Concepts and Methods in Organic Synthesis
A.Y. 2023/2024
Learning objectives
The purpose of this course is to furnish to chemistry students, interested in deepening organic synthesis, methods and tools for organizing and rationalizing all their organic chemistry knowledge, acquired in previous organic chemistry courses. In particular, the course will focus on the following aspects: concepts, methods and reagents useful for the design of organic systems, taking into account, in particular, methods to achieve reaction selectivity and commercially availability of starting reagents.
Expected learning outcomes
At the end of the course, the student will be able to face the issue of planning a synthetic procedure for marketable organic compounds.
Lesson period: First semester
Assessment methods: Esame
Assessment result: voto verbalizzato in trentesimi
Single course
This course can be attended as a single course.
Course syllabus and organization
Single session
Responsible
Lesson period
First semester
Course syllabus
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
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
Prerequisites for admission
Courses of Organic Chemistry I and II passed - Basic concepts of organic chemistry.
Teaching methods
Traditional teaching with PPT slides with written exercises included.
Teaching Resources
a) Copies of the lecture slides uploaded on https://ariel.unimi.it/
b) L. S. Starkey - Introduction to Strategies for Organic Synthesis. II Edition, 2018 Wiley.
c) S. Warren, P. Wyatt - Organic Synthesis: The Disconnection approach. 2008 Wiley.
d) S. Warren, P. Wyatt - Workbook for Organic Synthesis: The Disconnection approach. II Edition, 2008 Wiley.
e) J. Clayden, N. Greeves, S. Warren - Organic Chemistry, II Edition, 2012 Oxford.
f) F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Part B: Reactions and Synthesis, V Edition, 2007 Springer Science.
g) J.-H. Fuhrhop, G. Li, Organic Synthesis - Concepts and Methods, 3rd Edition, Wiley-VCH, 2003.
b) L. S. Starkey - Introduction to Strategies for Organic Synthesis. II Edition, 2018 Wiley.
c) S. Warren, P. Wyatt - Organic Synthesis: The Disconnection approach. 2008 Wiley.
d) S. Warren, P. Wyatt - Workbook for Organic Synthesis: The Disconnection approach. II Edition, 2008 Wiley.
e) J. Clayden, N. Greeves, S. Warren - Organic Chemistry, II Edition, 2012 Oxford.
f) F. A. Carey, R. J. Sundberg, Advanced Organic Chemistry, Part B: Reactions and Synthesis, V Edition, 2007 Springer Science.
g) J.-H. Fuhrhop, G. Li, Organic Synthesis - Concepts and Methods, 3rd Edition, Wiley-VCH, 2003.
Assessment methods and Criteria
Written examination: the exam usually consists of 6 exercises on retrosynthesis or on the application of reactions and concepts presented in the course.
Educational website(s)
Professor(s)