ORGANIC CHEMISTRY II
Learning outcomes of the course unit
At the end of the course the student is expected to be able to:
1. Knowledge and understanding.
1a. To recognize the main functional groups within complex molecules.
1b. To recognize nomenclature, structure and reactivity of the main classes of organic compounds, be they linear, cyclic, heterocyclic, or fused bicycles.
1c. To explain and appropriately exemplify the principles that guide the main organic reactions and allow the rational interpretation of reaction mechanisms.
2. Applied Knowledge and Understanding.
2a. To implement the theoretical knowledge acquired to solve simple problems.
2b. To predict the outcome of chemical transformations.
2c. To critically address the design of a credible synthetic plan to access simple molecules.
3. Communication and Learning Skills.
3a. To communicate in a clear way and with appropriate technical language conclusions and knowledge to specialist and non-specialist interlocutors, in accordance with the training objectives described above.
4. Making Judgements.
4a. To evaluate in a critical way a synthetic strategy aimed at obtaining a polyfunctionalized molecule of small dimensions.
5. Ability to Learn.
5a. To communicate the results of empirical research through the drafting of a critical research report.
The Course of Organic Chemistry II provides the good acquisition of all the topics covered during Organic Chemistry I and in particular:
1. Molecular electronic configuration: atomic orbitals, molecular orbitals and hybrid orbitals.
2. Structure and hybridization of carbon chains.
3. Conformational and configurational analysis of carbon chains.
4. Acid-base equilibria.
5. Nucleophiles and electrophiles.
6. Main classes of chemical reactions: addition, substitution, redox.
7. Structure and nomenclature of the main classes of functional groups treated during Organic Chemistry I.
8. Inductive effects and resonance effects.
NB: Passing the final examination of Organic Chemistry I is mandatory in order to attend the examination but NOT the lessons of Organic Chemistry II. That said, in order to better understand and follow the lessons of the course, it is important that the concepts listed above have been studied and understood by the student, even if the Organic Chemistry I exam has not yet been passed and/or taken.
Course contents summary
The course, divided into several phases, will deal with the chemistry of the main classes of organic compounds not covered in the Organic Chemistry I course, which can be traced back to three main areas:
1. reactivity of carbanions;
2. reactivity of carbocations;
3. pericyclic reactions.
Emphasis will be given to the problems related to the formation of new carbon-carbon bonds, formation and manipulation of functional groups, protections and deprotections in complex systems. Total synthesis methodologies, retro-synthetic analysis of simple targets and possible disconnections will be treated in parallel with the above-mentioned topics.
1. CARBANION REACTIVITY (2 CFU)
1a. Carbanions: structure, synthesis and reactivity
1b. Enols and enolates; keto-enolic tautomer; acidity and basicity of enolizable compounds.
1c. Enolization catalyzed by acids and bases; metal enolates; ammonium enolates; silicon stabilized enolates; kinetic enolates vs. thermodynamic enolates; control of the Z/E geometry of an enolate; non-carbonylic enolates; ilids.
1d. The Aldol reaction: the "classical" acidic and base-catalyzed aldol reaction; the cross aldol reaction; Mukaiyama variant; intramolecular aldol reaction; Henry's reaction; Nef's reaction. Reaction of Knovenagel.
1e. Mannich reaction: imine and imminium ions; direct and indirect Mannich reaction; Pictet-Spengler reaction.
1f. Conjugated addition reactions: organocuprates, inter- and intramolecular Michael reaction; Bayliss-Hillman reaction; Robinson annulation.
1g. Claisen and Dieckmann Reactions.
2. PRINCIPLE OF VINYLOGY (0.25 CFU)
2b. Vinylogous Aldol, Mannich, ad Michael reactions.
3. OLEFINATION REACTIONS (0.5 CFU)
3a. Stabilized and non-stabilized phosphorus ylides.
3b. Wittig reaction; Horner-Hemmons and its variants; Still-Gennari reaction.
3c. Sulfur ylides and Julia olefination.
4. CARBOCATION REACTIVITY (0.5 CFU)
4a. Carbocations: basic structure, synthesis and reactivity.
4b. Pinacolic and semi-pinacolic rearrangement; ring expansion and contraction; Wagner-Meerwein rearrangement; Grob fragmentation.
4c. Prins reaction.
5. AROMATIC COMPOUNDS (2 CFU)
5a. Aromaticity and nomenclature of aromatic compounds
5b. Reactivity of Benzene and its derivatives
5c. Electrophilic Aromatic Substitution (EAS)
5d. Diazonium salts
5e. Synthesis of mono- and multi-substituted benzene derivatives
5f. Nucleophilic Aromatic Substitution; Benzyne.
6. INTRODUCTION TO PALLADIUM CHEMISTRY (1 CFU)
6a. Transition metals
6b. Introduztion to the reactivity of Palladium complexes
6c. Palladium-catalyzed cross couplings: Heck, Suzuki, Stille, Sonogashira.
