Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

Abstract

Organosulfur compounds have long played a vital role in organic chemistry and in the development of novel chemical structures and architectures. Prominent among these organosulfur compounds are those involving a sulfur(IV) center, which have been the subject of countless investigations over more than a hundred years. In addition to a long list of textbook sulfur-based reactions, there has been a sustained interest in the chemistry of organosulfur(IV) compounds in recent years. Of particular interest within organosulfur chemistry is the ease with which the synthetic chemist can effect a wide range of transformations through either bond formation or bond cleavage at sulfur. This review aims to cover the developments of the past decade in the chemistry of organic sulfur(IV) molecules and provide insight into both the wide range of reactions which critically rely on this versatile element and the diverse scaffolds that can thereby be synthesized.

Scheme 1. Pummerer Reaction Types Depending on the Sulfoxide Substituent

Scheme 2. Stereoselective Pummerer Reaction Studied Computationally by Thiel and Co-workers

Scheme 3. Introduction of Arenes and Bases through a Classical Pummerer Reaction

Scheme 4. Pummerer Reaction with Azides

Scheme 5. Synthesis of Oxazolines via Pummerer Reaction

Scheme 6. Classical Pummerer Reaction and Pummerer Fragmentations That Lead to C–S Bond Cleavage

Scheme 7. Yorimitsu’s Double Pummerer Fragmentation Sequence

Scheme 8. O-Silylated Ketene Acetal Initiated Pummerer Reactions

Scheme 9. Mendoza’s Base-Promoted Pummerer Reaction

Scheme 10. One-Pot Procedure for Oxidation and Base-Promoted Pummerer Reaction

Scheme 11. Catalytic Pummerer Reaction by Pappo et al.

Scheme 12. Recent Pummerer-Type Transformations Not Employing a Sulfoxide Precursor

Scheme 13. Procter’s Connective Pummerer-Type Cyclization

Scheme 14. Pappo’s Copper-Catalyzed Thionium Chemistry

Scheme 15. Trost’s Key Step in the Total Synthesis of Asteriscunolide D

Scheme 16. Terada’s Enantioselective Ring Expansion of Dithianes

Scheme 17. Oxidative Pummerer-Type Reactions

Scheme 18. Zhao’s Aromatic Pummerer Reactions

Scheme 19. Yorimitsu’s Aromatic Additive Pummerer-Type Sulfanylation

Scheme 20. General Mode and Specific Applications of the Vinylogous Pummerer Reaction

Scheme 21. “Long-Distance” Vinylogous Pummerer Reaction

Scheme 22. Applications of Additive/Vinylogous Pummerer-Type Reactions

Scheme 23. Yorimitsu’s Extended Pummerer Reaction

Scheme 24. Yorimitsu’s Copper Catalyzed Extended Pummerer Reaction with Oxygen Transfer

Scheme 25. Interrupted, Dealkylative Pummerer Reaction for the Synthesis of Benzothiophenes

Scheme 26. Wan’s Glycosylation Using an Interrupted Pummerer Reaction

Scheme 27. Sulfanylation of Arenes by an Interrupted Pummerer Reaction

Scheme 28. Interrupted Pummerer Reaction to Form Diaryl Sulfides

Scheme 29. One-Pot Interrupted Pummerer/Cross Coupling Protocol

Scheme 30. Yorimitsu’s Early Work and Development of the [3,3]-Sigmatropic Thio-Claisen Rearrangement Enabled by Sulfoxide Activation

Scheme 31. Maulide’s α-Arylation of Ketones and Procter’s Allylation, Propargylation, and Arylation Reactions of Heterocycles with Activated Sulfoxides

Scheme 32. Propargylation of Activated Aryl Sulfoxides with Unactivated π-Systems

Scheme 33. Trapping of π-Activated Alkynes with Sulfoxides, Followed by Arylation via Sigmatropic Rearrangement

