Aryl Sulfoxides Research Articles

Cascades of Interrupted Pummerer Reaction-Sigmatropic Rearrangement.

A new class of Pummerer chemistry has emerged as a powerful tool in organic synthesis. The new technology consists of a beautiful cascade of an interrupted Pummerer reaction and the subsequent [3,3] sigmatropic rearrangement. The interrupted Pummerer reactions of alkenyl or aryl sulfoxides with unsaturated nucleophiles such as allylic silanes, ketones, and phenols provide sulfonium intermediates, which are ready to undergo smooth charge-accelerated [3,3] sigmatropic rearrangement with excellent to exclusive regioselectivity. Some of the transformations proceed with transient loss of aromaticity. The reactions afforded five-membered heterocycles, benzofurans, and biaryls of importance, depending on the sulfoxides and nucleophiles used. The reactions are unique and game-changing because they are efficient, robust, redox-neutral, regioselective, and metal-free, which perfectly fits the need of modern organic synthesis. This chemistry also underscores the synthetic potential of organosulfur chemistry.

Redox-Neutral α-Arylation of Alkyl Nitriles with Aryl Sulfoxides: ARapid Electrophilic Rearrangement.

A facile α-arylation of nitriles has been developed by simply introducing Tf2O and DABCO to the mixture of nitriles and aryl sulfoxides. The transformation consists of two sequential steps: (i) Tf2O-initiated electrophilic assembly and and (ii) DABCO-triggered rearrangement. Each step can be tuned independently by changing the temperature and/or base. This adjustability allows the method to accommodate a wide range of substrates. Notable features of this new protocol include remarkable efficiency (20 min, -30 °C), exclusive regioselectivity, and high functional group compatibility, which can be challenging issues in traditional approaches. NMR studies not only identified a unique, highly unstable sulfonium imine complex but also demonstrated the importance of temperature in the formation and manipulation of this key intermediate. Further DFT calculations suggested that an electrophilic assembly, followed by removal of HOTf (by base), and finally [3,3]-sigmatropic rearrangement are three key stages in the reaction. The versatile transformability of the products and easy scalability of this reaction are also exhibited here.

On the Origins of Nonradiative Excited State Relaxation in Aryl Sulfoxides Relevant to Fluorescent Chemosensing.

We provide herein a mechanistic analysis of aryl sulfoxide excited state processes, inspired by our recent report of aryl sulfoxide based fluorescent chemosensors. The use of aryl sulfoxides as reporting elements in chemosensor development is a significant deviation from previous approaches, and thus warrants closer examination. We demonstrate that metal ion binding suppresses nonradiative excited state decay by blocking formation of a previously unrecognized charge transfer excited state, leading to fluorescence enhancement. This charge transfer state derives from the initially formed locally excited state followed by intramolecular charge transfer to form a sulfoxide radical cation/aryl radical anion pair. With the aid of computational studies, we map out ground and excited state potential energy surface details for aryl sulfoxides, and conclude that fluorescence enhancement is almost entirely the result of excited state effects. This work expands previous proposals that excited state pyramidal inversion is the major nonradiative decay pathway for aryl sulfoxides. We show that pyramidal inversion is indeed relevant, but that an additional and dominant nonradiative pathway must also exist. These conclusions have implications for the design of next generation sulfoxide based fluorescent chemosensors.

Metal-Free Approach to Biaryls from Phenols and Aryl Sulfoxides by Temporarily Sulfur-Tethered Regioselective C-H/C-H Coupling.

We have developed metal-free regiocontrolled dehydrogenative C-H/C-H cross-coupling of aryl sulfoxides with phenols by means of trifluoroacetic anhydride. Because the reaction would proceed through an interrupted Pummerer reaction followed by sulfonium-tethered [3,3]-sigmatropic rearrangement, the C-H/C-H coupling takes place exclusively between the ortho positions of both substrates. Various functional groups including carbonyl, halo, siloxy, and even boryl moieties are compatible. The biaryl products naturally possess hydroxy and sulfanyl groups, which allows the products to be useful synthetic intermediates, as evidenced by the syntheses of π-expanded heteroarenes such as unprecedented 7,12-dioxa[8]helicene.

ChemInform Abstract: HOTf‐Catalyzed, Solvent‐Free Oxyarylation of Ynol Ethers and Thioethers.

A novel HOTf-catalyzed oxyarylation of ynol ethers and thioethers has been realized with aryl sulfoxides as the oxyarylating reagents, providing α-arylated esters or thioesters in good to excellent yields. Notably, all atoms of the starting materials were incorporated in the product (100% atom economy) and the reaction proceeded under very mild conditions. It was found that the reaction can be ran under air and that the best yields are obtained under solvent-free conditions.

