The module will be delivered in 44 1-hour lectures, 6 1-hour workshops, and 4 1-hour tutorials.

A written exam will test the student’s knowledge and understanding as elaborated under the learning outcomes. The coursework will allow the student to demonstrate his/her ability to judge and critically review relevant information.

Autumn Semester

Revision and conceptual models for bonding and mechanism

Review of substitution (S_N1 or S_N2) and elimination (E₁ or E₂) reactions, additions to carbonyls, and electrophilic addition and substitution reactions

Curly arrows, valence bonds and molecular orbitals

Thermodynamic and kinetic constraints on mechanisms

Kinetic vs thermodynamic control

More-O’Ferrall-Jencks diagrams

Solvent effects and non-covalent interactions

Hunter’s hydrogen bonding interactions

Hydrophobic interactions

Aldol reactions

Burgi-Dunitz trajectories

Conformational analysis and stereochemical representations

Zimmerman-Traxler model

Cyclisation reactions

Burgi-Dunitz trajectories and Baldwin’s rules

Ring strain

FMO theory

Introduction to MO theory

Diels-Alder reaction; symmetry-allowed and symmetry-forbidden reactions, regioselectivity

Sigmatropic rearrangements; 1,n hydride shifts, Cope and Claisen rearrangements

Electrocyclic reactions

Photochemical processes; alkene dimerisation

Reactive intermediates

Carbocations: solvolysis reactions  

Carbanions: kinetic vs thermodynamic acidity, elimination reactions

Carbenes & nitrenes: singlet and triplet states; carbenoids

Radicals and Biradicals: kinetics of biradical reactions

Electronic excited states and photochemistry

Spring Semester

Retrosynthetic analysis

Introduction to basic ideas, using a selection of relatively simple examples and schemes

Alpha-amino acid synthesis analysed in depth using retrosynthetic principles, asymmetric synthesis of amino acids

Peptide synthesis: the basic logic

Protecting groups for alcohols, aldehydes and ketones: why and how

Alkene and alkyne chemistry

Alkene synthesis by elimination methods; disconnection across the double bond

Reprise of alkene synthesis using Wittig and introduction of related methods

Julia and Peterson methods

Alkyne synthesis – deprotonation and ‘Wittig-like’ synthesis – Corey-Fuchs and Ortira-Bestmann

Palladium-catalysed coupling methods

Introduction to new disconnection for the synthesis of polyunsaturated systems

Definitions of Heck, Suzuki-Miyaura, Kumada, Negishi and Sonogashira methods

Catalytic cycle summary and key differences within these

Perspective on utility, practicalities etc.

Selected applications in synthesis, with emphasis on the retrosynthetic features

Precursor synthesis where appropriate

Pericyclic chemistry

Reprise of FMO theory

Aspects of perispecificity, stereoselectivity and regiochemistry in Diels-Alder cycloadditions, ene reactions, electrocyclic reactions, photochemical cycloadditions including Norrish type I and 2, Cope eliminations and Cope and Claisen rearrangements, all illustrated by applications in target synthesis

Metathesis

Definition and emphasis on catalyst types for both ring closure (ene-ene and ene-yne) and cross metathesis; experimental methods; brief mention of utility in polymer synthesis

Modern oxidative transformations

Epoxidation, SAE

Bis-hydroxylation; AD-mix; related osmylation methods; synthetic utility (examples); Baeyer-Villiger; allylic oxidation; refer back to Barton remote oxidation

An indicative reading and resource list will be included in the Course Handbook.