Recent advances in the synthesis of highly substituted imidazolidines

Abstract

Imidazolidine is a saturated heterocycle with a cyclic aminal core that can be found in natural products and biologically active molecules. Additionally, these heterocyclic compounds have been utilized as chiral ligands, N-heterocyclic carbene precursors, and catalysts in organic synthesis. This review is an attempt to compile the literature of various synthetic procedures of highly substituted imidazolidines, chiral imidazolidines with high diastereoselectivities and enantioselectivities, bis-imidazolidines, and spiro-imidazolidines, as well as their pharmacological properties during the period from 1949 to 2023.

Scheme 1. Solvent-free synthesis of 1,3-dialkylimidazolidines 1.

Scheme 2. Synthesis of 2-substituted-1,3-bis(p-chlorobenzy1)imidazolidines 3.

Scheme 3. HOAc catalyzed synthesis of 1,3-diarylimidazolidine derivatives 5.

Scheme 4. Synthesis of imidazolidine derivatives 10 and 11.

Scheme 5. Synthesis of 1-alkyl-2,4-diaryl-5-aroyl-3-(N-arylsulfonyl)-imidazolidines 12.

Scheme 6. Synthesis of dihydroimidazolidines 16 and 17.

Scheme 7. Preparation of imidazolidine derivatives 19.

Scheme 8. Synthesis of imidazolidine derivatives 20.

Scheme 9. Acid catalyzed preparation of imidazolidines 23.

Scheme 10. Synthesis of imidazolidine derivatives 25–32.

Scheme 11. Synthesis of imidazolidines 34 in the presence of sodium ethoxide in ethanol.

Scheme 12. Synthesis of imidazolidine derivatives 35, 38 and 39.

Scheme 13. Synthesis of 1,3-bis[2′-hydroxy-5′-substituted-benzyl]imidazolidines 40.

Scheme 14. TiCl₄/Mg promoted synthesis of imidazolidine derivatives 43.

Scheme 15. Preparation of imidazolidines 44 and 45 in the presence of K₂CO₃/MgSO₄.

Scheme 16. Preparation of imidazolidine derivatives 47 in the presence of TiCl₄/Zn.

Scheme 17. Synthesis of μ-bis (tetradentate)hydroxybenzamidoimidazolidine ligand 48.

Scheme 18. Synthesis of 1,3-diarylimidazolidines 53 starting from glyoxal.

Scheme 19. Synthesis of N,N′-unsubstituted imidazolidines 55.

Scheme 20. Water suspension medium synthesis of tetrahydroimidazoles 57.

Scheme 21. Synthesis of trans-imidazolidines 59.

Scheme 22. Preparation of imidazolidines 60.

Scheme 23. Synthesis of 2-substituted N,N′-diacylimidazolidines 62.

Scheme 24. Synthesis of tetrahydroimidazoles 64 starting from ethylenediamine.

Scheme 25. Preparation of imidazolidines 67 and 68.

Scheme 26. TiCl₄/Sm catalyzed synthesis of imidazolidines 71.

Scheme 27. NaOH catalyzed synthesis of tetraarylimidazolidines 73 and 74.

Scheme 28. Synthesis of unsymmetrical imidazolidines 75, 77, 78–81 by Mannich reaction.

Scheme 29. Synthesis of 1,2,3-trisubstituted tetrahydroimidazoles 82.

Scheme 30. Convenient syntheses of unsymmetrical imidazolidines 85, 88–92 and 94–97.

Scheme 31. Synthesis of imidazolidine derivatives 99, 100, 102, 104 and 105.

Scheme 32. Synthesis of 1,3-diacyl-2-[3,5-di(tert-butyl)-4-hydroxyphenyl]imidazolidines 107.

Scheme 33. Synthesis of 1,3-diphenyl-2-aryltetrahydroimidazoles 108.

Scheme 34. Montmorillonite KSF catalyzed synthesis of unsymmetrical imidazolidines 110.

Scheme 35. Asymmetric synthesis of imidazolidines 112–113.

Scheme 36. Synthesis of tetraaza m-bis(bidentate) acyclic ligand 116.

Scheme 37. Synthesis of imidazolidine derivatives 118 in various conditions.

Scheme 38. AgClO₄ catalyzed preparation of substituted imidazolidines 120.

Scheme 39. Synthesis of imidazolidine 123.

Scheme 40. Formic acid catalyzed synthesis of imidazolidine derivatives 125–127.

