Ring forming transformations of ynamides via cycloaddition

Abstract

Ynamides are N-alkyne compounds bearing an electron withdrawing group at the nitrogen atom. They offer unique pathways for the construction of versatile building blocks owing to their exceptional balance between reactivity and stability. Recently several studies have been reported that explore and illustrate the synthetic potential of ynamides and ynamide-derived advanced intermediates in cycloadditions with different reaction partners to yield heterocyclic cycloadducts of synthetic and pharmaceutical value. Cycloaddition reactions of ynamides are the facile and preferable routes for the construction of structural motifs having striking importance in synthetic, medicinal chemistry, and advanced materials. In this systematic review, we highlighted the recently reported novel transformations and synthetic applications that involved the cycloaddition reaction of ynamides. The scope along with the limitations of the transformations are discussed in detail.

Fig. 1. The general structure of ynamide.

Scheme 1. Synthesis of substituted aminocyclobutenes 3a and 3bvia [2 + 2]-cycloaddition of ynamides 1a and 1b and reaction partner isoimidium salt 1 and alcohol 2, respectively.

Scheme 2. Synthesis of substituted aminocyclobutenes 6a–cvia [2 + 2]-cycloaddition of ynamides 1b.

Scheme 3. Synthesis of 3-amino-1-naphthols 9a/9bvia cycloaddition and benzannulation of ynamide 1a/1b and ynol-ethers 7.

Scheme 4. Synthesis of cyclobutenones 11via [2 + 2]-cycloaddition between ynamide 1b and propargyl silyl ether 10.

Scheme 5. Synthesis of cyclobutenones 13via [2 + 2]-cycloaddition of ynamide 1a and acyl chlorides 12.

Scheme 6. Synthesis of substituted quinolones 17via [2 + 2]-cycloaddition of ynamide 1c with cyclobutenones 14 or diaoketones 15.

Scheme 7. Synthesis of 4-amino-2H-chromenes 19via [2 + 2]-cycloaddition of ynamide 1a and o-quinone methides 18.

Scheme 8. Synthesis of 7-nitroindoles 21via [3 + 2]-cycloaddition of ynamides 1a with benzofuran N-oxide 20.

Scheme 9. Synthesis of 2-aminoindoles 23a–dvia [3 + 2]-cycloaddition of ynamide 1a,b with anthranils 22.

Scheme 10. Synthesis of cyclopenta[b]indoles 24via intramolecular [3 + 2]-cycloaddition of ynamide 1d.

Scheme 11. Synthesis of polysubstituted pyrroles 26a–cvia [3 + 2]-cycloaddition of ynamides 1a/1b with 2H-azirines 25.

Scheme 12. Synthesis of polysubstituted 2-aminopyrroles 28a–cvia [3 + 2]-cycloaddition of ynamides 1a/1b with isoxazoles 27.

Scheme 13. Synthesis of pyrrole-fused scaffolds 30via [3 + 2]-cycloaddition of ynamides 1e and alkenes 29.

Scheme 14. Synthesis of 1,2,3-triazoles 32avia [3 + 2]-cycloaddition of ynamides 1a with azide 31a.

Scheme 15. Synthesis of 1,2,3-triazoles 32b/32cvia [3 + 2]-cycloaddition of ynamides 1a/1b with azide 31b.

Scheme 16. Synthesis of o–o′-heteroatom-linked imidazole derivative 34via [3 + 2]-cycloaddition of ynamide 1f and nitrenoid 33.

Scheme 17. Synthesis of 5-aminoimidazoles 36via [3 + 2]-cycloaddition of ynamides 1a and oxadiazolones 35.

Scheme 18. Synthesis of spiropseudoindoxyls 39via intramolecular [3 + 2]-cycloaddition of ynamide intermediate 1g.

Scheme 19. Synthesis of 4-aminooxazoles 41a from [3 + 2]-cycloaddition of ynamides 1a with dioxazole 40.

Scheme 20. Synthesis of 4-aminooxazoles 41b-c from [3 + 2]-cycloaddition of ynamides 1a/1b and dioxazoles 40.

Scheme 21. Synthesis of cyclopentene sulfonamides 43via [3 + 2]-cycloaddition of ynamides 1a with cyclopropanes 42.

Scheme 22. Synthesis of cyclopentadienes 45a/45b and cyclopentenones 46via [3 + 2]-cycloaddition between ynamides 1a/1b and cyclopropenes 44.

Scheme 23. Synthesis of 2-aminopyrrole 48via [4 + 1]-cycloaddition of 3-en-1-ynamide 1h with azide 47.

Scheme 24. Synthesis of 1,3-diaminoisoquinolines 50a and 50bvia [4 + 2]-cycloaddition of cyanamides 49 with ynamides 1i and 1j, respectively.

Scheme 25. Synthesis of tetrahydroquinoline 53via [4 + 2]-cycloaddition of cyclic ynamide 1k with cyclopentadienone 52.

Scheme 26. Synthesis of 1,2-dihydroisoquinolines 55a/55bvia [4 + 2]-cycloaddition of ynamides 1i/1j with imines 54.

Scheme 27. Synthesis of 1,2-dihydroquinazoline 57via [4 + 2]-cycloaddition of ynamides 1l with nitrile 56.

