Allylic Sulfones Containing Triene Moieties as Key Synthons for Carotenoid Synthesis

An efficient synthetic method for the allylic sulfone 2 containing a conjugated triene moiety has been proposed involving i) coupling of allylic sulfones 4 with the C₅ bromoallylic sulfide 5 , ii) base‐promoted dehydrosulfonation in the presence of allylic sulfide, and iii) selective oxidation of the resulting trienyl sulfide to the corresponding sulfone. Total synthesis of lycopene starting from the C₁₅ allylic sulfone 2b has been described, where the new C₁₀ bis(chloroallylic) sulfone 11 proved to be a useful substitute for the C₁₀ bis(chloroallylic) sulfide 3 , which did not require the problematic chemoselective sulfur oxidation in a conjugated polyene.     

Palladium(II)‐Catalyzed Synthesis of Sulfinates from Boronic Acids and DABSO: A Redox‐Neutral,Phosphine‐Free Transformation

A redox‐neutral palladium(II)‐catalyzed conversion of aryl, heteroaryl, and alkenyl boronic acids into sulfinate intermediates, and onwards to sulfones and sulfonamides, has been realized. A simple Pd(OAc)₂ catalyst, in combination with the sulfur dioxide surrogate 1,4‐diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO), is sufficient to achieve rapid and high‐yielding conversion of the boronic acids into the corresponding sulfinates. Addition of C‐ or N‐based electrophiles then allows conversion into sulfones and sulfonamides, respectively, in a one‐pot, two‐step process.     

Palladium(II)‐Catalyzed Synthesis of Sulfinates from Boronic Acids and DABSO: A Redox‐Neutral,Phosphine‐Free Transformation

A redox‐neutral palladium(II)‐catalyzed conversion of aryl, heteroaryl, and alkenyl boronic acids into sulfinate intermediates, and onwards to sulfones and sulfonamides, has been realized. A simple Pd(OAc)₂ catalyst, in combination with the sulfur dioxide surrogate 1,4‐diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO), is sufficient to achieve rapid and high‐yielding conversion of the boronic acids into the corresponding sulfinates. Addition of C‐ or N‐based electrophiles then allows conversion into sulfones and sulfonamides, respectively, in a one‐pot, two‐step process.     

Synthesis of Biologically Important N‐Heteroaryl‐2‐(heteroarylthio)acetamides

The synthesis of compounds having triazole and selena/thiadiazole rings connected by a chain having sulfur and nitrogen in the link has been described. The resultant N‐heteroaryl‐2‐(heteroarylthio)acetamide may be biologically important as related compounds found application in the inhibition of HIV 1 replications.     

Transition‐Metal‐Free Formal Sonogashira Coupling and α‐Carbonyl Arylation Reactions

Transition‐metal‐free formal Sonogashira coupling and α‐carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (S_NAr) of β‐carbonyl sulfones to electron‐deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α‐aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two‐step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α‐carbonyl arylated products from a range of electron‐deficient aryl fluorides with a variety of functional groups and aryl‐, heteroaryl‐, alkyl‐, and alkoxy‐substituted sulfone nucleophiles. These transition‐metal‐free reactions complement the metal‐catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions.     

Cross‐Coupling of Sodium Sulfinates with Aryl,Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.     

Cross‐Coupling of Sodium Sulfinates with Aryl,Heteroaryl, and Vinyl Halides by Nickel/Photoredox Dual Catalysis

An efficient photoredox/nickel catalyzed sulfonylation reaction of aryl, heteroaryl, and vinyl halides has been achieved for the first time. This newly developed sulfonylation protocol provides a versatile method for the synthesis of diverse aromatic sulfones at room temperature and shows excellent functional group tolerance. The electrophilic coupling partners are not limited to aryl, heteroaryl, and vinyl bromides and iodides, but also includes less reactive aryl chlorides as suitable substrates for this transformation.     

A Precoordination Complex of 1,2,3‐Trimethyl‐1,3,5‐triazacyclohexane with tert‐Butyllithium as Key Intermediate in Its Methylene Group Deprotonation

α‐Lithiated tertiary methylamines are important building blocks in all fields of chemistry, such as for the synthesis of new ligand or catalyst systems. However, the access to these compounds is still limited and the reaction mechanism, in general, not fully understood. We present herein X‐ray diffraction analyses of organolithium compounds with 1,2,3‐trimethyl‐1,3,5‐triazacyclohexane ( 1 ), such as a precoordination adduct of tert‐butyllithium, [(tBuLi)₃?C₆H₁₅N₃], which represents a potential intermediate of the lithiation of the methylene group of this ligand. By means of molecular structures and computational studies, the regioselectivity of this deprotonation reaction can be understood. Furthermore, the tBuLi adduct gives a hint to an alternative deaggregation process of organolithium compounds.     

