Introductory description

n/a.

Module web page

Module aims

Outline syllabus

This is an indicative module outline only to give an indication of the sort of topics that may be covered. Actual sessions held may differ.

Pericyclic reactions including photochemistry.
Cycloadditions, electrocyclisations and sigmatropic rearrangements. Frontier orbital theory will be used to explain the stereochemical observations made in pericyclic reactions.
Cyclisation reactions (Baldwin's rules)
Polar rearrangements
Carbocation induced alkyl and hydride shifts, Wagner-Meerwein, Pinacol, Tiffeneau-Demyanov, hydride shifts, cyclisations. Nucleophilic rearrangements to carbon involving carbanions, Favorskii.
Radical chain mechanisms, cyclisations and rearrangements e.g. 1,5-H translocations.
Carbenes and nitrenes
Structure, reactivity and generation. Insertion reactions, cyclopropanation
Rearrangement reactions to electron deficient nitrogen and oxygen.
Reactions of chiral compounds (3 Lectures DJF)
Nucleophilic Addition to alpha-stereogenic carbonyl compounds: non-polar-Felkin model, polar Felkin model, chelation model. Addition to beta-stereogenic carbonyl compounds. Electrophilic addition to chiral alkene containing compounds: Houk-type model for control of reaction stereochemistry, including steric, and chelation factors, including the reaction of chiral allyl silanes.
Synthesis of enantiomerically enriched compounds (2 Lectures DJF)
Evans Auxiliary:, alkylation, aldols, conjugate additions, Diels Alder reaction.
Chiral reagents: terpene-borane reductions, hydroboration, allylation.
Asymmetric catalysis (5 Lectures MW), including:
Asymmetric Hydrogenation (AH) of C=C and C=O bonds, including Dynamic Kinetic Resolutions.
Asymmetric dihydroxylation (AD). Menthol synthesis.
Asymmetric Organocatalysis.
Pd catalysed allylation
Asymmetric rearrangement and synthesis of menthol

Laboratory component:
Organic Laboratory (5 CATS); This features a multi-stage preparation and characterisation of a target molecule assigned at random. Students are required to plan and execute the synthesis of the required target using guidance provided in the laboratory manual.

Learning outcomes

By the end of the module, students should be able to:

• Understand how carbenes and nitrenes can be used in organic synthesis
• Understand and apply Baldwin's rules for intramolecular cyclisation reactions.
• Develop ability to formulate potential routes to compounds using their knowledge of reactive intermediates and their reactions.
• Understand how cation and anion rearrangements occur and can be used in organic synthesis
• Understand how radical rearrangements and cyclisations can be used in organic synthesis
• Understand how reactions can form different stereoisomers of products
• Building on Year 2 modules, be able to draw simple transition-states in 3 dimensions
• Successfully predict simple aldol stereochemistry based on metals and enolate geometry
• Use facial steric arguments to predict stereochemical outcome
• Use stereoelectronic arguments (e.g. Houk’s rule) to predict stereochemical outcome
• Understand basics of chiral resolution via diastereoisomer formation
• Identify useful amino acids and know how they can be turned into chiral auxiliaries and templates.
• Explain and predict the stereochemical outcome of Evans alkylations, aldols, conjugate additions and cycloadditions
• Explain and predict the stereochemical outcome of chiral reagent controlled reactions such as terpene / borane mediated reductions and additions.
• Understand and apply empirical rules and models related to stereoelectronically-controlled reactions of organic molecules.
• Understand and apply selection rules for pericyclic reactions and intramolecular cyclisations, and understand their theoretical basis.
• Understand the frontier orbital approach to pericyclic reactions and use this top predict the outcome of reactions.

Indicative reading list

Much of the material for this module is taken from compulsory organic chemistry text by Clayden et al.; “Organic Chemistry” by Clayden, Greeves, Warren and Wothers, Oxford 2001.

The following books will also be compulsory
“Reactive Intermediates” C. J. Moody and G. H. Whitham, Oxford University Press, 2001.
“Polar Rearrangements” L. M. Harwood, Oxford University Press, 1992.
“Pericyclic reactions” I. Fleming, OUP 1998, Primer
“Organic Synthesis – Strategy and Control” Wyatt and Warren, Wiley, 2007

The following texts may be consulted for further information on the contents of the module:
Review on Woodward-Hoffmann rules: R. B. Woodward and R. Hoffmann in Angew. Chem., Int Ed. Engl., 1969, 8, 781.
“Organic Reactions and Orbital Symmetry”, T. L Gilchrist and R. Storr, Cambridge Academic Press, 1979.

Subject specific skills

Problem solving
Critical thinking
Independence and initiative

Transferable skills

Problem solving
Critical thinking
Independence and initiative