Advances in the Synthesis of Azaspiro[4.5]trienones

doi:10.6023/cjoc202304004

Abstract

As one of the most important structural motifs in natural compounds and active pharmaceutical ingredients, aza- spiro[4.5]trienones derivatives have been widely used in the field of organic synthesis due to their excellent structural properties and biological activities. In recent years, several methods, such as transition metal involvement, visible light promotion, transition metal-free involvement and electrochemical promotion, have been used to efficiently construct various functional groups of azaspiro[4.5]trienones. The recent advances in the synthesis of azaspiro[4.5]trienones are reviewed, and the representative substrates and reaction mechanisms are summarized and discussed.

Key words: azaspiro[4.5]trienone, dearomatization, ipso-cyclization, N-alkylpropiolamide

Cite this article

Jing Tang, Wenkun Luo, Jun Zhou. Advances in the Synthesis of Azaspiro[4.5]trienones[J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3006-3034.

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Fig. & Tab. 59

Figure 1. Representative biologically active azaspiro[4.5]trienones

Scheme 1. Copper-catalyzed oxidative ipso-cyclization of activated alkynes

Scheme 2. Copper-catalyzed radical tandem cyclization of N-arylpropiolamides

Scheme 3. Copper-catalyzed oxidative ipso-cyclization of N-(p-methoxyaryl)propiolamides with disulfides and H2O

Scheme 4. Copper-catalyzed oxidative ipso-cyclization of propiolamides with alkanes

Scheme 5. Copper-catalyzed oxidative ipso-cyclization of propiolamides with silane

Scheme 6. Copper-catalyzed dearomatization and denitration of nitroaromatic derivatives

Scheme 7. Copper-catalyzed ipso-cyclization

Scheme 8. Iron-catalyzed oxidative ipso-cyclization

Scheme 9. Electrophilic selenocyanogen cyclization and dearomative spirocyclization

Scheme 10. Silver-catalyzed oxidative ipso-cyclization of propiolamides with phosphoric acid

Scheme 11. Silver-catalyzed oxidative ipso-cyclization of propiolamides with thiophenol

Scheme 12. Silver-mediated dearomatization of N-aryl propiolamides

Scheme 13. Dearomatization spirocyclization of N-aryl propiolamides

Scheme 14. Oxidative spirocyclization of N-aryl propiolamides

Scheme 15. Silver-mediated dearomatization of N-aryl propiolamides

Scheme 16. Silver-catalyzed dearomatization of N-aryl propiolamides

Scheme 17. Nickl-promoted oxidative ipso-cyclization

Scheme 18. ZnBr2-mediated dearomatization of propiolamides

Scheme 19. Palladium-catalyzed dearomatizing [2+2+1] carbocyclization

Scheme 20. AlCl3-catalyzed dearomatization of N-para-fluoroaryl propiolamides

Scheme 21. AlCl3-catalyzed dearomatization of propiolamides

Scheme 22. Visible light-induced oxidative cyclization reaction of N-aryl propiolamides

Scheme 23. Visible light-induced oxidative cyclization reaction of N-aryl propiolamides with mercaptan

Scheme 24. Oxidative cyclization reaction of propiolamides with diselenid compounds

Scheme 25. Radical addition/cyclization reaction of N-aryl acrylamides with NH4SCN

Scheme 26. Visible light-induced halogenated spirocyclization reaction of N-aryl acrylamides

Scheme 27. Radical addition/cyclization reaction of propiolamides with thiophenol

Scheme 28. Radical addition/cyclization reaction of propiolamides with triethyl tert-butyrate

Scheme 29. Radical addition/cyclization reaction of N-aryl propiolamides with diphenylphosphine

Scheme 30. Synthesis of 3-bromoazaspiro[4.5]trienones

Scheme 31. Visible light-induced decarboxylation arylation

Scheme 32. Visible light-induced decarboxylation arylation

Scheme 33. Visible light-induced difluoroalkyl spirocyclization

Scheme 34. Visible light-induced ipso-difluoromethylation

Scheme 35. Visible light-induced ipso-cyclization

Scheme 36. Visible light-induced vicinal difunctionalization

Scheme 37. Visible light-mediated ipso-cyclization of propiolamides

Scheme 38. Visible light-mediated ipso-cyclization of activated alkynes

Scheme 39. Visible light-induced oxidative cyclization reaction of N-aryl propiolamides with arylamine

Scheme 40. Visible light-induced spirocyclizative reaction of diaryl alkyl amides

Scheme 41. Visible light-induced acylation/cyclization reaction of alkynes with acyl oxime esters

Scheme 42. Intramolecular ipso-cyclization to synthesize azaspiro[4.5]trione

Scheme 43. Metal-free oxidative ipso-cyclization of alkynes with aldehyde

Scheme 44. Nitrative spirocyclization of alkynes

Scheme 45. Metal-free direct oxidative spirocyclization

Scheme 46. Ugi 4CC/electrophilic ipso-cyclization

Scheme 47. ispo-Cyclization under acidic conditions

Scheme 48. Na2S2O8-promoted radical cyclization of N-aryl propiolamides

Scheme 49. Acid-triggereed oxidative cascade reaction

Scheme 50. Selenium-promoted electrophilic cyclization

Scheme 51. Synthetic strategy of 3-organic selenium azospiric compounds

Scheme 52. Cascade annulation of propiolamides

Scheme 53. Metal-free spirocyclization of propiolamides with α-oxocarboxylatic acids

Scheme 54. SOCl2 mediated synthesis of 3-methylthiospiro[4.5]trienones

Scheme 55. Alkylation/ipso-cyclization of N-arylpropiolamides

Scheme 56. Electrochemical synthesis of azaspiro[4.5]trienones

Scheme 57. Electrochemical oxidative halogenation of N-arylpropiolamides

Scheme 58. Synthesis of 3-halozaspiro[4.5]trienones

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氮杂螺[4.5]三烯酮衍生物的合成研究进展