Iridium(III)-Catalyzed C-H Cyclization of Sulfoximines with Diazo Meldrum's Acids for the Synthesis of Cyclic Sulfoximines.

Iridium(III)-catalyzed C-H cyclization of sulfoximines with diazo Meldrum's acid provided cyclic sulfoximines with a carbonyl group in good to excellent yields. These compounds were easily converted into unsubstituted and arylated sulfoximines. Moreover, the vinyl triflates obtained from the cyclic sulfoximines underwent palladium(II)-catalyzed cross-coupling reactions with a variety of aryl, arylalkynyl, and heteroatom (N and S) nucleophiles, affording a wide range of monosubstituted sulfoximines in high yields.

Direct and Regioselective Palladium(II)-Catalyzed B(4)-H Monoacyloxylation and B(4,5)-H Diacetoxylation of o-Carborane Acids with Phenyliodonium Dicarboxylates.

A direct B(4)-H monoacyloxylation via a Pd-catalyzed regioselective B(4)-H activation of o-carborane acids with phenyliodonium dicarboxylates was developed, and a series of B(4)-H monoacyloxylated o-carboranes decorated with active groups were synthesized with moderate to good yields as well as excellent selectivity. In addition, a direct B(4,5)-H diacetoxylation from o-carborane acids with phenyliodonium diacetate was demonstrated.

Iridium-Catalyzed Cyclative Indenylation and Dienylation through Sequential B(4)-C Bond Formation, Cyclization, and Elimination from o-Carboranes and Propargyl Alcohols.

Described herein is the first iridium-catalyzed cyclative indenylation through sequential B(4)-C and intramolecular C-C bond formation from o-carboranes and propargyl alcohols, leading to the formation of B(4)-indenylated o-carboranes with excellent regioselectivity via direct B-H activation. Moreover, the iridium-catalyzed regioselective 1,3-dienylation has been accessed through sequential B-H activation, dehydration, and decarboxylation, producing B(4)-dienylated o-carboranes.

Expansion of Azulenes as Nonbenzenoid Aromatic Compounds for C-H Activation: Rhodium- and Iridium-Catalyzed Oxidative Cyclization of Azulene Carboxylic Acids with Alkynes for the Synthesis of Azulenolactones and Benzoazulenes.

Rhodium-catalyzed oxidative [4 + 2] cyclization reactions through the C-H activation of azulene carboxylic acids as nonbenzenoid aromatic compounds with symmetrical and unsymmetrical alkynes were developed under aerobic conditions, which produced azulenolactone derivatives with a wide substrate scope and excellent functional group tolerance. Interestingly, azulenic acids in reaction with alkynes underwent iridium-catalyzed [2 + 2 + 2] cyclization accompanied by decarboxylation to afford tetra(aryl)-substituted benzoazulene derivatives. The reactivity order for C-H activation reaction is greater toward azulene-6-carboxylic acid, azulene-1-carboxylic acid, and azulene-2-carboxylic acid. For the first time, the expansion of azulenes having directing group as nonbenzenoid aromatic compounds for C-H activation was successful, indicating that nonbenzenoid aromatic compounds can be used as good substrates for the C-H activation reaction. Therefore, the research area of C-H activation will certainly expand to nonbenzenoid aromatic compounds in future.

Pyrazinoindole-Based Lewis-Acid/Base Assembly: Intriguing Intramolecular Charge-Transfer Switching through the Dual-Sensing of Fluoride and Acid.

Pyrazinoindole-based Lewis-acid/base assemblies are prepared through the use of regioselective formal [3 + 3] cycloaddition reactions, and their intriguing photophysical properties are described. The assemblies exhibit strong emissions in THF solution, which are attributed to through-space intramolecular charge-transfer (ICT) transitions between the branched Lewis-acid/base moieties. Furthermore, these show ratiometric color-change responses in PL titration experiments, which give rise to new colors through turn-on emissions ascribable to ICT transitions that alternate between the pyrazinoindole units and each triarylboryl or amino moiety, a consequence of the binding of the fluoride or acid. Pieces of filter paper covered by these assemblies exhibited blue-shifted color changes when immersed in aqueous acidic solutions, suggesting that these are promising candidate indicators that detect acid through emissive color. Computational data for these assemblies and their corresponding adducts verify the existence of ICT transitions that alternate through fluoride or acid binding.

Regioselective Synthesis of Indolopyrazines through a Sequential Rhodium-Catalyzed Formal [3+3] Cycloaddition and Aromatization Reaction of Diazoindolinimines with Azirines.

