Sulfinate Salts Research Articles

Transition-Metal-Free Regioselective One-Pot Synthesis of Aryl Sulfones from Sodium Sulfinates via Quinone Imine Ketal.

A novel, efficient, and regioselective transition-metal-free one-pot synthesis of aryl sulfones via the reactive quinone imine ketal intermediate is demonstrated using easily accessible bench-stable sulfinate salts. A broad range of functionality on p-anisidine substrates as well as sulfinate salts was tolerated under mild reaction conditions to provide the corresponding aryl sulfones in good to excellent yields.

Organic photoredox catalysis enabled cross-coupling of arenediazonium and sulfinate salts: synthesis of (un)symmetrical diaryl/alkyl aryl sulfones.

We disclose herein the first transition-metal- and external oxidant/reductant-free visible-light-mediated synthesis of (un)symmetrical diaryl/alkyl aryl sulfones from arenediazonium tetrafluoroborates and sodium sulfinates using eosin Y as an organic photoredox catalyst. The utilization of visible light as an inexpensive and ecosustainable energy source, operational simplicity, ambient temperature and clean reaction in aqueous acetonitrile are the salient features of the developed protocol. The desired sulfones were also synthesized via a one-pot, two-step process directly from anilines and sulfinate salts in good to excellent yields.

A one-pot protocol for the synthesis of β-ketosulfones from α,α-dibromoketones

A one-pot debromination/sulfonylation strategy was developed for the direct transformation of α,α-dibromoketones into β-ketosulfones in the presence of sulfinate salts in a methanol solution.

Metal-Free Electrophilic Trifluoroethylthiolation with NaSO2CH2CF3.

Metal-free trifluoroethylthiolation with fluorinated sulfinate salt NaSO2CH2CF3 under reductive conditions has been developed. The strategy enables the installation of the SCH2CF3 moiety efficiently to form a number of unexplored stable trifluoroethylthiolated heterocycles, arenes, and thiols, which have the potential to be a new series of fluorine-containing chemical entities for medicinal chemists.

Generating Stereodiversity: Diastereoselective Fluorination and Highly Diastereoselective Epimerization of α-Amino Acid Building Blocks.

Diastereoselective fluorination of N-Boc ( R)- and ( S)-2,2-dimethyl-4-((arylsulfonyl)methyl)oxazolidines and a previously unknown diastereoselective epimerization at the fluorine-bearing carbon atom α to the sulfone was realized. Diastereoselectivities of both reactions were excellent for benzothiazolyl sulfones, allowing access to two enantiomerically pure diastereomers from one chiral precursor. To demonstrate synthetic utility, the benzothiazolyl sulfones were converted to diastereomerically pure ( S, S)- and ( R, S)-benzyl sulfones via sulfinate salts and to amino acids. To understand the diastereoselectivities, DFT analysis was performed.

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent.

An alternative method for forming sulfonates through hypervalent iodine(III) reagent-mediated oxidation of sodium sulfinates has been developed. This transformation involves trapping reactive sulfonium species using alcohols. With additional optimization of the reaction conditions, the method appears extendable to other nucleophiles such as electron-rich aromatic systems or cyclic ethers through a ring opening pathway.

A Class of Amide Ligands Enable Cu-Catalyzed Coupling of (Hetero)aryl Halides with Sulfinic Acid Salts under Mild Conditions.

The amide derived from 4-hydroxy-l-proline and 2,6-dimethylaniline is a powerful ligand for Cu-catalyzed coupling of (hetero)aryl halides with sulfinic acid salts, allowing the formation of a wide range of (hetero)aryl sulfones from the corresponding (hetero)aryl halides at considerably low catalytic loadings. The coupling of (hetero)aryl iodides and sodium methanesulfinate proceeds at room temperature with only 0.5 mol % CuI and ligand, representing the first example for Cu-catalyzed arylation at both low catalytic loading and room temperature.

