Ateneo - UPO

ORGANIC CHEMISTRY 2 module:
This course completes the teaching of Organic Chemistry program that is given to students of the degree course in Chemistry. It aims to complete the acquisition of the fundamental knowledge of the subject. In particular, with this course the student is introduced to the chemistry of organic compounds and synthetic strategies that were not covered in the first basic course.
Laboratory module:
Provide the student with the basic operations of synthetic organic chemistry. See “Programma esteso” (Extended Program) for more detailed information.

ORGANIC CHEMISTRY 2 module:
1) J. Clayden, N. Greeves, S. Warren, “Organic Chemistry”, 2nd Edition, Oxford University Press 2012 (ISBN 978-0-19-927029-3); 2) P.Y.Bruice, “Organic Chemistry”, EdiSES; 3) B. Botta, “Organic Chemistry”, Ed. Edi.Ermes, Milano (ISBN 9788870513271).
More detailed study: S. Warren, “Organic synthesis: the disconnection approach”, Wiley (ISBN 0471101613).
For exercises: 1) T.W. Solomons e altri, “La chimica organica attraverso gli esercizi”, Zanichelli 2) M.V. D’Auria, “Guida ragionata allo svolgimento di esercizi di chimica organica”, Loghia. The slides used during the course will be available through DiR.
Laboratory Module:
Carey, Sundberg, "Advanced Organic Chemistry", Plenum Press ed.
Clayden and al. "Organic Chemistry" Oxford University Press ed.

ORGANIC CHEMISTRY 2 module:
The course integrates with that of Organic Chemistry I, examining classes of reactions, organic compounds and synthetic strategies that have not been previously treated. Students will also acquire knowledge on the fundamental principles of organic synthesis and the ability to develop simple synthetic sequences of polyfunctional organic compounds and to apply the principles of modern synthetic strategies: approaches for disconnection, formation of carbon-carbon bonds, organometallic, protection/deprotection of functional groups. The student must also acquire the ability to understand and critically discuss the mechanism of reactions and the methodologies used. The student must demonstrate the ability to learn and autonomy in drawing conclusions as well as communication skills: the student must be able to achieve and communicate the results of a short bibliographic research carried out independently through the use of databases and scientific texts in the departmental library and expose it appropriately with the correct terminology.
Laboratory Module:
Comprehension skills: knowledge of the basic reactions of synthetic organic chemistry. Ability to work in an organic chemistry lab. Strictness in the scientific work.
Applying the knowledge: to be able to properly fill in the laboratory notebook. Critical comprehension of the observed behaviour of the chemical reactions performed in the lab.

ORGANIC CHEMISTRY 2 module:
Prerequisites of the course are the basics of organic chemistry acquired in the course of Organic Chemistry I. In particular: nomenclature of organic compounds and functional groups. Stereochemistry and chirality. Electronic delocalization. Acidity and basicity. Electrophilic addition to alkenes, nucleophilic substitution and elimination reactions. Electrophilic and nucleophilic aromatic substitution reactions. Carbonyl addition reactions and acyl nucleophilic substitution reactions.
Laboratory Module:
Organic Chemistry I and its Laboratory.

ORGANIC CHEMISTRY 2 module:
Lectures are scheduled for 48 hours. Discussion with students on the theoretical aspects will be privileged in order to bring out any foreknowledge of the topics covered and develop communication skills by using the appropriate lexicon. During the lessons, a part is always dedicated to the collegial solution of appropriately selected exercises to apply the theoretical concepts learned and stimulate the autonomy of judgment through comparison. However, all electronic files shown during the lessons will be provided to the students.
Laboratory Module:
The course features a series of laboratory experiences, where the students are divided in groups of two. At the beginning, the teacher will provide a written trace of the reaction to be performed. The information given is essential, and the pupils shall themselves find out the mechanism and the expected products of the reaction. The students will discuss among them the above issues, and at the end, one of them will come to the blackboard to explain the reaction details, in agreement with the knowledge acquired in the previous courses of organic chemistry (1 and 2). After the end of each reaction, the students will illustrate the development of the reaction itself, in particular if it yielded the expected products or not, and in the latter case trying to understand the reasons why. At the end of the lab, the students must carry out a bibliographic search about a historically significant reaction of organic chemistry. The pupils are taught how to correctly do such a research: trying to understand the innovative meaning of the reaction, as well as the limits and the application field of the novel method.

ORGANIC CHEMISTRY 2 module:
There will be also 14 extra hours of exercises as supplementary teaching in which exercises will be carried out by the teacher to facilitate the understanding and assimilation of the topics covered in the theoretical lessons and to guide students in preparing for the exam.
Ongoing learning is monitored by solving exercises on organic synthesis carried out in the classroom individually or collectively in order to stimulate preparation and to evaluate progress. At the end of the course a written test is carried out with exercises that cover the entire program, then corrected and commented with the teacher.
Laboratory Module:
The learning is checked at the beginning of each laboratory session: a student is called to the blackboard and asked to explain in detail the reaction of the previous day, highlighting the key steps, the mechanism and the results obtained. The discussion is collective: the other students are required to participate to the discussion.
Students with physical disabilities, Learning Disabilities or Special Education Needs can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e ale/gli studentesse/studenti, consulting the University webpage: https://www.uniupo.it/en/services/servicesstudents-physical-or-learning-disabilities
Students with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the tutor in charge of the course to define the examination modalities, concerning academic aspects.

