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Manganese Triacetate-Promoted Cyclizations & Annulations

Manganese Triacetate-Promoted Cyclizations & Annulations. Leading References: Melikyan, G. G. Aldrichimica Acta 1998 , 31 , 50 Snider, B. B. Chem. Rev. 1996 , 96 , 339 Melikyan, G. G. Synthesis , 1993 , 833. Daniel Beaudoin Literature Meeting – September 25, 2006

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Manganese Triacetate-Promoted Cyclizations & Annulations

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  1. Manganese Triacetate-Promoted Cyclizations & Annulations Leading References: Melikyan, G. G. Aldrichimica Acta 1998, 31, 50 Snider, B. B. Chem. Rev. 1996, 96, 339 Melikyan, G. G. Synthesis, 1993, 833. Daniel Beaudoin Literature Meeting – September 25, 2006 Under the supervision of Prof. André B. Charette

  2. Oxidative Radical ReactionsTransition Metal Oxidants Oxidative vs Reductive Radical Reactions Transition Metal One Electron Oxidants1 1Review on transition metal-promoted radical reactions: Iqbal, J. et al. Chem. Rev.1994, 94, 519.

  3. Mn(OAc)3An Underappreciated Oxidant Preparation1 Electronic and Redox Properties Distorted Octahedron (High Spin) Outer-Sphere Electron Transfer Inner-Sphere Electron Transfer 1 Heiba, E. I. et al. J. Am. Chem. Soc.1969, 91, 138.

  4. Mn(OAc)3Solid State Structure Mn(OAc)3.2H2O : [Mn2O(OAc)4].2AcOH.3H2O1 “Anhydrous Mn(OAc)3” : [Mn3O(OAc)7].AcOH2 1 Hessel, C. et al. Recl. Trav. Chim. Pays-Bas1969, 88, 545. 2 Christou, G. et al. Polyhedron2003, 22, 133.

  5. Mn(OAc)3Solution Structure (AcOH) • Polynuclear solution structure proposed • [Mn3O(OAc)7] and Mn(OAc)3.2H2O are indistinguishable in solution • [Mn3O(OAc)7] is slightly more reactive than Mn(OAc)3.2H2O (~1.7x) • Metathesis with other acids occurs readily

  6. Mn(OAc)3Initiation Most Common Substrates Classical Carbonyls Compounds (High T° Required) Activated Methylenes (Low T° Required) Enolization Precedes Inner-Sphere Electron Transfer 1 eV = 23.1 kCal/mol Fristad, W. E. et al.J. Org. Chem.1985, 50, 10.

  7. Mn(OAc)3Initiation Oxidation of Alkenes 1,2-Diacetate Formation Fristad, W. E. et al.Tetrahedron1986, 42, 3429.

  8. Mn(OAc)3Seminal Works First Reported Reactions Annulation to g-Lactone1,2 Annulation to 2,3-dihydrofuran3 Proposed Mechanism1,3 1 Bush, J. B. et al.J. Am. Chem. Soc.1968, 90, 5903. 2 Heiba, E. I. et al.J. Am. Chem. Soc.1968, 90, 5905. 3 Heiba, E. I. et al.J. Org. Chem. 1974, 39, 3456.

  9. Lactone AnnulationRate-Determining Step Enolization Proposed as the Rate-Determining Step Added Base Accelerates Lactone Formation Fristad, W. E. et al.J. Org. Chem.1985, 50, 10.

  10. Lactone AnnulationRate-Determining Step Enolization of Carboxylic Acids Acetic acid enol content negligible1 Mn(II) and Mn(III) have no effect on deuterium incorporation2 Enolization of a Complexed Acetate Conclusion: Enolization must occur irreversibly at a complexed acetate2 1 Guthrie, J. P. et al.Can. J. Chem.1995, 73, 1395. 2 Fristad, W. E. et al.Tetrahedron1986, 42, 3429.

  11. Lactone AnnulationRate-Determining Step Rate-Determining Step is Substrate-Dependant Concerted Oxidation-Addition Proposed Snider, B. B. et al.J. Org. Chem.1988, 53, 2137.

  12. Lactone AnnulationTermination Secondary Carbocation Not a Predominant Intermediate1,2 Fristad: Radical Cyclization1 Snider: MnIV Intermediate3 1 Fristad, W. E. et al.J. Org. Chem.1985, 50, 10. 2 Davies, D. I. et al.J. Chem. Soc. Perkin Trans. 11978, 227. 3 Snider, B. B. Chem. Rev.1996, 96, 339. Carbocations are generated from tertiary, alylic and benzylic radicals.

