Learning objectives
The course aims to provide an in-depth discussion of the use of protecting groups, the transformation of functional groups and the most important methods of synthesis of organic compounds, including those using organometallic compounds.
It is expected that at the end of the course the students will be able to:
• acquire a knowledge of the most modern and advanced organic synthesis strategies. To this end, the course aims to provide an in-depth discussion of synthetic methods involving the use of organometallic reagents in carbon-carbon binding synthesis, the use of protecting groups and the use of oxidation and reduction reactions for the transformation of functional groups.
• find important chemical information by consulting on-line databases.
• communicate chemical / scientific problems in written and verbal form;
• support a contradictory on the basis of a judgment developed independently on issues related to their studies.
Prerequisites
n/a
Course unit content
Advanced methods for the synthesis of organic compounds; use of protecting groups in organic synthesis; transformation of functional groups; use of organometallic compounds in organic synthesis; palladium-catalyzed reactions in organic synthesis; synthesis of double and triple carbon-carbon bonds; multi-step synthesis of organic compounds.
Full programme
Synthetic design. Retrosynthetic analysis, carbonyl umpolung, steps in planning a synthesis and choice of the synthetic method.
Stereochemical considerations. Conformational analysis, evaluation of non-bonded interactions, six-membered cyclic systems and cyclohexyl systems with sp2-hybridized atoms. Significant energy difference. Reactivity and product determination as a function of the conformation.
Protecting groups. Concept of orthogonality in protecting groups. Protection of alcohols and 1,2- and 1,3-diols; protection of carbonyl compounds; amine protection; thiol protection.
Transformation of functional groups. Oxidation and reduction reactions: overview, effect of heteroatoms on the oxidation state of carbon; common oxidation reactions and oxidizing agents. Oxidation of alcohols, diols, aldehydes, ketones, alkenes, alkynes, allyl carbons and benzyls, oxidation of ketones α-carbons. Common reduction reactions and reducing agents; catalytic hydrogenation; hydrides and metals as reducing agents.
Carbon-carbon bond formation using organometallic reagents. Grignard reagents, organolithium, organotitanium, organocerium, organocopper, organozinc, organoboron, organosilicon and organogold reagents.
Palladium-catalyzed carbon-carbon bond formation reactions: compatibility with functional groups, leaving group reactivity, selectivity, steric and electronic effects. Organolithium and organomagnesium reagents (Kumada reaction); organozinc reagents (Negishi reaction); organometallic reagents based on aluminum and zirconium; organotin reagents (Stille reaction); organoboron reagents (Suzuki reaction); organosilicon reagents (Hiyama reaction). Homocoupling reactions; coupling of enolates and phenoxides. Reaction of Buchwald-Hartwig and Ullmann coupling. Activation of the C-H bond. Reaction of Fujiwara-Moritani. Coupling of biaryl derivatives. Carbonyl coupling reactions: synthesis of ketones and carboxylic acid derivatives; carbonylation of alkenes and alkynes. The Heck reaction: reaction of insertion of alkenes and alkynes on arenas catalysed by palladium.
Unsaturated carbon-carbon bond formation. Formation of double bonds: reactions of phosphorus ilides (Wittig reaction, hints) and sulfur. Peterson elimination. Allyl silanes as nucleophiles. Formation of triple carbon-carbon bonds.
Introduction to multi-step reactions applied to the synthesis of compounds of pharmacological interest.
Bibliography
Lecture notes by the Professor, examples of exercises and cases of study proposed during the examination. All this material is available at the website on Elly platform from the beginning of the course. It constitutes the main support for the preparation of the exam.
Suggested readings:
• George S. Zweifel, Michael H. Nantz, Peter Somfai – Modern Organic Synthesis, An Introduction 2nd Ed., Wiley, 2017, ISBN: 9781119086536
• Michael Smith – Organic Synthesis, 4th Ed., Academic Press, 2016, ISBN: 9780128007204
Teaching methods
The format of the class will be lectures of two hours each spread over two days per week A regular class meetings will be composed of lecture and class exercises.
The lectures will be held in the classroom
Assessment methods and criteria
The demonstration of a basic knowledge of the contents of the course, evaluated through a written test with 4 questions, one of these focused on completing a synthetic sequence problem and includes the use of protecting groups and organometallic compounds in organic synthesis, together with the most common FGI reactions, determine a score of 18-25/30. The ability of the student to tackle the synthesis of organic compounds making use of the concepts learnt during the course and the ability to develop a critial approach to the synthetic problem determines a score of 29-30/30. Comprehensive and exhaustive answers given with the use of an approriate language and the ability to deal with new problems and applications determine the evaluation with honors.
Other information
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2030 agenda goals for sustainable development
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