1 / 49

Well-Defined Copper(I) Complexes: Useful Tools in Organic Synthesis Dr. Silvia D íez-González

Well-Defined Copper(I) Complexes: Useful Tools in Organic Synthesis Dr. Silvia D íez-González. Department of Chemistry, Imperial College London 03-Feb-2010. Overview: NHC–Metal Complexes. N-Heterocyclic Carbene Ligands (NHC). saturated/unsaturated substituted/unsubstituted tunable at will.

rhonda
Télécharger la présentation

Well-Defined Copper(I) Complexes: Useful Tools in Organic Synthesis Dr. Silvia D íez-González

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Well-Defined Copper(I) Complexes:Useful Tools in Organic SynthesisDr. Silvia Díez-González Department of Chemistry, Imperial College London 03-Feb-2010

  2. Overview: NHC–Metal Complexes

  3. N-Heterocyclic Carbene Ligands (NHC) saturated/unsaturated substituted/unsubstituted tunable at will tunable appending groups -donor and -acceptor (stabilization of the carbene) stabilized and localized lone pair excellent -donor ligand Strong NHC-metal bond, low degradation, low toxicity Reviews: (a) Special Issue Chem. Rev. 2009, 109, 3209–3884. (b) Angew. Chem., Int. Ed.2008, 47, 3122–3172.

  4. N-Heterocyclic Carbene Ligands

  5. Synthesis of NHCs: IPr as a Showcase Flexible and scalable synthesis

  6. Large Scale Synthesis: 3 Kg of IPr•HCl

  7. Large Scale Synthesis: 3 Kg of IPr•HCl IPrHCl DAB-Pr

  8. [(NHC)Cu] Complexes in Catalysis • Allylic Alkylation • N-Arylation ATRC • Aziridination • Diboration • Conjugate Addition • Hydroamination • Hydroalkoxylation Reviews: (a) Díez-González, S.; Nolan, S. P. Aldrichimica Acta2008, 41, 43–51. (b) Díez-González, S.; Nolan, S. P. Synlett 2007, 2158–2167.

  9. CATALYSTS PREPARATION

  10. Synthesis of [(NHC)CuX] Complexes X= Cl, Br or I 19 Highly Stable Complexes

  11. [(NHC)CuX]: Crystal Structures [(IPr)CuCl] [(ICy)CuCl] Cu–C1 = 1.956 Å C1–Cu–Cl = 180.0° Cu–C1 = 1.925 Å C1–Cu–Cl = 171.6°

  12. [(NHC)CuX]: Crystal Structures (II) [(IAd)CuI] [(ICy)CuI] Cu–C =1.927/1.973Å Cu(1)–Cu(2) = 2.453 Å Cu(1)–C(1) = 1.946 Å C(1)–Cu(1)–I(1) = 137.9°

  13. Undesired Reaction: New Family of Complexes First [(NHC)Cu] known in the literature: Arduengo, A. J., III; Rasika Dias, H. V.; Calabrese, J. C.; Davidson, F. Organometallics1993, 12, 3405-3409.

  14. Synthesis of [(NHC)2Cu]X Complexes X= PF6 or BF4 14 Highly Stable Complexes

  15. [(NHC)2Cu]X: Crystal Structures [(IAd)2Cu]PF6 [(IPr)2Cu]BF4 Cu–C(1) = 1.938 Å N1–C1–Cu–C1’–N1’ = 49.9° Cu–C1 = 1.933 Å N1–C1–Cu–C1’–N1’ = 86.8°

  16. Catalytic StudiesHYDROSILYLATION REACTIONS

  17. Previous work with [(NHC)CuX] Complexes ,-Unsaturated Ketones and Esters Jurkauskas, V.; Sadighi, J.; Buchwald, S. L. Org. Lett.2003, 5, 2417-2420. Simple Ketones Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics2004, 23, 1157-1160.

  18. Hydrosilylation of Challenging Substrates Hindered Ketones Functionalized Ketones Díez-González, S.; Kaur, H. Zinn, F. K.; Stevens, E. D.; Nolan, S. P. J. Org. Chem.2005, 70, 4784–4796.

  19. Hydrosilylation of Challenging Substrates (II) Heteroaromatic Ketones Díez-González et al. J. Org. Chem.2005, 70, 4784–4796.