Scheme 34. Interception of Keteniminium Ions (190) and Other sp-Hybridized Cations with Aryl Sulfoxides, Followed by [3,3]-Sigmatropic Rearrangement

Scheme 35. (a) Enantiopure Aryl Sulfoxides Enable the Induction of Chirality at Carbon via 1,4-Chirality Transfer; (b) Enantiopure Vinyl Sulfoxides Allow a Fully Stereodivergent Synthesis of 1,4-Dicarbonyl Compounds

Scheme 36. Generalized Representation of the Mislow–Braverman–Evans Rearrangement

Scheme 37. Recent Applications of the Mislow–Braverman–Evans Rearrangement in Natural Product Synthesis

Scheme 38. [2,3]-Sigmatropic Rearrangements Following Conjugate Addition to Vinyl Sulfoxide Derivatives

Scheme 39. Mislow–Evans Rearrangement Enables Deallylative Arylation of Allyl Sulfoxides

Scheme 40. Addition of Allyl Sulfides to Metal Carbenes Enables the Doyle–Kirmse Reaction

Scheme 41. Li’s Use of [2,3]-Sigmatropic Rearrangements of Sulfur Ylides for Allylic and Propargylic C–H Functionalization

Scheme 42. Reactivity Trends of Sulfoxides in the Context of Sigmatropic Rearrangements

Scheme 43. Application of Activated Sulfoxides in the Functionalization of Allyl Benzenes

Scheme 44. Oxidative (a) Allylic and (b) Benzylic Functionalization via Unusual Attacks On Sulfur

Scheme 45. Kawasaki’s Benzylic Functionalization of Indole Derivatives

Scheme 46. Metal-Free and Copper-Catalyzed Methylthiolations of Arenes with DMSO

Scheme 47. Kilogram-Scale Halogenation of Arenes Enabled through DMSO-Mediated Slow Release of X₂

Scheme 48. Sulfoxides as Nucleophiles for the Capture of Arynes

Scheme 49. Use of Sulfoxide–Aryne Adducts for Epoxidation

Scheme 50. (a) Polar, DMSO-Mediated Dibromination, and Bromohydrin Formation, (b) Oxysulfenylation of Alkenes via Radical Addition, and (c) Umpolung Halogenation/Halolactonization of Alkenes

Scheme 51. Application of Sulfoxides as (a) Electrophiles and (b) Nucleophiles in Alkene Functionalization

Scheme 52. Yoshida’s Electrochemical Olefinic and Benzylic Oxidation Mediated by DMSO

Scheme 53. Formation of Unusual Cationic Species through Elimination of Diphenyl Sulfide

Scheme 54. α-Ketoamide Formation by I₂-DMSO-Mediated Oxidation of Alkenes, Alkynes, and Ketones

Scheme 55. Recent Approaches to the Venerable Kornblum Oxidation

Scheme 56. Purported Intermediate in Metal–Sulfoxide Exchange

Scheme 57. Metal–Sulfoxide Exchange for the Synthesis of Chiral Sulfoxides

Scheme 58. Accessing Highly Strained Cycloalkynes through a Metal–Sulfoxide Exchange/Elimination Pathway

Scheme 59. Metal–Sulfoxide Exchange in the Synthesis of Highly Functionalized Targets

Scheme 60. Employing Metal-Exchange for the Generation of Chiral Metal Carbenoid Equivalents

Scheme 61. Stockman’s Exploration of Oae’s Ligand-Coupling Reaction

Scheme 62. Enthaler’s Cross-Coupling of Aryl Sulfoxides with Grignard Reagents

Scheme 63. Yorimitsu’s Palladium-Catalyzed Cross-Coupling Reactions of Diaryl Sulfoxides with Alkynes (left) and Amines (right)

Scheme 64. Yorimitsu’s Cross-Coupling of Aryl Sulfoxides with Diarylzinc Reagents

Scheme 65. (a,b) Palladium-Catalyzed Arylations of Sulfenate Anions and (c) Sulfonamide Synthesis

