66290 - Catalysis in Organic Synthesis

Learning outcomes

At the end of the course, the student is able to interpret, understand and design new catalytic reactions, through the understanding of the coordination geometries of complexes, properties of binders, and catalytic cycles, in stereoselective and non-selective reactions. The student also gains experience on some of the most modern experimental procedures in the field of asymmetric synthesis (catalysis) and in the instrumental resolution of stereoisomeric mixtures of organic compounds.

Course contents

Chapter 1. Introduction to the Mayr scale. The Mayr Staircase. Electrophiles and nucleophiles. Definition and use of the k-speed relation. Examples and discussion.

Chapter 2. Organocatalysis. Introduction and ways of activation. Main organocatalysts and use of the concepts of the Mayr scale for the main organocatalytic reactions. Examples of catalysis via enamine and iminium. Multicomponent organocatalytic reactions (outline). Cinchona alkaloids in organocatalysis. Catalysis via carbenes. Nucleophilic catalysis. Bronsted acid catalysis. Thiouree. ACDC catalysis. Phase transfer catalysis. SOMO catalysis. Fotoredox catalysis, introduction, key concepts and application to organocatalytic reactions.

Chapter 3. Hydrogenations and reductions. Properties of phosphines and important parameters. Classes of Phosphines. employed. Reactions of hydrogenation and mechanism. Chiral phosphines, their use and properties. Hydrogenation of non-functionalized alkenes. Hydrogenation of ketones, imines. Transfer hydrogenation reactions. Use of iron and cobalt in hydrogenations.

Chapter 4. Catalytic oxidation methods. The Katsuki-Jacobsen and the use of M(Salen)X in catalysis.

Chapter 5. Cross coupling reactions (palladium and nickel). Palladium salts. Sources of palladium (0). Pd (I), Pd (II) or Pd (III). Oxidative addition and reductive elimination. Various key points of the catalytic cycle. Differences in reactivity, type of binders and methodologies. Main classes of reactions (examples). Catalysis with Nickel. Photoredox catalysis with nickel. Buckwald-Hartwig reactions. Mechanism of reactions and ligands. Hartwig's phosphines and Buchwald's phosphines. Historical development of the reaction. modern variants. Examples of application of cross coupling reactions in the industrial field.

Chapter 6. Cross coupling reactions with copper (Buchwald-Hartwig and Chan-Lam-Evans). Comparison Copper-Palladium. History. Binders for copper. Modern binders. Buchwald-Hartwig couplings. Mechanism of reactions. Ma ligands. Hartley reaction. Examples of C-N bond formation with copper. The Chan-Lam-Evans reactions.

Chapter 7. BDE and CH activation. REactions of Shilov and Periana. Use of DGs. Mechanisms of C-H activation. Catalytic methods. Use of palladium. PdII / PdIV. C-H activation, direct arylations, and cross coupling. Palladium, Ruthenium and iridium in the C-H activation reactions. Catellani reaction. Use of Nickel. CH actvation with CP * Rh (III). Borylation via CH activation. CH activation via carbenes and carbenoids. Activation with metals such as cobalt, manganese and iron and other metals. Application examples.

Laboratory course Advanced laboratory techniques concerning aspects of asymmetric catalysis. Synthesis of hetero-aromatic polycyclic systems in enantiomerically enriched form through the use of gold-based chiral transition metal complexes. Synthesis of chiral building blocks for the anti-inflammatory preparation, through the use of chiral organ-catalysts. Use of inert gas lines.

 

Readings/Bibliography

Slides of the lessons are provided, commented and numbered.

Teaching methods

Frontal course with transparencies projected in class and commented with the help of interactive screens or blackboard.

Assessment methods

The grade is awarded based on three contributions. Each question is assigned a score (4.5 points, for a maximum of 18 points) and the response is evaluated with an overall grade. Failure to answer a question or an irrelevant answer will not result in a score. Inaccuracies, errors, or gaps in the response will lower the score. The question regarding the laboratory component provides a score, to which a rating of the student's aptitude, participation, and laboratory activity is added, for a total of a maximum of 12 points, evaluated by the instructor conducting the laboratory activity required for the course. A third part of the score is awarded for a report on a total synthesis of a drug assigned by an industry researcher (maximum 6 points). Students are divided into working groups (4-6 people) and have two months to complete this report, with all the literature and patents available for consultation. The use of at least two catalytic methods in the reactions proposed to solve the synthetic problem is mandatory. The presentation is intended to foster discussion and the ability to propose a solution to a complex problem that requires the skills acquired in the course and in previous courses taken by students. The presentation is evaluated by the industry researcher and the instructor, using objective parameters indicated in the problem posed to the students. The final grade is the sum of the scores obtained in the three parts. If the assignment is not considered satisfactory, this is due to gaps in the course content, a failure to answer the question, or inadequate responses. The score assigned for the laboratory practice and the presentation are never insufficient.

If the grade is satisfactory: The assignment received a sufficient score, but there are still gaps in knowledge or topics that were not covered. If the assignment is good, the student has achieved a good understanding of the course content and a good memorization of the subject matter; the student has also successfully addressed and solved the proposed problems, with minor errors. If the grade is excellent, the student, in addition to their skills, is able to present solutions to the proposed problems that are close to or similar to those published by industry researchers; the student has acquired a clear and comprehensive understanding of the topics, a high level of skill in using the various organic synthesis techniques, and broad skills.

The time required for the written exam is 1 hour and 30 minutes.

Students with learning disabilities (LD) or temporary or permanent disabilities: please contact the relevant University office promptly (https://site.unibo.it/studenti-con-disabilita-e-dsa/it). They will be responsible for suggesting any accommodations to the students concerned. However, these accommodations must be submitted to the instructor for approval 15 days in advance, who will evaluate their suitability also in relation to the educational objectives of the course.

Teaching tools

Slides of the course made available by the teacher.

Links to further information

https://site.unibo.it/stereoselective-metal-photoredox-catalysis-lab/en

Office hours

See the website of Pier Giorgio Cozzi

See the website of Marco Bandini