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Oxaziridines : What Can You Do With A Strained Three - Membered Heterocycle

Oxaziridines : What Can You Do With A Strained Three - Membered Heterocycle. ( organic chemists ) Literature meeting Carl Trudel February 7 th 2011. Some Generalities. First discovered by William D. Emmons in 1956. Worked for Rohm and Haas Company's (Dow Chemical Company)

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Oxaziridines : What Can You Do With A Strained Three - Membered Heterocycle

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  1. Oxaziridines : What Can You Do With A StrainedThree-MemberedHeterocycle (organicchemists) Literature meeting Carl Trudel February 7th 2011

  2. Some Generalities • First discovered by William D. Emmons in 1956. • Worked for Rohm and Haas Company's (Dow Chemical Company) • HWE (least imaginative of his work!) • Died in 2001 • Discovery followed by H. Krimm and... • ... L. Horner! Emmons, W. D. J. Am. Chem. Soc. 1956, 78,6208-6209.Horner, L.; Jürgens, E. Chem. Ber. 1957, 90,2184-2189.

  3. Davis’ Oxaziridines Davis, F. A. et al. J. Am. Chem. Soc. 1988, 110, 8477-8482. Davis, F. A.; Sheppard, A. C. J. Org. Chem. 1987, 52, 954-955. Evans, D. A. et al. J. Am. Chem. Soc. 1985, 107, 4346-4348.

  4. The Program • Some generalities • Oxaziridines’ preparation • Their properties • Their reactivity • Photoisomerisation • “O”-transfer agents • “N”-transfer agents • Dipolar cycloaddition agent

  5. Oxaziridines Preparation : Imines Oxidation Emmons, W. D. J. Am. Chem. Soc. 1956, 78,6208-6209.Horner, L.; Jürgens, E. Chem. Ber. 1957, 90,2184-2189. Widmer, J.; Keller-Schierlein, W. Helv. Chim. Acta 1974, 57, 657-664. Aube, J. et al. J. Am. Chem. Soc. 1995, 117,5169-5178.

  6. Stereochemical considerations • Syn-directing OH • Anti to EWG Wang, Y.; Chackalamannil, S.; Aube, J. J. Org. Chem. 2000, 65, 5120-5126.

  7. Proposed Mechanism • Imine geometry has little effect (stereoselectivity vs specificity). • Faster for electron poor imines and electron rich peracids. • Accelerated by protic solvents. • Electrophilic oxydant (DMDO) generates significant amount of nitrone. Aube, J. et al. J. Org. Chem. 2000, 65, 5120-5126. Belzecki, C.; Mostowicz, D. J.Org. Chem.1975, 40, 3878-3880. Ogata, Y.; Sawaki, Y. J. Am. Chem. Soc. 1973, 95, 4687-4692.Nose, Ž.; Kovač, F. Int. J. Chem. Kinet. 2007, 39, 492-497.

  8. Other Schiff Base Oxydation Davis, F. A.; Chattopadhyay, S.; Towson, J. C.; Lal, S.; Reddy, T. J. Org. Chem. 1988, 53, 2087-2089. Jain, S. L.; Singhal, S.; Sain, B. J. Organomet. Chem. 2007, 692, 2930-2935. Kraïem, J.; Ben Othman, R.; Ben Hassine, B. C. R. Chim., 2004, 7, 1119-1126.

  9. NH Oxaziridines : KetonesAmination Anreae, S.; Schmitz, E. Synthesis 1991, 327-341. Schulz, M.; Becker, D.; Rieche, A. ACIE 1965, 4, 525-526.

  10. Photololysis of Nitrones • This mechanism may be involved in the photochemical epimerization of oxaziridines. Ning, R. Y.; Field, G. F.; Sternbach, L. H. J. Heterocycl. Chem. 1970, 7, 475-478. Boyd, D. R. et al. J. Chem. Soc., Chem. Commun. 1976, 162-163.

