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.
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 C-X Disconnections 23
5. Strategy II: Chemoselectivity 29
6. Two-Group C-X 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 C-C Disconnections I: Alcohols 69
11. General Strategy A: Choosing a Disconnection 77
12. Strategy V: Stereoselectivity A 83
13. One Group C-C 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 C-C Disconnections I: Diels-Alder Reactions 121
18. Strategy VIII: Introduction to Carbonyl Condensations 129
19. Two-Group C-C Disconnections II: 1,3-Difunctionalised Compounds 133
20. Strategy IX: Control in Carbonyl Condensations 139
21. Two-Group C-C 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 C-C 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
