1. 2005-11-241 Chapter 12 Phosphorus reagents Topics: –For conventional Wittig reaction and developed Wittig reaction. –For conversion of hydroxy into halogen and for the formation of esters and amides from carboxylic acids. –For some reductive transformations.

2. 2005-11-242  Nomenclature for phosphorus reagents

3. 2005-11-243

4. 4  Phosphorus reagents for conventional Wittig reaction

5. 2005-11-245

6. 6

7. 7 In general: –Stabilized ylides (R 1 = -M group, e.g. an ester. E-isomer usually predominates. –Non-stabilized ylides (R, R 1 = hydrogen or simply alkyl, a mixture of E- and Z-isomers) –The ‘salt-Free’ wittig reaction of non-stabilized ylides gives the Z-alkene as the major product. –NaNH 2 or NaN(SiMe 3 ) 2 as bases yield increased Z-isomers. –Lithium halides present yield more of E-isomers.

8. 2005-11-248 For stabilized ylides, E-isomer usually predominates.

9. 2005-11-249  Unstabilized ylides yield most Z-isomers:

10. 2005-11-2410  Adding salts to unstabilized ylides yield most E-isomers:

11. 2005-11-2411 Another modification: the ylide is prepared by using PhLi and the addition to the aldehyde is carried out at –78 o C. Then a second mol. PhLi is added.

12. 2005-11-2412

13. 2005-11-2413 Azoylides

14. 2005-11-2414  Phosphorus reagents for developed Wittig reaction Horner-Wadsworth-Emmons Reaction

15. 2005-11-2415  Transition State Model (Compare stabilized ylides)

16. 2005-11-2416  Advantages for this reaction over the Wittig procedure include the following: Wittig reactions involving stabilized ylides are slow and, since additional stabilization by an electron-withdrawing group is required in almost all successful P=O stabilized carbanion reactions, the latter is the preferred procedure in such cases. A major problem in the Wittig procedure is the separation of the proceduct from the phosphine oxide; with P=O stabilized carbanion reactions the phosphorus is eliminated as a water-soluble phosphate anion.

17. 2005-11-2417 A. Lattanzi et al. /Tetrahedron Letters 44 (2003) 1333–1337 D. L. Comins, C. G. Ollinger /Tetrahedron Letters 42 (2001) 4115–4118

18. 2005-11-2418

19. 2005-11-2419  The Horner-Wittig reaction

20. 2005-11-2420 R’COOR’’

21. 2005-11-2421 Reactions of Carbon Nucleophiles with Carbonyl Groups. Wittig reaction The Aldol Condensation incl. Claisen cond. Robinson annulation Mannich reaction

22. 2005-11-2422 Phosphorus( Ⅲ ) reagents Mitsunobu esterification Reaction Mechanism:

23. 2005-11-2423 Mechanism: Side reaction:

24. 2005-11-2424

25. 2005-11-2425 Summary Phosphorus( Ⅲ ) reagents are nucleophilic but unlike their nitrogen analogues they are weakly basic. Trisubstituted phosphines and phosphites react with electrophiles of various kinds: –Alkylation of trialkyl- and triarylphosphines gives phosphonium salts, which may be precursors of ylides for use in the wittig reaction. –Alkylation of phosphites gives phosphonate esters (the Michaelis- Arbusov reaction), which may be the precursors of carbanions for use in the Horner-Wadsworth-Emmons alternative to the Wittig reaction: this variants yields predominantly the E-alkene. Other variants of the classical Wittig procedure may lead to cycloalkenes and alkynes.

26. 2005-11-2426 Phosphorus( Ⅲ ) reagents can be used for conversion of hydroxy into halogen and for the formation of esters and amides from carboxylic acids. Phosphorus( Ⅲ ) reagents readily abstract oxygen, sulfur and halogen from organic compounds. This property is used to effect the following reductive transformations: –thiiranes alkenes –1,2-diols alkenes –R 3 N + － O R 3 N –ArNO 2 ArN=O ArN:(a nitrene) various insertion products –R 2 S=O R 2 S –ArCl or ArBr ArH