ADVANCED SYNTHESIS IN ORGANIC CHEMISTRY PART. A
- Overview
- Assessment methods
- Learning objectives
- Contents
- Full programme
- Bibliography
- Teaching methods
- Contacts/Info
Deep knowledge of basic organic chemistry, with particular regard to aliphatic and aromatic reactivity. Extensive knowledge concerning the methods of transformation 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 course contents (both part A e part B), through open questions and specific questions on some chemical transformations. In addition, each student will present their own literature search preparing and illustrating an oral presentation, related to a total synthesis 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. The evaluation of the written test is approximately 80% of the final grade. The presentation, together with the possible oral exam, consists of the remaining 20%.
The course aims to provide students with advanced knowledge of organic synthesis including the most innovative methodologies for the formation of new carbon-carbon and new carbon-heteroatom bonds. The illustration of new syntheses and methodologies for the preparation of products with greater molecular complexity will be the subject of study of the entire course. The syntheses used to produce high added value compounds that play a fundamental role in the field of biologically and pharmacologically active derivatives will be particularly investigated. Particular attention will be devoted to the total synthesis of natural molecules containing a different number of stereocenters, thus investigating asymmetric preparation techniques.
Determination of reaction mechanisms in organic chemistry (8h). Actuality 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).
Actuality of organic synthesis. Organic synthesis as a synergy between different disciplines. Preparation of Indinavir and retrovirals (anti-AIDS drugs and HIV). The synthesis of Oseltamivir (anti-influenza drugs). Comparisons between different synthetic approaches to the same molecule. The development and the 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 labeling experiments. Double-marking experiments. Crossover experiments. Systematic structural variation. Hammett's report. The constant of the substituent: sigma of Hammett. The reaction constant: rho of Hammett. Equilibria and reactions with positive values of Hammett's rho. Reactions with negative values of Hammett's rho. Reactions with small Hammett values. Use of Hammett's rho values in the discovery of mechanisms. The transition state from Hammett diagrams. Non-linear 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 a common intermediate. Stereochemistry and mechanism. An example of a study: Ritter's reaction and Beckmann's fragmentation.
Checking the geometry of double bonds. Properties of alkenes depending on their geometry. Poor selectivity of elimination reactions. Julia's olefination reaction: connective and regospecific reaction. Stereospecific eliminations. Peterson's reaction: stereospecificity of the process. The Wittig reaction: transformation of a double bond C=O into a double bond C=C. Use of stabilized ylides and non-stabilized ylides. The Horner-Wadsworth-Emmons reaction. Alkenes E- and Z- from stereoselective additions to alkynes. Other olefination reactions: Bamford-Stevens-Shapiro, Eschenmoser-Stoltz olefination, Barton-Kellogg reaction, Corey-Winter reaction, McMurry olefination, Tebbe reaction, Hiyama-Kishi olefination.
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:Dragmacidin E, Pactamycin, Aspidophylline A, Tulearin C.
Milestones in the context 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.
The reference material used during the course will be provided. Literature articles in organic synthesis will also constitute study material and analysis in the classroom. Each individual topic may also have a different reference text. A basic text of certain interest for the development of some topics is:
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 indicated 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 be articulated through a series of lectures on the different topics covered in the program for a duration of approximately 32 hours. During the course there will be often the possibility to refer to the current scientific literature in order to frequently correlate the arguments developed with the most recent developments in the field of organic synthesis. A critical comparison of the various publications will therefore be able to illustrate with greater detail the program carried out with the contemporaneity and actuality of the organic synthesis.
The lecturer is available to more details and clarifications on any requests made by the students receiving at his office by previous contact via email: andrea.penoni@uninsubria.it or by phone (031-2386440).