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. Basicity and nucleophilicity. Mayr equation and prediction of organic reactivity. Examples. Classification of nucleophiles and electrophiles. Using the ladder. The (useless) principle of reactivity and selectivity. Chapter 1. pKa and pH scales in different solvents. When does a reaction happen and when it doesn't. Syncline and periplanar. Definitions. Cyclic compounds and conformations.

Chapter 2. Orbital. Review and clarifications. Molecular orbitals. Huckel's method. The energy scale. Frontier orbitals (HOMO and LUMO). How the energy of the orbitals varies with substitution.

Chapter 3. Aromaticity. Definition. Aromatic systems. Huckel's rule. Systems that follow the rule. Systems with 3, 4, 5, 6, 7, 8 and 9 orbitals. Shape and structure of benzene orbitals. The cyclobutadiene. The Cicloottadiene. Nomenclature of aromatic compounds. The aromatic electrophilic substitution and the main reactions (halogenation, nitration, sulfonation, alkylation and acylation). Intermediates, reactivity and mechanism. Retrosynthesis applied to benzene systems. Exercises in retrosynthesis and synthesis. Use of diazonium salts and other reactions. Hexa atomic, penta atomic and condensed heteroaromatic systems. Properties of pyridines. Pyridine reactions. Reactions of furan, thioffene, pyrrole and indole. Notes on other heteroaromatic systems.

Chapter 4 Alkylation of enolates. Kinetic and thermodynamic conditions. pKa. Enolates Z and E. Use of cosolvents. Enamines. Alkylations and enolates. LDA. Mechanism for controlling the geometry of enolates. Michael's reaction Diastereoselective alkylation of enolates. The oxazolidinones. Aldol condensation. Enolates of lithium and boron. Formations of enolates with Lewis acids. Tin enolates. Ketones boron enolates. Zinc enolates. The Reformatsky. Mukaiyama reaction. Silicon enolates. Coordination of Lewis acids to Carbonyls. Acyclic transition states. Examples and exercises.

Chapter 5. Advanced Stereochemistry. Symmetry operation. Necessary and sufficient condition for chirality. Other stereogenic elements. Axes and planes. Absolute configuration in stereogenic axes and planes Topological and mechanical chirality (outline). Nodes, links and chiral graphs.

 

Chapter 6. Protective Groups. Examples and applications. Derivatives of silicon, THP, ethers, benzyl. Unlocking groups. Groups for amines.

Chapter 7. Oxidations and reductions. Oxidants that are used very little (Chromium). Modern oxidation methods. Perrutenate, Dess-Martin, oxidations with TEMPO, oxidation according to Swern and variants. Oxidation from aldehydes to acids. Epoxidation Reduction. Hydrides and their different reactivity. Hydrogenation. Ni-Raney. Reductions with metals. Chelated Cram and Felkin-Ahn rule.

Chapter 8. Retrosynthetic analysis. Introduction to retrosynthesis and the main and simple disconnections. Synthesis and synthetic strategies. Interconversion of functional groups. Disconnections 1-2, 1-3, 1-4. Reactivity unpolung. Chapter 8.1 Retrosynthetic analysis. Guide to the retrosynthesis and reactivity of functional groups. Exercises in the synthesis of molecules and execution of synthetic plans.

Chapter 9. Chemistry of sulfur, silicon, and phosphorus Sulfur, reactivity and oxidation states. pKa in compounds. Thioacetals, dithians, sulfonium salts. Ilidi. Chemistry of silicon. Olefination of Pedersen, Allilsilani. Olefinations according to Julia, Julia-Kocienski, Wittig, Still-Gennari.

Chapter 10. Cycloadditions. Endo rule. Lewis acids. 1-3 dipoles Pericyclic, electrocyclic and sigmatropic reactions. Woodward-Hoffmann rules C.

hapter 11. Radical reactions. Reaction of carbenes. Nitrenes and nitrenoids.

Chapter 12. Organometallic Chemistry (Outline). Metals and oxidation states. The binders. Oxidative addition and reductive elimination. The catalytic cycle. Examples of reactions with transition metals. Electrophilic etching on palladium. Cross coupling reaction and metathesis.

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