Advanced Organic Synthesis

Overview

STAFF
NAME and CONTRIBUTION:

1. Synthetic Strategy (6 lectures) – Dr McLaughlin
• The concept of disconnection as a strategic framework for designing synthetic routes to complex molecules.
• The distinction between strategic and tactical considerations
• The concepts of “synthons” and “functional group interconversion”
• Protecting groups.

2. Asymmetric Synthesis and Catalysis (10 lectures) – Dr Berney
• The importance of stereocontrolled synthesis
• The concept of chiral auxiliaries exemplified by the Evans auxiliary.
• Asymmetric organocatalysis – enamine/iminium activation modes, chiral Brønsted acid catalysis.
• Asymmetric transition metal catalysis – examples may include Tsuji-Trost, Sharpless, Jacobsen, CBS reduction, Krische allylation, Noyori reduction.

3. Enabling Technologies for Synthesis (5 Lectures, 1 workshop) – Dr Dingwall
• Photochemistry: excitation, luminescence, single/triplet states, electron transfer. Key reactions: photoredox chemistry, photoinduced radical chemistry
• Electrochemistry: electron transfer, oxidation/reduction processes, electrode potentials and Faraday's laws, practical electrochemical setups. Key reactions: electrosynthesis, mediated electrochemical reactions, and electrochemical functionalisation.
• Mechanochemistry: energy transfer through mechanical force, bond activation without solvents, ball milling vs twin screw extrusion. Key reactions: solventless reactions, accessing unfavoured products, mechanoredox chemistry
• Continuous flow chemistry: reasons for use, reactor design, flow regimes (Reynolds number). Key reactions: telescoping, “flash” chemistry
• Statistical modelling, machine learning, and artificial intelligence: synthesis planning, data-driven insights, predictive modelling, optimisation. Key applications: process design and optimisation, reaction outcome prediction, catalyst design.

4. Advanced Pericyclic Chemistry (4 Lectures, 1 workshop) – Dr Knipe
• Molecular Orbital Theory, Woodward-Hoffmann Rules and their origin in correlation diagrams.
• Cycloadditions: Endo/exo selectivity, secondary orbital effects, Diels-Alder reaction, 1,3-dipolar cycloadditions, transannular Diels-Alder, inverse electron demand systems, stereoselectivity and stereospecificity
• Electrocylizations: Con/disrotatory, electrocyclic ring openings, cascade electrocyclic reactions.
• Sigmatropic Rearrangements: Claisen and Cope reactions, carbon and hydride shift reactions, other sigmatropic rearrangements, suprafacial / antarafacial selectivity.
• Group Transfer Reactions: Ene reaction, diimide reductions and thermal eliminations

5. Applied Supramolecular Chemistry (6 lectures) – Dr Crory
· The study of intermolecular interactions including non-covalent and dynamic covalent bonding interactions.
· Investigation into the design of supramolecular processes which provide solutions for real-world issues, including literature examples on the following topics:
o Drug delivery and medicinal applications: Controlled release of drugs, antimicrobial materials, targeted therapies.
o Smart materials and sensors: stimuli responsive materials, self-healing materials, soft robotics, sensors and detection.
o Catalysis and nanoreactors: switching on/off function, increasing reaction selectivity.
· Critical evaluation of literature and presentation skills (lecture/workshop).

Topic 5 to be assessed by coursework, with the other topics to be covered in the examination. The coursework will take the form of an assessed presentation on a recent research paper in the area of supramolecular chemistry.

Learning Objectives

 On completion of this module the students will:
 Have an understanding of the logic and methodology
employed in contemporary organic synthesis.
 Be able to identify key disconnections in molecules
containing multiple chiral centres and double bonds, to deal
creatively with new scenarios and to provide reagents and
mechanisms to achieve desired transformations.
 Be able to propose detailed mechanisms, stereochemical
models and were possible predict the stereochemical
outcome for stereoselective reactions.
 Understand the role of emerging and enabling technologies
and their strengths and weaknesses in enabling organic
synthesis
 Identify supramolecular design principles and critically evaluate research examples.

Skills

Enhanced problem solving skills in organic chemistry.

Assessment

Assessment:
Examination 80 %
Course work 20 %

Coursework will be an exercise on synthesis.
Deadlines for questions will be given on Canvas.

Course Requirements: Examination duration 3 hrs - answer 3 from 4 questions.
Examination and coursework must both be passed at 40%