1. 1 Single electron transfer reaction involving 1,3-dicarbonyl compounds and its synthetic applications Reporter: Jie Yu Oct. 31, 2009

2. 2 Introduction to the free-radical reaction Intramolecular cyclization Tandem annulations Triple and higher cyzlizations Asymmetric Induction  -hydroxylation with O 2 Radical reactions of [60]fullerene Oxidative addition 1,2-radical rearrangment Synthetic applications

3. 3 In the propagation steps, the most popular way to control enantioselectivity has been the use of a chiral Lewis acid. The chiral Lewis acid can be used to bind to substrate or radical species and determine the approach of the other reacting component while accelerating the chiral pathway relative to the background reaction. Sibi, M. P. Chem. Rev. 2003, 103, 3263 1.Introduction — Elementary Steps in Radical Reactions

4. 4 1) Reductive process: The metal acts as a reductant in this process and the carbon- centered radicals can be generated by an atom transfer or electron transfer from metal complex to the radical precursor. Such as pinacol coupling of dialdehyde using Ti(III) and Zn. 1.Introduction — Transition metal-promoted radical reaction Iqbal, J. Chem. Rev. 1994, 94, 519 Transition metal-promoted reaction of carbon-centered radicals may be divided into two categories:

5. 5 1.Introduction — Transition metal-promoted radical reaction 2) Oxidative process: The reaction proceeds via an organometallic reagent which may lead to the carbon-centered radical on homolytic cleavage of carbon-metal bond. Iqbal, J. Chem. Rev. 1994, 94, 519

6. 6 1.Introduction — Machanism of oxidation with Mn(III) involving  -keto esters  -alkyl  -keto ester:  -unsubstituted  -keto ester: 1)A methyl group should slow down the formation of Mn(III) enolate, since it is electron donating and decreases the acidity of the  -proton. 2)The methyl group should facilitate the oxidation since it will stabilize the radical. Why? Snider, B. B. Chem. Rev. 1996, 96, 339

7. 7 2. Intramolecular cyclization Snider, B. B. Chem. Rev. 1996, 96, 339 different type of the dicarbonyl compounds:

8. 8 2. Intramolecular cyclization A. The formation of cycloalkanones 6-endo-cyclization (n=1) to give the product is the exclusive reaction if the proximal carbon is more highly substituted than the distal carbon Snider, B. B. J. Org. Chem. 1988, 53, 2137

9. 9 The low yield is due to the further oxidation of the products. The cyclized radical is oxidized to a cation, which loses a proton to give alkene or reacts with solvent to give acetate. Snider, B. B. J. Org. Chem. 1988, 53, 2137 2. Intramolecular cyclization A. The formation of cycloalkanones

10. 10 Snider, B. B. Tetrahedron 1995, 51, 12983 2. Intramolecular cyclization A. The formation of cycloalkanones Snider, B. B. Org. Lett. 2004, 6, 1265 It can be trapped with azide and Mn(III) to give cyclic and bicyclic azides. Reduction of the azide gives bi- and tricyclic lactams.

11. 11 2. Intramolecular cyclization B. The formation of cycloalkanes Snider, B. B. J. Org. Chem. 1990, 55, 2427 Rama Rao, A. V. Chem. Commun. 1989, 400

12. 12 2. Intramolecular cyclization B. The formation of cycloalkanes Snider, B. B. Tetrahedron 2002, 58, 25

13. 13 Corey, E. J. J. Am. Chem. Soc. 1984, 106, 5384 Fristad, W. E. Tetrahedron Lett. 1985, 26, 3761 2. Intramolecular cyclization C. The formation of lactones & lactams

14. 14 2. Intramolecular cyclization C. The formation of lactones & lactams Cossy, J. J. Org. Chem. 2000, 65, 7257 Cossy, J. Tetrahedron Lett. 1989, 30, 4531 Conditions: Mn(OAc) 3, EtOH, K 2 CO 3 Conditions: Mn(OAc) 3, EtOH

15. 15 2. Intramolecular cyclization D. Additions to aromatic rings Ce IV = CAN; HX = MeOH Cetterio, A. Synthesis, 1990, 142 Muchowski, J. M. Can. J. Chem. 1992, 70, 1838

16. 16 3. Tandem annulations A. Intramolecular Snider, B. B. J. Am. Chem. Soc. 1990, 112, 2759 Snider, B. B. J. Org. Chem. 1991, 56, 328

17. 17 3. Tandem annulations A. Intramolecular access to the core skeletons of Oroidin Dimers : Chen, C. Angew. Chem. Int. Ed. 2006, 45, 4345

