Asymmetric Photochemistry Liu-Zhu Gong Group Meeting September 12, 2009 Wei-Jun Liu

1. Asymmetric Photochemistry Liu-Zhu Gong Group Meeting September 12, 2009 Wei-Jun Liu • Fundemental Reaction • Solid-Phase • Solution-Phase • Covalently-bound chiral auxilliaried • Chiral complexing agents • Chiral sensitizer Review: Rau, H. Chem. Review. 1983, 83, 535-547. Inoue, Y. Chem. Review. 1992, 92, 741-770. Konig, B. Chem. Review. 2006, 106, 5413-5430. Fagnoni, M. Chem. Review. 2007, 107, 2725-2756. Hoffmann, N. Chem. Review. 2008, 108, 1052-1103.

2. Fundmental Reactions 1.1 [2+2] photocycloaddition Synlett2002, 1305 J. Am. Chem. Soc.2009, 131, ASAP.

3. Paternò-Büchi Reaction (between a ketone and alkene) J. Org. Chem.2003, 68, 9899. J. Org. Chem.2004, 69, 33. Ang. Chem., Int. Ed.2003, 42, 1642

4. 1.2 Photochemical Rearrangments (di-ПЛ Synthesis2001, 1175

5. The Herteroatom Variant Photochemical Rearrangments Ang. Chem., Int. Ed.2002, 41, 4090

6. 1.3 Norrish-Yang Reaction Synthesis2001, 1253

7. 1.4 Intermolecular Addition onto Double or Triple C-C Bonds J. Org. Chem.2001, 66, 7320.

8. 1.5 Photo-oxygenation

9. Why Study Asymmetric Photochemistry? • Prebiotic photochemistry ---- enantiomeric excess of biomolecules may have been generated by circularly polarized light (CPL) • Environmentally benign processes ---- light is ubiquitous, generates no waste. • Different mode of reactivity ---- access to novel, strained compounds which are thermally inaccessible or diffcult to synthesize and low reaction temperature Why few Examples in Enantioselective Photochemical Transformations • Short excited lifetime • low activation energy for reactions in excited states A few energy difference of a few kilocalories per mole is sufficient to give >99% stereodifferentiation. Inoue, Y. Chem. Review. 1992, 92, 741-770.

10. 2. Enantioselective Solid-Phase Photochemistry 2.1 Host-Gest Cocrystals Toda, Chem. Comm.1995, 621

11. 100% ee Toda, TanakaACIE,1999, 38, 3523 91-99.5% ee TanakaOL,2002, 4, 3255

12. 2.2 Ionic Chiral Auxiliary SchefferACR,1996, 29, 203

13. 2.3 Chiral Modified Supercages of Zeolites Ramamurthy ACR,2003, 36, 509

14. 3. Enantioselective Solution-Phase Photochemistry 3.1 Covalently-bound chiral auxillaries Meyer, JACS,1986, 108, 306

15. Carreira, JACS,1994, 116, 6622 JACS,1997, 119, 2597

16. 3.2 Chiral Complexing Agents (Templated Photochemsitry) 3.2.1 Noncovalent Asseemblies EJOC,2002, 2298

17. Glycol-Metal Cation JOC,1995, 60, 7984

18. Diaminotriazine-barbiturate (二氨基三唑－巴比妥酸盐）

19. CR,2006, 106, 5413-5430

20. 3.2.2 Complementary DNA Strands as Templates CR,2006, 106, 5413-5430

21. 3.2.3 Templates with a Covalently Bound Chromophore and Recognition Site • The reaction did not proceed in the absence of the template

22. As an artificial functional model of a photolyase CR,2006, 106, 5413-5430

23. 3.2.4 Photochemical reaction in a molecular flask The molecular flask is significantly larger than the guest and can therefore protect Substrates from the surrounding environment and thus controls the course of a Photochemical reaction. Cyclodextrin • The syn isomers were the major. • The syn isomers changed to the minor. • Favorite temperate scaffolds • Good availability • Various sizes • Inherent chirality CR,2006, 106, 5413-5430

24. Self-Assembled Molecular Cage

25. 3.2.5 Templates Containing a Shield Mori and Nakamura, TL,1996, 37, 8523-8526

26. Bach, T. JACS,1999, 121, 10650-10651

27. Bach, T. ACIE,2000, 39, 2302-2304

28. Bach, T. JACS,2000, 122, 11525-11526

29. Bach, T. ACIE,2003, 42, 3693-3696

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31. Catalytic Enantioselective Photochemical Reaction Krische, J. JOC,2003, 68, 15-21

32. Bach, T. Nature,2005, 436, 1139-1140

33. Bach, T. ACIE,2009, 48, 1-4

34. Polymer-Bound Chiral Temple Bach, T. ACIE,2008, 47, 7957-7959

35. 3.3 Chiral Sensitizer

36. Photosensitized ant-Markovnikov methanol additiong to 1,1-diphenylpropene Inoue JCS CC,1993, 718 • [4+2] cycloaddition between electron-rich diene and electron-rich dienophile Schuster, JACS, 1990, 112, 9635

37. Sens* 2b : up to 70% ee • Switching the product chiralty by solvent • lower temperature higher ee • The higheat ee ever reported for an enantiodifferentiating photosensitization. Inoue, JACS, 2000, 122, 406-407

38. Garcia, JOC, 2002, 67, 5184-5189

39. 3.3 Activation of Substates by Chiral Catalysts (Organocatalysis) Cordova, JACS, 2004, 126, 8914 ACIE, 2004, 43, 6532

40. MacMillan Science, 2008, 322, 77 JACS, 2009, 131, 10875

41. 4 Photecatalysts A: Via electron transfer

42. B: Via H abstraction

43. 5. Conclusion • Solid-Phase asymmetric photochemistry can work very well, but has limited. • Solution-phase photochemistry is more attractive for the catalytic enantiosele- ctive photochemistry. More excellent catalysts as Bach’ catalysts and assymme- tric inducing model will be developed. • Asymmetric photochemistry using chiral sensitizers is usually poorly selective.