Scheme 41. Synthesis of 2-substituted 1-tosyl-3-(1-tosyliminoalkyl)imidazolidines 130.

Scheme 42. Preparation of imidazolidines 131 and 132 starting from heteroaryl amines.

Scheme 43. Formic acid catalyzed synthesis of imidazolidine derivatives 135 and 136 starting from aminodiazines.

Scheme 44. Synthesis of imidazolidines 138 as anti-trypanosoma cruzi agents.

Scheme 45. Chiral Brønsted acid catalyzed synthesis of chiral imidazolidines 139.

Scheme 46. Synthesis of chiral imidazolidine-pyridines 142.

Scheme 47. Synthesis of 1-acyl-3-arylimidazolidines 143 using montmorillonite clay K-10.

Scheme 48. Synthesis of imidazolidine derivatives 145.

Scheme 49. AgOAc catalyzed synthesis of highly substituted tetrahydroimidazole derivatives 146.

Scheme 50. Synthesis of trifluoromethylated imidazolidines 147.

Scheme 51. Synthesis of imidazolidines 148 in the presence of the lanthanide-originated zirconocene.

Scheme 52. Synthesis of trans-2,5-disubstituted imidazolines 151 using AgOTf as catalyst.

Scheme 53. Ru(bpy)₃Cl₂ catalyzed diastereoselective synthesis of tetrahydroimidazole derivatives 153.

Scheme 54. Synthesis of imidazolidines 154 in the presence of Pd(ii) as catalyst.

Scheme 55. Y(OTf)₃ catalyzed synthesis of imidazolidines 158.

Scheme 56. Preparation of 4-substituted-imidazolidines 163 and 164.

Scheme 57. Catalyst-free synthesis of 1,3,4-trisubstituted imidazolidines 167.

Scheme 58. Guanidinium chloride catalyzed synthesis of trans-4,5-dihydroxy-2-aryl-1,3-bis(heteroaryl)imidazolidines 172.

Scheme 59. Preparation of substituted-imidazolidine derivatives 174.

Scheme 60. Asymmetric synthesis of fluorinated 2,4-trans-imidazolidines 176.

Scheme 61. Fluorescein catalyzed synthesis of imidazolidines 179 using an 11 W fluorescent bulb.

Scheme 62. Palladium catalyzed synthesis of imidazolidines 189.

Scheme 63. Cd^II catalyzed synthesis of tetra-(2-pyridine)-substituted imidazolidine 190.

Scheme 64. SPINOL-derived chiral phosphoric acid-catalyzed synthesis of chiral imidazolidine scaffolds 192.

Scheme 65. CsF catalyzed diastereoselective synthesis of imidazolidines 193.

Scheme 66. Synthesis of substituted-imidazolidine derivatives 198.

Scheme 67. Preparation of imidazolidines 201.

Scheme 68. Copper(i) thiophene-2-carboxylate catalyzed regio- and chemoselective synthesis of indoloimidazolidines 202.

Scheme 69. Construction of imidazolidines 206 and 207 using TBAI as the catalyst and tert-butyl hydroperoxide as the oxidant.

Scheme 70. ^t BuXPhosAuCl catalyzed synthesis of imidazolidines 210.

Scheme 71. Pd(0)-catalyzed synthesis of polysubstituted imidazolidines 215.

Scheme 72. Silver/Xing-Phos-catalyzed synthesis of chiral imidazolidines 221.

Scheme 73. Enantioselective synthesis of imidazolidines 223 using AgOTs and ferrocenylphosphine P–N ligand.

Scheme 74. Cu(OTf)₂ catalyzed synthesis of functionalized imidazolidines 231.

Scheme 75. Metal-free synthesis of imidazolidines 237 in the presence of ^tBuOLi.

Scheme 76. Synthesis of N-sulfonyl imidazolidines 246 and sulfamidate fused imidazolidine 249.

Scheme 77. Iron-catalyzed synthesis of imidazolidine derivatives 251, 254 and 256.

Scheme 78. Organocatalytic asymmetric synthesis of 2,4-disubstituted imidazolidines 260.

Scheme 79. Synthesis of functionalized imidazolidine derivatives 267 using Cu(OTf)₂ and TFA.

Scheme 80. Synthesis of functionalized imidazolidine derivatives 271 in the presence of Ag(Tf₂N).

