Alkenyl Sulfones Research Articles

Efficient Desulfonylation of Alkenyl Sulfones Enabled by Cu‐Catalysis

AbstractThis study reported an efficient and operationally simple desulfonylation method. A one‐pot protoboration‐desulfonylation of alkenyl sulfones with various sulfone heads under copper catalysis using diboron, and an alkoxide base in DMF afforded high yields of the corresponding alkenes. This reaction operates well in the presence of water and air for unsaturated sulfones with an aryl or alkyl substituent and for widely used phenyl and other sulfonyl families. Use of ligand is not necessary and byproducts from the reaction are relatively benign.

Photoinduced Alkenylation of Alkenyl Sulfones with EDA Complexes between NHPI Esters and HE

AbstractA novel alkenylation reaction between N‐hydroxyphthalimide (NHPI) esters and alkenyl sulfones is reported. It undergoes the formation of electron donor‐acceptor (EDA) complex and a series of alkenes are obtained in good to excellent yields. It has the advantages of simple operation, mild reaction conditions, and metal‐free.

Unveiling the Use of 1,1-Bis(triflyl)ethylene as CF3SO2CH═CH2 Source with the Assistance of (n-Bu)4NF: Synthesis of 3-[(Trifluoromethyl)sulfonyl]cyclobut-1-enes.

Allylic sulfone-embedded cyclobutenes have been prepared in one pot from alkynes. The carbocycle and the alkenyl sulfone moieties were installed through consecutive bis(triflyl)cyclobutenylation of a triple bond and tetra-n-butylammonium fluoride (TBAF)-assisted hydrodesulfonylation of an allylic bis(sulfone). It is noteworthy that 1,1-bis(triflyl)ethylene acts as a CF3SO2CH═CH2 source for the first time.

Unified metal-free intermolecular Heck-type sulfonylation, cyanation, amination, amidation of alkenes by thianthrenation

Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful and attractive yet challenging transformation to access value-added molecules. Herein, a unified protocol for a variety of intermolecular Heck-type functionalizations of Csp2-H bond of alkenes has been developed by thianthrenation. The reaction features metal-free and operationally simple conditions for exclusive cine-selective C-H functionalization of aliphatic and aryl alkenes to forge C-C, C-N, C-P, and C-S bonds at room temperature, providing a general protocol for intermolecular Heck-type reaction of alkenes with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo cine-sulfonylation, cyanation, amination to afford alkenyl sulfones, alkenyl nitriles and enamines.

Copper-Catalyzed Diastereoselective Borylative Allylation of Alkenyl Sulfones and Base-Controlled Synthesis of Skipped Dienes.

Divergent functionalization of α,β-unsaturated sulfones under copper catalysis is reported. Diastereoselective borylative allylation of alkenyl sulfones was achieved with a copper catalyst, allyl phosphate, bis(pinacolato)diboron, and LiOMe. In this method, the addition of a copper-boryl complex to alkenyl sulfone and subsequent allylic substitution rendered boroallylated products in good yield with excellent syn-diastereoselectivity. In contrast, a stronger base (KOt-Bu) promoted the reaction further toward the formation of (E)-skipped dienes, through elimination of the sulfonyl and boryl groups.

Rh-Catalyzed Asymmetric Hydrogenation of α-Substituted Alkenyl Sulfones: Highly Chemo- and Enantioselective Access to Chiral Sulfones.

Rh-(R,R)-f-spiroPhos complex-catalyzed asymmetric hydrogenation of α-substituted alkenyl sulfones has been achieved, affording the chiral γ-keto sulfones and simple α-alkyl-substituted sulfones in high yields (96-99%) with excellent chemo-/enantioselectivities (86-96% ee) and high turnover numbers (TONs) of up to 4000. The method provides an efficient and high-enantioselectivity strategy for chiral γ-keto sulfones and simple α-substituted sulfones under mild conditions. Moreover, the obtained hydrogenation product was transformed into other important chiral α-substituted sulfones.

Highly E-Selective Olefin Synthesis Catalysed by Novel Quinoxalinone Photocatalyst under Visible Light Conditions.

In photo-induced olefin synthesis, the photocatalysts with high triplet energy could cause the isomerization of olefins. This study demonstrates a new quinoxalinone photocatalytic system for highly stereoselective alkenes preparation from alkenyl sulfones and alkyl boronic acids. Our photocatalyst could not convert the thermodynamically favored E-olefin to Z-olefin, guaranteeing the high E-configuration selectivity of the reaction. There is weak interaction between boronic acids and quinoxalinone according to NMR experiments, probably decreasing the oxidation potential of boronic acids. This system can be further extended to the allyl and alkynyl sulfones to give corresponding alkenes and alkynes.

