Concepts and Methods in Organic Synthesis

The course illustrates the retrosynthetic approach to the elaboration of strategies for preparing organic compounds, considering regio- and stereoselectivity aspects. Following the thread of the different types of disconnection, several synthetic methodologies are discussed, most of which are not included in the topics studied in the basic organic chemistry courses. Synthetic methods are discussed in terms of applicability, simplicity, and selectivity, thus bridging the gap between organic chemistry fundamentals and advanced synthesis problems. Success in organic synthesis requires not only familiarity with common reagents and functional group interconversions but also a deep understanding of functional group behaviour and reactivity. This course provides clear explanations of such reactivities and explicitly teaches students how to make logical disconnections of a target molecule. This course prepares students to progress into modern synthetic strategies by teaching them how to imagine the series of reactions needed to reach a desired target molecule.
The course is structured as follow:
PART I. Synthetic Toolbox 1
1.1 Retrosynthetic Analysis.
1.2 Protective Groups
PART II. Synthetic Toolbox 2
2.1 Nucleophiles and Electrophiles.
2.2 Oxidation and Reduction Reactions
PART III. Synthesis of Monofunctional Target Molecules
3.1 Alcohols
3.2 Alkyl and Aryl Halides
3.3 Ethers
3.4 Thiols and Thioethers
3.5 Amines and Anilines
3.6 Alkenes
3.7 Alkynes
3.8 Alkanes
3.9 Aldehydes and Ketones
3.10 Carboxylic Acids
3.11 Carboxylic Acid Derivatives
PART IV. Synthesis of Target Molecules with Two Functional Groups
4.1 β-Hydroxy Carbonyls and α,β-Unsaturated Carbonyls
4.2 More Enolate Reactions
4.3 "Illogical" Disconnections
PART V. Synthesis of Aromatic Target Molecules
5.1 Electrophilic Aromatic Substitution
5.2 Diazonium Salts
5.3 Nucleophilic Aromatic Substitution
PART VI. Synthesis of Compounds Containing Rings
6.1 Cyclopropanes
6.2 Cyclobutanes
6.3 Five-Membered Rings
6.4 Six-Membered Rings
PART VII. Predicting and Controlling Stereochemistry
7.1 Reactions That Form Racemates
7.2 SN2 Mechanism: Backside Attack
7.3 Elimination Mechanisms
7.4 Additions to Alkenes and Alkynes
7.5 Additions to Carbonyls
7.6 Additions to Enolates: Aldol Stereochemistry
7.7 Enantioselectivity and Asymmetric Syntheses
PART VIII. Useful strategies and exercises