66201 - Advanced Organic Chemistry M

Learning outcomes

At the end of the course, the student is acquainted with and masters the following aspects: -Stereoselectivity in C-C bond forming reactions: definitions and applications. -How to represent 3D chiral molecular structures on a plane. -Reaction models enabling the rationalization of C-C bond forming reaction outcomes. Special focus is set on the stereochemistry of the transformations. -Asymmetric catalysis: basic principles and innovative applications, involving both metal (e.g. Lewis acids) and organic (e.g. proline and its derivatives) catalysts. -Application of the aforementioned concepts to the synthesis of structurally and stereochemically complex compounds.

Course contents

Prerequisites:

basic knowledge of organic chemistry: reactivity, notions of stereochemistry, reaction mechanisms.

Contents:

Introduction

Stereochemistry of the aldol products

Direct vs indirect aldol addition reactions

Indirect aldol addition reactions

Simple diastereoselectivity

Simple diastereoselectivity with Li and B enolates: the Zimmerman-Traxler TS model

Simple diastereoselectivity with silicon enolates: the Mukaiyama aldol reaction and the open antiperiplanar (extended) TS model

Simple diastereoselectivity in other addition reactions: open synclinal TS models

Simple diastereoselectivity: concluding remarks

Facial diastereoselectivity

Facial diastereoselectivity with chiral enolates: the Evans-syn-aldol reaction, substrate induced stereoselectivity and 1,3-Allylic strain

Facial diastereoselectivity with chiral aldehydes: the Cram rule, the Felkin-Anh model and the effect of chelation

Facial diastereoselectivity with chiral oxocarbenium ions: the Fürst-Plattner rule

Enantioselectivity

Enantioselectivity, an introduction

Enantioselectivity with chiral Lewis acids

Enantioselectivity with Brønsted acids

Mukaiyama aldol reactions with donors different from simple silylenolethers

Indirect vinylogous aldol reaction: the principle of vinylogy

Formal hetero-Diels-Alder based on the indirect aldol reaction: the Danishefsky diene

Direct aldol addition reaction in biological systems

Type II direct aldol reactions: soft enolisation

Metal directed soft enolisation

Hydrogen bond directed soft-enolisation: bifunctional catalysis

The Lewis base promoted formation of enols: the Morita-Baylis-Hillman reaction

Type I direct aldol reactions: enamine activation

Proline catalysed asymmetric aldol reactions: background, the intermolecular aldol reaction, cross-aldol reactions of aldehydes, TS of proline catalysed aldol reactions

Proline catalysed intramolecular alkylation: Thorpe-Ingold (gem-dimethyl) effect, the Baldwin’s rules Catalysts different from proline: in sterically directed enamine catalysis

Iminium ion activation of α,β-unsaturated carbonyl compounds

Readings/Bibliography

Pdf slides in English are provided by the teacher  through the website https://virtuale.unibo.it

Teaching methods

Frontal lectures and exercises on the blackboard

Assessment methods

The final exam consists of an oral exam in which exercises related to the topics covered in the lessons are performed.

Teaching tools

Frontal lectures with possible video projection aid. Students with specific learning disabilities or disabilities can contact the Student Services for Disabilities and DSA of the University of Bologna (http://www.studentidisabili.unibo.it/) and the contact person of the Department (giorgio.bencivenni2@unibo.it) or the teacher of the course to agree on the most suitable ways to consult the teaching material and access the classrooms for the frontal lessons.

Office hours

See the website of Giorgio Bencivenni