Cu(OTf) 2 ‐Catalyzed Aerobic Cycloisomerization of Alkenyl Sulfones to Furans Using ( E )‐β‐Chlorovinyl Ketones and Sodium Sulfinates

Sodium sulfinate addition to (E)-β-chlorovinyl ketones followed by the aerobic cycloisomerization of alkenyl sulfone intermediates has been established for the synthesis of 3-sulfonyl furans. The optimal cycloisomerization catalyst system was identified to be Cu(OTf)2, where molecular oxygen acts as a terminal oxidant. With three points of structural variation in both β-chlorovinyl ketones and sodium sulfinates, the current aerobic cycloisomerization strategy allows the synthesis of highly functionalized and substituted furan derivatives.

One-Pot Synthesis of N-Hydroxypyrroles via Soft α-Vinyl Enolization of (E)-β-Chlorovinyl Ketones: A Traceless Arylsulfinate Mediator Strategy.

A traceless arylsulfinate mediator strategy has been developed to switch the reaction course of β-chlorovinyl ketones with N-hydroxyamine. The soft α-vinyl enolization of (E)-β-chlorovinyl ketones was conducted in the presence of sodium arylsulfinate to give transient alkenyl sulfones that in turn reacted with NH2OH to give novel access to N-hydroxypyrroles. The mechanistic studies revealed the initial formation of oxazine intermediates that rearranged to thermodynamically stable aromatic products, N-hydroxypyrroles, under microwave-assisted heating conditions.

Cobalt‐Catalyzed Redox‐Neutral Sulfonylative Coupling from (Hetero)aryl Boronic Acids, Ammonium Salts and Potassium Metabisulfite

AbstractAn efficient cobalt‐catalyzed redox‐neutral sulfonylative coupling to afford (hetero)aryl alkyl sulfones from boronic acids, ammonium salts and potassium metabisulfite has been realized. Commercially available and air‐stable CoCl2, in combination with phenanthroline ligand, is sufficient to achieve rapid and high‐yielding conversion of the reactants into the corresponding sulfones. This practical transformation proceeds smoothly through C−N bond cleavage under redox‐neutral catalytic conditions and shows broad functional‐group tolerance. Other carbon based electrophiles, including diaryliodonium salts, heteroaryl halides, and carbonates were compatible. Further transformation of aryl alkyl sulfones then allows conversion into olefins, alkenyl sulfones and halogenated sulfones, respectively, in a one‐pot process.

Visible-Light-Mediated Alkenylation of Alkyl Boronic Acids without an External Lewis Base as an Activator.

Herein we report a protocol for the direct visible-light-mediated alkenylation of alkyl boronic acids at room temperature without an external Lewis base as an activator, and we propose a mechanism involving benzenesulfinate activation of the alkyl boronic acids. The protocol permits the efficient functionalization of a broad range of cyclic and acyclic primary and secondary alkyl boronic acids with various alkenyl sulfones. We demonstrated its utility by preparing or functionalizing several pharmaceuticals and natural products.

Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Alkenyl Sulfones, Benzo[b]thiophene 1,1-Dioxides, with Mechanistic Studies.

A highly efficient catalytic system based on the cheap transition metal nickel for the asymmetric hydrogenation of challenging cyclic alkenyl sulfones, 3-substituted benzo[b]thiophene 1,1-dioxides, was first successfully developed. A series of hydrogenation products, chiral 2,3-dihydrobenzo[b]thiophene 1,1-dioxides, were obtained in high yields (95-99%) with excellent enantioselectivities (90-99% ee). According to the results of nonlinear effect studies, deuterium-labeling experiments, and DFT calculation investigations, a reasonable catalytic mechanism for this nickel-catalyzed asymmetric hydrogenation was provided, which displayed that the two added hydrogen atoms of the hydrogenation products could be from H2 through the insertion of Ni-H and subsequent hydrogenolysis.

Visible-light-mediated alkylation of 4-alkyl-1,4-dihydropyridines with alkenyl sulfones.

Herein we report a mild, general protocol for visible-light-mediated alkylation of 4-alkyl-1,4-dihydropyridines with alkenyl sulfones. The protocol permits efficient functionalization of sulfones with a broad range of cyclic and acyclic secondary and tertiary alkyl groups and is scalable to the gram level. Its excellent functional group tolerance and mildness make it suitable for late-stage functionalization of natural products and drug molecules.

Highly Selective and Switchable Access to Tetrasubstituted Alkenyl Sulfones and Naphthyl Sulfones: 1,4-Aryl Migration versus Cyclization.