  11. Some Considerations • Photochemical epimerization • Thermal nitrogen inversion is unfavored • Ring strain increases in TS‡ • Inductive effect of adjacent O Boyd, D. R. et al. J. Chem. Soc., Chem. Commun. 1976, 162-163. Boyd, D. R.J. Chem. Soc., Chem. Commun. 1992, 1078-1079.Boyd, D. R. J. Chem. Soc., Perkin Trans. 2 1973, 1575-1577.

  12. The Program • Some generalities • Oxaziridines’ preparation • Their properties • Their reactivity • Photoisomerisation • “O”-transfer agents • “N”-transfer agents • Dipolar cycloaddition agent

  13. Photo- Oxaziridine to Amide Rearrangement • Biradical mechanism • Concerted alkyl migration • C-C bond anti to the hydrogen lone pair Malrieu, J. P. et al. J. Am. Chem. Soc. 1979, 101, 318-322. Lattes, A. et al. J. Am. Chem. Soc. 1982, 104, 3929-3934.

  14. Oxaziridines to Amides • Photochemical process • Apparent «less stable radical» leads to the product • Nitrones also work altough with lower yields • More strained product is obtained Lattes, A. et al. J. Am. Chem. Soc. 1982, 104, 3929-3934. Girard, J.-P. et al. Org. Lett. 2001, 3, 3067-3070. Aube, J. Chem. Soc. Rev. 1997, 26, 269.

  15. Oxaziridines to Amides • Transition metal catalysed process • Opposed stereoselectivity • Stereospecific Suda, K.; Sashima, M.; Izutsu, M.; Hino, F. J. Chem. Soc., Chem. Commun. 1994, 949-950.

  16. Oxaziridines to Amide • Transition metal catalysed process • Stabilised intermediate • Substituent syn to the lone pair migrates • Towards an atom economic amid synthesis? Suda, K. et al. J. Chem. Soc., Chem. Commun. 1994, 949-950. Crabtree, R. H. et al. Green Chem. 2007, 9, 976-979.

  17. The Program • Some generalities • Oxaziridines’ preparation • Their properties • Their reactivity • Photoisomerisation • “O”-transfer agents • “N”-transfer agents • Dipolar cycloaddition agent

  18. “O” Transfer Agents • Can act as O or N transfer agents • N substituent tunes the reactivity • Steric and electronic effects • Electron poor imine derivatives react faster • Nucleophiles may react in a SN2 fashion (N-O bond)… • …Or via a concerted asynchronous TS • Epoxidations occurs in a spiro transition state Davis, F. A. et al. J.Org. Chem. 1986, 51, 4240-4245. Houk, K. N. et al. J. Am. Chem. Soc. 1997, 119, 10147-10152.

  19. AsymetricEnolate Oxidation • SN2-typem attack • Racemic oxaziridine Evans, D. A. et al. J. Am. Chem. Soc. 1985, 107, 4346-4348.

  20. Dynamic Kinetic Asymetric Hydroxylation Reddy, D. S.; Shibata, N.; Nagai, J.; Nakamura, S.; Toru, T. Angew. Chem. Int. Ed. 2009, 48, 803-806.

  21. O Transfer to Heteroatom : Sulfur Oxidation Clerici, F. et al. Tetrahedron: Asymmetry 2009, 20, 2247-2256.Guillen, F. et al. Tetrahedron: Asymmetry 2007, 18, 2959-2964.

  22. IntramolecularEpoxidation • Intramolecular process proven by competitive experiment with 13C and 18O labeled oxaziridine Anderson, D. R.; Woods, K. W.; Beak, P. Org. Lett. 1999, 1, 1415-1417.

  23. IntramolecularEpoxidation • Electron rich alkene • Regiocontrol via a six-membered ring transition state Armstrong, A.; Draffan, A. G. J. Chem. Soc., Perkin Trans. 1 2001, 2861-2873.

  24. Catalytic Epoxidation • Phosphonio imine can be converted in situ in oxaziridine oxidant. • Reaction takes 3 to 45 hours • Concerted mechanism • Electron rich alkene reacts first • Cyclohexene derivatives showed increased reactivity over linear alkene Prieur, D.; El Kazzi, A. e.; Kato, T.; Gornitzka, H.; Baceiredo, A. Org. Lett. 2008, 10, 2291-2294.

