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Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes

Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes. Tamio Hayashi. Erick Carreira. Daniela Sustac February 16, 2010. Outline. Transition Metal – Olefin Complexes. Alkenes not very basic, backbonding necessary to stabilize M-olefin bond;

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Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes

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  1. Rh-Catalyzed Asymmetric Additions: The Rise of Chiral Dienes Tamio Hayashi Erick Carreira Daniela Sustac February 16, 2010

  2. Outline

  3. Transition Metal – Olefin Complexes • Alkenes not very basic, backbonding necessary to stabilize M-olefin bond; • Olefins considered labile, easily displaced from M center. Crabtree, H.R. The Organometallic Chemistry of Transition Metals. Wiley: New Jersey, 2005.

  4. Transition Metal – Strained Alkene Complexes • Strained alkenes (cyclopropene, norbornene) bind very strongly to metals; • Rehybridization on binding relieves ring strain. Crabtree, H.R. The Organometallic Chemistry of Transition Metals. Wiley: New Jersey, 2005.

  5. Examples of Olefins in Complexes and Catalysis • Prepared by Zeise in 1827; • Structure elucidated in the 1950’s; • Norbornene in the Catellani reaction: “a sort of scaffold to be removed after the building of the molecule is complete; behaves as catalyst, excess necessary to push the reaction” Wunderlich, A.J.; Mellor, D.P. Acta Crystallogr. 1955, 8, 57. Catellani, M; Frignani, F.; Rangoni, A. Angew. Chem. Int. Ed. 2007, 36, 119.

  6. Who Binds the Strongest? • Electron deficient alkenes bind tighter; • Stronger binding with strained alkenes. Tolman, A.C. Organometallics 1983, 2, 614.

  7. Rh-Catalyzed 1,4-Addition (before chiral dienes) Consequently, the reaction can be done using directly [Rh(OH)(S-binap)]2 at 35 ºC. Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem. Soc. 2002, 124, 5052.

  8. Chiral Dienes: First Contact Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508. Hydrosylilation: Uozumi, Y.; Lee, S.-Y.; Hayashi, T. Tetrahedron Lett. 1992, 33, 7185.

  9. The (Only) One with A Lot of Scope Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.

  10. Explaining Stereochemistry Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.

  11. Chiral Dienes: First Contact • Advantages • Highest catalytic activity of all rhodium catalysts used for 1,4-addition; • Among the highest enantioselectivities (most over 90% ee); • Disadvantages • Long synthesis of chiral diene; • Bistriflate intermediate hard to isolate. Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem. Soc. 2003, 125, 11508.

  12. New Route to Chiral Dienes Berthon-Gelloz, G.; Hayashi, T. J. Org. Chem. 2006, 71, 8957. Vandyck, K.; Matthys, B.; Willen, M.; Robeyns, K.; Van Meervelt, L.; Van der Eycken, J. Org. Lett. 2006, 8, 363.

  13. One Unstable Chiral Diene, One Stable Rh Complex Berthon-Gelloz, G.; Hayashi, T. J. Org. Chem. 2006, 71, 8957.

  14. One More Carbon • Optical resolution by recrystallization inefficient route; • Alternatively, can do racemic synthesis and separate by chiral HPLC, either intermediate or final product. Otomaru, Y.; Okamoto, K.; Shintani, R.; Hayashi, T. J. Org. Chem. 2005, 70, 2503.

  15. To Be Stable or Not to Be Stable

  16. The One with iMean Arylation Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.

  17. Stereochemistry is Explained Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.

  18. The One with (a Bit) of Scope Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.; Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584.

  19. The One where They Do It Better? Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979. Boezio, A.A; Pytkowicz, J.; Cote, A.; Charette, A.B. J. Am. Chem. Soc. 2003, 125, 14260.

