This module shows: 1) how the concerted application of a collection of conceptual models and elementary reaction steps to problems in organic chemistry can provide a framework for understanding the bonding and reactivity of organic molecules; and 2) how modern reactions can be applied to the synthesis of target molecules.

Knowledge and Understanding

1. discuss the forces that control structure and reactivity of organic molecules;
2. analyse problems in organic chemistry employing the experimental techniques and theoretical models that have led to our current understanding of structure and reactivity in organic chemistry;
3. discuss the origins and consequences of the special reactivities of transient intermediates and propose how such transient intermediates might feature in organic reaction mechanisms;
4. apply the knowledge acquired in the field to problems in neighbouring disciplines, such as chemical synthesis, chemical biology, and materials chemistry;
5. judge the merit of proposed reaction mechanisms;
6. explain the mechansims by which a series of reactions proceeds;
7. understand the use of transition metal catalysts in organic synthesis;
8. perform a retrosynthetic analysis and propose a forward synthesis for any given target molecule.

Intellectual Skills

1. analyse the merit of proposed (reaction) mechanisms through the evaluation of the energetic viability of intermediates and activated complexes;
2. design synthetic routes for target molecules based on an understanding of chemical reactivity.

Discipline Specific (including practical) Skills

1. decide which theoretical model is most appropriate for analysing a problem in organic structure or reactivity, and then apply that model to solve the problem;
2. hypothesize whether a particular organic reaction is likely to involve a reactive intermediate, and if so, which type;
3. predict the probable outcomes for a wide variety of chemical transformations of organic molecules;
4. design syntheses of target molecules, including the use of protective groups as required for compatibility of reactivity.

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

Please see Learning Outcomes

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

Aldol reactions

Burgi-Dunitz trajectories

Conformational analysis and stereochemical representations

Zimmerman-Traxler model

Cyclisation reactions

Burgi-Dunitz trajectories and Baldwin’s rules

Ring strain

Solvent effects and non-covalent interactions

Hunter’s description of molecular interactions in solution

Hydrophobic interactions

Reactive intermediates

Carbocations: solvolysis reactions; CIRD; special salt effect; non-classical cations 

Carbanions: kinetic vs thermodynamic acidity, elimination reactions

FMO theory & pericyclic chemistry

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

Spring Semester

Retrosynthetic analysis

Introduction to disconnections and the logic of synthesis

C-X disconnections – halides, ethers, sulphides and amines and 1,2- & 1,3-difunctionalised compounds

C-C disconnections and synthesis using carbonyl group, including alkene synthesis, enolate alkylation selectivity

Synthesis of 1,3-, 1,4- and 1,5-dicarbonyl compounds

Use of protecting groups when chemoselectivity issues arise

Manipulation of double bonds, ring opening, ring expansion and ring formation techniques

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

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; Barton remote oxidation

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

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