ORGANIC CHEMISTRY 2 module:
The written exam consists of 10 exercises on reactivity covering the whole program divided into four types: 1) identification of the products starting from the reagents; 2) identify the reagents in a synthetic sequence; 3) formulate the mechanism of a reaction; 4) retrosynthetic analysis of a short synthesis. Within these 10 exercises the first 3 have score 1, the following 4 score 3 and the remaining 3 score 5.
If the written test is successfully passed, the student will face the oral exam which is designed to confirm his knowledge of the subject, the autonomy of judgment and the ability to communicate effectively and with the correct terminology. Sufficiency is achieved by demonstrating having acquired the fundamental theoretical bases and knowing how to apply them to the solution of simpler synthesis problems (points 1 and 2) and having an appropriate lexicon. Excellence can be achieved by demonstrating outstanding skills in solving complex synthesis problems and knowing reaction mechanisms (points 3 and 4).
Laboratory Module:
At the end of the course, the students shall bring the lab notebook to the teacher, correctly compiled for every experience carried out.
The examination will feature at least three open questions concerning the reactions performed in the lab, as to evaluate the students' communication skills, and both her/his theoretical and practical knowledge.
In addition, each of them has to perform a bibliographic search upon a historically significant reaction of organic chemistry.
The final grade will be formulated in a collegial way starting from the weighted average of the grades of the theoretical and laboratory course, considering the ability of the student to have assimilated the concepts of the two modules and to be able to apply the theoretical knowledge acquired.

ORGANIC CHEMISTRY 2 module:
1) MOLECULAR ORBITALS, CHEMO- and REGIOSELECTIVITY - PROTECTING GROUPS
Introduction to the course. Molecular orbitals applied to the reactivity of organic molecules. HOMO and LUMO. Chemoselectivity in reduction and oxidation reactions. Use of borane, DIBAL; hydrogenolysis reaction; reductions with dissolved metal; Birch reduction. Oxidations with Dess Martin periodinane; Swern oxidation; oxidation of allyl and benzyl alcohols. Kinetic and thermodynamic control of reactions. Intramolecular reactions. E1cB elimination. Chemoselectivity of dianions. Protective groups of amines, carboxylic acids, alcohols and carbonyls. Orthogonality of the protector groups. Protection and deprotection reactions.
2) ENOLS, ENOLATES, CONJUGATED ADDITIONS and CONDENSATIONS
Enols and enolates. Enolates of carbonyl compounds and derivatives of carboxylic acids. Aza-enolates. Enolate ion reactivity and alpha-halogenation. Nature of the base and regioselectivity in the formation of enolate ions. Enol ethers and silyl enol ethers. Alkylation of enolates. Alkylation of aldehydes using enamines. Alkylation of aldehydes through enamines and azaenolates. Alkylation of beta-dicarbonyl compounds and decarboxylation. Kinetic and thermodynamic control in the formation and alkylation of enolates. Alpha-beta-unsaturated compounds: Michael addition and direct addition. Molecular orbitals and reactivity. Factors influencing Michael's reaction. Hard and soft nucleophiles. Conjugated substitution reaction. Michael acceptors and Michael donors. Enolated from dicarbonyl compounds as donors. Enols, enamines, silyl enol ethers and nitrocompounds as Michael donors. Darsen and Henry reactions.
Aldolic cross-condensation: use of enolic equivalents (lithium enolates, silyl enol ethers, aza-enolates). Reactions of Cannizzaro, Mannich, Knoevenagel, Reformatski. Intramolecular aldolic reaction and Robinson ringing. Claisen condensation: direct and cross condensation. Non-enolizable reactive esters. Acylation. Dieckmann condensation.
3) REAGENTS WITH PHOSPHORUS, SULFUR, SILICON
Wittig reaction. Phosphonium ylids. Stereoselectivity. Use of phosphonium or alkyl phosphonates as enol equivalents in condensation reactions. Sulfonium and sulphoxonium ylids.
Peterson and Julia olefination reactions. E / Z stereoselectivity.
Sulfur and its compounds (structure and reactivity). Carbanion stabilization. Thioacetal. Ditianes and their use as equivalent acylanions. Hydrolysis and desulphurization of dithianes. Sulphinate anions and sulfones. Stabilization of carbocations adjacent to sulfur and participation in beta to sulfur. Nulcleophilic addition of bisulfite.
4) CYCLOADDITION and CARBENES REACTIONS
Diels Alder reaction. Dienes and Dienophiles. Stereochemistry of Diels Alder's reactions. Endo rule. Kinetic and thermodynamic product of the Diels Alder reaction. Approach with molecular orbitals. Influence of solvent and catalysis with Lewis acids. Intramolecular reactions. Regioselectivity in Diels Alder's reactions. Diels Alder's reaction to reverse electronic demand. Alder-ene and carbonyl-ene reactions. Cycloadditions [2 + 2] by photochemistry.
Diazomethane. Carbenes: structure, preparation and reactivity. Synthesis of cyclopropanes. Simmons Smith reaction. Insertion of carbenes in C-H and O (N) -H bonds.
Reaction of metathesis of alkenes. Ring closing metathesis. Catalysts and examples.
5) ORGANOMETALLIC REAGENTS AND CROSS-COUPLING REACTIONS
Introduction to organometallic chemistry. Synthesis of organometallic reagents by oxidative addition, transmetallation and metal-halogen exchange. Synthesis of organometallic reagents by deprotonation of alkynes or cyclopentadiene. Preparation and reactivity of benzyne. Use of organometallic reagents in SN2 reactions, epoxides and with carbonyls. Dialkylcuprates and their reactivity.
Rule of 18 electrons and types of ligands. Hapticity. Counting electrons in an organometallic complex. Oxidative addition. Reductive elimination. Insertion of ligand / migratory insertion. Carbonylation. Beta elimination. Palladium, reactivity and complexes of Pd(0) and Pd(II). In situ reduction of Pd(II) to Pd(0).
Heck reaction. Catalytic cycle. Regioselectivity and stereochemistry of Heck's reactions. Cross-coupling reactions. Generic catalytic cycle. Stille's reaction. Suzuki reaction. Catalytic cycle and boron activation. Examples for the formation of biaryls, dienes and arylalkenes. Negishi reaction. Sonogashira reaction.
Nucleophilic substitution on allyl systems and regioselectivity. Activation of allyl systems with Pd(0). Reactions with vinyl-epoxides and allyl carbonates. Buchwald and Hartwig reaction. Nucleophilic attack on alkenes mediated by Pd(II). Wacker oxidation.
6) RETROSYNTHESIS
Retrosynthetic approach. Definitions and examples of synthons and reagents. Retrosynthetic analysis of aromatic derivatives using electrophilic and nucleophilic substitutions. Retrosynthetic analysis with examples: C-C 1,1 disconnections; 1,2; 1,3; alpha-beta disconnection; disconnection of Mannich and Claisen. Disconnection 1,5. "Natural" reactivity and umpolung. Difunctional compounds 1,2. Strategies for multifunctional compounds 1,4. List of most common synthons.
Laboratory Module:
Aldol condensation: auto-condensation of a methylketon under both acidic and basic conditions; crossed condensation of a keton and a non-enolizable aldehyde. Additions to carbonyl: preparation of a Grignard reagent and its addition to an aldehyde (Wittig). Electrophilic aromatic substitutions: synthesis of crataegon. Elimination reactions (E1): synthesis of an olefin starting from a tertiary alcohol.
How to fill in the laboratory notebook.
How to browse the on-line scientific literature, and how to carry out the study case (literature search).

