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CHEM3205: Principles and Methods of Organic Synthesis

Course Organizer: Prof W B Motherwell

Lecturers: Professor J. C. Anderson, Professor W. B. Motherwell, Dr J. D. Wilden

Normal Prerequisite: CHEM2201

Units: 1/2 unit

Course evaluation: 2009/2010 (pdf)

Moodle page: http://moodle.ucl.ac.uk/course/view.php?id=9200

Aims

To provide a thorough knowledge and understanding of reactions which are the basis of organic synthesis. Emphasis will be placed not only on the mechanistic and stereoelectronic features of such reactions, but also on the way in which they are utilised in target synthesis.

Objectives

After completing this course, students should:

  • Understand key stereoelectronic principles involved in designing synthetic routes.
  • Recognise and apply key organometalic (Pd, Ru) mediated reactions in synthesis.
  • Appreciate the importance of chirality and asymmetric synthesis in organic chemistry.
  • Be able to apply the key principles of molecular orbital theory to a variety of organic reactions.

Course Structure

  • Lectures: 32 lectures

Assessment

  • Exam: 70%
  • Lab: 0%
  • Coursework: 30%

Recommended Texts

  • ‘Organic Chemistry’ J. Clayden, N. Greeves, S. Warren, P. Worthers. Oxford, 2001.
  • ‘Advanced Organic Chemistry Part B: Reactions & Synthesis’ Carey & Sundberg, Plenum, 1990.
  • ‘Frontier Orbitals and Organic Chemichal Reactions’ I. Flemming, Wiley, 2000.

Course Outline

A. Catalytic Palladium Chemistry in Organic Synthesis (4 Lectures, Prof. J. C. Anderson)
  • In depth look at common mechanisms, the fundamental disconnections this allows and then modern developments. Emphasis on bond conctruction. Some examples of relative stereocontrol.
  • Types of Pd salts and precursors, mechanisms of forming Pd(0). Fundamental mechanisms of Pd-oxidative addition, insertion, reductive elimination, transmetallation, beta-hydride elimination. Ligands.
  • Uses of Pd(II) complexes- Wacker oxidation, Pd(II) cat allylic rearrangements, cycloisomerisation of enynes.
  • Pd(0) complexes in Organic Synthesis- Negishi reaction (Zn), Kumada-Tamao-Corriu (MgX), Stille couplings (Sn) Suzuki reaction (B). Carbonylation reactions - CO at atmospheric pressure. Sonogashira reaction, Heck reaction, Pi-allyl chemistry.

B. An Introduction to Asymmetric Synthesus (6 Lectures, Dr. J. Wilden)

  • Enantiomers, diastereoisomers, meso-compounds, compounds from the chiral pool.
  • Prochiral nature of alkenes. Stereoselective alkene synthesis.
  • Asymmetric reaction of alkenes (dihydroxylation, epoxidation)
  • (E)- and (Z)-enolates and their use in simple aldol reactions: Stereochemical outcome.
  • Chiral auxiliaries in synthesis.

C. Frontier Orbitals in Organic Chemistry (8 Lectures, Dr. J. Wilden)

  • Simple orbital systems: Allyl anions and cations.
  • Orbitals and reactions of enolates
  • Hard and soft acids and bases.
  • Frontier orbitals applied to thermal pericyclic reactions (Diels-Alder).
  • 1,3-Dipolar cycloadditions and sigmatropic rearrangements.
  • Electrocyclic ring opening and closing reactions.

D. Stereoelectronic Control and Natural Product Synthesis (14 Lectures, Prof W. B. Motherwell)

The basic principle of effective orbital alignment will be illustrated using a range of examples taken from natural product chemistry, including:

  • Fragmentation Reactions (terpenes and macrolides).
  • Trans-diaxial ring opening (steroids).
  • Anomeric effect and protecting group strategy (carbohydrates).
  • Nucleophilic attack on cyclic iminium species (alkaloids)