Deciphering the Chameleonic Chemistry of Allenols: Breaking the Taboo of a Onetime Esoteric Functionality

Abstract

The allene functionality has participated in one of the most exciting voyages in organic chemistry, from chemical curiosities to a recurring building block in modern organic chemistry. In the last decades, a special kind of allene, namely, allenol, has emerged. Allenols, formed by an allene moiety and a hydroxyl functional group with diverse connectivity, have become common building blocks for the synthesis of a wide range of structures and frequent motif in naturally occurring systems. The synergistic effect of the allene and hydroxyl functional groups enables allenols to be considered as a unique and sole functionality exhibiting a special reactivity. This Review summarizes the most significant contributions to the chemistry of allenols that appeared during the past decade, with emphasis on their synthesis, reactivity, and occurrence in natural products.

Scheme 1. Classical Strategies for the Synthesis of Racemic Allenols

Scheme 2. Optimization of the Allenation of Terminal Alkynes for the Synthesis of Substituted Allenols

Scheme 3. Substituted α- and β-Allenols from Terminal Alkynes and Diazo Compounds

Scheme 4. α-Allenol Synthesis through Propargylboronic Addition onto Carbonyl Compounds

Scheme 5. α-Allenol Synthesis through Activated Allene Addition to Aldehydes

Scheme 6. Substituted α-Allenols from Alkyndiols

Scheme 7. Allenol Synthesis through Selective Ring Opening of Propargyl Epoxides

Scheme 8. Multicomponent Strategies for Allenol Synthesis

Scheme 9. Asymmetric Allenation of Terminal Alkynes Employing Chiral Amines

Scheme 10. Aldol Allenoate Addition to Aldehydes Promoted by Chiral Bromoboranes

Scheme 11. Chiral Oxiranes as α- and γ-Allenol Precursors

Scheme 12. Central-to-Axial Chirality Transfer from Ethynyl β-Lactams

Scheme 13. Chiral Allenoic Acids and Allenoates as α-, β-, and γ-Allenol Precursors

Scheme 14. Asymmetric Wittig Rearrangement in α-Allenol Synthesis

Scheme 15. Asymmetric Allenyl Boronate Addition to Aldehydes

Scheme 16. Multicomponent Asymmetric Reaction for the Synthesis of Allenyl Cyclohexenones

Scheme 17. DKR of α-Allenols Using Palladium Catalysis

Scheme 18. Desymmetrization of Allendiols

Scheme 19. Enzymatic KR of Centrally Chiral α-Allenols

Scheme 20. Chemical Kinetic Resolution of Aryl-Substituted Terminal Allenols

Scheme 21. Asymmetric Allenation of Terminal Alkynes Using Chiral Ligands

Scheme 22. Asymmetric Aldol-type Synthesis of Substituted α- and β-Allenols

Scheme 23. Axially Chiral Allenols from Enynes

Scheme 24. Cross-Coupling Reactions of Borane Complexes and Propargylic Compounds

Scheme 25. Allenol Asymmetric Synthesis from Propargylic Derivatives through Diverse Procedures

Scheme 26. Organocatalyzed Addition of Allenyl and Propargyl Boronic Complexes to Carbonyls

Scheme 27. Organocatalyzed Asymmetric Traceless-Petasis for the Synthesis of Allenols

Scheme 28. Organocatalyzed Alkynylogous Mukaiyama Aldol Synthesis of Allenols

Scheme 29. General Reaction Mechanisms for C–OH Cleavage in α-Allenols

Scheme 30. Methyl and Arylsulfonyl Chloride Promoted Synthesis of Dienes and Its Application toward the Synthesis of Polycyclic Structures

Scheme 31. Scope of Metal-Free [3,3]-Sigmatropic Rearrangement of α-Allenols

Scheme 32. Metal-Free 1,3-Migration Strategies for the Synthesis of Dienes from α-Allenols

Scheme 33. Acid Promoted Synthesis of Halogenated Phosphinoyl Dienes and Synthetic Applications