A regioselective synthetic method for the preparation of indolopyrazines was demonstrated through a sequential Rh-catalyzed formal [3+3] cycloaddition and aromatization reaction of a wide range of diazoindolinimines with azirines. Because the previously reported synthetic methods afforded mixtures of indolopyrazines, the present method using unsymmetrical azirines has a strong advantage from a regioselectivity viewpoint.

Synthesis of Diaryl Ketones through Oxidative Cleavage of the C-C Double Bonds in N-Sulfonyl Enamides.

An oxidative cleavage of a C-C double bond is developed from the photochemical [2+2]-cycloaddition of diaryl N-tosyl enamides, aryl heteroaryl N-tosyl enamides, and N-tosyl cyclic enamides with singlet molecular oxygen, followed by a ring-opening reaction mediated by Cs2CO3 under air and sunlight without the use of photosesitizer, producing symmetrical and unsymmetrical diaryl, heterodiaryl, and cyclic ketones in good to excellent yields. Moreover, the oxidative cleavage of C-C triple bonds from 1-alkynes is demonstrated for the synthesis of symmetrical and unsymmetrical ketones from the Cu-catalyzed [3+2]-cycloaddition, Rh-catalyzed alkoxyarylation, photooxygenation, and ring-opening reaction in one-pot. Because the synthesis of the symmetrical and unsymmetrical diaryl and/or heterodiaryl ketones bearing an electron-donating group is not easy, the present method is notable.

Synthesis of Azepinoindoles via Rhodium-Catalyzed Formal Aza-[4 + 3] Cycloaddition Reaction of 3-Diazoindolin-2-imines with 1,3-Dienes in One-Pot.

Rhodium-catalyzed formal aza-[4 + 3] cycloaddition reaction of 3-diazoindolin-2-imines with 1,3-dienes was demonstrated for the synthesis of azepinoindoles in good to excellent yields in one-pot. First, rhodium-catalyzed [2 + 1] cycloaddition reaction smoothly took place to produce iminyl vinyl cyclopropane intermediate at room temperature in chlorobenzene for 1 h, which was thermally converted to azepinoindoles via aza-Cope rearrangement.

Synthesis of Bicyclic Isothiazoles through an Intramolecular Rhodium-Catalyzed Transannulation of Cyanothiadiazoles.

An intramolecular rhodium-catalyzed transannulation of readily available cyanothiadiazoles containing an ester, amide, or ether as a linker is described. It provides a wide range of bicyclic isothiazoles in good to excellent yields together with the release of molecular nitrogen. These results indicate that the carbon atom in the α-thiavinyl carbene is nucleophilic and that the sulfur atom is electrophilic.

Rhodium-Catalyzed Intramolecular Transannulation Reaction of Alkynyl Thiadiazole Enabled 5,n-Fused Thiophenes.

A method for the synthesis of a wide range of fused thiophenes, including those fused with lactams, lactones, or cyclic ethers, was developed from a rhodium-catalyzed intramolecular transannulation reaction of alkynyl thiadiazoles. This transannulation reaction provides an efficient platform for the construction of a variety of 5,n-fused thiophenes from readily available starting materials together with the release of molecular nitrogen.

Synthesis of Imidazopyridines via Copper-Catalyzed, Formal Aza-[3 + 2] Cycloaddition Reaction of Pyridine Derivatives with α-Diazo Oxime Ethers.

The Cu-catalyzed, formal aza-[3 + 2] cycloaddition reaction of pyridine derivatives with α-diazo oxime ethers in trifluoroethanol was used to synthesize imidazopyridines via the release of molecular nitrogen and elimination of alcohol. These methods enabled modular synthesis of a wide range of N-heterobicyclic compounds such as imidazopyridazines, imidazopyrimidines, and imidazopyrazines with an α-imino Cu-carbenoid generated from the α-diazo oxime ethers and copper.

Synthesis of Benzofulvenes through Rhodium-Catalyzed Transannulation of Enynyl Triazoles.

Rhodium-catalyzed denitrogenative cyclization of (E)-ethyl 2-(1-alkyl and arylsulfonyl-1H-1,2,3-triazol-4-yl)-3-aryl acrylate generated from (E)-ethyl 2-benzylidenebut-3-ynoates and N-sulfonyl azides in the presence of a copper catalyst was developed for the synthesis of a large number of functionalized benzofulvenes. Moreover, the synthesis of benzofulvenes was demonstrated as a one-pot method through tandem copper-catalyzed [3 + 2] cycloaddition and rhodium-catalyzed denitrogenative cyclization from (E)-ethyl 2-benzylidenebut-3-ynoates and N-sulfonyl azides.

Synthesis of pyrazines from rhodium-catalyzed reaction of 2H-Azirines with N-sulfonyl 1,2,3-triazoles.