Scheme 66. Walsh’s Palladium-Catalyzed Arylation of Sulfenate Anions

Scheme 67. Outline of the Reactions of Sulfonium Salts and Vinylsulfonium Salts

Scheme 68. (a) Generic Structures of Fluoroalkylating Sulfonium Salts; (b) Reaction of Fluoroalkylated Sulfonium Salts with Nucleophiles

Scheme 69. (a) Representative Catalytic Cycle of Trifluoromethylation with Sulfonium Salts under Photoredox Catalysis; (b) Examples of Alkene Functionalizations

Scheme 70. Transition Metal-Catalyzed Trifluoromethylations: (a) Formation of Trifluoromethylated Organometallic Intermediates; (b) Cross Coupling of Arenes with Trifluoromethylsulfonium Salts; (c) Introduction of a Trifluoromethyl Group Using Directing Groups

Scheme 71. Arylsulfonium Salts Allow for Transition Metal-Catalyzed Cross-Coupling Reactions

Scheme 72. Palladium-Catalyzed Cross-Coupling Reactions of (a) Vinyl- and (b,c) Arylsulfonium Salts

Scheme 73. (a,b) Heck- and Sonogashira-Type Reactions of Sulfonium Salts, as well as (c) a One-Pot Sulfonium Salt Formation/Borylation Reaction

Scheme 74. An Aromatic Additive Pummerer Reaction Enables the Synthesis of Sulfonium Ions That Can Be Engaged in Palladium-Catalyzed Cross-Coupling Reactions

Scheme 75. Different Reaction Pathways for Reactions with Vinylsulfonium Salts

Scheme 76. N-Vinylation Reactions with Vinylsulfonium Salts

Scheme 77. Vinylsulfonium Salts in Biological Systems

Scheme 78. Annulation Reactions of Vinylsulfonium Salts with Dinucleophiles

Scheme 79. Annulation Reactions of Vinylsulfonium Salts with Indole Derivatives and Sulfinamides

Scheme 80. Heterocycle Formations from Carboxylic Acid Derivatives

Scheme 81. Lactam and Azetidine/Oxetane Formation by Virtue of Vinylsulfonium Electrophilicity

Scheme 82. Cyclopropanation of (a) α-Aminoketones and (b) Malonate Derivatives with Vinylsulfonium Salts

Scheme 83. Cyclopropanation of (a) Diketones and (b) Oxindoles as well as (c) Formation of Annulated Dihydrofurans with Vinylsulfonium Ions

Scheme 84. Aggarwal’s Enantioselective Formation of Fused Heterocycles Using Vinylsulfonium Salt 509 and Synthesis of (−)-Balanol

Scheme 85. Intermolecular Version of a Domino Epoxide/Aziridine Synthesis and α-Chiral Substrates

Scheme 86. Diastereoselective Synthesis of Azepins and Use of a Novel Chiral Sulfonium Salt

Scheme 87. (a) Diverging Reactivity of Vinylsulfonium and -Phosphonium Salts; (b) Cyclopropanation of Michael Acceptors with Vinylsulfonium Salts

Scheme 88. Aryl Substituted Vinylsulfonium Salts in the Synthesis of Fused Heterocycles

Scheme 89. Formal Cycloaddition Reactions of Vinylsulfonium Salts

Scheme 90. Application of a Trifluoromethylated Vinylsulfonium Salt

Scheme 91. Dependent on the Reaction Conditions, Trifluoromethylated Vinylsulfonium Salts Lead to Diverse Classes of Products

Scheme 92. Further Examples of the Formation of Trifluoromethyl-Containing Cyclic Structures

Scheme 93. Difluoromethylated Vinylsulfonium Salts in the Synthesis of Aziridines and Cyclopropanes