Cobalt‐Catalyzed Intermolecular C(sp2)O Cross‐Coupling

Cobalt(II)‐catalyzed C(sp²)?O cross‐coupling between aryl/heteroaryl alcohols and vinyl/aryl halides in the presence of Cu^I has been achieved under ligand‐free conditions. In this reaction, copper plays a significant role in transmetalation rather than being directly involved in the C?O coupling. This unique Co/Cu‐dual catalyst system provides an easy access to a library of aryl–vinyl, heteroaryl–styryl, aryl–aryl, and heteroaryl–heteroaryl ethers in the absence of any ligand or additive.     

Ligand and base-free Heck reaction with heteroaryl halides

Pd(CH₃CN)₂Cl₂-catalyzed Heck reaction of different heteroaryl halides with olefins is carried out in the absence of both the ligand and base to obtain the corresponding coupling products in good yields.     

Regioselective Synthesis of Benzofuran‐Annulated Six‐Membered Sulfur Heterocycles by Aryl Radical Cyclization

The tin hydride–mediated cyclization of a number of sulfides and sulfones under mild and neutral conditions has been investigated. The sulfides were in turn derived from 3(2H) benzothiofuranone and 2‐bromobenzyl bromides by phase‐transfer‐catalyzed reaction, and the corresponding sulfones were prepared by treatment of the corresponding sulfides with m‐CPBA at room temperature. The sulfides and sulfones were then reacted with ⁿ Bu₃SnH‐AIBN to afford regioselectively benzofuran‐annulated six‐membered sulfur heterocycles.     

Enantioselective Synthesis of 1,2-Benzothiazine 1-Imines via RuII/Chiral Carboxylic Acid-Catalyzed C−H Alkylation/Cyclization

Sulfondiimines are diaza-analogues of sulfones with a chiral sulfur center. Compared to sulfones and sulfoximines, their synthesis and transformations have so far been studied to a lesser extent. Here, we report the enantioselective synthesis of 1,2-benzothiazine 1-imines, i.e., cyclic sulfondiimine derivatives from sulfondiimines and sulfoxonium ylides via C−H alkylation/cyclization reactions. The combination of [Ru(p-cymene)Cl₂]₂ and a newly developed chiral spiro carboxylic acid is key to achieving high enantioselectivity.     

Synthesis and oxidation of sulfides containing an isocyanurate fragment

The reaction of 1-(ω-haloalkyl)-3,5-dimethylisocyanurates with sodium salt of methyl thioglycolate afforded the corresponding 1-[ω-(methoxycarbonylmethylthio)alkyl]-3,5-dimethylisocyanurates, the oxidation of which with the system 34% aqueous H₂O₂-0.2 M NaHCO₃-Mn^II leads to the corresponding sulfones. The oxidation of these compounds with 34% aq. H₂O₂ in Ac₂O gives alternative products, viz., sulfones, sulfoxides, or α-acyloxy sulfides, depending on the temperature and number of methylene groups between the isocyanurate fragment and the sulfur atom.     

N-Picolinamides as ligands in Ullman type C–O coupling reactions

Copper-catalyzed modified Ullmann coupling reactions creating C–O bonds, including diaryl ethers or phenols, are vital to organic synthesis. Synthesized N-phenyl-2-pyridinecarboxamide and its derivatives were used as ligands in conjunction with catalytic copper sources in the formation of various diaryl ethers and phenols. Various aryl and heteroaryl halides with electron donating and withdrawing groups were reacted with various phenols under mild reaction conditions providing moderate to excellent yields.     

Metal-free synthesis of (E)-vinyl sulfones via denitrative coupling reactions of β-nitrostyrenes with sodium sulfinates

Abstract

A practical metal-free procedure for the synthesis of (E)-vinyl sulfones has been developed through the coupling of β-nitrostyrenes with sodium sulfinates under microwave irradiation. This methodology provides a convenient and efficient approach to various (E)-vinyl sulfones from readily available starting materials with excellent regioselectivity. The present oxidative reaction involves an efficient denitrative radical cross-coupling of β-nitrostyrenes with sodium sulfinates via using AcOH as an additive.     