Scheme 34. Dihydrothiocarbazole Synthesis by Reaction of Indoline-2-thiones and In Situ Generated Dienes

Scheme 35. Iron-Promoted Halogenation/Rearrangement of Allenols and Synthetic Applications

Scheme 36. Chromium-Mediated Rearrangement of Allenyl Vinyl Alcohols

Scheme 37. Palladium-Catalyzed Synthesis of 1-Phosphoryl 1,3-butadienes

Scheme 38. Metal-Catalyzed Synthesis of Dienes in the Presence of Boronic Acids

Scheme 39. Palladium-Catalyzed Synthesis of Trienes from Allenyl Acetates and Mechanistic Rationale

Scheme 40. Synthesis of Enones by Iron-Catalyzed Meyer-Schuster Rearrangement and Mechanistic Rationale

Scheme 41. Vanadium-Catalyzed Transformations of α-Allenols

Scheme 42. One-Pot Synthesis of Spirocyclic Compounds from Allenols Involving Palladium-Mediated Enone Formation

Scheme 43. Allenol-enone Transformation by Electrophilic Attack of Bis(triflyl)ethene

Scheme 44. Gallium-Catalyzed Synthesis of Dihydrobenzafurans by Phenol Addition to α-Allenols

Scheme 45. Synthesis of Conjugated Enynes by Metal-Free OH-Activation/Elimination

Scheme 46. Copper-Catalyzed Synthesis of Enynes from α-Allenols

Scheme 47. Enynes as Reaction Intermediates in the Synthesis of 2H-Pyran-2-ones and Substituted Benzenes from α-Allenols

Scheme 48. Synthesis of 3-Allenyl Indoles through Acid-Mediated Allene Transfer and Synthetic Applications

Scheme 49. Palladium-Catalyzed Allene Transfer and Application toward the Synthesis of Vinyl Dihydrofurans

Scheme 50. Copper-Catalyzed Allene Transfer for the Synthesis of Allenamines and In Situ Aza-Cyclization Reactions

Scheme 51. Au-Catalyzed Synthesis of Carbazoles from Indole-Tethered Allenols

Scheme 52. Palladium-Catalyzed Cross-Coupling Reactions of Indole-Tethered Allenols and Allyl Bromides or Acetyl Protected Allenols

Scheme 53. DFT Computed Reaction Profile for Deacetoxypalladation Step in Allenol–Allenol Cross-Coupling Reaction

Relative free energies are given in kcal mol^–1.

Scheme 54. Divergent Reactivity on 3-Halo-(indol-2-yl)-α-allenols under Metal Catalysis

Scheme 55. DFT Computed Reaction Profile for the 1,3-Halogen Migration Step in Metal-Catalyzed Iodocarbazole Synthesis

Relative free energies are given in kcal mol^–1.

Scheme 56. Acid-Catalyzed Synthesis of Naphthols

Scheme 57. Metal-Catalyzed 4-exo-dig versus 5-endo-dig Oxycyclizations of α-Allenols

Scheme 58. Cycloetherification vs Carbocyclization under Gold and Palladium Catalysis

Scheme 59. Hg-Catalyzed Cycloetherification of α-Allenols

Scheme 60. Metal-Mediated Cycloetherification of Diverse Allenols

Scheme 61. Heterogeneous Palladium-Catalyzed Oxycyclization of α-Allenols

Scheme 62. Cycloetherification of Trifluoromethylated Allenols in Ionic Liquids

Scheme 63. Gold-Catalyzed Oxycyclization of Allenols for the Synthesis of Cyclophanes and Tetracyclic Indolines

Scheme 64. Metal-Free Conversion of Allenic Hydroxyketones into 3(2H)-Furanones

Scheme 65. Rhodium-Catalyzed Nucleophilic Addition of Allenols to 4-Substituted-1-tosyl-1,2,3-triazoles

Scheme 66. mCPBA-Mediated Synthesis of 1,2-Diketones from α-Hydroxyl Methoxyallenes

Scheme 67. Allenol vs Alkenol Reactivity in Metal Catalyzed Reactions of Enallenols

Scheme 68. Computed Reaction Profile for Allenol vs Alkenol Cyclization of Enallenols

Relative free energy data are given in kcal mol^–1. HCl-mediated oxycyclization is taken as model reaction for the Lewis acid-FeCl₃ alkenol oxycyclization reaction.