An efficient synthetic route to a wide range of trisubstituted pyrazines is developed from Rh-catalyzed reaction of 2H-azirines with N-sulfonyl-1,2,3-triazoles through the elimination of nitrogen molecule and arylsulfinic acid. The present reaction proceeds through formation of in situ generated dihydropyrazines.

Synthesis of 2-Alkoxyaryl-2-aryl Enamines via Tandem Copper-Catalyzed Cycloaddition and Rhodium-Catalyzed Alkoxyarylation from Alkynes, N-Sulfonyl Azides, and Aryl Ethers.

A synthetic route to a wide range of 2-alkoxyaryl-2-aryl enamines is developed from Rh-catalyzed alkoxyarylation of N-sulfonyl-4-aryl-1,2,3-triazoles with aryl ethers via the elimination of nitrogen molecule. In addition, 2-alkoxyaryl-2-aryl enamines are prepared via tandem Cu-catalyzed cycloaddition and Rh-catalyzed alkoxyarylation starting from alkynes, N-sulfonyl azides, and aryl ethers in one-pot.

Synthesis of fluorenes via tandem copper-catalyzed [3 + 2] cycloaddition and rhodium-catalyzed denitrogenative cyclization in a 5-exo mode from 2-ethynylbiaryls and N-sulfonyl azides in one pot.

An efficient synthetic method of fluorenes having an enamine moiety at C-9 methylene bridge is developed from N-sulfonyl-4-biaryl-1,2,3-triazole derivatives via Rh-catalyzed denitrogenative cyclization in a 5-exo mode. Rh-catalyzed denitrogenative cyclization followed by catalytic hydrogenation produces N-tosylaminomethyl-substituted fluorenes in one pot. Moreover, fluorenes are synthesized via tandem Cu-catalyzed [3 + 2] cycloaddition and Rh-catalyzed denitrogenative cyclization in a 5-exo mode starting from 2-ethynylbiaryls and N-sulfonyl azides in one pot.

Highly potent and selective pyrazolylpyrimidines as Syk kinase inhibitors.

A series of pyrazolylpyrimidine scaffold based Syk inhibitors were synthesized and evaluated for their biological activities and selectivity. Lead optimization efforts provided compounds with potent Syk inhibition in both enzymatic and TNF-α release assay.

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp(2))-H activation/C-O formation.

We report an efficient Pd-catalyzed C(sp(2))-H activation/C-O bond formation for the synthesis of ethoxy dibenzooxaphosphorin oxides from 2-(aryl)arylphosphonic acid monoethyl esters under aerobic conditions.

Rhodium-catalyzed oxidative C-H activation/cyclization for the synthesis of phosphaisocoumarins and phosphorous 2-pyrones.

Rhodium-catalyzed cyclization of phosphinic acids and phosphonic monoesters with alkynes has been developed. The oxidative annulation proceeds with complete conversion of phosphinic acid derivatives and allowed the atom-economic preparation of useful phosphaisocoumarins with high yield and selectivity. The reaction is tolerant of extensive substitution on the phosphinic acid, phosphonic monoester and alkyne, including halides, ketone, and hydroxyl groups as substituents. Furthermore, we found that alkenylphosphonic monoesters proceed to give a wide range of phosphorus 2-pyrones through oxidative annulation with alkynes. Mechanistic studies revealed that C-H bond metalation was the rate-limiting step.

Ruthenium-catalyzed C-H activation/cyclization for the synthesis of phosphaisocoumarins.

An efficient and cost-effective ruthenium-catalyzed oxidative cyclization of phosphonic acid monoesters or phosphinic acids with alkynes has been developed for the synthesis of a wide range of phosphaisocoumarins in good to excellent yields under aerobic conditions. A multitude of arylphosphonic acid monoesters and arylphosphinic acids having electron-donating and -withdrawing groups were oxidatively cyclized. Various diarylacetylenes, dialkylacetylenes, and alkylarylacetylenes effectively underwent the ruthenium-catalyzed oxidative cyclization. A substrate possessing benzoic acid as well as a phenylphosphonic monoester moiety was smoothly cyclized with hex-3-yne to afford a compound having both isocoumarin and phosphaisocoumarin moieties. Alkenylphosphonic monoester afforded phosphorus 2-pyrone through oxidative cyclization with alkyne. Competition experiments between diaryl- and dialkylalkynes and between diarylacetylenes having p-methoxy and p-chloro groups gave results which showed that the present oxidative cyclizations were not affected by the electronic effects of alkynes. Mechanistic studies revealed C-H bond metalation to be the rate-limiting step.