  13. Lactone Annulation Scope and Selectivity g-Lactone Annulation Isn’t Stereospecific Reaction Scope 1 Fristad, W. E. et al.J. Org. Chem.1985, 50, 10. 2 Fristad, W. E. et al.J. Org. Chem.1985, 50, 3143.

  14. Lactone Annulation Scope and Selectivity g-Lactone Annulation Isn’t Stereospecific Reaction Scope 1 Fristad, W. E. et al.J. Org. Chem.1985, 50, 10. 2 Fristad, W. E. et al.J. Org. Chem.1985, 50, 3143.

  15. Lactone AnnulationRadical Addition Selectivity Relative Rate of Addition (Competition Study)1 Relevant Examples2,3 1 Heiba, E. I. et al.J. Am. Chem. Soc.1968, 90, 5905. 2 Corey, E. J. et al.J. Am. Chem. Soc.1993, 115, 8871. 3 Garda, C. Synth. Coomm.1984, 14, 1191.

  16. 2,3-Dihydrofuran AnnulationReaction Scope 1 Heiba, E. I. et al.J. Org. Chem. 1974, 39, 3456. 2 Shi, M. et al.J. Org. Chem.2005, 70, 3859. 3 Corey, E. J. et al. Chem. Lett.1987, 223. 4 Mellor, J. M. et al. Tetrahedron1993, 49, 7557. 5 Mellor, J. M. et al. Tetrahedron Lett.1991, 7107. Reaction yield depends mostly on the ease of carbocation formation

  17. 2,3-Dihydrofuran AnnulationSynthetic Studies: Podophyllotoxin Fristad, W. E. et al.Tetrahedron Lett.1987, 28, 1493.

  18. 2,3-Dihydrofuran AnnulationChiral Auxiliaries Oxazolidinone Auxiliaries Scope & Cleavage Brun, F. et al.Tetrahedron Lett. 2000, 41, 9803.

  19. TerminationGeneral Scheme

  20. TerminationHydrogen Abstraction Hydrogen Abstraction Hydrogen abstraction predominates when primary or secondary radicals are involved Snider, B. B. et al.J. Org. Chem.1991, 56, 5544. Snider, B. B. et al.J. Org. Chem.1993, 58, 6217.

  21. TerminationCupric Salts Radical Oxidation by Cupric Salts1 Rate of Oxidation of Secondary Radicals2 1 Kochi, J. K. et al.J. Am. Chem. Soc.1968, 90, 4616. 2 Heiba, E. I. et al.J. Am. Chem. Soc. 1971, 93, 524. Rate of reaction between CuII and secondary radicals ~ 106 s-1M-1

  22. TerminationCupric Salts Oxidative Substitution SN1-Like Substitution1 Applications in Lactone Annulation2 1 Kochi, J. K. et al.J. Am. Chem. Soc.1968, 90, 4616. 2 Burton, J. W. et al.Chem. Comm. 2005, 4687.

  23. TerminationCupric Salts Oxidative Elimination Concerted Elimination1 Follows Hofmann Rule, Stereoselective for trans-Alkene2 1 Kochi, J. K. et al.J. Am. Chem. Soc.1968, 90, 4616. 2 Snider, B. B. et al.J. Org. Chem. 1990, 55, 1965.

  24. TerminationNitriles & Carbon Monoxide Nitriles1 Carbon Monoxide2 1Snider, B. B. et al. J. Org. Chem.1992, 57, 322. 2Alper H. et al. J. Am. Chem. Soc. 1993,115, 1543.

  25. CyclizationRadical Aromatic Substitution Mechanism Monocyclization Scope Citterio, A. et al. J. Org. Chem.1989, 54, 2713.

  26. Radical Aromatic SubstitutionModel Studies: Tronocarpine Synthesis of Tetrahydroindolizines Synthesis of the Tronocarpine Skeleton Kerr, M. A. et al.Org. Lett.2006, ASAP.

