spectra of the spin trapped experiments and by performing the spin trapping experiments on an alpha-deuterated substrate. This substrate was synthesized by performing a hydrogen-deuterium exchange experiment.

Another divalent samarium reagent, allylsamarium bromide, was studied in reactions with isatin and isatin derivatives. The samarium reagent has both nucleophilic and reductive properties. Substituted isatins were able to be allylated at the three-position forming 3-allyl oxindoles. In addition, two isatin derivatives, oxindole and isatoic anhydrides, were reacted with allylsamarium bromide. The reaction of substituted oxindoles yielded allylated indoles and indolines. Whereas, the reaction of substituted isatoic anhydrides yielded the double allylated and ring opened product. All of these compounds provided privileged scaffolds and/or compounds bearing multiple functional groups.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Christopher David-James Aretz

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

345 p.

Discipline

Organic chemistry

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