Allenyl Sulfones Research Articles

Diastereoselective Addition of Lithiated Allenyl Sulfones to Nonracemic Sulfinimines: Asymmetric Synthesis of Diverse Heterocycles.

The addition of lithiated allenyl sulfones to nonracemic sulfinimines furnished sulfinamides possessing the allenyl sulfonyl moiety with excellent diastereoselectivity. The formed products are transformed into different heterocycles, including the synthesis of pyrroline, pyran, and functionalized benzopyran.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

Nickel-catalyzed regiodivergent sulfonylarylation of 1,3-enynes to access allenes and dienes.

The radical-mediated difunctionalization of 1,3-enynes facilitates rapid access to structurally diverse allenes and dienes. Whereas, owing to the existence of multiple active sites in conjugated 1,3-enynes, regulating selectivity in difunctionalized addition via a single transition-metal-catalyzed radical tandem process remains elusive. Herein, we disclose an intriguing protocol of substrate-controlled nickel-catalyzed regiodivergent sulfonylarylation of 1,3-enynes with the assistance of sulfonyl chlorides and arylboronic acids. This valuable synthetic utility respectively delivers a series of highly functionalized and synthetically challenging allenyl sulfones and dienyl sulfones from fine-tuned 1,3-enynes by one step, which provides a facile approach for complex sulfone-containing drug molecules synthesis.

Brønsted Acid Promoted Sulfonylation of Propargylic Alcohols: Synthesis of Triaryl Allenyl Sulfones under Mild Conditions

AbstractAn efficient and practical approach for the synthesis of triaryl allenyl sulfones from easily accessible propargylic alcohols was developed, by using sodium sulfinates as a sulfonyl source in the presence of Brønsted acid. The reaction proceeded via allenyl carbocation as the key intermediate and was followed by a nucleophilic attack of sodium sulfinates to produce allenyl sulfones in moderate to excellent yields.

Sulfonylation of Propargyl Alcohols with Sulfinamides for the Synthesis of Allenyl Sulfones.

A regio- and chemoselective sulfonylation of propargyl alcohols with sulfinamides in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) was developed. It provided straightforward and mild access to multi-substituted allenyl sulfones by using sulfinamides as the sulfonyl sources. This transformation was promoted by HFIP and did not require any catalysts or oxidants, which allowed for the successful conversion of various tertiary and secondary propargyl alcohols into allenyl sulfones in high yields.

Metal-Free C-C Coupling of an Allenyl Sulfone with Picolyl Amides to Access Vinyl Sulfones via Pyridine-Initiated In Situ Generation of Sulfinate Anion.

Vinyl sulfones are privileged motifs known for their biological activity and synthetic utility. Synthetic transformations to efficiently access high-value compounds with these motifs are desired and sought after. Herein, a new procedure is described to form vinyl sulfone-containing compounds by selective functionalization of the C(sp3)-H bond adjacent to the pyridine ring of pharmacologically prevalent picolyl amides with an allenyl sulfone, 1-methyl-4-(propa-1,2-dien-1-ylsulfonyl)benzene. The reaction conditions are mild with no metal catalyst or additives required and display good functional group tolerance. Mechanistic studies for this unusual transformation suggest that the reaction operates via a rare pyridine-initiated and p-toluenesulfinate anion-mediated activation of the allenyl sulfone analogous to phosphine-triggered reactions.

Recent developments in the chemistry of allenyl sulfones

Allenyl sulfones are versatile building blocks that readily partake in a variety of transformations such as Michael additions, rearrangements, cycloadditions, electrophilic additions and redox reactions. Selected recent developments in the preparation and various reactions of allenyl sulfones are presented.

Synthesis, Structure, and Chemical Transformations of 2-Chloroprop-2-en-1-yl Sulfones

A green approach was proposed for the synthesis of 2-chloroprop-2-en-1-yl sulfones in 47–94% yield. The molecular and crystal structures of 2-chloroprop-2-en-1-yl phenyl sulfone and 2-chloroprop-2-en-1-yl methyl sulfone were determined by X-ray analysis. π-Stacking interaction between the benzene ring and double bond was revealed in the crystal structure of 2-chloroprop-2-en-1-yl phenyl sulfone. Chloropropenyl sulfones were found to readily undergo dehydrochlorination to give stable allenyl sulfones and alkaline hydrolysis to produce the corresponding acetonyl sulfones. The latter can be converted to oximes by treatment with hydroxylamine hydrochloride.

Rhodium-Catalyzed Highly Regio- and Enantioselective Hydrogenation of Tetrasubstituted Allenyl Sulfones: An Efficient Access to Chiral Allylic Sulfones.

A highly regio- and enantioselective hydrogenation of challenging tetrasubstituted allenyl sulfones has been developed, affording chiral allylic sulfones in good yields with excellent regio- and enantioselectivities (up to 99 % yield and 99 % ee). This method provides an efficient and concise route to chiral allylic sulfones, thus offering an atom-economic process with a wide range of potential applications in organic synthesis and medicinal chemistry.

Rhodium‐Catalyzed Highly Regio‐ and Enantioselective Hydrogenation of Tetrasubstituted Allenyl Sulfones: An Efficient Access to Chiral Allylic Sulfones

AbstractA highly regio‐ and enantioselective hydrogenation of challenging tetrasubstituted allenyl sulfones has been developed, affording chiral allylic sulfones in good yields with excellent regio‐ and enantioselectivities (up to 99 % yield and 99 % ee). This method provides an efficient and concise route to chiral allylic sulfones, thus offering an atom‐economic process with a wide range of potential applications in organic synthesis and medicinal chemistry.