Scheme 81. Rhodium-catalyzed synthesis of enantioenriched imidazolidines 275.

Scheme 82. Palladium-catalyzed synthesis of imidazolidine derivatives 283.

Scheme 83. Synthesis of 1,3-bis(pyrrol-2-ylmethyl)imidazolidine 291.

Scheme 84. ZnBr₂ catalyzed synthesis of functionalized imidazolidines 292.

Scheme 85. Synthetic of highly functionalized imidazolidines 295via S_N2-type ring-opening of aziridines.

Scheme 86. AgNO₃ catalyzed synthesis of trifluoromethylated imidazolidines 303.

Scheme 87. Synthesis of a series of imidazolidine frameworks 310 under sole visible light irradiation.

Scheme 88. Synthesis of 1,3-disubstituted imidazolidines 311.

Scheme 89. Synthesis of cyclic 5-(hydroxymethyl)-2-methyl-4-(4-methylimidazolidin-2-yl)pyridin-3-ol tautomer 317.

Scheme 90. Synthesis of imidazolidine derivative 318via domino-reaction.

Scheme 91. A facile BF₃·Et₂O-catalysed synthesis of 4-hydroxymethyl imidazolidines 324.

Scheme 92. 2-Picolinaldehyde and chiral YbIII-N,N′-dioxides catalyzed synthesis of a series of trisubstituted imidazolidines 329.

Scheme 93. Y(OTf)₃-catalyzed synthesis of substituted imidazolidines 332.

Scheme 94. Tungsten catalyzed synthesis of imidazolidines 337.

Scheme 95. TiO₂ photocatalytic synthesis of imidazolidines 341.

Scheme 96. TFA catalyzed synthesis of 1,3,5-trisubstituted imidazolidine derivatives 344.

Scheme 97. Synthesis of imidazolidines 350 and 351 using QDs as a visible light photocatalyst.

Scheme 98. Preparation of imidazolidines 353 and 354 under basic conditions.

Scheme 99. Synthesis of 1,3-imidazolidine 355.

Scheme 100. Visible-light photoredox catalyzed synthesis of imidazolidines 360.

Scheme 101. Cu-SKU-3-catalyzed synthesis of substituted imidazolidines 361.

Scheme 102. Cu-catalyzed synthesis of imidazolidines 367.

Scheme 103. Ni-catalyzed chiral trans-substituted imidazolidines 379.

Scheme 104. Copper-catalyzed synthesis of imidazolidine derivatives 382.

Scheme 105. Synthesis of imidazolidines 387 and 388.

Scheme 106. Synthesis of spiro-imidazolidines 392 and 393.

Scheme 107. Tetramethylguanidine (TMG) catalyzed synthesis of spiro imidazolidine-oxazolidine 394.

Scheme 108. Synthesis of spiro-imidazolidine derivatives 398 using catalytic amount of fly ash under microwave irradiation.

Scheme 109. Preparation of imidazolidine-dispirooxindoles 400 in the presence of Et₃N.

Scheme 110. 3,5-Dinitrobenzoic acid promoted synthesis of dispirooxindole-imidazolidine derivatives 404.

Scheme 111. Preparation of spiro[imidazolidine-2,3′-oxindole] 408 in the presence of chiral phosphoric acid.

Scheme 112. Copper(i) thiophene-2-carboxylate catalyzed synthesis of dispiroimidazolidine 412.

Scheme 113. Synthesis of imidazolidine derivatives 413a–c.

Scheme 114. Copper(i)-catalyzed synthesis of spiro[imidazolidine-4,3′-indolin]-2′-imines 414.

Scheme 115. Synthesis of imidazolidine 422 and spiroimidazolidine 424.

Scheme 116. Carbon nitride photocatalyzed synthesis of spiro-imidazolidines 425.

Scheme 117. Synthesis of bis-imidazolidine 430.

Scheme 118. Preparation of bis(3-arylimidazolidinyl-1)methanes 431.

Scheme 119. Synthesis of 2,4,6,8-tetraphenyl-2,4,6,8-tetraazabicyclo[3.3.0]octane 432.

Scheme 120. Synthesis of bis(3-alkyl-imidazolidin-1-yl)methanes 435.

Scheme 121. Preparation of imidazolidines 436 and trimer of benzylimidazolidine 439.

Scheme 122. Synthesis of macrocyclic imidazolidines 440a–f.

Abolfazl Olyaei

Mahdieh Sadeghpour