66288 - Methods of Synthesis and Characterization

Learning outcomes

At the end of the course, the student is able to choose the method best suited for the formation of carbon-carbon bonds using organometallic compounds (prepared in advance or generated in situ), with maximum control of regioselectivity, chemoselectivity and stereoselectivity. The students will be also mastering fundamental heterocyclic chemistry and will be able to design synthesis of biological active molecules containing heterocyclic compounds. The student is also able to analyze mono- NMR spectra and two-dimensional for the elucidation of molecules of complex structures.

Course contents

Part of synthetic methodologies: Chapter 1. Organic Lithium. Use and reactivity. Safety and preparation procedures. Methods of synthesis. Titrations. Use of activating and directing group groups. Additives. Magnesium functionalized derivatives. Preparation. Procedures Knochel. TurboGrignard. Use of LiCl.

Exercises: synthesis and use of organic lithium in pharmaceutical compounds, heterocyclic, and total synthesis.

Chapter 2. zinc derivatives. Reactions and preparation of derivatives zinc. Zinc dialkyl derivatives. Synthesis and properties. Allylzinc. Listing of derivatives and preparation intermediate zinc compounds. Procedures introduced by Knochel. Use of zinc derivatives in the synthesis of natural products. Allilzinco reactions and stereochemical control.

Chapter 3. Preparation and properties of organotitanio. Structures and use of reagents. Ate complexes. Titanium Omoenolati. diatsreoselettive reactions. Rules Cram, Cram chelate, Felkin. Use of titanium complexes in the diastereoselective synthesis. Olefination reagents and coupling type MacMurry. catalytic redox reactions. Examples with titanium. Coupling reaction pinacolinico stereoselective. Titanium enolates. stereoselection of rules. Evans type auxiliary. Haldol Evans and Non Evans. Applications. Organozirconio. Reaction idrozirconazione. Organozirconium in various reactions.
Examples of applications of titanium and zirconium reagents in the synthesis of natural substances. Control of diastereo and enantioselectivity.

Chapter 4 Organorame and cuprates. Synthesis and preparation. copper salts. Reactions of cuprates. mixed cuprates. Cyano cuprates at low and high order. conjugated reactions. Reactions trasmetallazione.Reagenti of tin and silica. Use of Grgnard. Use of catalytic amounts of copper salts. cuprates zinc. Examples of other organomettallici. Catalysis with copper. Click chemistry.

Use of cuprates in the synthesis, particularly in the synthesis of heterocyclic compounds.

Chapter 5. Catalytic Addition of organozinc. Leganti.Sistema catalytic. Use of amino alcohols. of titanium isopropoxide Presena. Organotitanio. Addition of double bonds. Addition of aryl derivatives. Alkinilzinco derivatives. Ketone and additions to imines. Michael reactions with organometallic compounds. copper hydride compounds. Selective reductions of imines, carbonyls, and Michael type reactions.

Capito 5.1 Preparations of organometallic reagents. Photos and explanations.

Chapter 6.La reaction Mukaiyama and acid-catalyzed reactions. Mechanism and structure of transition states. diastereoselective reactions. Control of anti selectivity. diastereoselective reaction. Transition states. Chelated and non-chelated. Examples in a complex synthesis applications.

Chapter heterocycles. .
Synthesis and properties of heterocyclic systems. Priincipali reactions and behavior of heterocyclic systems pyrrole, furan, thiophene. Indole, and pyridine. reactions of heterocyclic applications to the synthesis of drugs containing heterocyclic systems. Retrosintetici approaches and applications.

Part characterization:  Classroom lessons: 1. Summary of the basic concepts of monodimensional 1H and 13C NMR spectroscopy. 2. Two-dimensional techniques used most commonly (COSY, HSQC, HMBC, NOESY): theoretical outline, execution and interpretation. 3. Commonly used two-dimensional NMR techniques (COSY, HSQC, HMBC, NOESY): theoretical outline, execution and interpretation.3. Application of these techniques to a practical example. 4. Overview of the most up-to-date NMR techniques (TOCSY, DOSY, gradient techniques) 5. Computer lab exercises (each student has a PC available to work individually): Elaboration of a complete set of NMR spectra using Spinwork software (free download). Determination of the structure and conformation of a molecule of medium complexity.

Readings/Bibliography

Synthetic methodology: course PDF (teacher's notes) uploaded to the teaching materials and available.

Characterization Part: Classroom lessons (8 hours in November): Exercises in the computer lab (5 afternoons in December), compulsory attendance at the exercises with signature collection

Teaching methods

Synthetic methodologies: Discussion of synthetic methodologies through lessons on the blackboard for all course.

Characterization: Frontal lessons and lab practice.

Assessment methods

Synthetic methodologies: Written exam on a list of 200 questions provided after the first month of the course (3 questions 7 question marks), and on the synthesis of biological molecules (two syntheses, 10 question marks) pharmacologically or biologically active containing heterocyclic systems and the mechanism of heterocyclic reactions. Furthermore, applications of synthesis methodologies will be requested, seen in class in the preparation of advanced intermediates for the synthesis of biologically active substances.

Characterization: The preparation is tested by an oral exam, whose aim is to verify the knowledge of the theoretical lessons.

Teaching tools

Part of Synthesis methodologies: Written exam lasting 1.5 hours on a list of 200 questions provided after the first month of the course (3 questions 7 points on request) by the teacher, and on the synthesis of biological molecules (two summaries, 10 points to complete and correct synthesis) pharmacologically or biologically active containing heterocyclic systems and the mechanism of heterocyclic reactions. Furthermore, applications of synthesis methodologies will be requested, seen in class in the preparation of advanced intermediates for the synthesis of biologically active substances.

Characterization Part: Written exam lasting two hours. The set of NMR spectra of a molecule with a known structure is provided and the complete interpretation of all the analyzes is required.

Office hours

See the website of Pier Giorgio Cozzi

See the website of Alessandra Tolomelli