One approach to organic synthesis is retrosynthetic analysis. With this approach a chemist will start with the structure of their target molecule and progressively cut bonds to create simpler molecules. Reversing this process gives a synthetic route to the target molecule from simpler starting materials. This disconnection approach to synthesis is now a fundamental part of every organic synthesis course.

Organic Synthesis: The Disconnection Approach, 2nd Edition introduces this important technique, to help students to design their own organic syntheses. There are forty chapters: those on the synthesis of given types of molecules alternate with strategy chapters in which the methods just learnt are placed in a wider context. The synthesis chapters cover many ways of making each type of molecule starting with simple aromatic and aliphatic compounds with one functional group and progressing to molecules with many functional groups. The strategy chapters cover questions of selectivity, protection, stereochemistry, and develop more advanced thinking via reagents specifically designed for difficult problems.

Examples are drawn from pharmaceuticals, agrochemicals, natural products, pheromones, perfumery and flavouring compounds, dyestuffs, monomers, and intermediates used in more advanced synthetic work. Reasons for wishing to synthesise each compound are given.

This second edition has been fully revised and updated with a modern look. Recent examples and techniques are included and illustrated additional material has been added to take the student to the level required by the sequel, Organic Synthesis: Strategy and Control.

Several chapters contain extensive new material based on courses that the authors give to chemists in the pharmaceutical industry.

Organic Synthesis: The Disconnection Approach, 2nd edition provides a full course in retrosynthetic analysis for chemistry and biochemistry students and a refresher for organic chemists working in industry and academia.

Dr Stuart Warren, Department of Chemistry, University of Cambridge, UKDr Warren is the author of the bestselling textbooksOrganic Synthesis: The Disconnection Approach (Wiley),Organic Synthesis: Strategy and Control (Wiley) andOrganic Chemistry (OUP).

Dr Paul Wyatt, School of Chemistry, University of Bristol, UKDr Wyatt is Director of Undergraduate Studies for the School of Chemistry at Bristol University and also Director of BRISTOL ChemLabS - a HEFCE Centre for Excellence in Teaching& Learning. He is co-author, with Warren, ofOrganic Synthesis: Strategy and Control.

Preface ix

General References xi

1. The Disconnection Approach 1

2. Basic Principles: Synthons and Reagents Synthesis of Aromatic Compounds 7

3. Strategy I: The Order of Events 17

4. One-Group CX Disconnections 23

5. Strategy II: Chemoselectivity 29

6. Two-Group CX Disconnections 35

7. Strategy III: Reversal of Polarity, Cyclisations, Summary of Strategy 45

8. Amine Synthesis 53

9. Strategy IV: Protecting Groups 61

10. One Group CC Disconnections I: Alcohols 69

11. General Strategy A: Choosing a Disconnection 77

12. Strategy V: Stereoselectivity A83

13. One Group CC Disconnections II: Carbonyl Compounds 93

14. Strategy VI: Regioselectivity 101

15. Alkene Synthesis 107

16. Strategy VII: Use of Acetylenes (Alkynes) 115

17. Two-Group CC Disconnections I: Diels-Alder Reactions 121

18. Strategy VIII: Introduction to Carbonyl Condensations 129

19. Two-Group CC Disconnections II: 1,3-Difunctionalised Compounds 133

20. Strategy IX: Control in Carbonyl Condensations 139

21. Two-Group CC Disconnections III: 1,5-Difunctionalised Compounds Conjugate (Michael) Addition and Robinson Annelation 151

22. Strategy X: Aliphatic Nitro Compounds in Synthesis 161

23. Two-Group Disconnections IV: 1,2-Difunctionalised Compounds 167

24. Strategy XI: Radical Reactions in Synthesis 177

25. Two-Group Disconnections V: 1,4-Difunctionalised Compounds 185

26. Strategy XII: Reconnection 193

27. Two-Group CC Disconnections VI: 1,6-diCarbonyl Compounds 199

28. General Strategy B: Strategy of Carbonyl Disconnections 207

29. Strategy XIII: Introduction to Ring Synthesis: Saturated Heterocycles 217

30. Three-Membered Rings 229

31. Strategy XIV: Rearrangements in Synthesis 237

32. Four-Membered Rings: Photochemistry in Synthesis 245

33. Strategy XV: The Use of Ketenes in Synthesis 251

34. Five-Membered Rings 255

35. Strategy XVI: Pericyclic Reactions in Synthesis: Special Methods for Five-Membered Rings 261

36. Six-Membered Rings 269

37. General Strategy C: Strategy of Ring Synthesis 279

38. Strategy XVII: Stereoselectivity B 289

39. Aromatic Heterocycles 301

40. General Strategy D: Advanced Strategy 313

Index 325