Item – Theses Canada

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OCLC number
740465872
Link(s) to full text
LAC copy
LAC copy
Author
Weston, Mitchell Hugh,1976-
Title
Ring-expansions of tertiary [alpha]-vinylamines via novel aza-Cope rearrangements.
Degree
Ph. D. -- University of Calgary, 2009
Publisher
Ottawa : Library and Archives Canada = Bibliothèque et Archives Canada, [2010]
Description
4 microfiches
Notes
Includes bibliographical references.
Abstract
Tertiary amines containing [alpha]-vinyl substituents can undergo conjugate additions to acetylenic sulfones at the [beta]-position to form zwitterionic intermediates which rapidly undergo formal aza-Cope rearrangements. In contrast to many other traditional neutral aza-Cope rearrangements, the current process is facile and occurs under very mild conditions. In the case of cyclic [alpha]-vinylamines, the process results in a four-carbon ring-expansion. This protocol was studied by preparing various cyclic and acyclic tertiary avinylamines and treating them with acetylenic sulfones. The result was aza-Cope rearrangement products in moderate to high yields containing diverse ring sizes, substituents, and heteroatoms. A mechanistic investigation of one example of this ring-expansion provided, through kinetic data and a Hammett plot, where [rho] = 1.19, evidence for the formation of the postulated zwitterionic intermediates as the rate determining step. This methodology was showcased through the formal synthesis of two biologically interesting macrocyclic (13 and 14-membered) marine alkaloids: motuporamine A and B. These syntheses were performed using an iterative aza-Cope rearrangement and ring-expansion. Following the initial rearrangements of 'N'-benzyl-2-vinylpyrrolidine and 'N'-benzyl-2-vinylpiperidine with ('p'-toluenesulfonyl)ethyne, the resulting ring-expansion enamine products were hydrogenated and treated with vinylmagnesium bromide in the presence of triflic acid to directly afford the respective [alpha]-vinylamines. A subsequent ring-expansion of these new [alpha]-vinylamines afforded the required macrocyclic amines needed for completion of the syntheses of motuporamine A and B obtained in 13% and 11% overall yields respectively over nine steps. Finally an attempt to apply this protocol towards the synthesis of the structurally interesting alkaloid quebrachamine was undertaken. However, attempts to exploit the aza-Cope rearrangement protocol using 2-('N'-benzylpyrrolidin-2-y1)-1-(phenylsulfony1)-1' H'-indole as a simpler model system caused a cascading conjugate addition/aza-Cope rearrangement/67r-electrocyclization reaction resulting in a tetracyclic indole product.
ISBN
9780494544914
0494544910