Heterocycles from cyclopropenones

Abstract

Great attention has been paid to cyclopropenones as they are present in many natural sources. Various synthesized cyclopropenone derivatives also show a wide range of biological activities. The cyclopropenone derivatives undergo a variety of reactions such as ring-opening reactions, isomerization reactions, C-C coupling reactions, C-H activation, cycloaddition reactions, thermal and photo-irradiation reactions, and acid-base-catalyzed reactions under the influence of various chemical reagents (electrophiles, nucleophiles, radicals, and organometallics) and external forces (heat and light). Many previous reviews have dealt with the chemistry and reactions of cyclopropenones. However and to the best of our knowledge, the utility of cyclopropenones in the synthesis of heterocycles has not been reported before. Therefore, it would be interesting to shed light on this new topic. The present review article provides, for the first time, a comprehensive compilation of synthetic methods for the synthesis of various heterocyclic ring systems, as a significant family in the field of organic chemistry.

Fig. 1. Structure of cyclopropenone (1a).

Fig. 2. Resonance structures of 2,3-diphenylcyclopropenone (1b).

Fig. 3. Naturally occurring compounds A–C containing cyclopropenone molecules.

Fig. 4. Naturally occurring acids containing cyclopropenone structures.

Fig. 5. Structures of naturally occurring compounds F–H.

Scheme 1. Synthesis of cyclopropenone (1a) from perchlorocycloprop-1-ene (2). Reagents and conditions: A = (C₄H₉)₃SnH, B = H₂O.

Scheme 2. Synthesis of substituted cyclopropenones 1c–g using BF₃. Reagents and conditions: A = BF₃, Et₂O.

Scheme 3. Hydrolysis of 6,6-dimethyl-4,8-dioxaspiro[2.5]oct-1-ene derivatives 5 into 1. Reagents and conditions: A = Amberlyst-15, MeCOMe or aq. THF, rt.

Scheme 4. Synthesis of 2,3-diphenylcyclopropenone (1b). Reagents and conditions: A = KO-t-Bu, B = H₂O/H⁺.

Scheme 5. Synthesis of 1b from the cycloaddition of phenylmethoxy-acetylene (8a) with (dichloromethyl)benzene. Reagents and conditions: A = (i) KO-t-Bu, (ii) H₂O/H⁺.

Scheme 6. Formation of cyclopropenone 1h,ivia the reaction of acetylenes 8b,c with Cl₃COONa. Reagents and conditions: A = (i) Cl₃CCOONa, DME, reflux, (ii) H₂O.

Scheme 7. Synthesis of cyclopropenone 1b. Reagents and conditions: A = MeCOMe, H₂O/H₃O⁺.

Scheme 8. Synthesis of 2-methyl-3-phenylcycloprop-2-enone (1j). Reagents and conditions: A = Br₂, CH₂Cl₂, Et₃N, 0 °C.

Scheme 9. Synthesis of diphenylcyclopropenone (1b) from dibromodibenzyl ketone (11a).

Scheme 10. Synthesis of 2,3-diisopropylcycloprop-2-enone (1k). Reagents and conditions: A = (i) NaH, THF, (overnight) and (ii) HCl/H₂O.

Scheme 11. Formation of 2,3-bis(methyl(phenyl)-amino)cycloprop-2-enone (1l). Reagents and conditions: A = KOH/H₂O, MeOH, rt, 40 h.

Scheme 12. Synthesis of diferrocenylcyclopropenone (1m). Reagents and conditions: A = AlCl₃, CH₂Cl₂, H₂O.

Scheme 13. Synthesis of 2,3-diphenylcyclopropenone (1b) from (16). Reagents and conditions: A = benzene, H₂O.

Scheme 14. Oxidation of 17 into diphenylcyclopropenone (1b), 18 and 19. Reagents and conditions: A = MeOH, Ag₂O.

Scheme 15. Synthesis of 3-ethylidene-4,4-dimethyloxetan-2-one (20). Reagents and conditions: A = PPh₃ (5 mol%), CD₃OD, 25 °C.

Scheme 16. Synthesis of 2-pyrrolinones 23a–g. Reagents and conditions: A = MW, toluene, Bi(NO₃)₃·5H₂O, 30–90 min.

Scheme 17. Mechanism of the formation of 2-pyrrolinones 23a–g.

Scheme 18. Synthesis of compound 25. Reagents and conditions: A = toluene, reflux, 6 d.

Scheme 19. Synthesis of 3-pyrrolinones 27a–c. Reagents and conditions: A = EtOH, 2–5 h.

