3rd year students following this course will acquire:
- a certain number of new organic reactions;
- retrosynthetic analysis using one- and two-group disconnections;
- a rational approach towards multistep synthesis;
- an understanding of and the capability to apply the concepts of regio-, chemo-; and stereoselectivity to the planning of multistep sequences;
- the application of protecting groups in multistep synthesis;
- a first fundamental approach of pericylic reactions using FMO theory;
- a first approach of organometallic catalysis via the exploration of palladium-catalysed coupling reactions.
The aim of this lecture course is to provide students with a systematic approach to think about and plan the synthesis of complex, polyfunctional molecular targets using the tools of retrosynthesis and multistep organic synthesis methods. A specific focus is on issues of chemo-, regio- and stereoselectivity.
In order to favour a rational way of thinking about synthesis, the course introduces a very powerful strategy called retrosynthetic analysis. The systematic analysis of a variety of differently functionalised target molecules structures this course. On the other hand, each retrosynthetic operation requires knowledge of the corresponding reactions. This will lead us to examine the synthetic utility of the basic reactions already taught in first and second year, and to extend students' chemical toolkit to include ever more modern and sophisticated reactions. Since most of the target molecules examined contain multiple functional groups, and some might be complex in terms of stereochemistry, the main focus when dealing with organic reactions will be on all aspects of control. In particular, we will be most concerned with the following three types of selectivity : - chemoselectivity; - regioselectivity; - diastereoselectivity.
1. Introduction
2. Retrosynthesis - a brief history
3. Retrosynthesis - vocabulary and concepts
4. Benzene derivatives by aromatic substitution
5. Benzene derivatives: strategic considerations
6. One-group C-X Disconnections
7. Chemoselectivity issues in C-X disconnections
8. Two-group C-X Disconnections
9. Protecting groups for heteroatoms
10. One-group C-C disconnections via alcohols
11. One-group C-C disconnections via carbonyl compounds
12. Generation of specific enolates and their equivalents
13. Synthesis of alkenes and alkynes
14. Two-group C-C disconnections: carbonyl condensations
15. Two-group C-C disconnections: the aldol reaction
16. Two-group C-C disconnections: conjugate addition
17. Two-group C-C disconnections: acyl anion equivalents
18. Ring-forming reactions: cycloadditions
19. Editing ring size: ring contraction, expansion and fragmentation reactions
20. Introduction to organometallic chemistry: palladium-catalysed coupling reactions
The exercises are organised in parallel to the lectures and follow the same structure. They always aim to shed light onto all aspects of selectivity and on retrosynthetic analysis, which are the main topics of this course.
Students are evaluated in a 2 hour written examination followed by a 20 minute oral examination, organised during the second and third exam sessions.
J. Clayden, N. Greeves, S. Warren, P. D. Wothers « Organic Chemistry », Oxford University Press; S. Warren, P. Wyatt « Organic Synthesis: The Disconnection Approach», Second Edition, Wiley; S. Warren, P. Wyatt « Organic Synthesis: Strategy and Control», Wiley; R. Brückner « Advanced Organic Chemistry: Reaction Mechanisms », Academic Press.