Scheme 69. Palladium-Catalyzed Cascade Processes of Enallenols

Scheme 70. Prins-type Co-cyclization of Allenols and Aldehydes

Scheme 71. Palladium-Catalyzed Multicomponent Synthesis of Tetrasubstituted Furans and Oxazolidine Derivatives

Scheme 72. Palladium-Catalyzed Homo- And Heterodimeric Cross-Coupling Reaction of Allenols

Scheme 73. Rhodium-Catalyzed Oxycyclization/Cross-Coupling Reaction of α-Allenols and N-Methoxybenzamides

Scheme 74. Gold-Catalyzed Photoredox Cross-Coupling of α-Allenols and Diazonium Salts

Scheme 75. Metal–Ligand Cooperative Catalysis in Cycloetherification of α-, β-, and γ-Allenols

Scheme 76. Mechanistic Pathway for the Gold-Catalyzed Hydroalkoxylation of Allenols

Scheme 77. POM-Au Catalyzed Hydroalkoxylation of Acid-Sensitive Allenols

Scheme 78. Thiazolium Gold(I) Carbene-Catalyzed Hydroalkoxylation of Allenols

Scheme 79. Micellar-Supported Gold(I) Catalyzed Hydroalkoxylation of Allenols

Scheme 80. Supramolecular Gold GaL₆-Hosted Catalyst and Its Application to Hydroalkoxylation Reaction

Scheme 81. Supramolecular Gold(I) Catalysis in Selective Oxycyclization of γ-Allenols

Scheme 82. Pd-Mediated Synthesis of Allylic Alcohols

Scheme 83. Cooperative Pd/B-Catalyzed Transformation of Buta-2,3-dien-1-ol into Allylic Alcohols

Scheme 84. Allenol Transformations Promoted by Previous Metal-Hydroxyl Previous Coordination

Scheme 85. Synthesis of Cyclopentenones by Metal-Catalyzed Rearrangements of Allenols

Scheme 86. Halogen- and Selenium-Mediated Ring Expansion Reactions of Allenols

Scheme 87. Dual Gold-Photoredox Catalyzed Arylative Rearrengement of Allenols

Scheme 88. Reaction of Methoxyallenes with Anthraniland Isoxazole through Gold-Carbene Intermediates

Scheme 89. Synthesis of Enantiopure Tetrahydrofurans, Dihydropyrans, and Tetrahydrooxepines through Metal-Catalyzed Cyclization of Optically Pure β,γ- and γ,δ-Allendiols

Scheme 90. Metal-Catalyzed Cascade Oxycyclization from Enantiopure Allenols

Scheme 91. Enantioenriched Enallenols as Chirality Transfer Reagents in Palladium-Catalyzed Cyclization Reactions

Scheme 92. Asymmetric Multicomponent Reaction of Enantioenriched Allenols, Aryl Iodides, and Amines under Palladium Catalysis

Scheme 93. Racemization of Axially Chiral Allenes by Metal-Coordination

Scheme 94. Chirality Transfer in Gold-Catalyzed Cycloisomerization Reactions of γ- and δ-Allenols

Scheme 95. Synthesis of Optically Active Dihydrofurans through Gold-Catalyzed Oxycyclization of Enantioenriched Allenols

Scheme 96. Chirality Transfer in Micellar-Supported Gold-Catalyzed Oxycyclization Reactions of Allenols

Scheme 97. Chirality Transfer on Rhodium-Mediated C–H Insertion/Lactonization Reaction of N-Methoxybenzamide with Allenols

