ADVANCED ORGANIC CHEMISTRY
Learning outcomes of the course unit
The objective of the course is to provide an overview of the tools to determine reaction mechanisms and to evaluate the correlations between structure and reactivity, together with an in-depth description of the most modern synthetic techniques for the preparation of organic compounds.
It is expected that at the end of the course the students will be able to:
• acquire an understanding of the relationships between structure and chemical properties of organic substrates. To this end, the course will focus on the reaction mechanisms and the generation, structure and reactivity of the most common reactive intermediates (enolates, carbenes, radicals, ...).
• 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.
Course contents summary
Methods of studying organic reactions; structural effects on stability and reactivity; reactive intermediates; synthesis of C-C bond with organometallic compounds; protecting groups in organic synthesis; functional groups interconversion; the literature of organic chemistry.
Tools to determine reaction mechanisms. Kinetics in the study of reaction mechanism. Transition state theory. Kinetic isotopic effect. Substituent effect and linear free energy relationships.
Reactive intermediates: anions and nucleophilic reactions, cations and electrophiles, radicals and carbenes.
Synthetic strategies. Steric factors. Criteria to evaluate synthetic pathways. Application of synthetic methods. Introduction to organometallic reagents for the synthesis of C-C bonds. Synthesis of organometallic reagents through: a) oxidative addition, b) metallation c) metal-halide exchange. Preparation and reaction of organolithium and organomagnesium reagents. Preparation and reaction of organocopper and organocuprate reagents. Preparation and reactions of phosphorous ylids (Wittig reaction). Preparation and reactions of sulphur ylids. Silicon-based reagents for the synthesis of C-C bonds: Peterson’s elimination (synthesis of alkenes). Allyl sylanes as nucleophiles.
Carbon–Carbon Bond Formation using organometallic reagents. The Main-Group Metal: limitation, reactivity of the leaving group, selectivity, steric hindrance, electronic effects. Organolithium and organomagnesium reagents (Kumada Coupling): preparation, scope, limitation and examples. Organozinc reagents (Negishi Reaction): preparation, scope, limitation and examples. Aluminium and Zirconium-based organometallic reagents: preparation, scope, limitation and examples. Organotin reagents (Stille Reaction): preparation, scope, limitation and examples; coupling of Acid Chlorides; coupling of Triﬂates. Organoboron reagents (Suzuki Reaction): preparation, scope, limitation and examples. Organosilicon reagents (Hiyama Reaction): preparation, scope, limitation and examples. Homocoupling reactions. Enolate and Phenoxide Coupling. Buchwald-Hartwig and Ullmann couplings.
Activation of the C-H bond. Introduction and principles. Oxidative Heck reaction or Fujiwara–Moritani reaction. Coupling of biaryl derivatives. Carbonylative coupling reactions: synthesis of ketones and of carboxylic acid derivatives; carbonylation of alkenes and alkynes. The Heck reaction: palladium-catalyzed insertion reaction of alkene and alkyne on arenes.
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, Allylic and Benzylic carbons, oxidation of Ketone α-Carbons. Common reduction reactions and reducing agents; catalytic hydrogenation; hydride Reagents and metals as reducing agents.
Protective Groups: orthogonal sets of protective groups, protection of Alcohols and 1,2- and 1,3-Diols (ether-, ester- and acetal-based protective groups for Alcohols), protection of Mercaptanes, protection of Carboxylic Acids, Protection of Amines (Amide- and Carbamate Protective Groups for Amines).
Chemical Information for Chemists: Organic synthesis using Reaxys and Scifinder.
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.
Richard A. Jackson – Mechanisms in Organic Reactions, Tutorial Chemistry Text nr. 23, Royal Society of Chemistry, 2004
Felix A. Carroll, Perspectives in Structure and Mechanism in Organic Chemistry, 2nd Edition, John Wiley & Sons, 2010
James R. Hanson – Organic Synthetic Methods, Tutorial Chemistry Text nr. 12, Royal Society of Chemistry, 2002
Roderick Bates – Organic Synthesis using Transition Metals, 2nd ed. Wiley 2012
J. R. Hanson - Protective Groups in Organic Synthesis, Postgraduate Chemistry Series, Sheffield Academic Press, Blackwall Science, 1999
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.
Assessment methods and criteria
The demonstration of a basic knowledge of the contents of the course, evaluated through a written test with 7 questions, which includes the mechanisms of the main organic reactions, the kinetics of the reactions, the free energy linear correlations, the use of protecting groups and organometallic compounds in organic synthesis, together with the most common FGI reactions, determine a score of 18-21/30. In the subsequent oral test, carried out immediately after the written test, the student's ability to describe the methods for studying the mechanisms of organic reactions will be evaluated with a score of 21-24/30. The student's ability to deal with the synthesis of simple organic compounds through multistep reactions and using the synthetic methods described in the course results in a score of 24-27/30. An in-depth discussion of the topics determines a score of 27-30/30. 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.