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Rhodium(II)-catalysed C–H insertion/olefination strategy towards α-methylene-γ-butyrolactones: applications in natural product synthesis

Lloyd, Matthew (2016) Rhodium(II)-catalysed C–H insertion/olefination strategy towards α-methylene-γ-butyrolactones: applications in natural product synthesis. PhD thesis, University of York.

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Abstract

This Thesis describes the development of telescoped rhodium(II)-catalysed transformations of α-diazo(diethoxyphosphoryl)acetates for the formation of α-methylene-γ-butyrolactones. An overview of synthetic approaches to α-methylene-γ-butyrolactones is given in Chapter 1, in addition to a discussion of published Rh(II)-catalysed C–H insertion reactions. Previous efforts in the Taylor group have established effective methods for the synthesis of α-methylene-γ-butyrolactones, although these require relatively complex functionality in the precursors. The research in this Thesis focuses on the development of a one-pot Rh(II)-catalysed C–H insertion/olefination sequence for the synthesis of α-methylene-γ-butyrolactones III from α-diazo(diethoxyphosphoryl)acetates I, which are readily accessible from simple alcohols. The key C–H insertion step enables the formation of a new C–C bond in α-phosphonolactone II, via reaction of the rhodium carbenoid with a C–H bond typically considered completely unreactive. The scope of the reaction is explored in detail, concluding with the synthesis of two natural products, cedarmycins A and B (IV and V) and a Staphylococcus Aureus inhibitor VI (Chapter 2). The scope of the reaction was extended to the use of conformationally restricted substrates,facilitating the synthesis of α-methylene-γ-butyrolactones with complete diastereoselectivity,demonstrated through the synthesis of the natural product α-cyclocostunolide VII (Chapter 3). Finally, the development of a related procedure is described (Chapter 4). The rhodium(II)-catalysed cyclopropanation of allylic α-diazo(diethoxyphosphoryl)acetates is discussed as an alternative approach to the α-methylene-γ-butyrolactone framework. This work has been applied to the first total synthesis of peperomin E VIII as well as savinin IX and gadain X (Chapter 4).

Item Type: Thesis (PhD)
Academic Units: The University of York > Chemistry (York)
Identification Number/EthosID: uk.bl.ethos.685261
Depositing User: Mr Matthew Lloyd
Date Deposited: 17 May 2016 10:39
Last Modified: 24 Jul 2018 15:21
URI: http://etheses.whiterose.ac.uk/id/eprint/13069

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