Scheme 94. Fluorinated Cyclopropanes from α-Fluorovinylsulfonium Salts

Scheme 95. Base-Promoted Isomerization of Propargyl Sulfonium Salts

Scheme 96. Access to Hydroindol-5-ones from Propargylsulfonium Salts

Scheme 97. (a) Hexahydropyrrolo[3,2-b]indoles Formed with Propargylsulfonium Salts and (b) Domino Reaction with Michael Acceptors Affording Annulated or Trisubstituted Cyclopropanes

Scheme 98. Formal (5 + 1) Annulation of Bidentate Nucleophiles with in Situ-Generated Allenylsulfonium Ions

Scheme 99. Examples of General Sulfur Ylide Reactivity

Scheme 100. Copper-Catalyzed Asymmetric Formal (4 + 1)-Cycloaddition of Azoalkenes with Sulfur Ylides

Scheme 101. Palladium-Catalyzed Decarboxylative (4 + 1)-Cycloaddition for the Asymmetric Synthesis of Indoles

Scheme 102. Iron-Catalyzed Decarboxylative Formal (4 + 1)-Cycloadditions

Scheme 103. Cu-Catalyzed Decarboxylative Formal (4 + 1)-Cycloaddition

Scheme 104. Pd-Catalyzed Decarboxylative Formal (4 + 1)-Cycloadditions of CF₃-Benzoxazinanones

Scheme 105. Cu-Catalyzed Asymmetric Formal (3 + 1)-Cycloaddition

Scheme 106. Cu-Catalyzed Formal (4 + 2)-Cycloaddition of Enoldiazoimides and Sulfur Ylides

Scheme 107. Intermolecular and Intramolecular Au-Catalyzed Furan Synthesis

Scheme 108. Proposed Mechanisms for Furan Formation with Sulfur Ylides

Scheme 109. Au-Promoted Intramolecular Cyclopropanation of Sulfur Ylides with Allyl Esters

Scheme 110. Catalyst-Dependent Selectivity in Sulfur Ylide Cycloisomerization Reactions

Scheme 111. Intermolecular Cyclopropanation of Allenamides with Stabilized Sulfur Ylides

Scheme 112. Au-Catalyzed [1,4]-Vinyl Migration from Sulfur to Oxygen

Scheme 113. Iron-Catalyzed Cyclopropanation Using Sulfur Ylides

Scheme 114. Enantioselective Cyclopropanation of α,β-Unsaturated Aldehydes with Sulfur Ylides and Aminoacids

Scheme 115. Enantioselective Cyclopropanation of α,β-Unsaturated Ketones with Sulfur Ylides and Diamines

Scheme 116. Enantioselective NHC-Catalyzed Oxidative Cyclopropanation of Aldehydes with Sulfur Ylides

Scheme 117. DABCO-Catalyzed (3 + 3) Annulation of Allenoates with Sulfur Ylides to Deliver Achiral 4H-Pyrans

Scheme 118. Catalytic Asymmetric Cyclopropanation of β,γ-Unsaturated α-Ketoesters with Sulfur Ylides

Scheme 119. Sequential (4 + 1)-Cycloaddition/Rearrangement of Nitrostyrenes with Sulfur Ylides

Scheme 120. Asymmetric (4 + 1)-Cycloaddition of Sulfur Ylides with in Situ-Generated ortho-Quinone Methides

Scheme 121. Aggarwal’s Chiral Sulfonium Salt for Asymmetric Epoxidations and Aziridinations

Scheme 122. Aggarwal’s Synthesis of the Cyclopiazonic Acid Family Using a Chiral Sulfur Ylide

Scheme 123. Xiao’s Photocatalytic Insertion of Sulfonium Ylides into Aryl-C–H Bonds for Oxindole Synthesis

Scheme 124. Photocatalytic Synthesis of 2,3-Disubstituted Indoles Employing Stabilized Sulfur Ylides