Scheme 20. Mechanism of the formation of 3-pyrrolinone derivatives 27a–c.

Scheme 21. Synthesis of N-pyridymethyl-pyrrol-3-ones 29a and 29b. Reagents and conditions: A = [Rh(OAc)(cod)]₂ (5 mol%), toluene, 140 °C, 12 h.

Scheme 22. Synthesis of pyrrol-2-ones 29c,d. Reagents and conditions: A = [Rh(OAc)(cod)]₂ (10 mol%), toluene 2 ml, 140 °C, 1 h.

Scheme 23. Palladium-catalyzed synthesis of maleimides 31a–q. Reagents and conditions: A = Pd(OAc)₂ (15 mol%), KOAc (4 equiv.), Bu₄NBr (1 equiv.), K₂S₂O₈ (1.5 equiv.), DMF (0.25 M), 120 °C, 1 h.

Scheme 24. Synthesis and mechanism describing the formation of compounds 35a–f. Reagents and conditions: A = MeOH, rt.

Scheme 25. Synthesis of substituted butanolides 37a–m. Reagents and conditions: A = DBU (20 mol%), DME, rt, 24 h.

Scheme 26. Synthesis of 5-((ethylperoxy)-methyl)-3,4,5-triphenylfuran-2(5H)-one (40). Reagents and conditions: A = CH₂Cl₂, 50% aq KOH (1 equiv.), rt, 1 h, 39 (20 mol%).

Scheme 27. Synthesis of substituted diphenylfuranones 42a–d. Reagents and conditions: A = AgTOf (10 mol%), PhCl, 130 °C, 2 h.

Scheme 28. Mechanism of the formation of diphenylfuranones 42a–d. Reagents and conditions: A = AgTOf (10 mol%), C₆H₅Cl, 130 °C, 2 h.

Scheme 29. Synthesis of compound 42a–m. Reagent and conditions: A = AgSbF₆ (10 mol%), 80 °C, 20 h.

Scheme 30. TPP mediated the synthesis of 44a–l. Reagents and conditions: A = PPh₃ (5 mol%), MeOH, 23 °C.

Scheme 31. Synthesis of γ-alkenylbutenolide 47 from enones 45 and 1b. Reagents and conditions: A = Ni(cod)₂ (1–2 mol%), L* 46 (2–3 mol%), toluene, rt, 1–24 h.

Scheme 32. Mechanism describing the synthesis of γ-alkenylbutenolide 47.

Scheme 33. Reaction of 2-(thiophen-2-yl)malononitrile (48) with diarylcyclopropenones 1u,v. Reagents and conditions: A = Ac₂O, reflux.

Scheme 34. (IPr)AuNTf₂-catalyzed synthesis of compounds 51a–d. Reagents and conditions: A = (IPr)AuNTf₂ (2 mol), DCM, rt.

Scheme 35. Synthesis of spiro furano-indolinone 53a–h and 54a–h. Reagents and conditions: A = DMAP (20 mol%), toluene, 50 °C, 6 h.

Scheme 36. Synthesis of the spiro compound 55. Reagents and conditions: A = dioxane, CuCl, 12 h.

Scheme 37. Sc(OTf)₃ mediated the synthesis of 57a–j. Reagents and conditions: A = Sc(OTf)₃ (10 mol%), DCM, 25 °C 4 h.

Scheme 38. Synthesis of 1,2-bis(2-methoxy-5-methylphenyl)-6,7-diphenyl-4-oxaspiro[2.4]hepta-1,6-dien-5-one (59). Reagents and conditions: A = (i) AlCl₃, CH₂Cl₂, −20 °C, 45 min; (ii) H₂O; B = CuBr, CH₂Cl₂, 70 °C, 12 h.

Scheme 39. Synthesis of indoles 61a–g. Reagents and conditions: A = [RhCp*(OAc)₂], AgNTf₂, DCE, 120 °C, 24 h.

Scheme 40. Synthesis of compounds 66a,b. Reagents and conditions: A = TMS-OTf, Et₃N, DCM, TiCl₄, 0–35 °C; B = CHCl₃, DDQ, H₂O, 70 °C; C = MeOTf, CH₂Cl₂; D = MeCN, 50 °C.

Scheme 41. Synthesis of pyrrolizidine 68 and indolizidine 69. Reagents and conditions: A = toluene, reflux.

Scheme 42. Synthesis of benzo[b]furane derivatives 71a–d. Reagents and conditions: A = O₂, MeCN, reflux, 12 h.