A General Palladium‐Catalyzed Hiyama Cross‐Coupling Reaction of Aryl and Heteroaryl Chlorides

A general palladium‐catalyzed Hiyama cross‐coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)₂/ L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/ L2 system and the water addition protocol can efficiently catalyze a broad range of electron‐rich, ‐neutral, ‐deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis.     

Direct Arylation of N‐Heteroarenes with Aryldiazonium Salts by Photoredox Catalysis in Water

A highly effective visible light‐promoted “radical‐type” coupling of N‐heteroarenes with aryldiazonium salts in water has been developed. The reaction proceeds at room temperature with [Ru(bpy)₃]Cl₂ ? 6 H₂O as a photosensitizer and a commercial household light bulb as a light source. Pyridine and a variety of substituted pyridines are effective substrates under these reaction conditions, and only monosubstituted products are formed with different regioselectivities. Using aqueous formic acid as solvent, an array of xanthenes, thiazole, pyrazine, and pyridazine are compatible with this new arylation approach. The broad substrate scope, mild reaction conditions, and use of water as reaction solvent make this procedure a practical and environmentally friendly method for the synthesis of compounds containing aryl‐heteroaryl motifs.     

Carbon-13 chemical shifts of 3-substituted thietanes,thietane 1-oxides and thietane 1,1-dioxides

Carbon-13 chemical shifts of the α- and β-carbon atoms for 12 thietane 1,1-dixides, 9 thietane 1-oxides and 7 thietanes with a variety of 3-substituents [H, CH(CO₂Et)₂, SEt, Br, SPh, Ph, Cl, NMe₂, OH, OSiMe₃, OAc, OEt] are correlated according to the nature of the sulfur atom (Y=sulfone, sulfoxide, sulfide) and the nature of the 3-substituent (X) by the equations δ_α= a_Y+b_X and δ_β=a_X+b_Y, where a and b are parameters characteristic of X and Y. One-bond coupling constants [J(CH)] are reported for 21 compounds. The chemical shifts for the α- and the β-carbon atoms of the sulfones show the ‘fore-membered ring sulfone effect’ (α-carbon unusually deshielded, β-carbon unusually shielded), but the α-carbon-hydrogen coupling constants are similar to those of the sulfoxides and sulfides; the β-carbon-hydrogen coupling constants are sensitive to the nature of the substituent (X) but no special β-effect is observed. Comparison of the chemical shifts of the α-methylene carbon atoms of 3-phenyl-, 3-(β-naphthyl)- and 3-(α-thienyl)-thietes with those of the coresponding sulfones also reveals the ‘four-membered ring sulfone effect’ cis- and trans-3-Substituted thietane 1-oxides may be distinguished by the greater downfield shift for the β-carbon atom in the trans-isomer.     

Alkenylation of C(sp3)−H Bonds by Zincation/Copper‐Catalyzed Cross‐Coupling with Iodonium Salts

α‐Vinylation of phosphonates, phosphine oxides, sulfones, sulfonamides, and sulfoxides has been achieved by selective C?H zincation and copper‐catalyzed C(sp³)?C(sp²) cross‐coupling reaction using vinylphenyliodonium salts. The vinylation transformation proceeds in high efficiency and stereospecificity under mild reaction conditions. This zincative cross‐coupling reaction represents a general alkenylation strategy, which is also applicable for α‐alkenylation of esters, amides, and nitriles in the synthesis of β,γ‐unsaturated carbonyl compounds.     

Palladium-catalyzed regiocontrolled internal heteroarylation of electron-rich olefins with heteroaryl halides

A highly efficient palladium-catalyzed Heck coupling reaction of heteroaryl halides with electron-rich vinyl ether and hydroxyalkyl vinyl ethers is described. It was found that the choice of solvent, ligand, and reaction temperature had a fundamental influence on the regioselectivity and reactivity of the reaction, and the combination of Pd(OAc)₂ and DPPF in ethylene glycol led to the most effective catalytic system. Under these conditions, a variety of heteroaryl halides reacted very quickly with electron-rich olefins to afford exclusively the branched products in good to excellent yields without employing triflates, halide scavengers, or ionic liquids.