Scheme 125. General Proposed Mechanism for the Doyle–Kirmse Reaction

Scheme 126. Iron-Catalyzed Doyle–Kirmse Reaction of Allyl and Propargyl Sulfides

Scheme 127. Rhodium-Catalyzed thia-Sommelet–Hauser Rearrangement of Aryl Sulfides

Scheme 128. Wang’s Modified Gassman Oxindole Synthesis

Scheme 129. Enantioselective Doyle–Kirmse Reaction with Chiral Rhodium or Copper Complexes

Scheme 130. Enantioselective Ni-Catalyzed Doyle–Kirmse Reaction with Pyrazoleamide Diazo Compounds

Scheme 131. In Situ Generation of Diazo Compounds in the Doyle–Kirmse Synthesis of Thioether Imines

Scheme 132. Alkynes as Masked Ylides in Doyle–Kirmse Chemistry

Scheme 133. Synthesis of Sulfur Heterocycles from Alkynyl Sulfoxides through Doyle–Kirmse Reaction

Scheme 134. Doyle–Kirmse Reaction with Terminal Alkynes as Carbenoid Precursors

Scheme 135. Doyle–Kirmse Reaction from Cyclopropenes

Scheme 136. Metal-Free [2,3]-Sigmatropic Rearrangement of Sulfur Ylides Generated in Situ from Benzyne Intermediates

Scheme 137. General Mechanism of the thia-Stevens Rearrangement

Scheme 138. Proposed Synthesis of the Nuphar Thioalkaloids Core through Ring Expansion of Thietanes

Scheme 139. A thia-Stevens Rearrangement as a Key Step in the Formal Synthesis of (+)-Laurencin

Scheme 140. Copper-Catalyzed Enantioselective 1,2-Migration of 1,3-Oxadithiolanes for the Formation of 1,4-Oxathianes

Scheme 141. Study of Preferred Reaction Pathways (Stevens vs Sommelet–Hauser) in Dependence of Solvent and Electronic Properties

Scheme 142. Metal-Free Stevens Rearrangement of Sulfur Ylides Generated in Situ from Benzyne Intermediates

Scheme 143. A Sulfide Catalyst Enables the Sulfur Ylide-Mediated Cross-Coupling Reaction of Benzyl Halides with Arylboronic Acids

Scheme 144. Reactivity of Thiocarbonyl Ylides and Their Application in (3 + 2)-Cycloaddition Reactions

Scheme 145. General Mechanism of Sulfur Ylide Formation from Aryne and Sulfide

Scheme 146. Epoxidation of Isatins with Sulfur Ylides Formed in Situ

Scheme 147. Hoye’s Sulfide Addition to Arynes, Followed by Nucleophilic Ring Opening

Scheme 148. Addition of Vinyl Sulfides to Arynes Leads to the Formation of o-Thio Styrenes

Scheme 149. Difunctionalization of Arenes with Sulfur Ylides via a [2 + 2]-Cycloaddition

Scheme 150. Sulfinate Salts as Intermediates in Organic Synthesis

Scheme 151. Metal-Catalyzed Aryl Sulfinate Formation

Scheme 152. Sulfinate Formation through Degradation Pathways

Scheme 153. Sulfone and Sulfoxide Syntheses from Sulfinate Salts

Scheme 154. Sulfinate Halogenation Protocols

Scheme 155. Bleach-Mediated Amination of Sulfonates Affording Sulfonamides

Scheme 156. Desulfinylative Transformations

Scheme 157. One-Electron Oxidation of Langlois’ Reagent to 415 and Its Application in Alkene Functionalization Reactions

Scheme 158. Trifluoromethylation/Cyclization Reactions Using Langlois’ Reagent

Scheme 159. Overview of Methods for the Trifluoromethylation of (Hetero)arenes with Langlois’ Reagent

Scheme 160. Metal-Catalyzed Sulfonylative Multicomponent Reactions (MCRs)

Scheme 161. Radical-Based Sulfonylative MCRs

Scheme 162. Formation of Sulfonamides from Diazonium Salts Using Sodium Metabisulfite