Formation of Ternary Inclusion Crystal and Enantioseparation of Alkyl Aryl Sulfoxides by the Salt of Urea-Modified l-Phenylalanine and an Achiral Amine

Chiral supramolecular hosts comprising urea-modified l-phenylalanines and achiral primary amines were developed, which facilitated enantioselective inclusion of alkyl aryl sulfoxides (3) up to 89% ee owing to the formation of ternary inclusion crystals. From the structural optimization of the components, the combination of N-(phenylcarbamoyl)-l-phenylalanine (1a) and benzhydrylamine (2e) showed the best inclusion ability among the considered supramolecular hosts. The type of the hydrogen-bonding network of ammonium-carboxylate salts 1a·2 was dependent on the steric bulk of combined primary amine 2. The rigid phenylurea moiety of 1a and moderate steric bulk of 2e played an important role in their high inclusion ability. Host 1a·2e afforded two ternary polymorphic inclusion crystals with the inclusion of acetonitrile. Furthermore, the crystal structures of 1a·2e·3 revealed that the inclusion of 3 was assisted by hydrogen bonding to the host and that stereoselectivity reversal occurred for larger sulfoxides, which was attributed to packing variations of one-dimensional hydrogen-bonding networks.

ChemInform Abstract: Palladium‐Catalyzed Arylation of Aryl Sulfenate Anions with Aryl Bromides under Mild Conditions: Synthesis of Diaryl Sulfoxides.

A palladium-catalyzed arylation of aryl sulfenate anions generated from aryl 2-(trimethylsilyl)ethyl sulfoxides and CsF has been developed. This protocol is effective for the synthesis of diaryl sulfoxides and heteroaryl aryl sulfoxides under mild conditions employing aryl bromides. Various functional groups, including those with acidic protons, are well tolerated.

HOTf-Catalyzed, Solvent-Free Oxyarylation of Ynol Ethers and Thioethers.

A novel HOTf-catalyzed oxyarylation of ynol ethers and thioethers has been realized with aryl sulfoxides as the oxyarylating reagents, providing α-arylated esters or thioesters in good to excellent yields. Notably, all atoms of the starting materials were incorporated in the product (100% atom economy) and the reaction proceeded under very mild conditions. It was found that the reaction can be ran under air and that the best yields are obtained under solvent-free conditions.

ChemInform Abstract: Palladium‐Catalyzed Arylation of Alkyl Sulfenate Anions.

AbstractFunctionalized alkyl aryl sulfoxides are obtained by palladium‐catalyzed C—S bond formation between in situ generated alkyl sulfenate anions and aryl halides.

Brønsted Acid-Mediated Hydrative Arylation of Unactivated Alkynes.

The Brønsted acid-mediated reaction of unactivated alkynes with aryl sulfoxides leads to simultaneous hydration and intermolecular C-C bond formation. This solvent- and metal-free transformation directly delivers α-arylated carbonyl compounds as the products of a formal hydrative arylation in an atom-economical manner. The products bear useful synthetic handles for further functionalization.

Palladium-Catalyzed Arylation of Aryl Sulfenate Anions with Aryl Bromides under Mild Conditions: Synthesis of Diaryl Sulfoxides.

A palladium-catalyzed arylation of aryl sulfenate anions generated from aryl 2-(trimethylsilyl)ethyl sulfoxides and CsF has been developed. This protocol is effective for the synthesis of diaryl sulfoxides and heteroaryl aryl sulfoxides under mild conditions employing aryl bromides. Various functional groups, including those with acidic protons, are well tolerated.

Pummerer Reaction of Sulfoxides in Acetic Anhydride Catalyzed by Al-MCM-41

The Pummerer reaction of acetic anhydride with both alkyl aryl sulfoxides and dialkyl sulfoxides was efficiently promoted by a mesoporous aluminosilicate Al-MCM-41 to afford the corresponding α-acetoxy sulfides in high yields. The catalyst was easily recovered by filtration and could be reused three times without a significant loss of catalytic activity.

Efficient nickel-catalyzed phosphinylation of C-S bonds forming C-P bonds.

The first nickel-catalyzed phosphinylation of C-S bonds forming C-P bonds is developed. This transformation can proceed readily with the simple Ni(cod)2 at a loading down to 0.1 mol% at the 10 mmol scale. A variety of aryl sulfur compounds, i.e. sulfides, sulfoxides and sulfones all couple with P(O)-H compounds to produce the corresponding organophosphorus compounds in high yields, which provides an efficient new method for the construction of C-P bonds.

