ADVANCED SYNTHESIS IN ORGANIC CHEMISTRY
- Overview
- Assessment methods
- Learning objectives
- Contents
- Full programme
- Bibliography
- Teaching methods
- Contacts/Info
In-depth knowledge of basic organic chemistry, with particular regard to aliphatic and aromatic reactivity. Extensive knowledge concerning the transformation methods of the different functional groups. Fair knowledge of the concepts of retrosynthesis, protection and deprotection of functional groups, asymmetric synthesis, catalytic methods for the generation of new carbon-carbon and carbon-heteroatom bonds
The final exam is based on a written test on the contents of both modules of the course, through open questions and specific questions on some chemical transformations.
In addition, each student will present their own literature research by preparing and illustrating an oral presentation relating to a total summary published in a scientific journal.
The written test generally lasts 2.5-3 hours, while the presentation is briefly limited to 15-20 minutes of illustration and discussion.
In the written test, the level of in-depth study of the course material, the ability to organize knowledge discursively is positively assessed; the rigor and originality of the argument; the capacity for critical reasoning on the study carried out; the depth of the analysis; the quality of the exhibition, the skills in the use of preparatory methods and synthesis of complex organic derivatives, the use of a specialized lexicon, the effectiveness, linearity, feasibility and reproducibility of the proposed solutions.
To pass the written test, the student must achieve a sufficient score (18/30) in the various tests that are organized and spaced within the program.
Passing the written test allows the student to take the oral test in an average period fairly close to the written test, but also in a subsequent appeal, by agreement with the teacher.
The evaluation of the written test has a weight equal to about 80% of the final mark. The oral test also allows you to discuss some aspects of the written test in case clarifications are needed on its performance and provides for a presentation, relating to a total summary chosen by the student. The presentation is also a starting point which can therefore open a possible discussion relating to aspects covered also during the course. The assessment of the oral presentation consists of the remaining 20% of the final grade score.
OBIETTIVI FORMATIVI
Il corso ha lo scopo di fornire agli studenti conoscenze avanzate di sintesi organica comprendenti le metodologie più innovative per la formazione di nuovi legami carbonio-carbonio e carbonio-eteroatomo. La illustrazione di nuove sintesi e di metodologie di preparazione di prodotti a maggiore complessità molecolare sarà ambito di studio dell’intero corso. Saranno particolarmente indagate le sintesi in grado di produrre composti ad elevato valore aggiunto che svolgono un ruolo fondamentale nell’ambito dei derivati biologicamente e farmacologicamente attivi. Particolare attenzione verrà dedicata alla sintesi totale di molecole naturali contenenti un diverso numero di stereocentri investigando quindi tecniche di preparazione di tipo asimmetrico. Il corso prevede inoltre lo svolgimento di alcuni lezioni relative allo studio dei meccanismi di reazione in sintesi organica.
L’insegnamento è organizzato in due moduli
1. Advanced synthesis in organic chemistry part. A
2. Advanced synthesis in organic chemistry part. B
RISULTATI DI APPRENDIMENTO ATTESI
Al termine dell’insegnamento, lo studente sarà in grado di:
1. Comprendere differenti tipologie di reazione che possano essere condotte al fine di osservare processi di ordine chemoselettivo, regioselettivo e stereoselettivo su composti con struttura ad alto valore aggiunto.
2. Analizzare le metodiche sintetiche classificando le differenti tipologie di reazione attraverso differenti chiavi di lettura che implicano oltre ai concetti già espressi di selettività anche le dinamiche legate alle sintesi totali di molecole organiche estremamente complesse di origine naturale
3. Discutere differenti approcci sintetici per la preparazione di derivati ad elevata complessità molecolare
4. Valutare le possibili implicazioni meccanicistiche nell’ambito di una trasformazione organica compiendo uno studio globale sul meccanismo di reazione ipotetico che può essere postulato per una trasformazione di natura complessa e quindi verificato attraverso determinate prove sperimentali
Determination of reaction mechanisms in organic chemistry (8h). Topicality of organic synthesis (4h). Olefination reactions. Metathesis reactions (8h). Approach to the total synthesis (concepts and examples) of natural products and bioactive compounds (8h). New methodologies and new reagents in Organic Synthesis. Reviews and literature on new discoveries and applications in organic synthesis (4h)
Examples of total synthesis of a molecule with different methods (Total Synthesis of Lysergic Acid) (4h). Smart drugs: synthesis and properties (8h). Diastereoselection (Felkin-Ahn model) (6h). Carbocation chemistry (4h). Cyclization rules (Baldwin's rules) (4h). Radical chemistry and carbene and carbenoid chemistry (6h).
Topicality of organic synthesis. Organic synthesis as synergy between different disciplines. Preparation of Indinavir and retrovirals (anti-AIDS drugs and HIV virus). The synthesis of Oseltamivir (anti-flu drugs). Comparisons between different synthetic approaches to the same molecule. The development and future of organic synthesis.
