The University of Southampton
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CHEM3041 Synthetic Methods in Organic Chemistry

Module Overview

Aims and Objectives

Module Aims

The course aims to improve a students understanding of fundamental organic reactions and to add further transformations and principles to their knowledge base. They will encounter anion, radical, pericyclic and organometallic mediated processes, gaining new insights into the factors governing the mechanistic, stereochemical and regiochemical course of such reactions. Throughout the course the usefulness of the chemistry discussed with be highlighted through applications.

Learning Outcomes

Learning Outcomes

Having successfully completed this module you will be able to:

  • Describe different approaches to the formation of carbanions, discuss their structures, stabilities/reactivities and applications in synthesis.
  • Appreciate the likely course of a radical addition reaction when myriad options are, in principle, available (e.g. in casdade radical reactions).
  • Delineate the mechanistic and stereochemical course of some sophisticated cascade radical reactions and appreciate their value in target oriented synthesis.
  • Appreciate problems associated with the use of organotin reagents and some of the ‘get rounds’ available.
  • Describe the mechanistic course of various palladium catalysed coupling reactions (including Heck, Sonogashira, Negishi, Kumada Corriu, Stille, Suzuki etc.) and appreciate their value in synthesis.
  • Appreciate the class of pericyclic reactions and be able to identify them and draw mechanisms.
  • Use FMO theory to show that some pericyclic rections are allowed, others not, and that some have to take place with specific stereochemical consequences.
  • Understand how the energy levels and orbital coefficients of components affect the rates and regiochemistry of cycloaddition reactions.
  • Describe several groups of organosulfur compounds (e.g. thioethers, sulfoxides, sulfones, sulfur ylides, dithianes) and their structures. They should be able to discuss their reactivities, and methods of preparation.
  • Recognise the stabilisation of carbanions alpha to sulfenyl, sulfinyl and sulfonyl groups, and be able to explain the origins of the stabilisation.
  • Illustrate how organosulfur compounds can be used in synthesis, with a focus on C—C bond formation and functional group interconversions (e.g. reduction, Swern oxidation, syn-elimination, Pummerer).
  • Student should be able to plan syntheses using carbanions as nucleophiles or as precursors in palladium-catalysed C—C bond-forming reactions.
  • Describe the concept of chiral auxiliaries and their application in diastereoselective alkylation reactions. They should be able to explain the origins of the observed diastereoselectivity.
  • Apply their detailed knowledge of radical chain reactions to rationalise the outcome of previously unseen examples of this genre.
  • Describe the importance of kinetics and bond strength on the outcome of a radical chain reaction.
  • Appreciate when a radical addition reaction is likely or unlikely based on nature of the radical intermediate and the radical acceptor.

Syllabus

Carbon-carbon bond forming reactions and functional group transformations represent two crucial areas of organic synthesis. In presenting modern methods and describing new reagents, principles of selectivity will be emphasised e.g. chemoselectivity, regioselectivity and various aspects of stereoselectivity. The importance of various carbon-carbon bond-forming processes will be illustrated by examples taken from the literature. Cyclisation reactions will be discussed in detail, with emphasis given to organic compounds produced by nature with varied and significant biological/pharmacological activity. Formation of carbon-carbon bonds using carbanions: Methods for the formation of organolithium and organomagnesium compounds will be reviewed, and some reactions of these species (e.g. alkylation, transmetallation, transition-metal-catalysed cross-coupling and reactions with other electrophiles) will be discussed. Some fundamental aspects of organosulfur chemistry will be introduced and the structure and applications of sulfur-stabilised carbanions in synthesis will be examined. These include: umpolung, olefination, Swern oxidation, Pummerer reactions, and cyclopropanation processes. We will also look at methods to obtain regio- and stereocontrolled enolate formation, applications of dianions in synthesis and how chiral auxiliaries may be used to carry out stereoselective alkylation of enolates. Formation of carbon-carbon bonds using radicals: The fundamentals of radical reactions provide an introduction to the area. Discussion will then focus on tin-mediated intermolecular additions, intramolecular cyclisations and tandem and cascade processes. Baldwin’s guidelines for cyclisation reactions are discussed. Formation of carbon-carbon bonds using organometallic reagents: focusing on the use and application of palladium catalysis in organic synthesis. Pericyclic reactions: Diels-Alder-, 1,3-dipolar- and related cycloadditions; concerted electrocyclic ring opening and closure reactions (stereochemistry); sigmatropic rearrangements. The emphasis will be on how appreciation of the frontier molecular orbitals involved in the reactions allows prediction of which will occur, as well as their rates, regiochemistry and stereochemistry.

Learning and Teaching

Teaching and learning methods

Lectures and workshops. Some on-line resources provided on Blackboard including some recorded lectures and worked examples.

TypeHours
Follow-up work74
Lecture24
Practical classes and workshops6
Revision10
Preparation for scheduled sessions40
Total study time154

Resources & Reading list

I. Fleming (1976). Frontier Orbitals and Organic Chemical Reactions. 

I. Fleming (1998). Pericyclic Reactions. 

I. Fleming (2009). Molecular Orbitals and Organic Chemical Reactions Student Edition. 

Gilchrist and Storr (1979). Orbital Reactions and Orbital Symmetry. 

Clayden, Greeves, Warren and Wothers (2001). Organic Chemistry. 

F A Carey and R J Sundberg (1990). Advanced Organic Chemistry A and B. 

A J Kirby (1996). Stereoelectronic Effects. 

Assessment

Summative

MethodPercentage contribution
Examination  (2 hours) 100%

Referral

MethodPercentage contribution
Examination  (2 hours) 100%

Linked modules

Pre-requisites: CHEM3038 or CHEM6095.

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