The aim of the module is to extend second year knowledge of synthetic and physical organic chemistry.

(LO1) Students should have a good understanding of some modern synthetic reactions.

(LO2) Students should be able to deduce mechanisms on the basis of kinetic and other evidence

(S1) The ability to recognise the types of reaction taught and apply mechanistic knowledge to predict the outcome of unseen examples

This module consists of 30 lectures in the first semester, with up to 3 revision lectures in week 11.

The material presented in lectures is supported by 5 in-person small group tutorials (1 hr), which are not assessed.

Lectures: 30 hr
Tutorials 5 hr

- Pericyclic reactions (5 lectures)
Cycloadditions. The rules that govern cycloadditions. Photochemical reactions: reactions that need light. Making six-membered rings by the Diels–Alder reaction. Making four-membered rings by [2 + 2] cycloaddition. Making five-membered rings by 1,3-dipolar cycloaddition. Using cycloaddition to functionalize double bonds stereospecifically. Using ozone to break C=C double bonds.
Sigmatropic and electrocyclic reactions. Stereochemistry from chair-like transition states. Making γ,δ-unsaturated carbonyl compounds. What determines whether these pericyclic reactions go ‘forwards’ or ‘backwards’. Fischer Indole synthesis. Why substituted cyclopentadienes are unstable What ‘con’ and ‘dis’-rotatory mean. Reactions that open small rings and close larger rings.

- Rearrangements and Fragmentations (3 lectures)
Participation means acceleration and reten tion of stereochemistry and may mean rearrangement. Participating groups can have lone pairs or π-electrons. Carbocations often rearrange by alkyl migration. Ring expansion by rearrangement. Using rearrangements in synthesis. Electron donation and electron withdrawal combine to create molecules that fragment. Anti-periplanar conformation is essential. Small rings are easy to fragment, medium and large rings can be made in this way. Double bond geometry can be controlled using fragmentations in synthesis.

- Radical reactions (4 lectures)
Radical reactions follow different rules to those of ionic reactions. Bond strength is very important. Radicals can be formed with Br, Cl, Sn, and Hg. Efficient radical reactions are chain reactions. There are electrophilic and nucleophilic radicals. Radicals favour conjugate addition. Cyclization is easy with radical reactions. Dissolving metal reductions with metal-ammonia systems applied to aromatic systems (Birch reduction) and enones and their synthetic applications. Dissolving metal reductions applied to carbonyl groups - Pinacol coupling and acyloin condensation.

- Organophosporous, organsulfur, and organoselenium chemistry (7 lectures)
Phosphorus: Wittig, Wittig-Horner and Wadsworth-Emmons reactions and their use in synthesis. Aza-Wittig reaction. Mitsunobu reaction, mechanism and applications.
Sulfur: Introduction to organosulfur compounds (oxidation states, names etc.). Synthesis and chemistry of sulfoxides, allylic sulfoxide-sulfenic ester rearrangement. Pummerer reaction, syn elimination of sulfoxides. Sulfones - Julia reaction, Ramberg Backlund reaction and extrusion of SO2 from sulfolenes. Chemistry of sulfur ylids, Corey/Trost reagents.
Selenium: Comparison of sulfur and selenium compounds. Reactions of selenoxides, syn elimination and [2,3] sigmatropic rearrangements. Oxidation reactions of selenium dioxide. Selenium mediated cyclisation reactions (PhSeCl etc.).

- Ph ysical organic chemistry (11 lectures)
Equilibria, transition states and rates: Free energy diagrams, transition states, connection between equilibrium and rate constants, K = k1/k-1, Hammond’s postulate, thermodynamic vs kinetic control, Curtin-Hammett.
Kinetics: Revision of elementary kinetics, steady state for multistep reactions, primary deuterium kinetic isotope effect.
S-N-2, S-N-1: Mostly revision of year 2 material
Elimination reactions: Revision of E1, E2, E1cb, kinetics, mechanistic continuum
Addition reactions: Revision of HX, X 2 additions with kinetics, some synthetic applications
Nucleophilic substitution at carbonyls: Tetrahedral intermediates and mechanisms for ester hydrolysis.
The Hammett equation: Substituent constants, reaction constants, correlation of rates and equilibria, multistep reactions, physical basis of LFER.