Rhodium-catalysed [(3+2)+2] carbocyclisation of heteroatom-substituted alkenes and synthetic studies towards (+)-repin

Baikstis, Tomass
Rhodium-catalysed [(3+2)+2] carbocyclisation of heteroatom-substituted alkenes and synthetic studies towards (+)-repin. PhD thesis, University of Liverpool.

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The stereoselective construction of fused 5,7-bicycles has attracted considerable attention due to the ubiquity of this motif in complex biologically active sesquiterpene lactones (dehydrocostus lactone, helenalin). Transition metal-catalysed carbocyclisation reactions represent a highly attractive approach towards the construction of functionalised cyclic and polycyclic molecules. Generation of 5- and 7-membered rings from strained 3-membered cycles has emerged as a particularly effective strategy, which is complementing more traditional pericyclic reactions. The description of the transition metal-catalysed carbocyclisation reactions of alkylidenecyclopropanes (ACPs) is provided in the introductory review, which seeks to highlight the evolution of these processes and their application in the context of the construction of 7-membered rings. Despite the numerous advantages that are afforded by this approach, the methods, that allow the synthesis of the suitably functionalised carbocycles for the synthesis of complex natural products, are still rare. Chapter 2 describes our work on the cycloaddition reactions of functionalised olefins, which resulted in the development of highly regio- and diastereoselective rhodium-catalysed [(3+2)+2] carbocyclisation of vinyl silanes with various monosubstituted alkynes. The transformation provides silylated cis-fused 5,7-bicyclic systems, which can be further modified in a number of ways. We have demonstrated that selective oxidation of the silyl group affords C6 hydroxylated 5,7-bicycles – a motif reminiscent of guaianolide and pseudoguaianolide natural products. We anticipate that the methodology outlined herein will find significant application in target directed synthesis. Chapter 3 provides an account of our synthetic efforts towards guaianolide (+)-repin. Rhodium-catalysed [(3+2)+2] carbocyclisation was successfully employed for the construction of the cis-fused 5,7-bicyclic system at the core of the molecule. In the course of these studies we developed an effective strategy for the functionalisation of the 7-membered ring through a series of oxidative transformations. The lactone moiety was introduced via substrate-controlled radical reaction of bromohydrin with silyl ketene acetal and constitutes the first application of these reaction conditions to bromohydrins for the direct synthesis of lactones. We believe that our strategy towards the tricyclic core of repin could also find application in related natural products, providing a general entry to the guaianolide family of compounds.

Item Type: Thesis (PhD)
Additional Information: Date: 2014-11 (completed)
Subjects: ?? QD ??
Depositing User: Symplectic Admin
Date Deposited: 15 Sep 2015 09:01
Last Modified: 17 Dec 2022 00:48
DOI: 10.17638/02010539
URI: https://livrepository.liverpool.ac.uk/id/eprint/2010539