Palladium-Catalyzed Carbene Migratory Insertion and Trapping with Sulfinic Acid Salts toward Allylic Sulfones.

Allylic sulfones were synthesized with excellent selectivity and good yield via Pd-catalyzed cross-coupling of vinyl iodide with N-tosylhydrazone. This process involves palladium carbene migratory insertion/trapping with sulfinic acid salts. For the previous Pd-catalyzed N-tosylhydrazone cross-coupling, sulfinic acid salt is generated as a byproduct. In this transformation, the diazo compound and the sulfinic acid salt, which are all generated from N-tosylhydrazone, were used as cross-coupling partner.

Mechanistic aspects of copper (II)-catalyzed synthesis of sulfones from sulfinate salts and aryl halides under C-S coupling

Copper(II)-catalyzed synthesis of sulfones from sulfinate salts and aryl halides was investigated by means of a combination of experiment and DFT calculation. Experimental results demonstrated the wide applicability of the title approach. The reaction mechanisms are revealed by in-situ IR and theoretical study. It reveals remarkable ligand effect the bidentate amine plays in the reaction, that is, it initially activats the C-I bond of iodobenzene so as to enhance the whole catalytic process.

A Versatile Reagent and Method for Direct Aliphatic Sulfonylation

AbstractAn efficient methodology has been developed for the two‐step synthesis of aliphatic sulfinate salts, sulfonamides, sulfonyl fluorides, and unsymmetrical sulfones on the basis of alkylation of a new versatile sulfonylating reagent. The new reagent is easily accessible in one step; the developed protocols are conducted under mild conditions and have a broad substrate scope.magnified image

Convenient and Inexpensive Route to Sulfonylated Pyridines via SNAr Reaction of Electron-Rich Pyridines by Iron Catalysis

Sulfonylated pyridines were synthesized in moderate to excellent yields, with a wide scope of substituted pyridines and sulfinate salts as starting materials, by an iron-catalyzed SNAr reaction. This new methodology exhibits advantages for the synthesis of these useful substrates, such as the use of a readily available, inexpensive catalyst, prevention of the disproportionation of the sulfinate salts, and, more importantly, providing access to electron-rich pyridine substrates.

Nickel‐Catalyzed Synthesis of Diaryl Sulfones from Aryl Halides and Sodium Sulfinates

A novel nickel‐catalyzed cross‐coupling of sulfinic acid salts with aryl halides is described. The reaction provides access to various diaryl sulfones in moderate to excellent yields. A broad range of functional groups and heteroaromatic compounds is tolerated under the reaction conditions.

Visible-Light Photoredox/Nickel Dual Catalysis for the Cross-Coupling of Sulfinic Acid Salts with Aryl Iodides.

An efficient cross-coupling of sodium or lithium sulfinates with aryl iodides, using a combination of nickel and photoredox catalysis, is described. The dual catalyst system enables a versatile synthesis of aryl sulfones at room temperature in good yields and displays a broad functional group compatibility. The potential utility of this method in the late-stage diversification of complex molecules and in the conversion of organolithium reagents and sulfur dioxide into sulfones is demonstrated.

Micelle-enabled clean and selective sulfonylation of polyfluoroarenes in water under mild conditions

Proline-based designer surfactant FI-750-M has been demonstrated to enable selective nucleophilic aromatic substitution of polyfluoro(hetero)arenes by sulfinate salts in water under mild micellar conditions.

Eosin Y photoredox catalyzed net redox neutral reaction for regiospecific annulation to 3-sulfonylindoles via anion oxidation of sodium sulfinate salts.