7. NOMENCLATURE OF HETEROCYCLIC COMPOUNDS (0.5 CFU)
7a. Nomenclature of carbocyclic and heterocyclic compounds; Hantzsch-Widman systematic nomenclature; alternative systematic nomenclature; current names of heterocyclic compounds; nomenclature of condensed heterocyclic systems;
7b. Nomenclature of bridge cyclic systems
8. PERICYCLIC REACTIONS (1.0 CFU)
8a. Classification of pericyclic reactions.
8b. Woodward-Hoffmann Rules
8c. Diels-Alder Reaction
8d. Sigmatropic transpositions.
9. PRINCIPLES OF CHEMICAL SYNTHESIS (0.25 CFU)
9a. Introduction to chemical synthesis: divergent vs convergent synthesis
9b. Protecting groups
9c. Applications to the total synthesis of drugs
1. For general issues: W. H. BROWN, B. l. IVERSON, E. V. ANSLYN, C. S. FOOTE, "Chimica Organica", Sesta Edizione, EdiSES 2019.
2. For advanced issues: J. CLAYDEN, N. GREEVES, S. WARREN, "Organic Chemistry", Second edition, Oxford 2012.
Reference books (available at the library and at the professor office):
3. Kurti Laslo, Czako Barbara "STRATEGIC APPLICATIONS OF NAMED REACTIONS IN ORGANIC SYNTHESYS", Academic Press, 2005.
1. “CHEMISTRY BY DESIGN” also available at: https://chemistrybydesign.oia.arizona.edu
2. “REACTION FLASH”, Elsevier
Free App for 3D animations of molecules and mechanisms of action:
Attendance at the course is compulsory even if provided in "remote" mode.
Lessons will be organized in presence with the possibility to use the Teams and Elly platforms also by "remote". The activities will take place in telepresence using Teams and Elly platforms. Lessons will be realized in both synchronous (via Teams) and asynchronous mode (uploaded on the Elly page of the course for a limited period of time). During the lessons in synchronous mode (direct), will alternate mainly frontal moments with interactive moments with the students. To promote active participation in the course, various activities will be proposed both individually and in small groups, using some resources such as the Elly discussion forums. The didactic activities will be conducted privileging active learning methods alternating with socratic heuristic lessons. During the socratic heuristic lessons will be privileged the dialogical comparison with the classroom on the theoretical aspects of the topics of the course, also in order to bring out any preconceptions on the topics in question by the students. In the second part of the lesson will be activated cycles of experiential learning in which students will be required to apply the theoretical concepts learned to the resolution of appropriate written exercises.
In addition, "case studies" taken from the scientific literature (empirical research projects) will be analyzed and students will have to critically analyze them according to the methodological criteria illustrated in the lessons and in the bibliographic and didactic material. The slides used to support the lessons will be uploaded weekly on the Elly platform. To download the slides students need to register to the online course. The slides are considered an integral part of the didactic material. Students not attending the course are reminded to check the available didactic material and the indications provided by the teacher through the Elly platform.
Assessment methods and criteria
The final examination consists of a colloquium and a written assay on a reported total synthesis to be discussed at the end of the colloquium. The colloquium deals with the execution of exercises on asymmetric synthesis and reactivity of organic compounds. This test is aimed at verifying whether the student has developed the skill and ability of 1) recognizing the relationship between structure and properties of organic compounds, 2) predicting the behavior of a given organic chemistry transformation among those comprised in the program, 3) selecting and deploying information from the theory study in order to furnish solutions to a given practical organic synthesis problem, and finally 4) acquiring learning skills and communication skills by employing appropriate language to both specialized and non-specialized audience.
The written assay will focus on a critical comment on the published synthesis of a target, as well as on the mechanisms and transition states of key reactions exploited during the synthesis. Each student has to submit its own written assignment within two weeks of the date of the colloquium. All information related to the execution of the assay will be discussed during the course lessons and will be uploaded on the Elly platform.
The colloquium is evaluated on a 0-30 scale and will affect the 80% of the final grade.
The written assay is evaluated on a 0-30 scale and will affect the 10% of the final grade.
The critical discussion on the written assay is evaluated on a 0-30 scale and will affect the 10% of the final grade.
The final grade, defined not analytically but subjectively by the teacher, will be communicated immediately at the end of the oral test.
Please note that online registration is REQUIRED.
If, due to the continuation of the COVID-19 emergency, it is necessary to integrate with the remote mode, the carrying out of the profit examinations will proceed as follows: the final verification will consist of an oral interview conducted at a distance (via Teams) in three phases:
1. Written test of nomenclature (preparatory to the remaining part of the examination);
2. Oral exam regarding the topics of the course;
3. Oral presentation of the written report
Each student enrolled in the call will receive (about 5 days before the date of the call) an email from the teacher in which they will be indicated:
1. Date and time of convocation
2. Teams links to access the exam session
3. Links to upload the identity document, as defined by University
4. Operating instructions about the examination and which materials carrying on.