Easy-to-execute carbonylations: microwave synthesis of acyl sulfonamides using Mo(CO)(6) as a solid carbon monoxide source

The development of a robust palladium-catalyzed amidocarbonylation protocol for the preparation of aromatic acyl sulfonamides utilizing high-density microwave heating is described. This synthetic approach employs Mo(CO)(6) as a convenient CO-releasing reagent and allows for the direct preparation of acyl sulfonamides from both aryl iodides and aryl bromides. The reactions can be performed under air, employing only 15 min of microwave irradiation, to produce acyl sulfonamide derivatives in good to excellent yields. To illustrate the usefulness of this method, we reported the synthesis of a novel hepatitis C virus NS3 protease inhibitor.     

Synthesis of 4-azepanones and heteroaromatic-fused azepines

Two syntheses of versatile intermediate azepinones 2 and 3 are described. A 6-step intramolecular Dieckmann cyclization and decarboxylation led to the intermediate 3 while an alternate 4-step synthesis of 2 was developed and used for scale-up. The highlight of the second synthesis is the one-step per-bromination/elimination protocol from readily available azepinone 13a to provide a versatile scaffold in vinyl bromide 5, which enables SAR around the aryl moiety. An example of the elaboration of the intermediate 2 toward a heteroaryl azepinone is also described.     

Oxidation of Alkynyl Boronates to Carboxylic Acids,Esters, and Amides

A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)−B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.     

Oxidation of Alkynyl Boronates to Carboxylic Acids,Esters, and Amides

A general efficient protocol was developed for the synthesis of carboxylic acids, esters, and amides through oxidation of alkynyl boronates, generated directly from terminal alkynes. This protocol represents the first example of C(sp)?B bond oxidation. This approach displays a broad substrate scope, including aryl and alkyl alkynes, and exhibits excellent functional group tolerance. Water, primary and secondary alcohols, and amines are suitable nucleophiles for this transformation. Notably, amino acids and peptides can be used as nucleophiles, providing an efficient method for the synthesis and modification of peptides. The practicability of this methodology was further highlighted by the preparation of pharmaceutical molecules.     

Sulfonamidation of Aryl and Heteroaryl Halides through Photosensitized Nickel Catalysis

Herein we report a highly efficient method for nickel‐catalyzed C?N bond formation between sulfonamides and aryl electrophiles. This technology provides generic access to a broad range of N‐aryl and N‐heteroaryl sulfonamide motifs, which are widely represented in drug discovery. Initial mechanistic studies suggest an energy‐transfer mechanism wherein C?N bond reductive elimination occurs from a triplet excited Ni^II complex. Late‐stage sulfonamidation in the synthesis of a pharmacologically relevant structure is also demonstrated.     

Palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate: a practical synthesis of unsymmetrical ureas

An efficient method for palladium-catalyzed cross-coupling of aryl chlorides and triflates with sodium cyanate is reported. The protocol allows for the synthesis of unsymmetrical N,N'-di- and N,N,N'-trisubstituted ureas in one pot and is tolerant of a wide range of functional groups. Insight into the mechanism of aryl isocyanate formation was gleaned through studies of the transmetalation and reductive elimination steps of the reaction, including the first demonstration of reductive elimination from an arylpalladium isocyanate complex to produce an aryl isocyanate.     

Zn/CuI-mediated coupling of alkyl halides with vinyl sulfones, vinyl sulfonates, and vinyl sulfonamides

A novel high-yielding Zn/CuI-mediated coupling method of alkyl halides with vinyl sulfones, vinyl sulfonates, and vinyl sulfonamides is described. This protocol is applicable for primary, secondary, and tertiary alkyl iodides and bromides. Alkyl chlorides and aryl and vinyl halides were unreactive under the reaction conditions. Formamide was found to be a superior solvent for obtaining high yields.     

Copper-catalyzed N-arylation of sulfonamides with aryl bromides under mild conditions

This Letter describes a copper catalyzed sulfonamide coupling reaction with aryl bromides to form N-aryl sulfonamides under mild conditions, including the first examples of Cu-catalyzed sulfonamide coupling at room temperature. The reaction protocol tolerates a broad range of substrates including a variety of primary and secondary sulfonamides and challenging heteroaryl bromides such as 2-bromothiazole.     

Copper catalyzed aryl amidation between Nα-Fmoc-protected amino-acid azides and aryl boronic acids

Abstract

A simple and efficient method for the synthesis of aryl amides via oxidative copper-catalyzed coupling of commercially available aryl boronic acids and bench stable N^α-protected amino-acid azides is reported. The potential utility of this protocol is demonstrated through a survey of diversely substituted aryl boronic acids and several side-chain functionalized amino-acid azides, leading to the preparation of the desired amidated products in good to excellent yields. This amide synthesis is suitable for the preparation of amides (such as peptide aryl amides and sterically hindered amino acids) that are not or hardly accessible via classical approaches.     

A novel approach for the synthesis of alkyl and aryl sulfonamides

A novel approach for the synthesis of alkyl and aryl sulfonamides by the reaction of sulfonic acids, isocyanides and water in dichloromethane is reported at ambient temperature in excellent yields within 20 min. To the best of our knowledge this is the first report on the synthesis of this biologically important family using easily available sulfonic acids and isocyanides.     

