The aim of the course is to consolidate and extend second year knowledge of synthetic and physical organic chemistry. Basic synthetic reactions are reviewed and more advanced synthetic methodology introduced. The retrosynthetic approach is then developed, enabling students to devise syntheses of a range of target molecules. Concurrently, the basic concepts and techniques of physical organic chemistry are explained, providing a deeper understanding of organic mechanisms and reactivity.

By the end of the module, students should:

• Have a good understanding of modern synthetic reactions and their mechanisms.
• Be able to perform retrosynthetic analyses and devise plausible syntheses of a variety of target molecules.
• Be able to deduce mechanisms on the basis of kinetic and other evidence.

Lecture -

Tutorial -

Organic synthesis and reactions (20 lectures)

 Pericyclic reactions 1: cycloadditions (3 lectures)  
   
     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   
 
 Pericyclic reactions 2: Sigmatropic and electrocyclic reactions (2 lectures)  
   
     Stereochemistry from chair-like t
ransition 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 retention 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 molecule
s 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 (3 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 a
nd their synthetic applications. Dissolving metal reductions applied to carbonyl groups - Pinacol coupling and acyloin condensation.         
 
 ·               Synthesis of alkenes -- controlling double bond geometry   (2 lectures)     
   
     
Stereospecific eliminations reactions      
   
   
     
Wittig, Peterson and Julia reactions        
   
   
     
Reduction of alkynes        
   
 
 ·               Retrosynthesis       (7 lectures)  
o Disconnections, synthons, synthetic equivalents, target molecules         
 
o Chemoselectivity· Functional group interconversion         
 
o C-X dis
connections: one and two group disconnections.         
 
o C-C bond disconnections: One group disconnections, Two group disconnections:         
 
o 1,X-dioxygenated systems (X = 1,3,5) and natural reactivity.        
 
o 1,2 and 1,4 disconnections and Umpolung reactivity          
 
Physical organic chemistry (12)
 ·               Revision of basic mechanisms         
o SN2, SN1         
 
o E1, E2, E1cb        
 
o Electrophilic addition and substitution reactions        
 
o Nucleophilic substitution at carbonyls         
 ·               Equilibrium and rates         
o Revision of basic thermodynamics: DGo = -RTln(K) = DHo - TDSo        
 
o Acid-base equilibria: pKa of common acids         
 
o Reaction coordinate, transition state, microscopic reversibility        
 
o Connection between equilibrium and rate constants K = k1/k-1        
 ·               Rates, Equilibria and Free Energy Diagrams         
o Hammond''s postulate         
 
o Thermodynamic vs. kinetic control         
 
o Curtin-Hammett principle         
 ·               Kinetics         
o Revision of elementary kinetics         
 
o Multistep reactions, bottlenecks, rate determining step and steady state    
approximation, connection with free energy diagrams          
 
o Primary deuterium kinetic isotope effect        
 ·               The Hammett equation         
o Substituent constants     
 
o Correlation of rates and reaction constants    
 
o Correlation of equilibria and reaction constants     
 
o Physical basis of LFER