Date of Award

Spring 1-1-2016

Document Type


Degree Name

Doctor of Philosophy (PhD)


Chemistry & Biochemistry

First Advisor

Tarek Sammakia

Second Advisor

Maciej Walczak

Third Advisor

Xiang Wang

Fourth Advisor

Michael Marshak

Fifth Advisor

Peter Cogan


This dissertation describes a new method for the synthesis of hindered carbon-carbon bonds via the reaction of N-vinyl nitrones with ketenes and ketenimines. The reaction proceeds via a cascade sequence wherein an initial (3+2) cycloaddition is followed by a [3,3]-sigmatropic rearrangement and a subsequent [1,3]- / [3,3]-sigmatropic rearrangement to provide lactone aminal derivatives with high levels of diastereoselectivity. These products can be hydrolyzed to afford 1,4-imino-acids as the ring-closed tautomer. The scope of this reaction is described as is the mechanism using 17O-isotopic labeling of the ketene to trace the fate of this oxygen in the product. This study indicates that the final rearrangement occurs via two paths, a [1,3]- rearrangement path and a [3,3]-rearrangement path with a 2.5:1 preference for the [1,3]-path. Additionally, an asymmetric variation of the reaction is described using chiral auxiliary approach with the auxiliary attached to the N-vinyl nitrones. The reaction of N-vinyl nitrones with ketenimines is also described and proceeds via a similar cascade reaction; however, the reaction only undergoes the sequence of (3+2) cycloaddition followed by a [3,3]-sigmatropic rearrangement to provide a 7-membered ring intermediate that is reluctant to undergo the final transformation to the 1,4-imino-amide derivative. This thesis also describes a method for the selective protection/deprotection of 1,3-diols via the regioselective alkyl lithium-induced ring opening of 1,3-di-isopropylsilylenes. The reaction affords a differentially substituted 1,3-diol bearing a silane that resides at the oxygen in the sterically more demanding position. The reaction can be highly selective with a regiochemical preference of >50:1 and likely proceeds via an alkoxy-silane intermediate. This intermediate can by trapped by a proton source to provide the corresponding alcohol, or by methyl iodide to provide the corresponding silyl methyl ether. In both products the silane resides at the oxygen in the more sterically demanding position.

Included in

Chemistry Commons