This module consists of a range of examples exposing the students to sophisticated methods in stereoselective synthesis. Building on previous knowledge, advanced methods for stereocontrol in total synthesis, preparation of enantiomerically pure drug molecules, development of stereoselective rearrangement processes as well as the introduction of various enabling technologies will be the main focus of this module. Throughout, the ability to extract stereochemically relevant information from complex syntheses will be a major focus.

Knowledge

• Appreciate the range of synthetic methods available to prepare enantiomerically pure molecules.
• Know the strategies and reagents required to generate and implement new stereochemical elements within target oriented syntheses.
• Identify key problems in both small scale academic synthesis and large scale industrial synthesis of stereochemically pure compounds.
• Identify different reaction technology equipment and summarise the key criteria to consider before using it.

Understanding

• Understand the principles and strategies of stereoselective alkene functionalization.
• Understand main principles in the use of enabling technologies and related industrial issues together with application to target molecules.
• Recognize where rearrangements can be applied in synthesis and be able to devise retrosynthetic strategies involving rearrangements for all reaction types covered in the course.
• Explain when alternative tools and techniques may offer significant benefit to a desired reaction outcome.

This module will be delivered in 10 two-hour lectures, supplemented by 4 1-hour class tutorials, and consists of three blocks, each covering a different aspect of asymmetric synthesis. An initial set of lectures will be used to revise already known principles and reactions and introduce novel methods that can be used to tackle certain problems in asymmetric synthesis together with their theoretical background and any strengths or weaknesses associated with them. These will be followed by three units in which such methods are applied to chemical problems.

Ability to analyse stereochemical problems and provide synthetic solutions.

The module will be assessed by a combination of coursework (20%) and written examination (80%). Coursework will be broken down into 2 short, problem-based pieces of work (10% each).

Alkene Functionalisations

Introduction to advanced asymmetric synthesis. Stereoselective functionalisations of double bonds: Briefly revising Sharpless AE and ADH, Jacobsen (year 3), then introduction of other electrophilic reagents including selenium- and iodine-based compounds.

Enabling Tools for Organic Synthesis

As synthesis moves in to the modern era so too does the way in which chemists can conduct chemistry. This part of the course introduces the technical considerations needed for using existing and futuristic synthesis tools such as microwave reactors, photochemical reactors, electrochemistry and continuous flow chemistry. Important factors are being considered when conducting reactions using these methods, there will also be a strong focus on the types of synthetic chemistry suited to these modes.

Rearrangements

The pinacol and semipinacol rearrangement, with a focus on applications to target synthesis. Rearrangements of organoboron compounds, focusing on the migration of alkyl groups from boron to carbon. Migration to electron-deficient nitrogen and oxygen (Baeyer-Villiger, Beckmann, Curtius and related rearrangements).

An indicative reading and resource list will be provided in the first lecture.

An indicative reading and resource list will be provided in the first lecture.