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Synthesis of Medium-Sized Oxygen and Nitrogen Heterocycles via Stevens Rearrangement of Sulfonium Ylides and Formal Synthesis of (+)-Laurencin
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- Author / Creator
- Lin, Rongrong
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Medium-sized cyclic ether and amine motifs often constitute the framework of a variety of natural products with interesting biological activities. As a result, the construction of these heterocycles is an important subject in organic synthesis, which has triggered the development of many strategies. The Stevens [1,2]-shift of sulfonium ylides is a versatile way to form new C–C bonds, which could be applied in the synthesis of medium-sized heterocycles. Chapter 1 is a review of recent developments on the generation of sulfonium ylides from metallocarbenes and sulfur nucleophiles and their subsequent transformations, including [2,3]-sigmatropic rearrangement, Stevens [1,2]-shift and S-H insertion. Background information on the metallocarbene generation via decomposition of diazocarbonyl compound is also discussed. However, synthetic applications using the Stevens [1,2]-shift of sulfonium ylides were under explored, which intrigued our investigation in this area. A novel approach to medium-sized cyclic ethers was previously developed by the West group using a Stevens [1,2]-shift of a sulfonium ylide derived from a readily accessible six membered monothioacetal precursor. Chapter 2 provides a detailed discussion on an application of this methodology as the key step in an enantioselective formal synthesis of (+)-laurencin. The concise and efficient transformation offers a surprising degree of chirality transfer with observed retention of stereochemical configuration on the migrating carbon. The resulting sulfur bridge could be efficiently removed by reductive desulfurization. An extension to this strategy to access medium-sized cyclic amines is described in Chapter 3. The substituted thiazolidine ring with a diazoketoester tether was prepared from readily available starting materials. Although the resulting diastereomeric products could not be separated, when they were subjected to the Stevens rearrangement conditions, the desired sulfur-bridged azepine was obtained in quantitative yield. This promising result proved the feasibility of the methodology. Additional investigation is currently in progress to study the stereoselectivity of this transformation. In the future, this methodology could be applied as the key step to synthesize Stemona alkaloids, such as stemoamide.
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- Graduation date
- Fall 2017
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.