Conformational Isomerization as a Process to Determine Selectivity over Reaction Pathways: Effect of Alkene Rotation in Chain Walking via Cis Alkene Intermediates.

In organic reactions, bond-forming and bond-cleaving processes are generally considered to be more important than other processes such as conformational isomerization. We report herein an example where a conformational isomerization process, propeller-like alkene rotation, is considered to determine the selectivity over the reaction pathways. The transition state with the highest energy barrier in some alkylpalladium isomerization (chain walking) events was theoretically indicated to correspond to alkene rotation, while transition states for bond-cleaving ß-hydride elimination and bond-forming migratory insertion were not even observed. It was also suggested both theoretically and experimentally that the palladium chain walking over internal carbons in alkyl chains proceeds via cis alkene intermediates rather than thermodynamically more stable trans alkene intermediates, due to their relative difficulty to undergo alkene rotation.

Palladium-Catalyzed Electrochemical Iodination of 1-Arylpyridine N-Oxides.

The palladium-catalyzed C-H iodination of 1-arylpyridine N-oxides proceeded under electrochemical oxidation conditions using I2 as an iodine source. The reaction of isoquinoline N-oxides possessing various para- or meta-substituted aryl groups at the 1-position proceeded to give the corresponding iodination products. Electron-donating groups on the aryl group facilitated the reaction to give relatively high yields of the product. The reaction was also found to be applicable to 2-aryl-3-picoline N-oxides.

Rhodium-Catalyzed ß-Acylalkylation of Allylbenzene Derivatives with Allyl Alcohols via C-C Bond Cleavage.

We report here a deallylative ß-acylalkylation reaction of allylbenzene derivatives with allyl alcohols in the presence of Cp*Rh catalysts. Allylbenzenes possessing pyridyl and pyrazolyl directing groups were converted to ß-aryl ketones via the cleavage of C(aryl)-C(allyl) bonds. Synthesis of a quinoline derivative from a ß-aryl ketone product bearing a pyrazolyl group was also achieved.

Palladium-Catalyzed Hydroboration/Cyclization of 1,n-Dienes.

While the hydroboration of alkenes is well established, the corresponding cyclization reaction of dienes remains challenging. Here, we report a new method for hydroboration/cyclization applicable to various 1,n-dienes and hydroboranes. The method features the direct synthesis of borylalkyl cyclopentanes from common 1,6-dienes, which is highlighted by syntheses of elaborated pyrrolidine cores from easily accessible diallylamines. Notably, 1,n-dienes (n > 6) also undergo five-membered ring formation, offering "remote" hydroboration/cyclization that would be otherwise difficult to achieve.

Iron-Catalyzed Regio- and Stereoselective C-H Alkenylation of Pivalophenone Derivatives with Unsymmetric Internal Alkynes.

Here we report an ortho-C-H alkenylation of aromatic ketones with unsymmetric internal alkynes catalyzed by an iron phosphine complex, Fe(PMe3)4. The use of a catalytic amount of PtBu3 as an additive was found to improve the product yields. The alkenylation proceeds regio- and stereoselectively to give the corresponding styrene derivatives.

Palladium-Catalyzed Remote Diborylative Cyclization of Dienes with Diborons via Chain Walking.

A novel method for catalytic remote bismetalation of alkene substrates by the addition of dimetal reagents is accomplished by using chain walking. In the presence of a palladium catalyst, the reaction of various 1,n-dienes and diborons were converted into cyclopentane derivatives with two boryl groups at remote positions via facile regioselective transformation of an unactivated sp3 C-H bond to a C-B bond. Sequential construction of three distant bonds, which is difficult to achieve by any method, was accomplished for the reactions of 1,n-dienes (n ≥ 7).

Rhodium-Catalyzed Anti-Markovnikov Hydroamination of Aliphatic and Aromatic Terminal Alkynes with Aliphatic Primary Amines.

Anti-Markovnikov hydroamination of both aliphatic and aromatic terminal alkynes with primary amines was achieved using an 8-quinolinolato rhodium catalyst to form aldimines and enamines in high yields. This catalytic system realized high functional group tolerance including hydroxy, bromo, cyano, and thioester groups.

Remote Arylative Substitution of Alkenes Possessing an Acetoxy Group via ß-Acetoxy Elimination.

