Use of organometallic intermediates in organic synthesis

Alshammari, Mohammed ORCID: https://orcid.org/0000-0001-9687-8747 2012. Use of organometallic intermediates in organic synthesis. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Chapter One: Chapter one describes a historical overview and the practical consideration of lithiation reactions and highlight of some of the factors that could influence the site of lithiation. It also provides reviews of the directed and side-chain lithiation of substituted aromatics. Chapter Two: Chapter two deals with lithiation of N′-phenethyl-N,N-dimethylurea with three equivalents of t-BuLi in THF at –78 °C followed by reaction with various electrophiles to give side-chain substituted products due to lithiation and substitution at the CH2 next to the phenyl ring (α-lithiation). The 2-lithio isomer can be obtained via Br–Li exchange of 2-bromo derivative using MeLi followed by t-BuLi in THF at –78 °C. The lithium reagents thus obtained react with various electrophiles to give the corresponding 2-substituted derivatives in excellent yields. Lithiation of N′-(3-phenylpropyl)-N,N-dimethylurea takes place on the α-CH2 with t-BuLi at 0 °C. On the other hand, lithiation of N′-(4-phenylbutyl)-N,N-dimethylurea with t-BuLi at 0 °C takes place on one of the methyl groups of the urea unit. Chapter Three: Chapter three includes lithiation of N'-(2-(2-methylphenyl)ethyl)-N,N-dimethylurea with three equivalents of n-BuLi in THF at 0 C followed by reaction with various electrophiles to give side-chain products in excellent yields due to α-lithiation. Similarly, lithiation of the pivalamide derivative followed by reaction with benzophenone as a representative electrophile gave the corresponding α-substituted product in high yield. Surprisingly, no products resulting from lateral lithiation were observed under the conditions tried, which sharply contrast with the reported results for lateral lithiation of the carbamate derivative. Chapter Four: In this chapter, N-(2-(4-methoxyphenyl)ethyl)amine derivatives are reported to undergo directed ortho-lithiation next to the directing group with n-BuLi at 0 ºC, followed by treatment with various electrophiles, to give high yields of the corresponding substituted products. This contrasts sharply with the earlier results for the α-substitution of the pivaloyl derivative using t-BuLi at a lower temperature. Chapter Five: Chapter five includes variations in the site of lithiation of N-acyl-3-(aminomethyl)pyridine derivatives with different N-substituents using different lithiating reagents. Ring lithiation has been achieved by the use of t-BuLi at 78 C followed by reaction with various electrophiles to give the corresponding 4-substituted products in high yields. On the other hand, the reaction was regioselective towards the side-chain when LDA was used as the lithium reagent at 20 to 0 C. A mixture of ring and side-chain substitution products was obtained when n-BuLi was the lithium reagent. Chapter Six: Chapter six investigates the use of various chiral ligands containing different coordinating groups in Matteson homologation. Some stereoselectivity (de = 252%) was obtained depending on the type of chiral catalyst used. The best %de (52%) was obtained when Yb(OTf)3 as a Lewis acid and (1R,2R)-1,2-bis((R)-2,2-dimethyl-1,3-dioxolan-4-yl)ethane-1,2-diol as a chiral ligand were used in combination. However, significant %de (46%) could be obtained with the diol chiral ligand in the absence of the Lewis acid, which is very interesting and open windows for further improvement.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Chemistry
Subjects:	Q Science > QD Chemistry
Date of First Compliant Deposit:	30 March 2016
Last Modified:	11 Aug 2023 14:38
URI:	https://orca.cardiff.ac.uk/id/eprint/45471

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