2-Sulfinyl Oxetanes: Synthesis, Stability and Reactivity

The synthesis of 2-sulfinyl oxetanes is described by a C–C bond-forming cyclisation strategy. Oxetanes bearing electron-poor aryl sulfoxides are shown to be viable targets using this strategy. We report investigations into the sulfoxide magnesium exchange on 2-sulfinyl oxetanes, which resulted in products formed via ligand exchange and ligand coupling pathways. The sulfinyl oxetanes can be readily oxidised to the sulfonyl oxetanes.

Palladium-Catalyzed Arylation of Alkyl Sulfenate Anions.

A unique palladium-catalyzed arylation of alkyl sulfenate anions is introduced that affords aryl alkyl sulfoxides in high yields. Due to the base sensitivity of the starting sulfoxides, sulfenate anion intermediates, and alkyl aryl sulfoxide products, the use of a mild method to generate alkyl sulfenate anions was crucial to the success of this process. Thus, a fluoride triggered elimination strategy was employed with alkyl 2-(trimethylsilyl)ethyl sulfoxides to liberate the requisite alkyl sulfenate anion intermediates. In the presence of palladium catalysts with bulky monodentate phosphines (SPhos and Cy-CarPhos) and aryl bromides or chlorides, alkyl sulfenate anions were readily arylated. Moreover, the thermal fragmentation and the base promoted elimination of alkyl sulfoxides was overridden. The alkyl sulfenate anion arylation exhibited excellent chemoselectivity in the presence of functional groups, such as anilines and phenols, which are also known to undergo palladium catalyzed arylation reactions.

ChemInform Abstract: tert‐Butyl Sulfoxides: Key Precursors for Palladium‐Catalyzed Arylation of Sulfenate Salts.

AbstractSulfenate salts, generated in situ by pyrolysis of tert‐butyl sulfoxides in the presence of K3PO4 undergo Pd‐catalyzed cross‐coupling reaction with aryl iodides, bromides, and triflates to give aryl sulfoxides.

Tert‐Butyl Sulfoxides: Key Precursors for Palladium‐Catalyzed Arylation of Sulfenate Salts

AbstractThe present report describes an efficient and clean generation of sulfenate salts (R1SO−) by pyrolysis of readily available tert‐butyl sulfoxides to give sulfenic acids (R1SOH) and traceless isobutene, followed by hydrogen abstraction with a weak inorganic base (K3PO4). The relevance of this process was exemplified through an in situ palladium‐catalyzed cross‐coupling reaction with aryl halides/triflates leading to aryl sulfoxides. The operationally simple CS bond‐forming protocol developed uses Pd(dba)2 as catalyst and Xantphos as ligand in toluene or a toluene/H2O mixture. Further extensions include the use of di‐tert‐butyl sulfoxide as an equivalent for sulfur monoxide dianion (SO2−) and the development of diastereoselective versions in the [2.2]paracyclophane and biaryl series.magnified image

Enzyme-promoted kinetic resolution of acetoxymethyl aryl sulfoxides

A simple and efficient method of the synthesis of enantiomerically enriched, unknown acetoxymethyl aryl sulfoxides has been developed which is based on an enzyme-catalyzed hydrolysis of racemic substrates under the kinetic resolution conditions. The hydrolysis was performed not only in a buffer solution but also in diisopropyl ether in the absence of the external water added to give in some cases the products with ee up to 98%. The enantioselectivity of both procedures was dependent on the enzyme used and the aryl substituent, being lower for p-tolyl than for phenyl. A comparative asymmetric synthesis based on the oxidation of the corresponding sulfides using chiral oxidizing reagent turned out to be inferior to the method described. Absolute configuration of the newly synthesized compounds was ascribed on the basis of CD spectra.

ChemInform Abstract: A Broensted Acid Catalyzed Redox Arylation.

AbstractThe metal‐free procedure can be applied to various aryl sulfoxides and ynamides bearing a terminal oxazolidone to afford α‐arylated acyl compounds in a redox‐neutral, atom‐economic fashion.

Symmetric diarylsulfoxides as asymmetric sulfinylating reagents for dialkylmagnesium compounds.

At −78 °C, primary dialkylmagnesium compounds reacted with diarylsulfoxides when 1.5 equiv of the dilithium salt of (S)-BINOL was added as a promotor. Alkyl aryl sulfoxides resulted in up to quantitative yield and with up to 97% ee. This demonstrates the feasibility of asymmetric sulfinylations by achiral sulfinylating agents (from the perspective of Alkyl2Mg) as well as the feasibility of asymmetric sulfoxide–magnesium exchanges (from the perspective of Ar2SO).