66173 - Organic Chemistry with Laboratory M

Learning outcomes

At the end of the course the student will be able to design retrosynthetic pathways, using catalytic coupling reactions for the formation of new C-C bonds as well as C-heteroatom bond. The studetnwill be able to plan asymmetric syntheses of organic compounds of medium complexity. The course will focus on the application of the principal techniques used for the structural identification and analysis of organic molecules The course will apply basic knowledge on spectroscopic methods such as Nuclear Magnetic resonance and Mass Spectroscopy to the solution of the structures of organic molecules.. The main part of the course will be carried out with exercitations on experimental data, and by exercitations on the spectrometers.

Course contents

INSTITUTIONAL PART

1. Determination of the reaction mechaninsm of organic reactions
1. Thermodynamics and kinetic considerations
2. Substituent effect
3. Basic concepts:
1. Thermodynamic and kinetic control
2. Hammond's postulate
3. Principles of Curtin-Hammett
4. Eyring's equation
4. Isotope effect
5. Other useful techniques for the determination of the reaction mechanism
1. Crossed experiments
2. Trapping of intermediates
3. Isotopical marking
   
   
2. Organic reactions mediated by transition metals
1. Palladium in organic synthesis
2. Reactions of organopalladium with:
1. Alkenes: Heck reaction
2. Aryl boronic acids: Suzuki-Miyaura reaction
3. Terminal alkynes cuprates: Sonogashira reaction
4. Aryl stannanes (Stille); organo-zinc (Negishi); organo-silicon (Hiyama)
3. Carbon-heteroatom coupling: Buchwald-Hartwig amination
4. Cobalt: the Pauson-Khand reaction
5. Olefine metathesis
   
   
3. Concerted reactions
1. Diels-Alder reaction: dienes e dienophiles
2. The frontier orbital description of cycloaddition: Woodward-Hoffmann rules
3. Stereochemistry of the Diels-Alder reaction: the “endo” rule
4. Catalysis of the Diels-Alder reaction. Effect of water as the solvent.
5. Thermal and photochamical [2+2]-cycloadditions.
6. 1,3-dipolar cycloadditions
7. Sigmatropic rearrangements and elettrocyclic reactions
8. Rearrangements
1. Neighbouring group effect. Stereochemical considerations. Migratory aptitude
2. Wagner-Meerwein; Pinacolic; Baeyer-Villiger; Beckmann
   
   
4. Asymmetric synthesis
1. Stereochemistry of dynamic processes
2. Prochirality
3. Enantiomeric excess and optical purity
4. Thermodynamic description of asymmetric reactions
5. Methods for the obtainment of enantiomerically enriched substances:
1. Classical resolutions
2. Dynamic resolutions of the first and the second kind
3. Synthesis from the chiral pool
4. Stoichiometric methods with chiral auxiliaries
5. Asymmetric catalysis
1. Metallocatalysis
2. Organocatalysis and asymmetric chiral phase transfer catalysis
3. Biocatalysis
6. Chiral amplification: The origin of homochirality in Nature.
   
   
5. Multistep synthesis and retrosynthesis
1. Selected case-studies will be developed with a problem-solving approach

 

LABORATORY

The course will focus on the application of the principal techniques used for the structural identification and analysis of organic molecules The course will apply basic knowledge on spectroscopic methods such as Nuclear Magnetic resonance and Mass Spectroscopy to the solution of the structures of organic molecules.. The main part of the course will be carried out with exercitations on experimental data, and by exercitations on the spectrometers.

1. NMR Spectroscopy
1. Nuclear spin and resonance
2. NMR spectromers and FT technique.
3. Spin relaxation theory
4. Acquisition parameters, spectral width and RF pulses
5. 1H spectra: chimica shift, cpupling constants and integration
6. 13C spectra and DEPT techniques for the signal assignment
7. NOE spectra
8. exercitations
   
   
2. Mass Spectroscopy
1. Ionization techniques: electron impact, electron spray, MALDI
2. Ion analyzers: magnetic secton, quadrupolem ionic trap, TOF and FT-ICR
3. Fragmentation mechanism
4. Fragmentation analysis for the structural assignment of simple molecules
5. Practical exercitations on experimental mass spectra
   
   
3. Analysis of optically active compounds
1. Enantioselective HPLC
   
2. Optical purity by NMR spectroscpy
3. Optical purity by optical methods: polarimetry, circular dichroism
4. Use of X-ray diffraction for the absolute configuration.
   
   
4. Laboratory activities
1. Two multi-step syntheses related to the theoretical contents will be held by students in the chemical laboratory

Readings/Bibliography

Lectures' handouts available via web at AlmaDL

Clayden, Greeves, Warren & Wothers "Organic Chemistry - 2nd Ed." - OUP 2012
Laboratory

1. D.H.Williams, I.Fleming; 'Spectroscopic Methods in Organic Chemistry' 5° ed. Inglese; McGraw-Hill Book Company. ISBN 0-07-709147-7
2. R.M.Silverstein, F.X.Webster, D.J.Kiemle, "Spectrometric identification of Organic Compounds", 7° ed,; Wiley International Edition. ISBN 0-471-42913-9

Teaching methods

PowerPoint presentations Exercises

Assessment methods

Written exercises on the course topics including a structural determination on an unknown compound by means of NMR and mass spectroscopy data.

Teaching tools

PDF presentations available via web, through AlmaDL - the University delivery system of teaching materials

LABORATORY
The teacher will use Powerpoint Presentations (available to the students at the beginning of the lessons) for the theoretic part, and printed spectra for the exercitations. The course will proceed with theoretical concepts, followed by examples and exercise

Office hours

See the website of Paolo Righi

See the website of Andrea Mazzanti