Metal Free Bi(hetero)aryl Synthesis: A Benzyne Truce–Smiles Rearrangement

A new benzyne transformation is described that affords versatile biaryl structures without recourse to transition‐metal catalysis or stoichiometric amounts of organometallic building blocks. Aryl sulfonamides add to benzyne upon fluoride activation, and then undergo an aryl Truce–Smiles rearrangement to afford biaryls with sulfur dioxide extrusion. The reaction proceeds under simple reaction conditions and has excellent scope for the synthesis of sterically hindered atropisomeric biaryl amines.     

Visible‐Light‐Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions

Despite significant progress in aliphatic decarboxylation, an efficient and general protocol for radical aromatic decarboxylation has lagged far behind. Herein, we describe a general strategy for rapid access to both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters followed by their successive use in divergent carbon–heteroatom and carbon–carbon bond‐forming reactions. Identification of a suitable activator for carboxylic acids is the key to bypass a competing single‐electron‐transfer mechanism and “switch on” an energy‐transfer‐mediated homolysis of unsymmetrical σ‐bonds for a concerted fragmentation/decarboxylation process.     

Highly Efficient One-Pot Synthesis of N-Alkyl Sulfonamides from Alcohols Using N-(p-Toluenesulfonyl) Imidazole (Tsim)

Abstract

A facile and efficient method for one-pot synthesis of N-alkyl sulfonamides from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this protocol, treatment of various potassium sulfonylamide salts and alcohols in the presence of TsIm and triethylamine in refluxing DMF furnishes the corresponding N-alkyl sulfonamides in good to excellent yields. This methodology is highly efficient for reaction of various structurally diverse primary and secondary alcohols as well as potassium sulfonylamides. Also, the density functional theoretical calculations are employed to mechanistically study this protocol.

[Supplementary materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements for the following free supplemental files: Additional text and figures.]     

Unexpected C-Se cross-coupling reaction: copper oxide catalyzed synthesis of symmetrical diaryl selenides via cascade reaction of selenourea with aryl halides/boronic acids

Selenourea is used as an effective selenium surrogate in the C-Se cross-coupling reaction catalyzed by copper oxide nanoparticles under ligand free conditions. This protocol has been utilized for the synthesis of a variety of symmetrical diaryl selenides in good to excellent yields from the readily available aryl halides/boronic acids.     

Synthesis of β‐Arylacyl/β‐Heteroarylacyl‐β‐alkylidene Malonates and Their Application in Substituted Pyridone Synthesis

A novel approach has been developed for the synthesis of β‐arylacyl/β‐heteroarylacyl‐β‐alkylidine malonates in moderate to good yields by the reaction of Stork aryl and heteroaryl enamine with β‐chloroalkylidene malonates. The reaction involves conjugate (Michael) addition of Stork enamine on β‐chloroalkylidene malonates and elimination of chloride ion. These Michael adducts were utilized as intermediates for the synthesis of highly substituted 1,4‐dialkyl‐2‐oxo‐6‐aryl/hetreoaryl‐1,2‐dihydro‐pyridine‐3‐carboxylic acid ethyl esters via 5 + 1 ring annulation protocol.     

Solvent-Free Synthesis of Thiophenol Using Uncatalyzed Transfer Hydrogenation

Clean and sustainable transfer hydrogenation for aryl sulfonamides and sulfonyl chlorides is described. The protocol is chemoselective and uses neither catalyst nor solvent.     

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.     

The double reduction of cyclic sulfonamides for the synthesis of (4S-Phenylpyrrolidin-2R-yl)methanol and 2S-methyl-4S-phenylpyrrolidine

The synthesis of (4S-phenylpyrrolidin-2R-yl)methanol and 2S-methyl-4S-phenylpyrrolidine has been achieved via the double reduction of their cyclic sulfonamide precursors which themselves were prepared following the stereoselective intramolecular Heck reaction of a chiral pool derived 2,5-dihydropyrrole. We have recently described a process whereby cyclic aryl sulfonamides, such as 2, are reductively ring-opened to furnish amino products in which the aryl group is incorporated in the final compound. (Evans, P.; McCabe, T.; Morgan, B. S.; Reau, S. Org. Lett. 2005, 7, 43.) The precursors for this reaction were assembled using an intramolecular Heck reaction followed by reduction of the alkene. Overall, this sequence represents an efficient means to construct molecules of this type in which the aryl sulfonyl moiety acts as both an N-protecting group and as an aryl donor. Use of Benkeser's stronger reducing conditions enables molecules such as 4 to be prepared in which both the sulfonamide functional group and the aromaticity of the aryl substituent have been destroyed.     

A convenient synthesis of (E)-conjugated polyene sulfonyl derivatives with excellent stereospecificity

A highly selective synthesis of conjugated polyene sulfonyl derivatives is described via the elimination of disulfonyl chloride with readily accessible raw material dihaloalkane. The protocol offers a convenient way to form sulfonamides, sulfonates and even sulfones. Furthermore, this method was manipulated under mild condition with simple operation in high yield to afford only trans products.