Special Synthesis Techniques in Organic Chemistry
A.Y. 2024/2025
Learning objectives
The course intends to explain the basic concepts in the synthesis of complex organic molecules. The most significant methodologies of the modern organic synthesis will be discussed, also including asymmetric ones, with attention to both the general aspects and illustrative applications. Also some special techniques will be described, among the most recent and of wide spread, which are aimed to improve the efficiency, the economy and the environmental impact of the chemical organic synthesis.
Expected learning outcomes
The course allows a consolidation of the knowledge on the general strategies of formation of the single and multiple carbon-carbon bond; provides basic skills of asymmetric synthesis; allows a first contact with special techniques applied to chemical synthesis. The student acquires the ability to solve the synthesis of molecules with different degrees of structural complexity.
Lesson period: First semester
Assessment methods: Esame
Assessment result: voto verbalizzato in trentesimi
Single course
This course cannot be attended as a single course. Please check our list of single courses to find the ones available for enrolment.
Course syllabus and organization
Single session
Responsible
Lesson period
First semester
Course syllabus
The teaching program includes the presentation and discussion of the following topics:
- basic concepts in the modern synthesis of complex organic molecules: insights into the alkylation reactions of enolates (lithium enolates, enol-equivalents (enamines, silyl ethers, azaenolates, beta-dicarbonyl compounds)), alkylation of nitriles and nitroalkanes, alkylation of non-symmetrical ketones; aldol condensation (thermodynamic control and direct aldol), Mannich reaction; carbon acylation (Claisen reaction, thermodynamic control and direct acylation); conjugate addition of enolates, Robinson anellation; control of the double bond geometry (stereospecific eliminations, Julia olefination, Peterson reaction, Wittig reaction, reduction of alkynes); elements of stereochemistry (conformation, configuration, optical activity, relative and absolute stereochemistry, diastereoisomers, enantiomers, stereospecific or stereoselective reactions); diastereoselectivity (prochirality, Felkin Anh model, Houk model, Zimmerman-Traxler model) (2 credits);
- synthesis of optically active molecules: kinetic resolution, chiral pool, use of chiral auxiliaries (Evans oxazolidinones), evaluation of enantiomeric excess (optical purity, chiral HPLC, NMR with chiral reagents); asymmetric synthesis: chiral reagents (asymmetric deprotonation with (-)-sparteine), chiral catalysts (metal catalysis (reduction of ketones with CBS-oxazaborolidine, asymmetric hydrogenation Ru-BINAP, Rh-DIPAMP, Sharpless asymmetric epoxidation and dihydroxylation), enzymatic catalysis (kinetic resolution of racemates, transformation of prochiral substrates), organocatalysis (covalent catalysis via iminium ions (McMillan imidazolidinones) and via enamine (proline), non-covalent catalysis (acid catalysis with thioureas (Jacobsen) and basic catalysis with Cinchona alkaloids (Jorgensen ) (1 credit);
- use of transition metal complexes in organic synthesis: Pd(0) and Pd(II) complexes, catalytic cycles (oxidative addition, insertion, betaH-elimination, reductive elimination, transmetallation); Heck reaction (regiochemistry, intramolecular Heck), insertion of alkynes (synthesis of heterocycles and carbocycles), Sonogashira coupling, cross coupling reactions (Suzuki, Negishi, Stille), Buchwald reaction; olefin metathesis reactions (metal-carbene complexes, catalytic cycle, ring closing metathesis, cross metathesis, ring opening-ring closing metathesis, enynes metathesis) (1 credit);
- technologies in organic synthesis: principles of green chemistry, alternative activation methods (microwaves, ultrasound, mechanochemistry), alternative reaction media (ionic liquids, deep eutectic solvents, water), alternative separation techniques (perfluorinated solvents, supercritical fluids); use of reagents, catalysts and scavengers supported on polymers; solid phase synthesis (soluble and insoluble supports, linkers, peptide synthesis, synthesis of nucleic acid oligomers, synthesis of small molecules); flow chemistry (2 credit).
Within the 6 credits, moments of guided practice are foreseen, to allow better assimilation of the course contents and promote their application in a progressively autonomous way by the students.