  20. The One with the iMean Mechanism Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.

  21. More Stereochemistry Explained Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979.

  22. Is Nine the Lucky Number? Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307.

  23. The One with the Deprotection By far the mildest approach! Boezio, A.A; Pytkowicz, J.; Cote, A.; Charette, A.B. J. Am. Chem. Soc. 2003, 125, 14260. Nishimura, T; Yasuhara, Y.; Hayashi, T. Org. Lett. 2006, 8, 979. Otomaru, Y.; Tokunaga, N.; Shintani, R.; Hayashi, T. Org. Lett. 2005, 7, 307.

  24. The One with the Cyclization of Alkynals *[Rh(OH)(cod)]2 used directly Shintani, R.; Okamoto, K.; Otomaru, Y; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.

  25. The One with the Mechanism Shintani, R.; Okamoto, K.; Otomaru, Y; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.

  26. The One with the Cyclization of Alkynals *Et instead of Me. Shintani, R.; Okamoto, K.; Otomaru, Y; Ueyama, K.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 54.

  27. Let’s Do Some Cycloadditions Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.

  28. [4+2] Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.

  29. Cycloaddition Mechanism Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.

  30. Stereochemistry Explained Shintani, R.; Sannohe, Y.; Tsuji, T.; Hayashi, T. Angew. Chem. Int. Ed. 2007, 46, 7277.

  31. 1,6-Enynes Cycloisomerization Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.

  32. Tfb (tetrafluorobenzobarrelene) Diene Synthesis • Chiral HPLC to separate enantiomers; • Low yielding steps. Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem. Commun. 2009, 5713.

  33. The One with the Catalyst Design A chiral diene and a phosphine on the same catalyst! Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.

  34. “Dig” the Mechanism Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.

  35. Stereochemistry Explained Nishimura, T.; Kawamoto, T.; Nagaosa, M.; Kumamoto, H.; Hayashi, T. Angew. Chem. Int. Ed. 2010, 49, In Press.

  36. More Chiral Dienes Most effective ligands reported so far for Rh-catalyzed asymmetric addition! Okamoto, K.; Hayashi, T.; Rawal, H.V. Org. Lett. 2008, 10, 4387.

  37. Last Stereochemistry Picture Okamoto, K.; Hayashi, T.; Rawal, H.V. Org. Lett. 2008, 10, 4387.

  38. Hayashi’s Dienes: Summary

  39. Ir-Catalyzed Allylic Displacement Potential for the diene to be synthesized asymmetrically from cheap (R) or (S)-carvone. Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E.M. J. Am. Chem. Soc. 2004, 126, 1628.

  40. Spin-Off: Carreira’s Diene Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E.M. J. Am. Chem. Soc. 2004, 126, 1628.

  41. Carreira’s Dienes Generation II“The Long Way Home” Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E.M. Org. Lett. 2004, 6, 3873.

  42. Again with the Enones? • Additional substrates in the scope (not covered by Hayashi) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E.M. Org. Lett. 2004, 6, 3873.

  43. One Ligand, One Day, Two Papers

  44. The Short Way Home Carreira Darses • Ortho substituted boronic acids a challenge; • Most accessible route; • Library of 14 ligands; • High enantioselectivities (over 90%). Gendrineau, T.; Chuzel, O.; Eijsberg, H.; Genet, J.-P.; Darses, S. Angew. Chem. Int. Ed. 2008, 47, 7669. Fischer, C.; Defieber, C.; Suzuki, T.; Carreira, E.M. J. Am. Chem. Soc. 2004, 126, 1628.

  45. Enantioselective Diene Synthesis Brown, K.M.; Corey, E.J. Org. Lett. 2010, 12, 172.

  46. Order of Addition Is Important • Diene is inhibited • Less strained system necessary Brown, K.M.; Corey, E.J. Org. Lett. 2010, 12, 172.

  47. Adding One More Carbon Brown, K.M.; Corey, E.J. Org. Lett. 2010, 12, 172.

  48. Summary Reviews: Defieber, C.; Grutzmacher, H.; Carreira, E.M. Angew. Chem. Int. Ed. 2008, 47, 4482. Johnson, B.J.; Rovis, T. Angew. Chem. Int. Ed. 2008, 47, 840.

  49. A Bit of Shopping: Chiral Dienes at Aldrich

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