  20. Proposed Mechanism Díez-González et al. J. Org. Chem.2005, 70, 4784–4796.

  21. [(NHC)2Cu]X: Hydrosilylation of Simple Ketones [(IPr)2Cu]BF4 vs [(IPr)CuCl] 0.5 h, 98% 1 h, 96% 0.33 h, 99% 4 h, 94% 0.33 h, 98% 2 h, 93% 4 h, 88% 5 h, 86% 3 h, 93% 1 h, 97% [(IPr)CuCl] (3 mol%), NaOt-Bu (12 mol%), Et3SiH (3 equiv), toluene, RT Díez-González, S.; Scott, N. M.; Nolan, S. P. Organometallics2006, 25, 2355–2358. [(IPr)CuCl]: Kaur et al.Organometallics2004, 23, 1157–1160.

  22. [(NHC)2Cu]X: Hydrosilylation of Aldehydes Also an ester: Díez-González et al. Organometallics2006, 25, 2355–2358.

  23. [(NHC)2Cu]X: Hydrosilylation of Hindered Ketones [(ICy)2Cu]BF4 vs [(ICy)CuCl] 1.5 h, 98% 5 h, 96% 0.5 h, 95% 2.5 h, 94% 1.5 h, 50% 0.5 h, 99% 0.25 h, 99% 0.6 h, 96% 1.5 h, 97% [(ICy)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, 80°C [(ICy)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (2 equiv), toluene, 55ºC Díez-González et al.Chem.–Eur. J.2008, 14, 158–168. [(ICy)CuCl]: Díez-González et al. J. Org. Chem.2005, 70, 4784–4796.

  24. Mechanistic Studies: Decomposition and Exchange Rates Díez-González, et al.Chem.–Eur. J.2008, 14, 158–168.

  25. Mechanistic Studies: Active Species Mono-NHC species as “true” catalyst Díez-González et al.Organometallics2006, 25, 2355–2358.

  26. Mechanistic Studies: Role of the Base Base as a pre-catalyst activator Díez-González et al.Organometallics2006, 25, 2355–2358.

  27. Postulated Mechanism Díez-González, et al.Chem.–Eur. J.2008, 14, 158–168. Díez-González, et al.J. Org. Chem.2005, 70, 4784–4796.

  28. Hydrosilylation Reactions: The Director’s Cut Initial Screening: Azolium Salts [(NHC)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, RT Kaur, H.; Zinn, F. K.; Stevens, E. D.; Nolan, S. P. Organometallics2004, 23, 1157–1160. Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted.

  29. Hydrosilylation Reactions: The Director’s Cut Formation of [(IPr)2Cu]X (~ 10 %) [(NHC)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, RT [(NHC)2Cu]X (3 mol %), NaOt-Bu (12 mol %), Et3SiH (2 equiv), THF, RT Díez-González, et al.Chem.–Eur. J.2008, 14, 158–168. Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted. Initial Screening: Azolium Salts

  30. Hydrosilylation Reactions: The Director’s Cut ~ 70% [(SIMes)2Cu]X [(NHC)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, RT [(NHC)2Cu]X (3 mol %), NaOt-Bu (12 mol %), Et3SiH (2 equiv), THF, RT Díez-González, et al.Chem.–Eur. J.2008, 14, 158–168. Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted. Hydrosilylation Reactions: The Director’s Cut Initial Screening: Azolium Salts

  31. Hydrosilylation Reactions: The Director’s Cut Sluggish formation of the complex Hydrosilylation Reactions: The Director’s Cut Initial Screening: Azolium Salts [(NHC)CuCl] (3 mol %), NaOt-Bu (12 mol %), Et3SiH (3 equiv), toluene, RT Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted.

  32. Hydrosilylation Reactions: [(SIMes)CuCl] Excellent activity under smoother conditions Compared to [(IPr)CuCl] Compared to [(ICy)CuCl], reactions at 80ºC Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted.

  33. Catalytic Studies[3+2] CYCLOADDITION REACTIONSCLICK CHEMISTRY

  34. Click Chemistry [Cu]: (a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064. (b) Rostovtev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596–2599. Assembly processes inspired by Nature - Modular reactions under simple reaction conditions - Straightforward isolation (no chromatography!) for very high yields Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed.2001, 40, 2004–2021. Huisgen [3+2] Cycloaddition Huisgen, R. Pure Appl. Chem. 1989, 61, 613–628.

  35. [(NHC)CuX] Screening Díez-González, S.; Correa, A.; Cavallo, L.; Nolan, S. P. Chem.–Eur. J.2006, 12, 7558–7564.

  36. Scope of the Reaction Díez-González et al. Chem.–Eur. J.2006, 12, 7558–7564.

  37. [(SIMes)CuBr] vs [(IAd)CuI] for Click Chemistry Díez-González, S.; Escudero-Adán, E.; Benet-Buchholz, J.; Stevens, E. D.; Slawin, A. M. Z.; Nolan, S.P., submitted.

