The aim of the course is to consolidate and extend second year knowledge of synthetic and physical organic chemistry, and introduce some aspects of biological chemistry.

By the end of the module, students should:

• Demonstrate a good understanding of modern synthetic reactions and their mechanisms.
• Demonstrate familiarity with some of the more important aspects of biological chemistry

Organic synthesis and reactions (14)

• 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

• Stereochemistry from chair-like transition states
• Making γ,δ-unsaturated carbonyl compounds
• Wh at 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

• 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 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 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.

Synthesis of alkenes -- controlling double bond geometry (2 lectures)            

• Stereospecific eliminations reactions.                            

• Wittig, Peterson and Julia reactions                            

• Reduction of alkynes                                      

Physical organic chemistry (8 lectures)

• 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




                            

Introduction to bioorganic chemistry -- essay and web based project

Topics:

• Carbohydrate chemistry            

This module consists of 22 50-minute lectures to be given in the first semester.  The material presented at the lectures is supported by three 1-hour tutorials (common to CHEM333) given fortnightly.  The students will write an essay on a specified topic in biological chemistry and subsequently collaborate to present the topic as a web page. They will receive an introduction to web page design and use VITAL as an interactive resource for online advice.

 Essential:

• "Organic Chemistry", Clayden, Greeves, Warren and Wothers, Oxford University Press (2001)

Additional Reading:

• "Mechanisms of Organic Reactions", H. Maskill, Oxford University Press (1996)
• "Organic Synthesis", C. L. Willis and M. R. Wills, Oxford University Press (1996).
• "Organic Synthesis - The Disconnection Approach", S. Warren, Wiley (1982).
• "Workbook in Organic Synthesis - The Disconnection Approach", S. Warren, Wiley (1982).
• "Advanced Organic Chemistry", F. A. Carey and R. J. Sundberg, Plenum/Rosetta (1997).