Scheme 98. Tetrahydrofuran Synthesis through Prins-type Cyclization of β-Allenols

Scheme 99. Synthesis of Enantioenriched Vinyl Tetrahydrofuran Systems through Metal-Catalyzed/Phosphine Ligand-Mediated Oxycyclization

Scheme 100. Synthesis of Enantiopure Vinyl Tetrahydrofurans through Chirality Transfer from Gold-Based Catalytic Systems

Scheme 101. Silver-Catalyzed Enantioselective Oxycyclization of Allenols

Scheme 102. Metal-Catalyzed Desymmetrization of Allendiols

Scheme 103. Chirality Transfer from Enantiopure Chiral Ligands and Chiral Counterions on Gold-Catalyzed Oxycyclization of γ-Allenols

Scheme 104. Enantioselective S_N1-type Reactions Involving Iridium-Based Allenic Carbocations

Scheme 105. Palladium-Catalyzed Enantioselective Synthesis of Functionalized Allenes from Allenyl Esters

Scheme 106. Hybrid Enzymatic/Transition Metal Catalyzed Synthesis of Dihydrofuran Compounds

Scheme 107. Hybrid Enzymatic/Transition Metal Catalyzed Synthesis of Enantioenriched Cyclobutenols

Scheme 108. Hybrid Enzymatic/Transition Metal Catalyzed Oxycyclization of Allenols Using Supramolecular Hosts

Scheme 109. Silver-Catalyzed Oxycyclization of α-Allenols in Natural Product Synthesis

Scheme 110. Silver-Mediated Oxycyclization of α-Allenols in the Total Synthesis of Amphidinolide F and Leiodolide B

Scheme 111. Ruthenium-Catalyzed Carbonylation of α-Allenols toward the Synthesis of the γ-Butyrolactone Scaffold in Natural Products

Scheme 112. Synthesis of (+)-Xylogiblactone A through Gold-Catalyzed Cycloisomerization of Enantioenriched Allenols

Scheme 113. Synthesis of the Dihydropyran and Tetrahydropyran Fragments of Sorangicin A, Eribulin, and Halichondrin

Scheme 114. Synthesis of (−)-Gilbertine through Photoinduced Cyclization of Azido-allenols

Scheme 115. Synthesis of (−)-Centrolobine Natural Product from an Enantioenriched Internal Allenol

Scheme 116. Synthesis of Rosuvastatin and Pitavastatin Natural Products from an Enantiopure β-Allenol

Scheme 117. Synthesis of Carbazole Alkaloids from Indole-Tethered Allenols

Scheme 118. Synthesis of Natural Products from Allenol Cycloaddition Processes

Scheme 119. Formal Synthesis of Jogyamycin through Rhodium-Catalyzed Azacyclization of a β-Allenol

Scheme 120. Total Synthesis of Lasonolide A from Enantioenriched α-Allenols

Scheme 121. Total Synthesis of Trachelanthamidine and Supinidine

Scheme 122. Linear Allenols Exhibiting Antibiotic Properties

Scheme 123. Enantioselective Allenation of Terminal Alkynes for the Synthesis of Naturally Occurring Allenol Structure

Scheme 124. Conjugated Hydride Addition to Epoxy Alkynes Towards the Total Synthesis of Allenol-Based Puna’auic Fatty Acid

Scheme 125. Alternative Approaches to the Allenic Moiety Generation in (+)-Iso-A82775C Total Synthesis

Scheme 126. Synthesis of the Grasshopper Ketone

Scheme 127. Allenol-Based Natural Products from the Norcarotenoid Family

Scheme 128. Retrosynthethic Strategies for the Synthesis of Peridinin and Deoxy-Peridinin Natural Products

Scheme 129. Synthesis of Paracentrone and Fucoxanthin Natural Products

Scheme 130. Proposed Structure of Allenol-Containing Natural Products As Determined by NMR Investigations

Scheme 131. Allenol Motifs in Nucleoside Analogous with Pharmaceutical Activities