Scheme 43. Synthesis of spiro oxazoles 73a–g. Reagents and conditions: A = K₂CO₃ (0.8 mmol), HFIP (2 ml), 50 °C, 12 h.

Scheme 44. Mechanism illustrating the formation of spiro oxazoles 73a–g.

Scheme 45. Synthesis of spiro compound 75. Reagents and conditions: A = n pentane, −40 °C, overnight.

Scheme 46. Synthesis of dithiolone derivatives 76a–j. Reagents and conditions: A = KF, DMF, air, rt, 12 h.

Scheme 47. Synthesis of [1,2]dithiolo[5,1-e][1,2]dithioles 78a–d. Reagents and conditions: A = CuBr (5 mol%), DCM, 75 °C, N₂,12 h, B = KF (2 equiv.), S₈, DMF, 50 °C, air, 5 h.

Scheme 48. Synthesis of diselenolone derivatives 79a–f. Reagents and conditions: A = DMSO, N₂, 120 °C, 12 h.

Scheme 49. Synthesis of 2,2′-(2,3-diphenylcycloprop-2-ene-1,1-diyl)bis(4-phenyl-2H-1,2,3-triazole) (81). Reagents and conditions: A = DCE, 80 °C, 2.5 h.

Scheme 50. Synthesis and mechanism of thiadiazoles 83a–p. Reagents and conditions: A = EtOH, 4–8 h.

Scheme 51. Synthesis of pyrrolo[2,1-b](1,3,5-oxadiazolyl)-2-amines 85a–e. Reagents and conditions: A = AcOH, 4–8 h.

Scheme 52. Mechanism of the formation of pyrrolo[2,1-b](1,3,5-oxadiazolyl)-2-amines 85a–e.

Scheme 53. Synthesis of 4-isopropyl-3,6-diphenyl-2H-pyran-2-one (87a). Reagents and conditions: A = benzene, reflux, 5 h.

Scheme 54. Synthesis of 2-pyranone derivatives 87b–j. Reagents and conditions: A = (Cp*RhCl₂)₂, NaOAc, MeCN, 100 °C, 12 h.

Scheme 55. Synthesis of compound 90a–n. Reagents and conditions: A = DABCO (20 mol%), MeCN, 25 °C, 1 h.

Scheme 56. Mechanism describing the formation of 90a–n.

Scheme 57. Synthesis of substituted diaryl spiro[cycloprop[2]ene-1,9′-xanthene] derivatives 92a–j. Reagents and conditions: A = CsF, MeCN, 30 °C, 24 h.

Scheme 58. Rhodium(iii)-catalyzed synthesis of quinoline-4-one derivatives 93a–f. Reagents and conditions: A = (Cp*RhCl₂)₂ (2 mol%), AgBF₄ (1.2 equiv.), NaF, DCE, 100 °C, 12 h.

Scheme 59. Synthesis of 4-quinolones 93a–h. Reagents and conditions: A = [RhCp*(OAc)₂] (0.5 mol%), [Rh(COD)Cl]₂, AgBF₆ (0.02 mmol), DCM, 120 °C, 36 h.

Scheme 60. Synthesis of compounds 95a–d. Reagents and conditions: A = mesitylene, rt, cat 96.

Scheme 61. Synthesis of phenanthridine derivatives 98a–d. Reagents and conditions: A = [Ru(p-cymene)Cl₂]₂, Ag₂CO₃, H₃BO₃, DCM, reflux, 48 h.

Scheme 62. Synthesis of 100a–j. Reagents and conditions: A = EtOH, rt, 5–50 h.

Scheme 63. Synthesis of biindolizines 101a,b. Reagents and conditions: A = pyridine, Cu(OAc)₂, 15 min.

Scheme 64. Synthesis of the fused heterocyclic compounds 103a,b. Reagents and conditions: A = EtOH, rt.

Scheme 65. Synthesis of pyranopyrandiones 102a–c. Reagents and conditions: A = toluene, Ru₃(CO)₁₂, Et₃N, 150 °C, 20 h.

Scheme 66. Synthesis of compounds 107a–h. Reagents and conditions: A = PdCl₂, P(4-CF₃-C₆H₄)₃ (20 mol%), Cs₂CO₃, C₆H₅F, 100 °C, 24 h.

Scheme 67. Synthesis of tetrasubstituted pyrano[2,3-b]indol-2(9H)-ones (109a–l). Reagents and conditions: A = [(Me₃Si)₂N]₃La(μ-Cl)Li(THF)₃, toluene, 110 °C, 2.5 h, (108), HOP(OEt)₂.

