69080 - Organic Chemistry II

Learning outcomes

At the end of the module, the student knows how to use structure-reactivity correlations to predict the behavior of organic and multifunctional molecules; knows the mechanistic bases of reactivity; is able to offer a short multistage synthesis of a simple organic molecule; knows the structure and properties of the most important classes of natural organic substances.

Course contents

Chapter 1. The Mayr scale

Definitions of nucleophile, electrophile, nucleofuge and electrofuge. Basicity and nucleophilicity. Mayr equation and prediction of organic reactivity. Examples. Classification of nucleophiles and electrophiles. Use of the ladder. The (useless) principle of reactivity and selectivity. Introduction to bidentate nucleophiles.

Chapter 2. Atomic orbitals, molecular orbitals, hybrid orbitals. Review and clarifications. Huckel's method, semiempirical methods and meaning. The energy scale. Frontier orbitals and perturbation method (outline). HOMO and LUMO in simple organic systems.

Chapter 3. Aromaticity. Definition. Huckel's rule. Systems that follow the rule. Systems with 3, 4, 5, 6, 7, 8 and 9 orbitals. Form and structure of benzene orbitals. Cyclobutadiene. The Cyclooctadiene.

Hex atomic hexa atomic, penta atomic and condensed systems. The annuleni. Cyclic loaded systems. Benzene condensed systems.

Different nucleophilicity of aromatic and heteroaromatic systems. Look at the Mayr scale. Nomenclature of arenic systems (Cenni).

Systems replaced and with more substituents. Systems with two substituents. Garden, meta and para nomenclature.

The electrophilic aromatic substitution. Intermediates, conditions, reactivity.

Regiochemistry of substitution in substituted arenic systems.

Reactions in activating and deactivating. Reactions on aromatic systems: nitration, sulfonation, halogenation, bromination, iodination. Friedel-Crafts' reactions. Formations, hydroalkylations. Acylation

Aromatic reactions. Schedule the summary and choose the conditions. Reactions and conditions with deactivators. The different orientation of aromatic electrophilic substitution. CHimcia of the nitro group. Lewis acids and alcohol reactions. Aromatic nuleophilic substitution. Benzine and its reactions.

Reaction of hexatomic and pentaatomic heterocyclic systems (outline).

Useful reactions for heterocycles. Vielsmeier, Mannich. Deprotonation of heterocycles.

Benzosubstituted systems. The indole.

Examples of heterocycle synthesis (outline).

Chapter 2

Alkylation of enolates. Kinetic and thermodynamic conditions. pKa. Enolates Z and E. Use of co-solvents. Enamines. Alkylations and enolates. LDA. Mechanism for checking the geometry of the enolates. Michael's reaction

Diastereoselective alkylation of enolates. Oxazolidinones. Myers' auxiliary.

Aldol condensation. Lithium and boron enolates.

Enolate formations with Lewis acids. Enolates of Tin and Titanium.

Enolated with boron of ketones. Zinc enolates. The Reformatsky.

Mukaiyama reaction. Silicon enolates. Coordination of Lewis acids to Carbonyls. Acyclic transition states. Examples

Chapter 3. Advanced stereochemistry.

Symmetry operation. Necessary and sufficient condition for chirality. Other stereogenic elements. Axes and planes. Absolute configuration in axes and stereogenic planes

Topological and mechanical chirality (outline). Knots, links and chiral graphs.

Chapter 4. Protective groups. Examples and applications. Silicon, THP, ether, benzyl derivatives. Unlocking groups. Groups for amines.

Chapter 5. Oxidations and reductions. Very little oxidizers used (Chromium). Modern oxidation methods. Perrutenate, Dess-Martin, oxidations with TIME, oxidation according to Swern and variants.

Oxidation from aldehydes to acids. Epoxidation

Reduction. Hydrides and their different reactivity. Hydrogenation. Ni-Raney. Reductions with metals

Chapter 5. Retrosynthetic analysis. Introduction to retrosynthesis and the main and simple disconnections. Tunings and synthetic strategies. Interconversion of functional groups. Disconnections 1-2, 1-3, 1-4. Unpolung reactivity

Chapter 6. Sulfur, silicon, and phosphorus chemistry

Sulfur, reactivity and oxidation states. pKa in compounds. Thioacetals, ditians, sulfonium salts. Ilidi.

Silicon chemistry. Olefination of Pedersen, Allilsilani. Olefinazioni secono Julia, Julia-Kocienski, Wittig, Still-Gennari

Chapter 7. Cycloadditions. Endo rule. Lewis acids. 1-3 dipolar

Pericyclic, electrocyclic and sigmatropic reactions. Woodward-Hoffmann rules

Chapter 8. Radical reactions. Carbene reaction. Nitrenes and nitrenoids.

Chapter 9. Organometallic Chemistry (Outline). Metals and oxidation states. The ligands. Oxidative addition and reductive elimination. The catalytic cycle. Examples of reactions with transition metals. Electrophilic attack to palladium. Cross coupling and metathesis reaction.

Readings/Bibliography

Course lecture notes provided by the teacher and course slides provided by the teacher.

Teaching methods

Lessons with power point and overhead projector with comments on transparencies.

Discussion of groups of retrosynthesis students. disconnections, analysis of synthetic strategies with TEAMS or ZOOM.

Assessment methods

Written test. 2 hours.

Questions (2 x 3 points);

1 exercise mechanism (3 points);

1exercise of synthesis methodologies (intermediate, 3 points);

2 reaction exercises, 2 x 3 points);

two synthesis exercises (2 x 6 points). Total 30 points + 5/7 starting points = 35/37 points.

Score for praise 32 points.

Teaching tools

Use in Reaxys or WOS TEAMS or ZOOM sessions for retrosynthetic analysis. Use of Merck, TCI, STREM catalogs to search for starting products for syntheses.

Office hours

See the website of Pier Giorgio Cozzi