  25. Oxaziridinium Salt • Faster than m-CPBA • C=O directed (vs O-H) Hanquet, G. et al.Tetrahedron Lett. 1993, 34, 7271-7274. Lusinchi, X.; Hanquet, G. Tetrahedron 1997, 53, 13727-13738.Bohé, L.; Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55, 141-154.

  26. Oxaziridinium Salt • Faster than m-CPBA • C=O directed (vs O-H) • Stoechiometric oxaziridinium gave 42% ee. • 5 mol% of iminium, oxone/NaHCO3 system at RT Hanquet, G. et al.Tetrahedron Lett. 1993, 34, 7271-7274. Lusinchi, X.; Hanquet, G. Tetrahedron 1997, 53, 13727-13738.Bohé, L.; Lusinchi, M.; Lusinchi, X. Tetrahedron 1999, 55, 141-154.

  27. Improving the Asymmetric Epoxidation Page, P. C. B. et al. J. Org. Chem. 1998, 63, 2774-2777. Page, P. C. B. et al. J. Org. Chem. 2001, 66, 6926-6931.

  28. Improving Asymmetric Epoxidation • Oxidation step is less selective at 0°C. Page, P. C. B. et al. J. Org. Chem. 2001, 66, 6926-6931.

  29. Improving the Asymmetric Epoxidation Page, P. C. B. et al. J. Org. Chem. 1998, 63, 2774-2777. Page, P. C. B. et al. J. Org. Chem. 2001, 66, 6926-6931.

  30. PerfluorinatedOxaziridines • Perfluorinated Oxaziridines are stable up to 120°C • Fairly strong oxidant • Oxidizes sulfides to sulfoxides or sulfones, pyridine and tertiary amines to N-Oxides, silanes to silanol and alcohol and ethers to ketones… • Can perform epoxidation on unactivated or electron poor alkenes. Petrov, V. A.; Resnati, G. Chem. Rev. 1996, 96, 1809.Resnati, G. et al. J. Org. Chem. 1994, 59, 5511-5513.

  31. PerfluorinatedOxaziridines • … And capable of C-H bond activation! • Enantiospecific • 3° C-H > 2° C-H >> 1° C-H • Equatorial > Axial • Oxidized alcohol and ethers Resnati, G. et al. J. Org. Chem. 1994, 59, 5511-5513. Sorochinsky, A. E.et al. Tetrahedron 1997, 53, 5995-6000.

  32. Catalytic Hydroxylation of 3° C-H Bonds Brodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127, 15391-15393.Litvinas, N. D.; Brodsky, B. H.; Du Bois, J. Angew. Chem. Int. Ed. 2009, 48, 4513-4516.

  33. Catalytic Hydroxylation of 3° C-H Bonds Brodsky, B. H.; Du Bois, J. J. Am. Chem. Soc. 2005, 127, 15391-15393.Litvinas, N. D.; Brodsky, B. H.; Du Bois, J. Angew. Chem. Int. Ed. 2009, 48, 4513-4516.

  34. The Program • Some generalities • Oxaziridines’ preparation • Their properties • Their reactivity • Photoisomerisation • “O”-transfer agents • “N”-transfer agents • Dipolar cycloaddition agent

  35. “N” Transfer Agents • Can act as O or N transfer agents • N substituent tunes the reactivity • Smaller alkyl groups • Carbonyl derivatives • R1 and/or R2 are EWG • Betaine intermediate? Vidal, J. et al. Chem. Euro. J. 1997, 3, 1691-1709.

  36. N-N Bond Formation • Bulkier amines • Aminoesters • Anilines • One-pot 1,3,5-pyrazoles Vidal, J. et al. Tetrahedron Lett. 1998, 39, 8845-8848.Armstrong, A. et al. Org. Lett. 2005, 7, 713-716.

