Item – Theses Canada

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OCLC number
435871338
Link(s) to full text
LAC copy
LAC copy
Author
Zhai, Huimin.
Title
Synthesis of nitrogen heterocycles using unsaturated sulfones.
Degree
Ph. D. -- University of Calgary, 2007
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2007]
Description
4 microfiches
Notes
Includes bibliographical references.
Abstract
Acetylenic sulfones are versatile synthetic reagents that undergo conjugate addition reactions with amine nucleophiles at the [beta]-position. The [alpha]-protons of the resulting vinyl sulfones can then be deprotonated with a suitable base and the resulting anions can in turn react with a variety of electrophiles. If the amine also contains a suitable electrophilic substituent, intramolecular cyclization results in the formation of a nitrogen heterocycle. Acetylenic sulfones can also undergo a variety of Diels-Alder and 1,3-dipolar cycloadditions. Four applications of the previously developed addition-cyclization methodology and of other properties of acetylenic sulfones were further studied. First, the methodology using acetylenic sulfones was extended toward the preparation of saturated sulfone products by conjugate additions of amino alcohols derived from [alpha]-amino acids to vinyl sulfones, followed by ' N'-benzylation, chlorination and intramolecular alkylation. This approach to substituted pyrrolidines was accompanied by the stereospecific rearrangement of substituents from the [alpha]-position of the amine to the [beta]-position of the product via aziridinium ion intermediates during the chlorination step. Another type of rearrangement was observed during the reaction of (2-piperidine)methanol or 2-(2-piperidine)ethanol with phenyl 'trans'-1-propenyl sulfone, in which the methyl group appeared to migrate from the [beta]- to the [alpha]-position of the sulfone moiety. This resulted from isomerization of the original sulfone to phenyl 2-propenyl sulfone via addition-elimination of sulfinate anion, followed by cyclization with the amino alcohol in the usual manner. Secondly, the first syntheses of polymer-supported acetylenic sulfones were achieved and their applications to the preparation of various cyclized products were exploited. Thirdly, several unexpected rearrangements were observed during the reaction of acetylenic sulfones with 1,3-diphenylisobenzofuran (DPIBF). The mechanisms of these rearrangements of the Diels-Alder cycloadducts were investigated under pyrolytic, acid-catalyzed and photolytic conditions. The mechanisms involved carbocation rearrangements or pericyclic processes, depending on the conditions. In addition, the synthesis of (-)-julifloridine was accomplished from (2'S',3'S')-2-benzyloxy-3-benzylamino-1-chlorobutane and 3-('t'-butyldimethylsilyloxy)-1-('p'-toluenesulfonyl)-1-propyne in an overall 20% yield over seven steps. The established conjugate addition and cyclization reactions yielded an enamine sulfone, which underwent acid-catalyzed desulfonylation to afford an enamine aldehyde. Stereoselective reduction, followed by a Swern oxidation constructed the 2,6-'trans' disubstituted piperidine. Chain extension and hydrogenation, followed by a Birch reduction, afforded the target alkaloid.
ISBN
9780494257210
0494257210