BSc Chemistry

Weeks 1-4: Rings and Stereoelectronics (Dr Nathan Owston)

Weeks 5-8: Introduction to Biomolecules (Dr Michael James)

Weeks 9-12: Retrosynthetic Analysis (Dr Andrew Regan)

Pre-requisite units 

All year 1 and year 2 semester 1 core CHEM modules. 

The unit aims to extend the concepts presented in previous courses to the structural, mechanistic, physical and biological properties of organic molecules.

On successful completion of the course students should be able to:  

Predict whether organic reactions will occur through consideration of stereoelectronic effects, basic kinetics and thermodynamics.

Evaluate and propose strategies for the synthesis of cyclic and acyclic molecules based on consideration of stereoelectronic effects, basic kinetics and thermodynamics.

Describe, evaluate and propose strategies for the synthesis of amino acids, peptides and carbohydrates based on selective protecting group strategies.

Apply the concepts of reactivity, stereochemistry, and stereoelectronics to evaluate the nature of amino acids, peptides and carbohydrates.

Choose appropriate disconnections for difunctional target molecules, based on stabilities of the synthons generated

Analyse the relationships between functional groups in difunctional compounds

Choose appropriate synthetic equivalents for synthons resulting from retrosynthetic analysis

Choose appropriate reagents for the reactions involved in planned syntheses

Decide whether any extra methods of control are required for a synthesis to proceed as planned 

Weeks 1-4: Rings and Stereoelectronics (Dr Nathan Owston)

• Rates and barriers in organic reactions
• Rotation, interconversion, conformers and rotamers  
• Stereoelectronic effects: 6 membered rings - substituted cyclohexanes and cyclohexane epoxides, ring closing reactions, stereo and regiochemical considerations. 
•     Electrophilic addition to cyclic alkenes  

Synthesis of small, medium and large rings – ring formation and ring stability. 

•   The Thorpe-Ingold Effect, kinetic and thermodynamic considerations
• Ring-closing and ring-opening reactions: Baldwin’s rules. 
• Neighbouring group participation: stereo- and regio-chemical outcomes.
• Molecular rearrangements: Migration, Carbocation Rearrangements, Pinacol-type rearrangements, the Beckmann rearrangement, applications of these in ring synthesis.
• Fragmentation reactions: ring expansion, applications in ring synthesis. 

Weeks 5-8 Introduction to Primary Metabolites (Dr Michael James) 

• Amino acids & Peptides
• Basic structure and ionisation – zwitterions, isoelectric points
• Side chains – acidity, basicity, electrostatic effects, hydrogen bonding
• Stereochemistry – Enantiomers, diastereomers
• Peptide chains – primary structure, nomenclature, abbreviations, N & C termini, sequence & composition
• Synthesis of racemic mixtures – nucleophilic substitution, reductive amination, Strecker synthesis
• Amino & Carboxy Protecting groups – e.g. Cbz, Fmoc, Boc
• Peptide synthesis – DCC + HOBt or HBTU

Carbohydrates

• Basic structure – functional groups, chain length, aldose & ketose
• Stereochemistry – Enantiomers, diastereomers & epimers
• Hemiacetal formation reaction mechanism – cyclic hemiacetals, lactols, equilibrium
• Cyclic structures – 2D, 3D, wedge & dash bonds, R/S centres, chair, axial, equatorial
• Anomeric centre – anomeric effect, mutarotation
• Selective functionalisation and protection of alcohols – Fischer glycosidation, benzyl and trityl ethers, silyl ethers, tosyl groups, cyclic acetals, esterification
• Selective synthesis of monosaccharides and disaccharides – glycosyl bromides, thiogylcosides, neighbouring group participation

Weeks 9-12: Retrosynthetic Analysis (Dr Andrew Regan)

•    Retrosynthetic analysis of compounds containing one functional group:

Disconnections of alcohols and α-alkylated carbonyl compounds

Control of enolate reactions.

•    Retrosynthetic analysis of compounds containing two functional groups:

Disconnections of 1,2- 1,3- 1,4- 1,5- and 1,6-difunctional compounds

Disconnections of difunctional compounds in rings: intramolecular cyclisation reactions. 

• Problem-solving skills

• Analytical skills 

• J. Clayden, N. Greeves, and S. Warren, Organic Chemistry, 2nd edition (Oxford University Press, 2012), ISBN 978-0199270-29-3.

• S. Doonan, Peptides and Proteins, RSC Tutorial Chemistry Texts (RSC, Cambridge, 2002), ISBN 0-85404-692-5

• S. Warren, Organic Synthesis: the Disconnection Approach, Wiley, 2nd edition, 2008; also Workbook for 2nd edition (both available as online e-books). 

• The following Oxford University Press Chemistry Primers are recommended, and are freely available to students as e-books via the University Library catalogue and Bibliotech:

•    A. J. Kirby, Stereoelectronic Effects, 1996.

•    B. G. Davis & A. G. Fairbanks, Carbohydrate Chemistry, 2002.

•    C. M. Dobson, J. A. Gerrard & A. J. Pratt, Foundations of Chemical Biology, 2001

•    J. Jones, Amino Acid & Peptide Synthesis, 2002.

•    C. L. Willis and M. Wills, Organic Synthesis, 1991.

•    R. S. Ward, Bifunctional Compounds, 1994.

•    J. Jones, Core Carbonyl Chemistry 1997.

A set of molecular models is also highly recommended.