ORGANIC CHEMISTRY II
Learning outcomes of the course unit
Aim of the course is to acquire knowledge and understanding, concepts and learning skills within the following domains:
1) students should learn, understand and deepen the advanced principles which connect the structure of organic compounds with their physicochemical properties, related to organic reactivity;
2) students should learn, understand and deepen the principles underlying advanced organic reactions allowing them to rationally interpret reaction mechanisms and to understand similarities and differences among different reaction pathways;
3) students should learn and understand close connections between organic chemistry and neighboring disciplines such as biochemistry and medicinal chemistry;
4) students should select information and ideas in order to make judgments and apply such information to solve ever emerging problems of organic synthesis, to propose ways to design and synthesize simple chiral organic compounds in a stereoselctive way;
5) students should acquire learning skills and communication skills by employing appropriate language to both specialized and non-specialized audience, in line with the above mentioned objectives. At the end of the course, students having followed all the theory and exercise lessons are expected to be able to applying knowledge and understanding of the above mentioned subject areas through the correct execution of problems and exercises about:
1) recognizing and analyzing the relationship between structure and properties (reactivity) of organic molecules;
2) proposing viable solutions as how to retro-synthesize, synthesize, transform, and interconvert the above mentioned organic compounds.
To fully appreciate the content of the course, it is necessary to acquire knowledge of general and inorganic chemistry and organic chemistry basics in previous courses. To access the final examination, it is necessary to pass the “Organic Chemistry I” exam.
Course contents summary
The first part of the course is devoted to recall and advance knowledge acquired in the Organic Chemistry I course. Particular attention will be devoted to the topics related to the stereochemirty of organic compounds and reaction stereocontrol. The following subjects are then treated: carbon-carbon bond forming reactions; functional group interconversion, protecting group insertion and cleavage. The second part of the course allows students to acquire knowledge on stereoselective synthesis of organic compounds focusing on retrosynthetic analysis, stereoselective methodologies, and asymmetric catalysis and organocatalysis. The course will be introduced by a brief dissertation on scientific literature and bibliographic search, with a description of the main features of scientific articles that are accessible from online databases.
1. Resources and Tools for Bibliographic Research
Scientific articles and most important Organic Chemistry Journals. Bibliographic references, search engines and bibliometric indexes.
2. Enol and Enolates
Keto-enol tautomer equilibria, acidity and basicity of enols and enolates; acid- and base-catalyzed enolization; metal enolates, ammonium enolates; silicon-stabilized enolates; kinetic vs thermodynamic enolates; Z/E geometry control of enolates; non cabonylic enolates; ylides.
3. Enolate Reactivity
Alkylation, the Michael reaction, The Claisen and Dieckmann reactions, acetoacetyc synthesis, malonic synthesis.
4. The Aldol Reaction
The “classic” acid- and base-catalyzed aldol reaction, the crossed aldol reaction, the Mukaiyama aldol reaction, the intramolecular aldol reaction, the vinylogous aldol reaction, the Henry reaction, the Nef reaction.
5. The Mannich Reaction
Imines and iminium ions, the direct and indirect Mannich reaction, the vinylogous Mannich reaction, the Knovenagel reaction.
6. Double Bond-Forming Reaction
Stabilized and non stabilized phosphorus Ylides, the Wittig reaction, Horner-Hemmons reaction, Still-Gennari variant of the HWE reaction, sulfur ylides and Julia olefination, Peterson reaction.
7. Allylation Reaction
Allyl-silanes, allyl-boranes, allyl-stannanes in organic synthesis.
8. Asymmetric Synthesis
Regioselectivity, diastereoselectivity, enantioselectivity. Asymmetric transformations, models of asymmetric induction like Felkin-Ahn model, Cram-chelated model and Zimmermann-Traxler model. Open-chain models.
9. Retrosynthetic analysis and total synthesis
J. CLAYDEN, N. GREEVES, S. WARREN, "Organic Chemistry", Second edition, Oxford 2012.
Scientific articles suggested by the teacher
1. Kurti Laslo, Czako Barbara "STRATEGIC APPLICATIONS OF NAMED REACTIONS IN ORGANIC SYNTHESYS", Academic Press, 2005.
2. Francis A. Carey, Richard J. Sundberg "Advanced Organic Chemistry. Part A: Structure and Mechanisms", Springer-Verlag; Fifth Ed. 2007.
3. Francis A. Carey, Richard J. Sundberg "Advanced Organic Chemistry. Part B: Reaction and Synthesis", Springer-Verlag; Fifth Ed. 2007.
According to the abovementioned objectives and contents, the course is carried out through frontal oral lessons and includes exercises at the blackboard dealing with the design, synthesis, and transformation of simple organic molecules which could be connected with the pharmaceutical and biological domains. These exercises are open for free discussion between teacher and students and they are considered an essential part of the course.
Assessment methods and criteria
The final examination consists of a written exam followed by an oral colloquium. The written exam 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.