Scheme 28. Synthesis of 2-amino-4H-chromenes 59via [4 + 2]-cycloaddition of ynamides 1a/1b with silyl ether 58.

Scheme 29. Synthesis of 2-amino-4H-chromenes 59d–evia [4 + 2]-cycloaddition of ynamides 1a/1b.

Scheme 30. Synthesis of six-membered oxa-heterocycle 63 and aza-heterocycle 64via [4 + 2]-cycloaddition of ynamide 1a and oxetane 62a/azetidine 62b.

Scheme 31. Synthesis of substituted coumarins 66via [4 + 2]-cycloaddition of ynamide 1b with 4-vinylcoumarins 65.

Scheme 32. Synthesis of 4-aminopyridines 67via intramolecular inverse [4 + 2]-cycloaddition of ynamide 1m.

Scheme 33. Synthesis of 2,6-diaminopyridines 69via hetero-TDDA reaction between enynamide 1n and cyanamide 68.

Scheme 34. Synthesis of polycycles 72via [4 + 2]-cycloaddition of ynamide 1o.

Scheme 35. Synthesis of 3-amino-β-carboline 74via [4 + 2]-cycloaddition between ynamides 1a and azides 73.

Scheme 36. Synthesis of benzo[b]carbazole derivatives 75via intramolecular tetrahydro-Diels–Alder reaction of ynamides 1p.

Scheme 37. Synthesis of dihydrobenzoindole derivatives 76via intramolecular tetrahydro-Diels–Alder reaction of ynamides 1q.

Scheme 38. Synthesis of 2-aminonaphthalenes 78via IEDDA reaction between ynamides 1a and 1,2-diazines 77.

Scheme 39. Synthesis of bicyclic compounds 81 and 82via one-pot Diels–Alder reaction of ynamide 1r.

Scheme 40. Synthesis of 4H-azepines 84via [4 + 3]-cycloaddition of ynamides 1s and substituted isoxazoles 83.

Scheme 41. Synthesis of 2-amido-1,4-dihydrocycloheptapyrroles 86a/86bvia [8 + 2]-cycloaddition of ynamides 1a and 1b with 8-aryl-8-azaheptafulvenes 85, respectively.

Scheme 42. Synthesis of highly substituted furan rings 88a–b and macro-cyclic furan derivatives 88c–dvia [2 + 2 + 1]-cycloaddition of ynamides 1a, 1a′, 1t, and 1u with 2,3-dichloroquinoxaline-N-oxide 87.

Scheme 43. Synthesis of 2,4-diaminopyridines 90avia [2 + 2 + 2]-cycloaddition of ynamide 1a with substituted nitrile 89.

Scheme 44. Synthesis of 2,4-diaminopyridines 90via [2 + 2 + 2]-cycloaddition of ynamides 1a with substituted nitrile 89.

Scheme 45. Synthesis of substituted pyrimidines 91 by [2 + 2 + 2] cycloaddition of substituted nitrile 89 and ynamide 1a.

Scheme 46. Synthesis of 2,4,6-triaminopyrimidines 92a and 92bvia [2 + 2 + 2]-cycloaddition of cyanamides 49 and ynamides 1a and 1b, respectively.

Scheme 47. Synthesis of 2-aminocarbolines 94 and 3-aminocarbolines 96via [2 + 2 + 2]-cycloaddition of ynamide 1a with alkyne-cyanamide 93 or ynamide-nitrile 95.

Scheme 48. Synthesis of six-membered heterocycles 98 and seven-membered heterocycles 99via [5 + 1] and [5 + 2]-cycloaddition of ynamide 1a and 1,2-benzisoxazole 97.

Scheme 49. Synthesis of tetrahydro-1,4-oxazepine derivatives 101via [5 + 2 + 1]-cycloaddition of ynamide 1a, and isoxazole 100.

Scheme 50. Synthesis of 4-aminopyrazoles 103 and 4,5,6,7-tetrahydro-2H-pyrazolo[x,y-b]pyridine 104a and 104bvia sydnone-alkyne cycloaddition of aliphatic ynamides 1a and 1k with sydnones 102.

Scheme 51. Synthesis of FTI 108via [2 + 2]-cycloaddition ynamide 1v with diazo ketone 105.

Scheme 52. The total synthesis of the anticancer agents 116a and 116bvia [2 + 2]-cycloaddition of ynamide 1w and cyclobutenone 114.

Scheme 53. Synthesis of (−)-herbindole A 118via intramolecular [2 + 2 + 2]-cycloaddition of ynamide 1x.

Scheme 54. Synthesis of 4-deoxycarbazomycin B 121b, carazostatin 122a, carbazomycin B 125a, and carbazomycin A 125bvia [2 + 2 + 2] cycloaddition of ynamides 1y/1z.

Scheme 55. Synthesis of tetracyanobutadiene 127 by [2 + 2]-cycloaddition of ynamide 1a and tetracyanoethylene 126.

Scheme 56. Synthesis of tetracyanobutadiene derivatives 129a and 129bvia [2 + 2]-cycloaddition of between pyrene/perylene substituted ynamide 1aa and 1ab and tetracyanobutadiene 128, respectively.