An eosin Y photoredox catalyzed net redox neutral process for 3-sulfonylindoles via the anionic oxidation of sodium sulfinate salts and its radical cascade cyclization with 2-alkynyl-azidoarenes was developed with visible light as a mediator. The reaction offers metal and oxidant/reductant free, visible light mediated vicinal sulfonamination of alkynes to 2-aryl/alkyl-3-sulfonylindoles and proceeds via the generation of a sulfur-centered radical through direct oxidation of the sulfinate anion by an excited photocatalyst with a reductive quenching cycle. The mild conditions, use of an organic dye as photo-catalyst, bench stability and easily accessible starting materials make the present approach green and attractive.

Engaging sulfinate salts via Ni/photoredox dual catalysis enables facile Csp2 -SO2R coupling.

This report details the development and implementation of a strategy to construct aryl- and heteroaryl sulfones via Ni/photoredox dual catalysis. Using aryl sulfinate salts, the C-S bond can be forged at room temperature under base-free conditions. An array of aryl- and heteroaryl halides are compatible with this approach. The broad tolerance and mild nature of the described reaction could potentially be employed to prepare sulfones with biological relevance (e.g., in bioconjugation, drug substance synthesis, etc.) as demonstrated in the synthesis of drug-like compounds or their precursors. When paired with existing Ni/photoredox chemistry for Csp3 -Csp2 cross-coupling, an array of diverse sulfone scaffolds can be readily assembled from bifunctional electrophiles. A mechanistic manifold consistent with experimental and computational data is presented.

Ru/Ni Dual Catalytic Desulfinative Photoredox Csp2-Csp3 Cross-Coupling of Alkyl Sulfinate Salts and Aryl Halides.

A mild Ru/Ni dual catalytic desulfinative photoredox Csp2-Csp3 cross-coupling reaction of alkyl sulfinate salts with aryl halides has been developed. The optimized catalyst system, consisting of Ru(bpy)3Cl2, Ni(COD)2, and DBU, smoothly mediates the coupling of a diverse set of secondary and primary nonactivated alkyl sulfinate salts with a broad range of electron-deficient aryl bromides, electron-rich aryl iodides, and heteroaryl bromides under irradiation with blue light. The procedure is ideal for late-stage introduction of alkyl groups on pharmaceutical intermediates, and the Csp2-Csp3 cross-coupling reaction allowed the rapid synthesis of caseine kinase 1δ inhibitor analogues via a parallel medicinal chemistry effort.

Radical-Mediated Dearomatization of Indoles with Sulfinate Reagents for the Synthesis of Fluorinated Spirocyclic Indolines.

The dearomative introduction of trifluoromethyl and 1,1-difluoroethyl radicals, generated from their corresponding sulfinate salts, into the C2 position of indole derivatives allows the diastereoselective synthesis of three-dimensional 3,3-spirocyclic indolines over C-H functionalized indoles.

A New Class of Amide Ligands Enable Cu‐Catalyzed Coupling of Sodium Methanesulfinate with (Hetero)aryl Chlorides

((2S,4R)‐4‐Hydroxy‐N‐(2‐methylnaphthalen‐1‐yl)pyrrolidine‐2‐carboxamide (HMNPC), an amide derived from 4‐hydroxy‐L‐proline and 2‐methyl naphthalen‐1‐amine, is a powerful ligand for Cu‐catalyzed coupling of (hetero)aryl halides with sulfinic acid salts, allowing for first time the metal‐catalyzed coupling of (hetero)aryl chlorides and NaSO2Me. A considerable number of (hetero)aryl chlorides worked well, providing the pharmaceutically important (hetero)aryl methylsulfones in good to excellent yields.

Accounting for Different Reactivities of Sulfinate and Thiosulfate Salts in Regioselective Azetidine Coupling via C–H Sulfenylation of Indoles

The regioselective incorporation of azetidines into heteroaromatic compounds is reported via a formal C–H sulfenylation reaction. While sodium sulfinate salts undergo C3 sulfenylation of electron-rich indoles only, the corresponding thiosulfate salts have proved to be more generally useful. A mechanistic hypothesis for the different reactivities of sulfinate and thiosulfate salts is provided.