ORGANIC CHEMISTRY 2 module:
Knowledge and understanding: 1) in depth knowledge of the structure-reactivity relationship in poly-functional organic compounds 2) knowledge of the principles that drive organic reactions and that allow to interpret the mechanisms.
Ability to apply knowledge and understanding: 1) to be able to describe the reaction mechanisms in poly-functional organic molecules 2) to be able to classify organic transformations based on the interactions between the different functional groups present in an organic molecule 3) to be able to describe the design of a simple synthetic sequence.
Autonomy of judgment: 1) propose synthetic strategies with particular regard to the protection/deprotection of functional groups; 2) ability to easily cope with a simple retrosynthetic analysis.
Communication skills: 1) to be able to clearly describe the use of the various notions learned in the course with appropriate scientific language; 2) to be able to clearly expose the reaction mechanisms in an appropriate language.
Learning skills: 1) demonstrate the ability to find and apply new information needed to design the synthesis of organic molecules both directly and via retrosynthesis.
Laboratory Module:
1. Knowledge and comprehension skills: the understanding of the basic reactions of synthetic organic chemistry is the main goal of this course. Moreover, both the theoretical, and the practical knowledge of how to operate in an organic lab, are required.
2. Ability to apply one's own comprehension and knowledge:
the student will have to demonstrate her/his knowledge of the basic reactions of synthetic organic chemistry, and in addition, to be able to apply the the acquired knowledge to lab operativity.
The student shall also be able to apply the above theoretical learnings to everyday laboratory practice. Hence, it is expected that he/she will be able to operate autonomously in the organic laboratory. Finally, the ability to fill in the lab notebook is requested.
3. Communication skills: the student will have to carry out the bibliographic search autonomously, demonstrating a correct exposition of the bibliographic search, demonstrating to possess an adequate scientific language.
4. Judgement ability: the pupil shall know how to discriminate among apparently equal synthetic pathways, thus showing a deep comprehension of the investigated reaction.
5. Learning abilities: they will be evaluated as the to face autonomously the study case (i.e., the bibliographic search).