66290 - Catalysis in Organic Synthesis

Learning outcomes

The course gives a complete and updated overview of the modern tecniques in catalysis. Coordination geometry, properties of ligands and catalytic cycles will be examined from a point of view of the most important reactions applied in organic synthesis. The student will aquire a considerable knowledge on teh modern catalytic reactions and their applications in different contests, such as total syntehsis, syntehsis of drug and intermediates. Emphasis will be given towards green methodologies, nont exepensive and abudant metals, and modern tecniques.

Course contents

Introduction to catalysis. Catalytic cycles. The rate determing step: Does it Exist? Problems in the definition of TOF and TON. Aspects of a catalytic cycle. The Mayr Scale. Electrophiles and nucleophiles. Definition and use of the k rate costant following Mayr. Organocatalysis. Introduction. Activation modes. Main organocatalysts. Use of Mayr's concepts for major organocatalytic reactions. Examples of enamine and imminium catalysis. Multi-component organo-catalytic reactions (few notes). Cinchona alcaloids in organocatalysis. Catalysis via carbenes. Hydroacylations. The Stetter reaction. Catalysis nucleophilic. Catalyst from Bronsted acids. Thioureas. ACDC catalysis. Alchilation of enolates and enamines. Catalysis SOMO. Fotoredox catalysis. Catalytic hydrogenation. Phosphines and their properties. Carbenes Ligands. Complexes of rhodium, iridium and ruthenium. Catalytic cycles. Hydrogenation of ketones. Transfer idrogenation. Hydrogenation of dienes, amides, esters, nitriles. Use of iron and cobalt in hydrogen. The Corey-Batski-Shibata. Hydrosilylation. Use phosphine copper in hydrogenation. Palladium salts. Sources of palladium (0). Pd (I), Pd (II) or Pd (III)? Oxidative addition and reductive elimination. Several key points of the catalytic cycle. Complexes of carbenes. PEPSI ligands. Cross coupling reactions. Mechanism of various reactions (Stille, Negishi, Suzuki, Kumada, etc.). Detailed examination of Suzuki's reaction. Cross-coupling of enolates. Nickel in cross coupling. Photoredox catalysis and nickel. Other metals in the cross-coupling reaction. Use of modern ligands. Buckwald-Hartwig's Reactions. Mechanism of reactions and ligands. Hartwig phosphines and Buchwald phosphines. Historical course of the reaction. Modern variants. Examples of cross-coupling reactions in the industrial field. Copper in cross-coupling reactions. Ligands and mechanism of reactions. Chan -Evans- Lam coupling. Examples with Cobalt and Iron in C-X cross-coupling reactions. The direct activation of the CH bond and cross coupling. Various metals. Palladio, Rodio. Ruthenium. Iridium. Catellani's reaction. Activation with cobalt, manganese and iron metals. Buchwald-Hartwig with CH activation. Metathesis. Introduction. Carbene Complexes of Molybdenum and Ruthenium and properties. The metathesis. Methates of alchene and alkynes. Use of chiral complexes in catalysis. Stereoselective metathesis. Z-metathesis control with molybdenum and ruthenium catalysts. Non-linear effects in catalysis. Model ML2. Examples and applications. The reservoir effect.

Laboratory course

Advanced laboratory techniques inherent in aspects of asymmetric catalysis. Synthesis of heterogeneous polycyclic systems enantiomerically enriched by the use of chiral transition metal complexes. Synthesis of chiral building blocks for anti-inflammatory preparations, using chiral organo-catalysts. Use of inert gas lines

Readings/Bibliography

SLides and material given by the teacher

Teaching methods

Frontal lessons. Discussion and exercises on material during lessons.

Assessment methods

Written exam with five questions and one bonus questions.

The five questions are taken by a list of 200 questions distributed at the end of the course.

Score.

Catalysis Exam Score 20 Exam Points (5 questions x 4 points). 10 points to the laboratory report. 4 bonus points (question NOT inserted in the list)

ASSESSMENT METHODS

Preparatory of a laboratory report.

Teaching tools

Power point slides available. Notes and literature given. Discussion on article published on line.

Office hours

See the website of Pier Giorgio Cozzi

See the website of Marco Bandini