Organic Chemistry 3: Structure and Reactivity

Overview

Staff
NAME CONTRIBUTION
Dr P. C. Knipe
p.knipe@qub.ac.uk Stereochemistry and Stereocontrol 8 lectures/seminars
Dr. S. Cochrane
s.cochrane@qub.ac.uk Peptide And Protein Synthesis - 6 Lectures/Seminars.
Dr. P. Dingwall
p.dingwall@qub.ac.uk Physical Organic Chemistry - 6 Lectures/Seminars
Dr. M .McLaughlin
mark.mclaughlin@qub.ac.uk Applications Of Organometallic Reagents In Organic Synthesis - 8 Lectures/Seminars
Dr. G Sheldrake
g.sheldrake@qub.ac.uk Synthesis of Biocatalysis - 5 Lectures/1 Workshop

Physical Organic Chemistry (6 Lectures/Seminars):
 This section of the module studies some of the physicochemical principles which provide the foundations of organic chemistry. It introduces the subject in terms of the concepts and the terms which are commonly encountered. In particular, it examines the basis of linear free energy relationships as applied to the effects arising from substituents and by solvents. Some examples of these will be considered. One of the situations under which linear free energy relationships break down will be studied, as well as its consequences. As an example of this, we will study the participation of neighbouring groups in reactions.
 Learning outcomes: by the end of the module the students should -
 understand and be able to apply the fundamental concepts and terminology;
be able to identify functional groups and substituents within a chosen molecule;
 have a grasp of linear free energy relationships;
 have an understanding of the different substituent effects in terms of substituent parameters;
 have an understanding of the different medium effects in terms of solvent parameters;
 have an understanding of situations where linear free energy relationships break down, e.g. neighbouring group participation.

Stereochemistry and Stereocontrol (8 Lectures/Seminars):
This course will provide an in-depth and detailed discussion of stereochemistry in organic molecules, including:
 Definitions and concepts – types of isomer; stereochemical relationships between stereocentres and between molecules; types of chirality; types of topicity.
 Resolution and spectroscopy – methods for separating and measuring stereoisomeric mixtures; e.e., e.r., d.e. and d.r.; NMR of molecules containing stereogenic centres.
 Cyclic stereocontrol – nucleophilic addition to cyclohexanones; bicyclic systems and exo/endo approach; opening epoxides (the Furst-Plattner rule)
 Acyclic stereocontrol – addition to carbonyl with adjacent stereocentres (Felkin-Anh control); Felkin chelate and polar models; stereoselective in the Aldol reaction (Ireland model for enolization, Zimmerman-Traxler cyclic transition state).
 The fundamentals of pericyclic chemistry – stereocontrol in cycloadditions and sigmatropic rearrangements.

Applications Of Organometallic Reagents In Organic Synthesis (8 Lectures/Seminars):
 Basic transformations involving transition metal based organometallic reagents;
 Formation of C-C bonds in cross-coupling reactions;
 Heck, Suzuki and Stille reactions;
 Application of cross-coupling reactions in organic synthesis;
 the Grubbs, the Hoveyda and related Ru-alkylidene RCM catalysts;
 Furstner's ring-closing diyne metathesis reaction;


Peptide And Protein Synthesis 6 Lectures/Seminars:
 In this lecture series we will learn how synthetic chemists synthesize peptides and proteins. Topics will include the structure of amino acids and peptides, common protecting groups used in peptide synthesis, the concept of solid-phase peptide synthesis, total protein synthesis using native-chemical ligation and KAHA ligation, and biorthogonal chemistry applied to post-translational protein modifications.

Biocatalysis (6 lectures of which 3 assessed)

Introduction to Biocatalysis for Organic synthesis
 What does an enzyme do, and why use one?
 Assessing an enzyme: Michaelis Menten kinetics and related measurements.
 Mode of application. Isolated enzyme versus whole cell biocatalysis.
Classes of enzyme, by reaction catalysed.
 Cofactor and cofactor recycling.
 Immobilization.


Industrial Application of Enzymes for Organic Synthesis (delivered by Stefan Mix, Almac group)

 Where do industrial biocatalysts come from?
 Enzyme discovery and genome mining.
 Enzyme engineering.
 Recombinant expression systems.
 Genes to GMP: work flow from screening to bulk: examples.
 Bioprocess design.

Learning Objectives

 On completion of this module students will be able to think about organic chemistry in a clear and logical manner which will build the foundations for them becoming ‘problem solvers.’ In particular they will be confident with the mental manipulation of organic structures, including natural products, and will be able to predict the likely chemistry and reactivity of unseen organic molecules with given reagents and experimental conditions. Student will be able to perform these mental tasks in reverse and possess the ability to predict and identify reaction mechanisms and pathways. The students will be able to apply a wide range of chemical methods to the analysis or planning of multi-step syntheses, and understand the role of protecting groups. Students will appreciate the principal roles of natural products (primary metabolites), understand their structural and chemical properties, and be able to devise methods for their preparation.
 A strong emphasis on mechanism, stereochemistry, synthesis and retrosynthesis will provide the necessary tools to achieve these outcomes.

Skills

Subject specific problem-solving skills in exams and seminars.
Ability to recognise and analyse novel problems and plan strategies for their solution.

Assessment

Assessment:
Examination (180 mins) 85%
Tutorials (3 X 1h) 15%

Course Requirements:
Examination must be passed at 40%