Determination of reaction mechanisms. Types of reaction mechanisms in organic chemistry. Example of a mechanistic study: Cannizzaro's reaction. Structural variations as a characterizing element in the determination of a mechanism. Safety on the structure of the reaction product. Isotopic and non-isotopic marking experiments. Double marking experiments. Crossover experiments. Systematic structural variation. Hammett's report. The constant of Hammett's substituent sigma. The reaction constant: Hammett's rho. Hammett balances and reactions with positive rho values. Reactions with negative values of Hammett's rho. Reactions with small values of Hammett's rho. Use of Hammett's rho values in the discovery of mechanisms. The transition state from Hammett's diagrams. Nonlinear Hammett diagrams. Other kinetic evidence. Kinetic isotopic effect of deuterium. Activation entropy. Specific acid catalysis. Specific basic catalysis. General acid catalysis. General basic catalysis. Detection of reaction intermediates. Trapping reactions. Different reactions with an intermediate municipality. Stereochemistry and mechanism. An example of a study: Ritter's reaction and Beckmann's fragmentation.
Checking the geometry of the double bonds. Properties of alkenes as a function of their geometry. Poor selectivity of elimination reactions. Julia's olefination reaction: connective and regiospecific reaction. Stereospecific eliminations. Peterson's reaction: stereospecificity of the process. Wittig's reaction: transformation of a double bond C = O into a double bond C = C. Use of stabilized ilidia and non-stabilized ilidia. The Horner-Wadsworth-Emmons reaction. E- and Z- alkenes from stereoselective additions to alkynes. Other olefination reactions: Bamford-Stevens-Shapiro, Eschenmoser-Stoltz olefination, Barton-Kellog reaction, Corey-Winter reaction, McMurry olefination, Tebbe reaction, Hiyama-Kishi olefination.
Milestones in the area of total synthesis. New synthetic methodologies emerged in the context of total synthesis in recent years. Discovery of new reactions. Introduction of new reagents. Study of new reactivity.
Total synthesis of natural products and bioactive compounds. Brief history of organic synthesis (from urea to palitoxin). New and old concepts in the field of organic synthesis. Total synthesis of: dragmacidine E, Pactamycin, Aspidophylline A, Tulearin C.
Diastereoselectivity. Diastereoisomers from stereospecific reactions of alkenes. Stereoselective reactions. Prochirality. Diastereoselective additions to carbonyl compounds. Felkin-Anh model. Curtin-Hammett principle. Cram rule. Burgi-Dunitz corner. The effect of chelation reverses stereoselectivity. Stereoselective reactions of acyclic alkenes. Stereoslelective aldol reactions. Zimmermann-Traxler transition state.
Radical reactions and unpaired electrons. Radical initiators. Stable radicals. Reactivity of radical species. ESR or EPR spectroscopy. Radical species stability. McMurry reaction. Acyloinic reaction. Chain reactions. Selectivity in chain reactions. Allylic bromination. Radical substitution of Br with H. Reactions with Bu3SnH and AIBN. Formation of carbon-carbon bonds. Effects of the concentration. Effects of border orbitals. Electrophilic radicals. Copolymerization. Radical processes and polar reactions. Polarization inversion. Hg based radicals. Alkyl radicals from boranes and oxygen. Radical intramolecular reactions.
Synthesis and reactions of carbenes and carbenoids. Use of diazomethane in the synthesis of methyl esters. Photolysis of diazomethane and carbenes. Carbene formation. Types of carbenes: triplet carbenes and singlet carbene
During the course the reference material used during the lesson will be provided. Articles in organic synthesis will also constitute classroom study and analysis material. Each individual topic may also have a different reference text. A basic text of certain interest for the development of some topics turns out to be:
Clayden, Warren, Wothers, Greeves
Organic Chemistry
1st Edition - Oxford University Press
Clayden, Warren, Greeves
Organic Chemistry
2nd Edition - Oxford University Press
Some of the titles listed below are examples of possible reference texts that can be used for some topics:
F.A.Carey, R.J.Sundberg Advanced Organic Chemistry Part B (Reactions and Synthesis) Springer Science 2007, 5th Edition
S. Warren, P. Wyatt - Organic Synthesis: the Disconnection Approach
S. Warren, P. Wyatt - Organic Synthesis: Strategy and Control
E. J. Corey, Xue-Min Cheng - The Logic of Chemical Synthesis
K. C. Nicolaou, E.J. Sorensen - Classics in Total Synthesis
K. C. Nicolaou, S.A. Snyder - Classics in Total Synthesis II
K. C. Nicolaou, J.S. Chen - Classics in Total Synthesis III
T. Hudlicky, J.W. Reed - The Way of Synthesis
K. C. Nicolaou, T. Montagnon - Molecules that changed the world
E.J. Corey, L. Kurti, B. Czako - Molecules and Medicine
M.B. Smith - Organic Synthesis
L. Kurti, B. Czako - Strategic Applications of Named Reactions in Organic Synthesis
The course will consist of a series of lectures on the different topics covered in the program for the duration of approximately 32 hours. During the course, reference will often be made to the current scientific literature so as to be able to frequently correlate the topics carried out with the most recent developments in the field of organic synthesis. A critical comparison of the various publications will therefore illustrate the program carried out with the contemporary and topical nature of the organic synthesis in greater detail.
The teacher is available for further details and clarifications on any requests from students by receiving at his office after contacting by email: andrea.penoni@uninsubria.it or by telephone (031-2386440).