A highly efficient, chemo-, and regioselective approach has been developed for the switchable synthesis of tetrasubstituted alkenyl sulfones and naphthyl sulfones from homopropargylic alcohols via sulfonylation/1,4-aryl migration and sulfonylation/cyclization. The present switchable processes are characterized by mild and metal-free conditions, high selectivities, good functional group tolerance, the use of inexpensive and easily handled sulfonyl hydrazides as sulfonyl sources, and the release of the nontoxic byproducts H2O and N2.

Cu-catalyzed regio- and stereoselective sulfonylation of multi-substituted allenes

Regio- and stereoselective sulfonylation of allenes under Cu catalysis is described. Allenyl sp carbons exclusively react with TsCN to give the corresponding alkenyl sulfones. The reaction is initiated by addition of tosyl radical to form benzyl radical intermediates, which determines the reaction pathway. The structure of the products is highly dependent on the substituents on allenes.

Photocatalytic cyanation of carbon nitride scaffolds: Tuning band structure and enhancing the performance in green light driven C[sbnd]S bond formation

A new photocatalytic reaction process is described that cyano groups (CN) are successfully grafted on carbon nitride (g-C3N4 materials). The cyano group substitutes the previous surface terminating amino group (NH2) on g-C3N4 by a radical reaction pathway, modifying the electron structure of the conjugated covalent system and engendering favorable properties for the visible-light driven photocatalysis. Cyanidated g-C3N4 (g-C3N4-xCN) has a narrowed band gap of 2.29 eV, as compared to 2.73 eV for the pristine g-C3N4, showing expanded visible light absorbance to 590 nm. Moreover, the photo-induced charge-carrier separation is improved as well. In consequence, g-C3N4-xCN exhibits significantly enhanced performance in photocatalysis, here exemplifyed with the model coupling reaction towards alkenyl sulfones under green light (520 nm) irradiation. The methodology reported herein reveals the potential of the carbon nitride scaffold to be modified as such and illustrates the possiblities of the as-created novel carbon nitride materials grafted with various functional groups on their surface.

Direct Functionalization of Azepane via Azomethine Ylides: A Highly Efficient Synthesis of Spirooxindoles Bearing a 1‐Azabicyclo[5.3.0]decane Moiety

AbstractSpirooxindoles bearing a 1‐azabicyclo[5.3.0]decane moiety were synthesized in one step via direct functionalization of the azepane without a transition metal or oxidants. This is an efficient process for the synthesis of fused 7/5‐heterobicyclic systems in one step. Furthermore, cycloaddition of the in‐situ‐generated azomethine ylide only proceeded for alkenyl sulfone dipolarophiles.

Palladium-Catalyzed Regio- and Stereoselective Hydrosulfonation of Propiolate Esters

An efficient palladium-catalyzed addition reaction of alkyl- and arylsulfonic acids to propiolate esters to yield alkenyl sulfonates is demonstrated. The formation of alkenyl sulfonates is highly regio- and stereoselective with favorable yields of up to 95%, and two of the alkenyl sulfonates are utilized for a Sonogashira cross-coupling reaction to produce (Z)-1,3-enynoates.

Hydrogen Bonding Cluster-Enabled Addition of Sulfonic Acids to Haloalkynes: Access to Both (E)- and (Z)-Alkenyl Sulfonates.

We developed an efficient synthesis of alkenyl sulfonates via hydrogen bonding cluster-enabled addition of sulfonic acids to haloalkynes. The reactivity of sulfonic acids could be significantly enhanced in the presence of strong hydrogen bonding donors. This metal-free method results in good chemical yields for a wide range of haloalkyne substrates and demonstrates good functional group tolerance. What is more, we can control the stereoselectivity of addition (cis vs trans) by varying the steric bulk of the sulfonic acid.

Visible-Light-Mediated Alkenylation, Allylation, and Cyanation of Potassium Alkyltrifluoroborates with Organic Photoredox Catalysts

Iridium- and ruthenium-free approaches to protected allylic amines and alkyl nitriles under photoredox conditions are reported. An inexpensive organic dye, eosin Y, catalyzes coupling of Boc-protected potassium α-aminomethyltrifluoroborates with a variety of substituted alkenyl sulfones through an α-aminomethyl radical addition–elimination pathway. Allylic and homoallylic amines were formed in moderate yields with high E/Z selectivity. The mechanistic approach was extended using tosyl cyanide as a radical trap, enabling the conversion of alkyltrifluoroborates to nitriles via a Fukuzumi acridinium-catalyzed process.