  38. Further Applications of [(NHC)CuX] as Click Catalysts Porphyrine Functionalisation: Séverac, M.; Le Pleux, L.; Scarpaci, A.; Blart, E.; Odobel, F.Tetrahedron Lett.2007, 48, 6518–6522. Carbanucleosides as anti-pox agents (a) Broggi, J.; Díez-González, S.; Petersen, J. L.; Berteina-Raboin, S.; Nolan, S. P.; Agrofoglio, L. A. Synthesis2008, 141–148. (b) Broggi, J.; Joubert, N.; Díez-González, S.; Berteina-Raboin, S.; Zevaco, T.; Nolan, S. P.; Agrofoglio. L. A. Tetrahedron2009, 65, 1162–1170. Chelators for anti-cancer drugs Maisonial, A.; Serafin, P.; Traïkia, M.; Debiton, E.; Théry, V.; Aitken, D. J.; Lemoine, P.; Viossat, B.; Gautier, A.Eur. J. Inorg. Chem.2008, 298–305..

  39. Latent Click Catalyst Díez-González, S.; Stevens, E. D.; Nolan, S. P. Chem. Commun. 2008, 4747–4749.

  40. In Situ Generated Azides Previously reported conditions: Water/t-BuOH, 75 - 125°C MW 10 – 15 min Appukkuttan et al.Org. Lett. 2004, 6, 4223–4225 Díez-González et al. Chem.–Eur. J.2006, 12, 7558–7564.

  41. Accepted Reaction Mechanism Internal alkynes would not react under these conditions… Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc.2004, 127, 210–216.

  42. Internal Alkynes Copper AND Ligand Effect: Mechanistic implications… Díez-González et al. Chem.–Eur. J.2006, 12, 7558–7564. For another example, see: Candelon, N.; Lastécouères, D.; Diallo, A. K.; Ruiz Aranzaes, J.; Astruc, D.; Vincent, J.-M. Chem. Commun. 2008, 741–743.

  43. DFT Calculations: Novel Activation of Alkynes The NHC facilitates the  -Cu-alkyne binding and permits the cycloaddition Díez-González et al. Chem.–Eur. J.2006, 12, 7558–7564. Activation towards cycloaddition via-binding unfavoured Himo et al.J. Am. Chem. Soc.2004, 127, 210–216.

  44. Distinct Mechanisms Depending on the Alkyne Nature Díez-González et al. Chem.–Eur. J.2006, 12, 7558–7564.

  45. [(NHC)2Cu]X as Click Catalysts: Very Low [Cu] Loadings TONs up to 20 250; TOFs up to 5000 h-1 Díez-González, S.; Nolan, S. P. Angew. Chem., Int. Ed. 2008, 47, 8881–8884.

  46. Proposed Mechanism for [(NHC)2Cu]X Catalysts Díez-González, S. et al.Angew. Chem., Int. Ed. 2008, 47, 8881–8884.

  47. [(NHC)CuI] Complexes: CONCLUSIONS [(NHC)CuX] & [(NHC)2Cu]X • Practical preparation, high stability • Excellent catalysts for hydrosilylation and [3+2] cycloaddition reactions [(NHC)CuX] [(NHC)2Cu]X • Catalysts of choice for very challenging ketones • Low catalyst loading (< 1 mol %) • Use of internal alkynes • Latent catalyst • Active under smoother conditions • Enhanced catalytic activity • Active at ppm levels • KEY ROLE OF THE SECOND NHC

  48. [(NHC)CuI] Complexes: CONCLUSIONS Preparation of a library of well-defined complexes • Organometallic interest: - Synthetic procedures - Coordination chemistry • Better chances of finding the optimal catalysts • Improved control of the species present in the reaction media - Catalytic performance - Mechanistic implications

  49. ACKNOWLEDGEMENTS • Crystallography: Prof. Edwin D. Stevens & Dr. Natalie M. Scott (UNO) Prof. Jeffrey Petersen (West Virginia) Eduardo Escudero, Dr. Jordi Benet (ICIQ) Prof. Alex M. Z. Slawin (St. Andrews) • DFT Calculations: Dr. Andrea Correa & Prof. Luigi Cavallo (Salerno) • Hosting: Prof. Deryn Fogg (Ottawa) • Collaborators: Prof. Hélène Lebel (Montreal) Prof. Arnaud Gautier (Blaise-Pascal – Clermont) Prof. Olivier Riant (Louvain)

More Related