- basic concepts in the modern synthesis of complex organic molecules: insights into the alkylation reactions of enolates (lithium enolates, enol-equivalents (enamines, silyl ethers, azaenolates, beta-dicarbonyl compounds)), alkylation of nitriles and nitroalkanes, alkylation of non-symmetrical ketones; aldol condensation (thermodynamic control and direct aldol), Mannich reaction; carbon acylation (Claisen reaction, thermodynamic control and direct acylation); conjugate addition of enolates, Robinson anellation; control of the double bond geometry (stereospecific eliminations, Julia olefination, Peterson reaction, Wittig reaction, reduction of alkynes); elements of stereochemistry (conformation, configuration, optical activity, relative and absolute stereochemistry, diastereoisomers, enantiomers, stereospecific or stereoselective reactions); diastereoselectivity (prochirality, Felkin Anh model, Houk model, Zimmerman-Traxler model) (2 credits);
- synthesis of optically active molecules: kinetic resolution, chiral pool, use of chiral auxiliaries (Evans oxazolidinones), evaluation of enantiomeric excess (optical purity, chiral HPLC, NMR with chiral reagents); asymmetric synthesis: chiral reagents (asymmetric deprotonation with (-)-sparteine), chiral catalysts (metal catalysis (reduction of ketones with CBS-oxazaborolidine, asymmetric hydrogenation Ru-BINAP, Rh-DIPAMP, Sharpless asymmetric epoxidation and dihydroxylation), enzymatic catalysis (kinetic resolution of racemates, transformation of prochiral substrates), organocatalysis (covalent catalysis via iminium ions (McMillan imidazolidinones) and via enamine (proline), non-covalent catalysis (acid catalysis with thioureas (Jacobsen) and basic catalysis with Cinchona alkaloids (Jorgensen ) (1 credit);
- use of transition metal complexes in organic synthesis: Pd(0) and Pd(II) complexes, catalytic cycles (oxidative addition, insertion, betaH-elimination, reductive elimination, transmetallation); Heck reaction (regiochemistry, intramolecular Heck), insertion of alkynes (synthesis of heterocycles and carbocycles), Sonogashira coupling, cross coupling reactions (Suzuki, Negishi, Stille), Buchwald reaction; olefin metathesis reactions (metal-carbene complexes, catalytic cycle, ring closing metathesis, cross metathesis, ring opening-ring closing metathesis, enynes metathesis) (1 credit);
- technologies in organic synthesis: principles of green chemistry, alternative activation methods (microwaves, ultrasound, mechanochemistry), alternative reaction media (ionic liquids, deep eutectic solvents, water), alternative separation techniques (perfluorinated solvents, supercritical fluids); use of reagents, catalysts and scavengers supported on polymers; solid phase synthesis (soluble and insoluble supports, linkers, peptide synthesis, synthesis of nucleic acid oligomers, synthesis of small molecules); flow chemistry (2 credit).
Within the 6 credits, moments of guided practice are foreseen, to allow better assimilation of the course contents and promote their application in a progressively autonomous way by the students.
Prerequisites for admission
To adequately address the contents of the course, preliminary knowledge of organic chemistry is necessary, for example reactivity of functional groups and basic notions of stereochemistry. This knowledge is generally acquired in the Organic Chemistry courses (1 and 2).
Teaching methods
There will be lectures and guided exercise sessions. Students can also pursue thematic insights, to be carried out in small groups and brought back to the classroom.
Attendance is strongly recommended.
Attendance is strongly recommended.
Teaching Resources
The teaching material (lesson slides) is available on the University Ariel portal.
The following text is recommended for reference: Organic Chemistry, by Jonathan Clayden, Nick Greeves, Stuart Warren. Oxford Ed., 2012.
The following text is recommended for reference: Organic Chemistry, by Jonathan Clayden, Nick Greeves, Stuart Warren. Oxford Ed., 2012.
Assessment methods and Criteria
The assessment method is through a written test, which includes both the carrying out of exercises of organic synthesis and open answers on the methods and technologies described in the teaching. The written test generally takes 3 hours. An ongoing intermediate test is foreseen, on the first 3 credits of teaching provided.
At the request of the individual student, it is possible to integrate the written test with an oral test, which consists in the presentation and discussion of a recent work of literature, inherent to the technologies studied and chosen by the student in agreement with the teacher (example of reference journal: Green Chemistry, Royal Society of Chemistry Ed).
The evaluation criteria consider the correctness in carrying out the exercises, the competence in the use of specialized vocabulary and the ability to discursively organize knowledge. In the case of an oral test, the quality of the prepared presentation and the ability to critically discuss what is presented is also evaluated.
For the written test, including the ongoing one, the evaluation in thirtieths is used. The oral test contributes to the final mark with an increase or decrease of a maximum of two marks (in thirtieths).
The results of the written tests, including ongoing ones, are published on the University's Ariel portal, where there are also written exam models.
At the request of the individual student, it is possible to integrate the written test with an oral test, which consists in the presentation and discussion of a recent work of literature, inherent to the technologies studied and chosen by the student in agreement with the teacher (example of reference journal: Green Chemistry, Royal Society of Chemistry Ed).
The evaluation criteria consider the correctness in carrying out the exercises, the competence in the use of specialized vocabulary and the ability to discursively organize knowledge. In the case of an oral test, the quality of the prepared presentation and the ability to critically discuss what is presented is also evaluated.
For the written test, including the ongoing one, the evaluation in thirtieths is used. The oral test contributes to the final mark with an increase or decrease of a maximum of two marks (in thirtieths).
The results of the written tests, including ongoing ones, are published on the University's Ariel portal, where there are also written exam models.
CHIM/06 - ORGANIC CHEMISTRY - University credits: 6
Lessons: 48 hours
Professor:
Silvani Alessandra
Shifts:
Turno
Professor:
Silvani AlessandraEducational website(s)
Professor(s)