The aim of this module will develop and extend the knowledge of modern organic synthesis to prepare students for a career as a professional chemist in the fine chemical industry or for a PhD programme. Specifically, students will learn the concepts that enable stereocontrol in reactions and the fundamental methods in organic synthesis.

(LO1) To propose a likely mechanism of reactions involving palladium catalysts and main group elements.

(LO2) To propose a plausible rationale for the stereochemical outcome of a reaction creating one or more chiral centres.

(LO3) To design strategies that enable the synthesis of complex molecules.

(S1) Critical thinking - To use knowledge and understanding of the reactivity of molecules to explain and predict the outcome of reactions of molecules that are useful to the fine-chemical industry, mainly pharmaceuticals and agrochemicals and problem-solving.

(S2) Problem-solving - To use knowledge and understanding of the reactivity of molecules to propose an efficient multiple-step synthesis of previously unseen targets.

Lectures. 30 x 1 hr in-person lectures, with additional revision sessions.
All lectures on palladium-catalysed reactions and stereoselectivity in organic reactions will include mini workshops on worked examples (totalling approximately 20 minutes per session) during which students have the opportunity to test their understanding and ability to solve problems that are representative of real-life situations. In addition, a large number of corrected problems will be made available online for students to train in the skills S1-S3 listed in section 5.

Tutorials. 2 x 1 hr. The tutorials will be revision sessions in preparation of the class tests.

Coursework. One closed-book class test (1 hr) and one open-book class test (2 hr), each worth 15%.

*Lectures: 30 hr
*Tutorials: 2 hr

Synthetic strategies
Definition of retrosynthetic analysis.
Basic principles of retrosynthesis disconnections, synthons, synthetic equivalents and reagents.
The concept of umpolung.
Revision of key reactions in synthesis.
Methods for the synthesis of dicarbonyl compounds.
Methods for the synthesis of alkenes.
Functional group interconversions.
C-C bond disconnections.
Aromatic and heterocyclic compounds and sp2-sp2 coupling reactions.
Key ring-forming reactions.

Main group chemistry
Chemistry of Lithium: Lithium amide bases, structure and aggregation of organolithiums. Use of sterically hindered bases in controlling enolate formation via kinetic deprotonation. Lithium-mediated cyclisation reactions. α-Heteroatom functionalised organolithiums. Transmetallation of organolithiums. Modern application of Grignard reagents.
Chemistry of Boron: Structure and synthesis of organoboranes. Hydroboration reaction. Reactions of organobo ranes. Introduction of heteroatoms via borane intermediates. Use of organoboranes in the synthesis of carbon-carbon bonds. Chemistry of allylboranes.
Chemistry of Silicon: Comparison of silicon and carbon compounds. Peterson olefination. Chemistry of vinyl, aryl silanes and allylsilanes. Silyl enol ethers, formation and reactions.

Palladium-catalysed reactions
Fundamental mechanistic steps of organopalladium chemistry (revision): oxidative addition, reductive elimination, migratory insertion, carbonylation, β-hydride elimination.
Palladium(0)-catalysed bond formation: C-C cross-coupling with organometallics (Sonogashira, Suzuki, Stille, Negishi, Hiyama, Kumada), and olefins (Heck, Trost)
Palladium(0)-catalysed carbonylative coupling.
Palladium(0)-catalysed C-N, C-O, C-S cross-couplings (Buchwald-Hartwig).

Stereoselectivity in organic reactions
Asymmetric synthesis by cyclic control, reactions of endocyclic olefins (revision).
Acyclic contro l by 1,3-allylic strain and 1,2-allylic strain.
Hydrogen-bond directed stereocontrol.
Acyclic control in nucleophilic attack of aldehydes and ketones.
Zimmerman-Traxler transition state and its application to aldol reactions, pericyclic rearrangements, and allylation reactions.
Chiral auxiliaries in aldol and other reactions.