Synthetic Principles and Methodologies

1. Synthetic Principles and Methodologies Chung-Yi Wu Assistant Research Fellow Genomics Research Center Tel: 02-2789-9930 ext 349 Email: cyiwu@gate.sinica.edu.tw

4. Text books • Designing Organic Syntheses: A Programmed Introduction to the Synthon Approach. Stuart Warren Wiley, 1978. • The Logic of Chemical SynthesisE.J. CoreyWiley, 1989. • Modern Organic Synthesis: An Introduction • George S. Zweifel, Michael H. Nantz Freeman 2006.

5. TM:target molecules. • Retrosynthetic analysis (antithesis):The construction of a synthetic tree by working backward from the target molecule. • Transfrom: The symbol signifies a reverse synthetic step. • Disconnections: The main transforms are disconnections, or cleavage of C-C bonds, and functional group interconversions (FGI). • Synthons: the fragments resulting from disconnection of C-C bonds of the TM. • Synthetic equivalents (SE):The actual substrates used for the forward synthesis.

6. Chemical bonds can be cleaved heterolytically, homolytically, or through concerted transform Electrophilic Acceptor Nucleophilic Donor

7. Dornor and Acceptor Synthons

9. Alternating Polarity Disconnections • ?How one chooses appropriate C-C bond disconnections. • Answer: The concept of alternating polarities or latent polarities (imaginary charges) often enables one to identify the best positions to make a disconnection within a complex molecule.

10. The positive charge (+) is placed at the carbon attached to the E class function group (e.g.,=O,-OH, -Br) Consonant pattern: Positives charges are placed at carbon atoms bonded to the E class groups Dissonant pattern: One E class group is bonded to a carbon with a positive charge, whereas the other E class group resides on a carbon with a negative charge. If a consonant pattern is present in a molecule, a simple syjthesis often be achieved

12. One Functional Group

29. Wittig Reaction

31. Friedel-Crafts alkylation and acylation reactions of aromatic substrates

33. (ortho direction) (meta direction)

34. (more active)

35. Sometimes, rather than protect one part of a molecule, it is better to activate another (poor yield)

36. By hydrolysis and decarboxylation

37. A general synthesis for ketones and the corresponding disconnection

38. (Diels-Alder reaction)

39. (diene)

40. (acetone anion equivalent)

42. Acid derivatives

44. (amide bond formation)

46. Fully saturated hydrocarbons

49. Summary and Revision