LEARNING OUTCOMES

The student will deepen various aspects of organic cgemistry not yet treated in previous modules (in particular C-C bond forming reactions) and will be guided to reach a good capacity to understand retrosynthetic strategies, design simple syntheses of aliphatica and aromatic compounds, to interpret reaction mechanisms and the strategies used to corroborate them.

AIMS AND LEARNING OUTCOMES

The student will deepen various aspects of organic cgemistry not yet treated in previous modules (in particular C-C bond forming reactions) and will be guided to reach a good capacity to understand retrosynthetic strategies, design simple syntheses of aliphatica and aromatic compounds, to interpret reaction mechanisms and the strategies used to corroborate them.

PREREQUISITES

For an optimal fruition of the course, the knowledge of the basic notions of  Organic Chemistry 1 and 2 and of the Laboratory of Organic Chemistry is essential.

TEACHING METHODS

The course includes only frontal lessons, with the prevalent use of slides.

SYLLABUS/CONTENT

1. C-C and C=C bond formation (8 hours)
   • Homoaldol reaction and homocrotonic condensation under acid or basic catalysis
   • Cross aldol reactions.
   • Allyl derivatives as synthetic equivalents of aldehydes
   • Claisen, Dieckmann, Darzens and Reformatsky reactions
   • Active methylene compounds. malonic and acetoacetic synthesis.
   • Knoevenagel reaction.
   • Reactions of α,β-unsaturated systems: kinetic and thermodynamic control. Addition of organometal compounds (Cu, Ce) and selective reductions.
   • Michael reactions with active methylene compounds.
   • Robinson annulation.
   • Use of enamines.
   • Nitroaldol reaction. Trasformations of nitro group.
   • Aldol and Claisen reactions in biology.
   • Wittig and Horner-Wadsworth-Emmons reactions.
   • Synthesis of α,β-unsaturated systems: summary
   • Cross-coupling reactions (hints).
2. Chemistry of aromatic and heteroaromatic compounds (6 hours)
   • Polycyclic aromatic hydrocarbons. Naming.
   • Naphthalene: properties and reactions.
   • Anthracene and phenanthrene
   • Review of main electrophilic and nucleophilic substitutions. Mechanism of Sandmeyer reactions. Vicarious nucleophilic substitution (Chichibabin).
   • Formylation and carboxylation reaction.
   • Benzylic oxidations.
   • Hantzsch-Widmann nomenclature of heterocyclic compounds.
3. Synthesis design: aromatic compounds (5 hours)
   • General concepts: linear, convergent synthesis. Total synthesis and semi-synthesis. Retrosynthetic approach. 
   • Synthetic equivalence.
   • Strategies for the synthesis of polysubstituted aromatic compounds. Removable groups. Clemmensen and Wolff-Kishner reactions.
   • Exercises on the synthesis of aromatic compounds.
4. Synthesis design: aliphatic compounds (6 hours)
   • Synthesis of C-X bonds.
   • Synthesis of amines
   • Retrosynthesis of C-C bonds (1 functional group).
     • Alcohols
     • Ketones.
     • Carboxylic derivatives
     • Alkenes
   • Retrosynthesis of C-C bonds (2 functional groups). Logical and illogical disconnections
   • Logical disconnections: synthesis of 1,3 and 1,5 derivatives
   • Synthesis of 1,3 and 1,5 derivatives:
     • Use of alpha-halocarbonyl compounds: alpha-halogenation under acid and basic conditions
     • Use of cyanide
     • Synthesis of 1,2-diols and epoxides. Pinacol reaction. Corey-Chaikovski reaction.
   • Synthesis design exercises
5. Protecting groups (5 hours)
   • Protection of amines. Peptide synthesis.
   • Protection of alcohols.
   • Protection of carbonyl compounds.
6. Synthesis of cyclic compounds (6 hours)
   • General issues of cyclization reactions
   • Examples of synthesis of 5-membered rings
   • Examples of synthesis of 6-membered rings
   • Hints on synthesis of 3- and 4-membered rings
   • Hints to olefin metatesis
   • Diels-Alder reaction.
   • 1,3-dipolar cycloadditions
7. Rearrangements (4 hours)
   • Carbocation rearrangement with 1,2 hydride shif
   • Pinacol rearrangement (also in tandem with Corey-Chaikovski reaction)
   • Wagner-Meerwein rearrangement
   • Baeyer-Villiger reaction
   • Hoffmann and Schmidt rearrangements
   • Arndt-Einstert rearrangement
   • Sigmatropic rearrangements: Cope and Claisen reactions
8. Diversity oriented synthesis (4 hours)
   • General concepts
   • Biological example of combinatorial synthesis: antibodies.
   • Multicomponent reactions
9. Reaction mechanisms (6 hours)
   • Non kinetical methods for delucidating a mechanism.
   • Kinetical methods for delucidating a mechanism.

RECOMMENDED READING/BIBLIOGRAPHY

The slides of the lessons will be available in pdf format on Aulaweb.

For the review / deepening of basic organic chemistry topics, the latest editions of the same texts recommended for the courses of Organic Chemistry I and II can be used; in particular:

-- Brown, Foote, Iverson, Anslyn - Organic Chemistry - EdiSES

-- Bruice - Organic Chemistry - EdiSES

For topics not included in the above quoted texts, students may look at:

Carey-Sundberg: "Advanced Organic Chemistry: Reaction and Synthesis"

Carey-Sundberg: "Structure and mechanisms"

For retrosynthesis, we recommend reading the text:

-- Stuart Warren, Paul Wyatt - Organic synthesis - The Disconnection Approach, 2nd Edition - J. Wiley & Sons (2008).