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. Definition of catalysis, its various forms, and effects. Economic importance of catalysis. Areas of catalysis. Important homogeneous processes. Synthesis of fine chemicals through catalysis. Atom economy (TON, TOF): definitions. Energy span. Catalytic cycles and organometallic complexes. Cost of metals. Solvents. Catalytic cycles and solvents. Thermodynamics and kinetics

Chapter 2. Organocatalysis. Introduction and activation modes. Main organocatalysts and use of Mayr scale concepts for the main organocatalytic reactions. Examples of enamine and iminium catalysis. Multicomponent organocatalytic reactions (outline). Cinchona alkaloids in organocatalysis. Catalysis via carbenes. Nucleophilic catalysis. Catalysis by Bronsted acids. Thioureas. ACDC catalysis. Phase transfer catalysis. SOMO catalysis. Photoredox catalysis: introduction, key concepts, and applications to organocatalytic reactions.

Chapter 3. Hydrogenations and reductions. Properties of phosphines and important parameters. Classes of phosphines used. Hydrogenation reactions and mechanisms. Chiral phosphines, their uses and properties. Hydrogenation of nonfunctionalized alkenes. Hydrogenation of ketones and imines. Transfer hydrogenation reactions.

Chapter 4. Catalytic reactions. Hydroformylations, carbonylations, oligomerizations, metathesis, telomerizations, oxidations, aminations, hydrofunctionalizations. Oxidations: Jacobsen oxidation, Salens oxidation, use of Co(Salen) in the kinetic resolution of epoxides.

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, ligand type, and methodologies. Main reaction classes (examples). Nickel catalysis. Photoredox catalysis with nickel. Buckwald-Hartwig reactions. Reaction mechanism and ligands. Hartwig phosphines and Buchwald phosphines. Historical development of the reaction. Modern variants. Examples of industrial applications of cross-coupling reactions.

Chapter 6. Cross-coupling reactions with copper (Buchwald-Hartwig and Chan-Lam-Evans). Comparison of copper and palladium. History. Ligands for copper. Modern ligands. Buchwald-Hartwig couplings. Reaction mechanism. Ma ligands. Hartley reaction. Examples of C-N bond formation with copper. Chan-Lam-Evans reactions.

Chapter 7. BDE and CH activation. 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 C-H activation reactions. Catellani reaction. Use of nickel. CH activation with CP*Rh(III). Borylation via CH activation. CH activation via carbenes and carbenoids. Application examples. Laboratory course Advanced laboratory techniques related to aspects of asymmetric catalysis. Synthesis of polycyclic hetero-aromatic systems in enantiomerically enriched form using chiral gold-based transition metal complexes. Synthesis of chiral building blocks for the preparation of anti-inflammatory drugs using chiral organocatalysts. 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

Course materials provided by the instructor. Slide notes prepared by the instructor. Miscellaneous articles

Exam essays from previous years

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