The aim of this module is to introduce important carbon-carbon bond forming reactions within a mechanistic and synthetic framework, together with exposure to a selection of stereochemical issues.

(LO1) Students will be able to solve problems featuring the scope and mechanisms of basic reactions (nucleophilic and electrophilic substitutions, addition and elimination)

(LO2) Students will be able to solve problems featuring basic carbonyl chemistry (alkylation, acylation, aldol, conjugate additions).

(LO3) Students will be able to solve problems featuring the structure, reactivity and synthesis of simple heterocycles (including pyridines, pyrroles, furans).

(LO4) Students will be able to solve problems featuring functional group interconversions and stereochemistry.

(LO5) Students show engagement and are able to explain their approach to solving unseen problems during tutorials

(S1) The critical thinking and problem solving involved in drawing mechanisms and routes for the synthesis of unfamiliar molecules from given starting compounds (a precursor to retrosynthetic analysis)

Lectures: 30 x 1 hr lectures, plus 1 or more revision lectures at the end of the course.

Tutorials: 5 x 1 hr small-group tutorials, given fortnightly, with students uploading answers beforehand.
Extra problems are then attempted in the tutorial.
There is an extra revision tutorial (1 x 1 hr) which is not assessed.

*Lectures: 31 hours
*Tutorials: 6 hours

The Chapters below refer to "Organic Chemistry" by Clayden et al

Revision of year 1 reactions and concepts.
Synthesis and hydrolysis of acetals, esters, amides, nitriles.
Preparation of alkyl halides from alcohols.
Preparation and reactions of Grignard and organolithium reagents.
Electrophilic additions to alkenes – halides, dihalides, epoxides.
Electrophilic aromatic substitutions.
Cyclohexane conformers.
Orbitals of conjugated and aromatic systems.

Extension of year 1 reactions and concepts.
Nucleophilic substitution at saturated carbon, SN1&2 (Ch 15)
Elimination reactions. E1cb and E1, E2 revision. (Ch 17)
Electrophilic addition to alkenes. Bromination, epoxidation, iodolactonisation. Synthetic applications. (Ch 20)
Synthetically useful reductions including metal hydride reagents, catalytic hydrogenation, and deoxygenation of carbonyl groups. (Ch 23)
Synthetically useful oxidations including chromium (VI) based reagents, Swern and other DMSO systems, Baeyer-Villiger and other per-acid oxidations. (Ch 23)
Enantiomers and diastereoisomers (Ch 14)
Chirality and resolution (Ch 14)

Carbanion chemistry
Acids, bases, enolate anions and other stabilised carbanions: pKas, choosing a base for carbon acids. Reversible and irreversible formation of enolates. (Ch 8,20)
Alkylation of enolate ions and other carbanions: Alkylating agents, direct alkylation with weak bases and LDA. (Ch 25)
Alkylation of enolate ions and other carbanions: Alkylation of 1,3-dicarbonyls, hydrolysis and decarboxylation. Use of enamines and silyl enol ethers. (Ch 25)
Acylation of carbanions: Acylating agents, acylation of ketones with formate and carbonate esters. Acylation of esters with esters.
Acylation of carbanions: Claisen and Dieckmann reactions, acylation of enamines and silyl enol ethers. Acylation using LDA. (Ch 26)
Aldol and related reactions: Self-aldol and mixed aldo ls, Knoevenagel and intramolecular aldol. Lithium and zinc enolates, Reformatsky reaction. (Ch 26)
Conjugate addition reactions: activated alkenes. Selectivity of addition of organometallics and use of organocuprates. (Ch 22)
Conjugate addition reactions: Robinson annelation and dimedone synthesis as routes to 6-membered rings. (Ch 26)

Introduction to aromatic heterocyclic chemistry (ch. 29, 30)
Pyridine: Introduction to aromatic heterocyclic chemistry. Electrophilic aromatic substitution of hydrogen.
Pyridine: Nucleophilic aromatic substitution of hydrogen, Chichibabin reaction. Nucleophilic additions.
Substituted pyridines: Nucleophilic aromatic substitution of halopyridines, reactivity of methylpyridines, hydroxypyridines and aminopyridines, pyridine N-oxides.
Quinolines, isoquinolines and diazines: nucleophilic, electrophilic and addition reactions.
Pyrroles: pKas, electrophilic substitution, regiochemistry, Vilsmeier-Haack and other reactions.< br/>Indoles: Electrophilic substitution, regiochemistry, Mannich reaction.
Furans and thiophenes: Furans: electrophilic and addition reactions, lithiation, other reactions. Thiophenes, reactions, desulfurisation.
Diazoles, triazoles and tetrazoles: pKas and some reactions.
Synthesis of pyridines and pyrimidines: Hantzsch pyridine synthesis, modifications, other methods. Pyrimidines from common reagent combinations.
Synthesis of pyrroles, furans, thiophenes: from 1,4-diketones, Knorr pyrrole synthesis. Diazoles and isoxazoles from 1,3-dicarbonyls and hydrazine or hydroxylamine.
Synthesis of quinolines, isoquinolines, indoles: Friedlander, Skraupp, Bishler-Napieralski, Pomerantz-Fritsch, Reissert, Fischer.