Sulfinate‐Organocatalyzed (3+2) Annulation Reaction of Propargyl or Allenyl Sulfones with Activated Imines

An operationally simple methodology for the synthesis of 4‐sulfonyl‐3‐pyrrolines is described using a propargylic sulfone and N‐sulfonyl imines as substrates. This annulation process is initiated by an arenesulfinate organocatalyst, which allows a smooth isomerization of the alkynyl precursor into the corresponding allene, followed by the generation of a highly reactive allyl sulfone anion. An asymmetric version involving an unprecedented enantiopure sulfinate–ammonium cooperative ion pair (PhSO2– R4N+*) was investigated. A proof‐of‐concept, with enantiomeric excesses of up to 41 %, was obtained according to a preliminary screening of commercially available chiral phase‐transfer catalysts.

Sulfinate‐Organocatalyzed (3+2) Annulation of Allenyl Sulfones with 1,1‐Dicyano Olefins in the Presence of a Quaternary Ammonium Phase Transfer Agent

AbstractThe benzenesulfinate‐catalyzed (3+2) annulation between allenyl sulfones and aryl(alkyl)idenemalononitriles has been developed under mild phase transfer conditions, affording a breadth of functionalized sulfonyl cyclopentenes in good to excellent yields (22 examples, 49–99%) and high diastereoselectivities. These adducts were likely generated, via an allylsulfone anion featuring a quaternary ammonium cation.magnified image

On the NHC/DBU-Mediated Tosyl Group Transfer to Allenes: Is There an Organocatalytic Role for DBU?

The reactions of allenylphosphonates/allenylphosphine oxides or an allenyl sulfone [4-Cl-C6H4-SO2C(R)=C=CMe2] with the aldimine PhCH=NTs in the presence of a carbene [NHC·HCl/DBU] afford tosylated allylic phosphonates/phosphine oxides or a sulfone. This reaction involves C–S bond formation and not C–O bond formation, and thus is different from similar reactions of allenes with PhCH=NTs in the presence of bases like DMAP, DBU or Ph3P/(alkyl)3P wherein cycloaddition products are generally observed. The reactions of phosphorylated allenes with DBU lead to the unprecedented formation of products in which the DBU ring is cleaved, as evidenced by single crystal X-ray crystallography. This observation suggests a ‘reactant’ role for DBU when using this base in the reactions of allenes.

N-Heterocyclic Carbene-Promoted [3+2] Cycloaddition of Allenyl Sulfone and Arylidenemalononitriles

N-Heterocyclic Carbene-Promoted [3+2] Cycloaddition of Allenyl Sulfone and Arylidenemalononitriles

Unique Reactivity of α‐Substituted Electron‐Deficient Allenes using Sulfinate Salts as Lewis Base Organocatalysts

AbstractThe efficient sulfinate‐catalyzed intermolecular addition reaction of α‐substituted allenyl sulfones and allenoates with Michael acceptors is highlighted. The sequence proceeds under mild conditions to provide a scalable and efficient access to versatile functionalized alkynes, displaying a quaternary stereocentre at the propargylic position. This work enriches the diversity of Lewis base organocatalysts in the field of allene chemistry, in addition to the well‐established phosphine and amine catalysts.magnified image

ChemInform Abstract: Facile Synthesis of 4H‐Chromene Derivatives via Base‐Mediated Annulation of ortho‐Hydroxychalcones and 2‐Bromoallyl Sulfones.

The cesium carbonate-mediated reaction of 2-bromoallyl sulfones and ortho-hydroxychalcones furnished 3-arylsulfonyl-4H-chromene derivatives in 58-67% yield (18 examples). 2-Bromoallyl sulfones functioned as synthetic surrogates for allenyl sulfones in the reaction.

Facile synthesis of 4H-chromene derivatives via base-mediated annulation of ortho-hydroxychalcones and 2-bromoallyl sulfones.

The cesium carbonate-mediated reaction of 2-bromoallyl sulfones and ortho-hydroxychalcones furnished 3-arylsulfonyl-4H-chromene derivatives in 58–67% yield (18 examples). 2-Bromoallyl sulfones functioned as synthetic surrogates for allenyl sulfones in the reaction.

ChemInform Abstract: Synthesis of Allenyl Sulfones via a TBHP/TBAI‐Mediated Reaction of Propargyl Alcohols with Sulfonyl Hydrazides.

AbstractThe construction of polysubstituted allenyl sulfones is achieved in a functional‐group‐compatible manner via TBHP/TBAI‐mediated reaction of propargyl alcohols with sulfonyl hydrazide in the presence of AcOH.

ChemInform Abstract: Cu‐Catalyzed Silylation of Alkynes: A Traceless 2‐Pyridylsulfonyl Controller Allows Access to Either Regioisomer on Demand.

AbstractThe copper‐catalyzed silylation of alkynes (I) leads regioselectively to β‐silylated (E)‐alkenes (III), whilst treatment of alkynes (VIII) with tetrabutylammonium dihydrogen phosphate followed by silylation of intermediate allenyl sulfones affords α‐silylated (E)‐alkenes (IX).

Base-Mediated Cyclocondensation of Salicylaldehydes and 2-Bromoallyl Sulfones for the Synthesis of 3-Sulfonylchromene Derivatives and Their Regioselective Friedel-Crafts Heteroarylation Reactions.

Cesium carbonate-mediated reaction of 2-hydroxybenzaldehydes and 2-bromoallyl sulfones afforded 2H- and 4H-chromenol derivatives endowed with a 3-arylsulfonyl group. 2-Bromoallyl sulfones functioned as synthetic equivalents of allenyl sulfones under these conditions. The 2H- and 4H-chromenol derivatives underwent regioselective Friedel-Crafts reactions with heteroarenes in the presence of p-toluenesulfonic acid to afford 4-heteroaryl-4H-chromene derivatives in excellent yields.