  37. N-O Bond formation Foot, O. F.; Knight, W. Chem. Commun. 2000, 975-976.

  38. N-S Bond Formation • Competitive oxidation pathway • Solvant and temperature play an important role • Not a steric effect Vidal, J. et al. Chem. Euro. J. 1997, 3, 1691-1709. Armstrong, A.; Cooke, R. S. Chem. Commun. 2002, 904-905.

  39. N-S Bond and Sigmatropic Rearrangement Armstrong, A.; Cooke, R. S. Chem. Commun. 2002, 904-905. Armstrong, A. et al. J. Org. Chem. 2006, 71, 4028-4030. Armstrong, A.; Cooke, R. S.; Shanahan, S. E. Org. Biomol. Chem. 2003, 1,3142.

  40. N-H Oxaziridines : C Aminating Agents • Very reactive towards nucleophilic attack • Good aminating agents Andreae, S.; Schmitz, E. Synthesis 1991, 327-341.

  41. C-N Bond Formation Andreae, S.; Schmitz, E. Synthesis 1991, 327-341. Bulman Page, P. C. et al. J. Org. Chem. 2002, 67, 7787-7796.

  42. N-Substituted Oxaziridines Issues • Competitive aldol addition with enolates • Competitive diamination Armstrong, A.; Edmonds, I. D.; Swarbrick, M. E.; Treweeke, N. R. Tetrahedron 2005, 61, 8423-8442.

  43. ElectrophilicAmination Of Diorganozinc • Low reactivity of R2Zn towards ketones or aldehydes Ghoraf, M.; Vidal, J. Tetrahedron Lett. 2008, 49, 7383-7385.

  44. IntramolecularAmination of C-H Bonds • Teshik P. Yoon • A.B., Harvard University (Evans), 1996 • M.S., Caltech (Carreira), 1998 • Ph.D., Caltech (MacMillan), 2002 • Postdoc, Harvard (Jacobsen), 2002-2005 • Assistant Professor of Chemistry, 2005–present • University of Wisconsin, Madison • Total synthesis, visible light photocatalysis… • …New reactions of oxaziridines. • Same State as the Green Bay Packers!

  45. IntramolecularAmination of C-H Bonds • Various exemples, 61 – 87% yields • Aliphatic oxaziridines work as well. • Hemiaminal can also be trapped with other reagent to afford, in one pot, ketoamine, homoallylamine, etc. Allen, C. P.; Benkovics, T.; Turek, A. K.; Yoon, T. P. J. Am. Chem. Soc. 2009, 131,12560-12561.

  46. The Program • Some generalities • Oxaziridines’ preparation • Their properties • Their reactivity • Photoisomerisation • “O”-transfer agents • “N”-transfer agents • Dipolar cycloaddition agent

  47. Dipolar Cycloadditions • Three cycloaddition pathway should be tuneable with appropriate reaction conditions. Michaelis, D. J.; Ischay, M. A.; Yoon, T. P. J. Am. Chem. Soc. 2008, 130, 6610-6615.

  48. Hydroxyamination • CuCl2/BuN4+Cl- showed enhanced reactivity • N-Nosyl oxaziridines were proven more reactive • A FeIII has been developped. Knappke, C. E. I.; Jacobi von Wangelin, A. ChemCatChem, 2010, 2, 1381-1383. Yoon, T. P. et al. J. Org. Chem. 2009, 74,5545-5552. Williamson, K. S.; Yoon, T. P. J. Am. Chem. Soc., 2010, 132, 4570-4571.

  49. StereoselectiveHydroxyamination • Cationic or radical pathways are proposed Yoon, T. P. et al. J. Org. Chem. 2009, 74,5545-5552. Shao, P.-L.; Chen, X.-Y.; Ye, S. Angew. Chem. Int. Ed., 2010, 49, 8412-8416.

  50. Isoxazolidines Preparation Partridge, K. M.; Guzei, I. A.; Yoon, T. P. Angew. Chem. Int. Ed., 2010, 49, 930-934.

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