18. 18 3. Tandem annulations B. Intermolecular First Tandem Cyclization of Alkylenecyclopropanes Huang, X. J. Org. Chem. 2004, 69, 5471

19. 19 3. Tandem annulations B. Intermolecular Shi, M. J. Org. Chem. 2005, 70, 3859

20. 20 3. Tandem annulations B. Intermolecular Further oxidized by a sencond equiv of CAN to the corresponding cation Ruzziconi, R. Synth. Commun. 1988, 18, 1841 Nair, V. J. Chem. Soc., Perkin Trans. 1 1995, 187

21. 21 3. Tandem annulations C. Group-transfer reaction —— bromine atom Yang, D. Angew. Chem. Int. Ed. 2002, 41, 3014 Yang, D. J. Am. Chem. Soc. 2001, 123, 8612 The addition of molecular sieves led to reversed enantiofacial selectivity of the cyclization

22. 22 3. Tandem annulations C. Group-transfer reaction —— chlorine atom Yang, D. Org. Lett. 2006, 8, 5757

23. 23 Transition-state: Yang, D. Angew. Chem. Int. Ed. 2006, 45, 255 3. Tandem annulations C. Group-transfer reaction —— PhSe-group

24. 24 4. Triple and higher cyzlizations Snider, B. B. J. Am. Chem. Soc. 1990, 112, 2759 Gonzalez, M. A. J. Org. Chem. 2007, 72, 7462

25. 25 5. Asymmetric Induction Snider, B. B. J. Org. Chem. 1991, 56, 328

26. 26 5. Asymmetric Induction Snider, B. B. Tetrahedron Lett. 1992, 33, 5921. Snider, B. B. J. Org. Chem. 1993, 58, 7640

27. 27 Kurosawa, K. Bull. Chem.Soc. Jpn. 1991, 64, 3557 Kurosawa, K. Bull. Chem.Soc. Jpn. 1992, 65, 1371 Kurosawa, K. J. Org. Chem. 1993, 58, 4448 Ruveda, E. A. Tetrahedron 1990, 46, 4149 6.  -hydroxylation with O 2 Christoffers, J. J. Org. Chem. 1999, 64, 7668

28. 28 6.  -hydroxylation with O 2 use dioxygen as oxidant; the cerium salt can be considered as the optimal catalyst since it is non-toxic and inexpensive. Christoffers, J. Eur. J. Org. Chem. 2003, 425 Christoffers, J. Eur. J. Org. Chem. 2006, 2601 Christoffers, J. Adv. Synth. Catal. 2004, 346, 143 Christoffers, J. Chem. Eur. J. 2004, 10, 1042

29. 29 7. Radical reactions of [60]fullerene Wang, G. W. Org. Biomol. Chem., 2006, 4, 2595 Wang, G. W. Org. Biomol. Chem., 2005, 3, 794 mechanism:

30. 30 8. Oxidative addition Perumal, P. T. J. Heterocyclic Chem. 2007, 44, 827 Wang, G. W. J. Org. Chem. 2008, 73, 7088

31. 31 9. 1,2-radical rearrangment Nishino, H. J. Org. Chem. 2009, 74, 3978

32. 32 10. Synthetic applications Helichrysum dendroideum 3, 4 was isolated from the leaves of Helichrysum dendroideum Snider, B. B. J. Org. Chem. 1998, 63, 7945

33. 33 10. Synthetic applications Snider, B. B. J. Org. Chem. 1998, 63, 7945 Key step:

34. 34 10. Synthetic applications Snider, B. B. J. Org. Chem. 1998, 63, 7945

35. 35 10. Synthetic applications Yang, D. J. Am. Chem. Soc. 1999, 121, 5579 Tripterygium wilfordii Hook F

36. 36 10. Synthetic applications (a) Mn(OAc) 32H 2 O(2.2equiv),Yb(OTf) 3 H 2 O (1.0 equiv), CF 3 CH 2 OH, -5 o C, 77%; (b) KHMDS, THF, -78 o C to -30 o C, then PhNTf 2, 95%; (c) DIBAL-H (2.2 equiv), CH 2 Cl 2, -78 to -30 o C, 20 h, 63%; (d) CO, Bu 3 N, Pd(Ph 3 P) 4, LiCl, CH 3 CN, 65 o C, 12 h, 93%; (e) BBr 3, CH 2 Cl 2, -78 o C to rt, 98%; Yang, D. J. Am. Chem. Soc. 1999, 121, 5579

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