Palladium-catalyzed remote arylative substitution was achieved for the reaction of arylboronic acids with alkenes possessing a distant acetoxy group to provide arylation products having an alkene moiety at the remote position. The use of ß-acetoxy elimination as a key step in the catalytic cycle allowed for regioselective formation of unstabilized alkenes after chain walking. This reaction was applicable to various arylboronic acids as well as alkene substrates.

Palladium-Catalyzed Aromatic C-H Functionalizations Utilizing Electrochemical Oxidations.

Transition-metal-catalyzed electrochemical C-H functionalizations have been extensively studied as atom- and step-economical clean methods in organic synthesis. In this account, we described our efforts on the palladium-catalyzed electrochemical C-H functionalizations, including C-H halogenations of arylpyridines and benzamide derivatives using HCl/HBr and I2 as a halogen source, a one-pot process giving teraryls via the palladium-catalyzed electrochemical C-H iodination and subsequent Suzuki-Miyaura coupling, and an iodine-mediated oxidative homo-coupling reaction of arylpyridines.

2:1 versus 1:1 Coupling of Alkylacetylenes with Secondary Amines: Selectivity Switching in 8-Quinolinolato Rhodium Catalysis.

Both 2:1 and 1:1 couplings of alkylacetylenes with secondary amines were achieved using 8-quinolinolato rhodium catalysts and CsF. The 2:1/1:1 selectivity was switched by choosing the reaction solvent. In DMA, an unprecedented 2:1 coupling reaction of alkylacetylenes with amines proceeded to give 2-aminodiene products. One-pot 2:1 coupling/reduction provided rapid access to various allylamines, while one-pot coupling/hydrolysis gave enones as products. In toluene, anti-Markovnikov hydroamination occurred under relatively mild conditions to give 1:1 coupling products.

Iron-Catalyzed Ortho C-H Homoallylation of Aromatic Ketones with Methylenecyclopropanes.

We report here a C-H homoallylation reaction of aromatic ketones with methylenecyclopropanes (MCPs) only using a catalytic amount of Fe(PMe3)4. A variety of aromatic ketones and MCPs are applicable to the reaction to form ortho-homoallylated aromatic ketones selectively via regioselective scission of the three-membered rings. The homoallylated products are amenable to further elaborations, providing functionalized 1,2-dihydronaphthalenes.

Carbon-Carbon Bond Formation via Catalytically Generated Aminocarbene Complexes: Rhodium-Catalyzed Hydroaminative Cyclization of Enynes with Secondary Amines.

We report a hydroaminative cyclization of enynes using phosphine-quinolinolato rhodium catalysts. The hydroaminative cyclization of 2-vinylphenylacetylene derivatives with secondary amines gives 2-aminoindenes in good yields. The reaction is considered to proceed through carbon-carbon bond formation on a catalytically generated aminocarbene ligand.

Efficient synthesis of 3,6,13,16-tetrasubstituted-tetrabenzo[a,d,j,m]coronenes by selective C-H/C-O arylations of anthraquinone derivatives.

An efficient synthesis of tetrabenzo[a,d,j,m]coronene derivatives having alkyl and alkoxy substituents at the 3, 6, 13, and 16-positions was achieved based on the ruthenium-catalyzed coupling reactions of anthraquinone derivatives with arylboronates via C-H and C-O bond cleavage. The reaction sequence involving the arylation, carbonyl methylenation, and oxidative cyclization effectively provided various tetrabenzo[a,d,j,m]coronenes in short steps from readily available starting materials. Tetrabenzo[a,d,j,m]coronenes possessing two different types of substituents were obtained selectively by sequential chemoselective C-O arylation and C-H arylation. The 1H NMR spectra of the tetrabenzo[a,d,j,m]coronene product indicated its self-assembling behavior in CDCl3.

Catalytic, Directed C-C Bond Functionalization of Styrenes.

A method for catalytic conversion of C(aryl)-C(alkenyl) bonds in styrene derivatives to new C-C bonds is developed. In the presence of a rhodium catalyst, the alkenyl groups of styrenes bearing a pyrazolyl directing group were efficiently converted to other carbon substituents upon reacting with various alkenes including styrenes, aliphatic alkenes, and allyl alcohols. It is also indicated that the C-C bond cleavage proceeded via a hydrometalation/ß-carbon elimination pathway.