Scheme 68. Synthesis of 5,6-dihydropyrimidine 113. Reagents and conditions: A = conc. HCl, 1,4 dioxane, 20 °C; B = NH₂CN, pH 8–9, H₂O, reflux, 5 h; C = passed through Amberlite IRA-401 (hydroxide form); D = benzene : EtOH (1 : 1), rt, 18 h.

Scheme 69. Synthesis of diphenyl pyrimidinediones 115a–f. Reagents and conditions: A = toluene, 110 °C, 13 h.

Scheme 70. Synthesis of pyrimidines 117a–f. Reagents and conditions: A = EtOH, Et₃N, reflux 6–10 h.

Scheme 71. Mechanism of the formation of pyrimidines 117a–f.

Scheme 72. Synthesis of substituted 3-aryl-2,5,6-triphenylpyrimidin-4(3H)-ones (119a–e). Reagents and conditions: A = EtOH, reflux, 10–16 h.

Scheme 73. Synthesis of substituted 1,3-oxazin-6-ones 121a–j. Reagents and conditions: A = PPh₃ (1 equiv.), DCM, rt, 15 min.

Scheme 74. Mechanism of the formation of substituted 1,3-oxazin-6-ones 121a–j.

Scheme 75. Scandium-catalyzed synthesis of substituted 1,3-oxazin-6-ones 121k–q. Reagent and conditions: A = CsOAc (1 equiv.), DCE, rt, 6 h.

Scheme 76. Synthesis of 1,3-oxazine-4-ones 124a–g. Reagents and conditions: A = Ag₂O, cyclohexane, 80 °C, 18 h.

Scheme 77. Mechanism describing the formation of 1,3-oxazine-4-ones 124a–g.

Scheme 78. Synthesis of substituted 1,3-oxazin-6-ones 123r–y. Reagents and conditions: A = DCM, reflux, Et₃N, 2 h.

Scheme 79. Synthesis of 2,4,5-triphenyl-6H-1,3-oxazin-6-one (123z). Reagents and conditions: A = K₂CO₃ (0.5 equiv.), THF, 60 °C, 2 h.

Scheme 80. Synthesis of thiazinanes 128a–e. Reagents and conditions: A = EtOH, reflux.

Scheme 81. Mechanism of the formation of thiazinanes 128a–e.

Scheme 82. Synthesis of thiazines 131a–c. Reagents and conditions: A = DDQ, EtOH, reflux, 4–7 h.

Scheme 83. Synthesis of substituted quinazolin-ones 133a–j. Reagents and conditions: A = [Ru(p-cymene)Cl]₂, AgSbF₆, AdCOOH, DCE, reflux, 24 h.

Scheme 84. Synthesis of compounds 135a–f and 136a–f. Reagents and conditions: A = Rh[Cp*(OAc)], TFE, 110 °C, 48 h; B = Pd(OAc)₂, Ag₂O, TFA, 140 °C, 24 h.

Scheme 85. Synthesis of quinazoline derivatives 138a–i. Reagents and conditions: A = (Cp*RhCl₂)₂, AgSbF₆, DCM, reflux, 36 h, O₂.

Scheme 86. Synthesis of 2-benzyl-3-isopropylquinoxaline (140). Reagents and conditions: A = Et₂O, 8 h.

Scheme 87. Synthesis of 6,7-diphenylpyrrolo[1,2-b]pyridazin-5-yl acetate (143). Reagents and conditions: A = DCE, reflux, B = Ac₂O, DMAP.

Scheme 88. Synthesis of pyridazines 145 and 147. Reagents and conditions: A = MeCOMe, 110 °C, 48 h.

Scheme 89. Synthesis of pyridazines 149a,b. Reagents and conditions: A = p-xylene, reflux, 138 °C, 20 min.

Scheme 90. Synthesis of pyridazines 150, 151. Reagents and conditions: A = MeOH, reflux, 48 h, B = MeOH, reflux, 6–12 h.

Scheme 91. Synthesis of triazines (154a–d). Reagents and conditions: A = Et₃OBF₄, CH₂Cl₂; B = Et₂NH; C = NaN₃, CH₂Cl₂, DMF.

Scheme 92. Synthesis of tetrasubstituted-6,7-dihydro-1H-silepin-4(5H)-ones 156a–h. Reagents and conditions: A = (1 mol%), Pd(OAc)₂ toluene, rt, 48 h.

Scheme 93. Mechanism of the formation of 6,7-dihydro-1H-silepin-4(5H)-ones 157a–h.

Scheme 94. Synthesis of compounds 159a–c. Reagents and conditions: A = EtOH, reflux.