  27. CyclizationExo vs Endo Cyclization Mode Diastereoselectivity (Beckwith-Houk Model) 5-exo & 6-exo Cyclizations Reversibility of Cyclization Representative rates k5-exo:2 x 105 s-1 k6-endo : 4 x 103 s-1 k6-exo: 5 x 103 s-1 k7-endo : 7 x 102 s-1 kopen:1 x 104 s-1 kterm : 3 x 106 s-1M-1(Bu3SnH)

  28. CyclizationExo vs Endo Cyclization Mode Reversible Cyclization Rate of Iodine Abstraction > Rate of Ring Opening1 kI = 2 x 109 s-1M-1 Rate of Hydrogen Abstraction < Rate of Ring Opening2 kopen = 1 x 104 s-1 Rate of Oxidation > Rate of Ring Opening3 kOx = 1 x 106 s-1M-1 1 Halpern, J. Acc. Chem. Res. 1971, 4, 386. 2 Curran, D. P. et al.J. Org. Chem. 1989, 54, 3140. 3 Snider, B. B. J. Am. Chem. Soc. 1991, 113, 6609.

  29. Hexenyl Radical Cyclization5-exo vs 6-endo Cyclization Mode Baldwin Rules for sp2-sp2 cyclization

  30. Hexenyl Radical Cyclization5-exo vs 6-endo Cyclization Mode Presence of heteroatoms favors 5-exo cyclization mode Snider, B. B. et al.Tetrahedron 1993, 49, 9447.

  31. Hexenyl Radical CyclizationFormal Synthesis: Gibberelic Acid Snider, B. B. et al. J. Org. Chem. 1987, 52, 5487. Snider, B. B. et al.J. Org. Chem. 1991, 55, 5544.

  32. Hexenyl Radical Cyclization Model Studies: Nemorosone Kraus, G. A. et al. Tetrahedron Lett.2003, 44, 659. Kraus, G. A. et al. Tetrahedron2003, 59, 8975.

  33. Hexenyl Radical Cyclization Model Studies: Bilobalide Corey, E. J. et al.J. Am. Chem. Soc. 1984, 106, 5384.

  34. Hexenyl Radical Cyclization Synthesis : Podocarpic Acid Snider, B. B. et al.J. Org. Chem. 1985, 50, 3659.

  35. Today’s Question(Beer Break) Predict Diastereoselectivity of this Cyclization (32 possible diastereoisomers!)

  36. Hexenyl Radical Cyclization Synthesis : Isosteviol Snider, B. B. et al.J. Org. Chem. 1998, 63, 7945.

  37. Hexenyl Radical Cyclization Chiral Auxiliaries Snider, B. B. et al.J. Org. Chem. 1991, 56, 328; J. Org. Chem. 1993, 58, 7640

  38. Hexenyl Radical CyclizationChiral Auxiliaries β-Ketosulfoxide Auxiliary Snider, B. B. et al.J. Org. Chem. 1991, 56, 328.

  39. Hexenyl Radical CyclizationChiral Auxiliaries Phenylmethyl and Pyrrolidine Auxiliaries Selectivity difficult to rationalize with tertiary radicals. Porter, N, A, et al.J. Am. Chem. Soc. 1991, 113, 7002.

  40. Hexenyl Radical CyclizationChiral Auxiliaries Phenylmenthyl and Sultam-Based Auxiliaries Similar example Snider, B. B. et al.J. Org. Chem. 1993, 58, 7640. Zoretic, P. A. et al.Tetrahedron Lett. 1992, 33, 2637. Curran; Porter; Geise In Stereochemistry of Radical Reactions,VCH: Weinheim, 1996, 198.

  41. Heptenyl Radical Cyclization6-exo vs 7-Endo Cyclization Mode

  42. Heptenyl Radical CyclizationSynthesis: Upial & epi-Upial Snider: Formal Synthesis1,2 Paquette: 14-epi-Upial3 Snider, B. B. et al.Tetrahedron 1995, 51, 12983. Taschner, M. J. et al.J. Am. Chem. Soc. 1985, 107, 5570. Paquette, L. A. et al.Tetrahedron 1987, 43, 5567.

  43. Heptenyl Radical CyclizationSynthesis: Dihydropallescensin D White, J. D. et al.Tetrahedron Lett. 1990, 31, 59.

  44. Heptenyl Radical CyclizationSynthesis:Gymnomitrol Application to the acetylene zipper reaction: Brown, C. A. et al. J. Am. Chem. Soc.1975, 97, 891. Snider, B. B. et al.J. Org. Chem. 1997, 62, 1970.

  45. Oxidative Ring OpeningSynthesis: Silphiperfolene Snider, B. B. et al.J. Org. Chem. 1994, 59, 5419.

  46. Summary • Mn(OAc)3 is a unique one electron oxidant. • There are no reliable equivalent to the one-step Mn(OAc)3- mediated lactone and dihydrofuran annulations. • Cyclizations often exhibits very high selectivity. • Selectivity observed with chiral auxiliaries aren’t well understood. • Low yields and large amounts of by-products are common.

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