In Situ Generation of Ruthenium Carbonyl Phosphine Complexes as a Versatile Method for the Development of Enantioselective C-O Bond Arylation.

We report here a method for in situ generation of various ruthenium carbonyl phosphine catalysts for arylation via cleavage of inert aromatic carbon-oxygen bonds. The use of catalyst systems consisting of [RuCl2 (CO)(p-cymene)], CsF, styrene, and phosphines enabled facile screening of phosphine ligands. Asymmetric C-O arylation was also achieved for atropo-enantioselective biaryl synthesis using a chiral monodentate phosphine ligand.

Selective Monoarylation of Aromatic Ketones via C-H Bond Cleavage by Trialkylphosphine Ruthenium Catalysts.

A catalyst system consisting of RuHCl(CO)(PiPr3)2, CsF, and a styrene derivative was found to be applicable to selective monoarylation of aromatic ketones via ortho C-H bond cleavage. The reaction of 2'-methoxyacetophenone with arylboronates gave C-H arylation products without cleaving the ortho C-O bond. Acetophenone was also converted to monoarylation products with high selectivity. Cyclohexanone was found to be an effective solvent for the C-H arylation using the catalyst system.

Synthesis of N-Arylpyrazoles by Palladium-Catalyzed Coupling of Aryl Triflates with Pyrazole Derivatives.

A method for the synthesis of N-arylpyrazoles by palladium-catalyzed coupling of aryl triflates with pyrazole derivatives is described. Using tBuBrettPhos as a ligand, the palladium-catalyzed C-N coupling of a variety of aryl triflates including ortho-substituted ones with pyrazole derivatives proceeded efficiently to give N-arylpyrazole products in high yields. 3-Trimethylsilylpyrazole was found to be an excellent pyrazole substrate for the coupling, and the corresponding product, 1-aryl-3-trimethylsilylpyrazole, also served as a great template for the syntheses of N-arylpyrazole derivatives, as demonstrated by regioselective halogenation at the 3-, 4-, and 5-positions of the pyrazole ring.

Metal-Catalyzed Sequential Formation of Distant Bonds in Organic Molecules: Palladium-Catalyzed Hydrosilylation/Cyclization of 1,n-Dienes by Chain Walking.

Sequential formation of distant bonds in organic molecules was achieved for the palladium-catalyzed hydrosilylation/cyclization of various 1,n-dienes by chain walking of the metal catalyst. The reaction was applicable to various 1,n-dienes, including a 1,13-diene, to form a cyclopentane ring as well as a carbon-silicon bond at a remote site. The use of "nondissociative" chain walking provides a fascinating strategy in organic synthesis to functionalize distant parts of organic molecules, in a particular order, within a catalytic cycle by effectively moving the reactive center from a remote position.

Antiaromatic character of cycloheptatriene-bis-annelated indenofluorene framework mainly originated from heptafulvene segment.

Fully π-conjugated polycyclic hydrocarbons with antiaromatic character have attracted research attention because of their unique properties such as narrow energy gaps, and thus should find application as optical and electronic materials. Although antiaromatic 16π-electron frameworks can be constructed by the incorporation of multiple seven-membered rings in a fused fashion to install methylenecycloheptatriene (heptafulvene) segments, the development of corresponding benzo[1,2:4,5]di[7]annulene (BDA)-containing π-conjugated systems remains challenging due to the difficulty of their molecular design and synthesis. In this study, we develop an unprecedented chemical structure of cycloheptatriene-bis-annelated indenofluorene, which possesses both BDA and indenofluorene frameworks in a fused fashion. Physical measurements and X-ray analyses, along with theoretical calculations, indicated that antiaromaticity appeared in the BDA framework. By using the conjugated polycyclic hydrocarbon possessing both seven-membered and five-membered rings, this study provides fundamental insight into the strong antiaromatic nature of heptafulvene-based BDA framework.

Selective Long-Distance Isomerization of Terminal Alkenes via Nondissociative Chain Walking.

Selective long-distance isomerization of terminal alkenes to silyl enol ethers proceeded via nondissociative chain walking using phenanthroline palladium catalysts. Notable features achieved taking advantage of the nondissociative chain walking mechanism include high efficiency obtained regardless of the chain length, high chemoselectivity toward terminal alkenes over internal ones, and retention of the stereoconfiguration of the stereocenter on the alkyl chain.