Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation.

The radical hydroarylation of alkenes is an efficient strategy for accessing linear alkylarenes with high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free conditions.

One-pot C(sp)-H difluoroalkylation of tetrahydroisoquinolines and isochromans electrochemical oxidation and organozinc alkylation.

The C(sp)-H difluoroalkylation for the introduction of carbonylated CF groups into tetrahydroisoquinolines (THIQs) and isochromans has been achieved by using electrochemical oxidation and organozinc alkylation. This one-pot process proceeded smoothly under transition-metal catalyst- and chemical oxidant-free conditions, and the desired products were obtained in good to high yields with a broad scope, except for -Boc-THIQ. In addition, the gram-scale experiment successfully demonstrated the promising scalability.

Synthesis of ω-Chloroalkyl Aryl Ketones via C-C Bond Cleavage of -Cycloalkanols with Tetramethylammonium Hypochlorite.

An oxidative C-C bond cleavage of -cycloalkanols with tetramethylammonium hypochlorite (TMAOCl) has been developed. TMAOCl is easy to prepare from tetramethylammonium hydroxide, and the combination of TMAOCl and AcOH effectively promoted the C-C bond cleavage in a two-phase system without additional phase-transfer reagents. Unstrained -cycloalkanols were transformed into ω-chloroalkyl aryl ketones in moderate to excellent yields under metal-free and mild reaction conditions.

(3+2) Cycloaddition of Heteroaromatic -Ylides with Sulfenes.

A (3+2) cycloaddition of heteroaromatic -ylides with sulfenes, which are generated in situ from sulfonyl chlorides, has been developed. A variety of ylides were transformed into the corresponding sulfone-embedded N-fused heterocycles in high yields. Hexafluoroisopropyl mesylate was demonstrated to be a suitable reactant for quinolinium ylides.

Copper-Catalyzed Asymmetric Sulfonylative Desymmetrization of Glycerol.

Glycerol is the main side product in the biodiesel manufacturing process, and the development of glycerol valorization methods would indirectly contribute the sustainable biodiesel production and decarbonization. Transformation of glycerol to optically active C3 units would be one of the attractive routes for glycerol valorization. We herein present the asymmetric sulfonylative desymmetrization of glycerol by using a CuCN/(,)-PhBOX catalyst system to provide an optically active monosulfonylated glycerol in high efficiency.

Electrochemical formal homocoupling of -alcohols.

Electrochemical pinacol coupling of carbonyl compounds in an undivided cell with a sacrificial anode would be a promising approach toward synthetically valuable -1,2-diol scaffolds without using low-valent metal reductants. However, sacrificial anodes produce an equimolar amount of metal waste, which may be a major issue in terms of sustainable chemistry. Herein, we report a sacrificial anode-free electrochemical protocol for the synthesis of pinacol-type -1,2-diols from -alcohols, namely benzyl alcohol derivatives and ethyl lactate.

Organocatalytic Synthesis of Phenols from Diaryliodonium Salts with Water under Metal-Free Conditions.

The metal-free synthesis of phenols from diaryliodonium salts with water was developed by using -benzylpyridin-2-one as an organocatalyst. In this process, sterically congested, functionalized, and heterocycle-containing iodonium salts were smoothly converted to the desired products, and the clofibrate and mecloqualone derivatives were also synthesized in high yields. In addition, the gram-scale experiment was successfully carried out with 10 mmol of a sterically congested substrate.

Copper-Catalyzed Asymmetric Oxidative Desymmetrization of 2-Substituted 1,2,3-Triols.

Asymmetric oxidative desymmetrization of 2-substituted glycerols has been achieved by using a new chiral bisoxazoline ligand/copper catalyst system with 1,3-dibromo-5,5-dimethylhydantoin and MeOH. The present transformation smoothly proceeds with readily accessible 2-(hetero)aryl- and alkyl-substituted glycerols and provides straightforward access toward various glycerate derivatives in good to high yields with high enantioselectivities. The synthetic utility of the present protocol was demonstrated by the transformation of the optically active glycerol into a glyceraldehyde derivative.

Electrophotochemical Ring-Opening Bromination of -Cycloalkanols.

An electrophotochemical ring-opening bromination of unstrained -cycloalkanols has been developed. This electrophotochemical method enables the oxidative transformation of cycloalkanols with 5- to 7-membered rings into synthetically useful ω-bromoketones without the use of chemical oxidants or transition-metal catalysts. Alkoxy radical species would be key intermediates in the present transformation, which generate through homolysis of the O-Br bond in hypobromite intermediates under visible light irradiation.

- and -arylation of pyridin-2-ones with diaryliodonium salts: base-dependent orthogonal selectivity under metal-free conditions.

Metal-free - and -arylation reactions of pyridin-2-ones as ambident nucleophiles have been achieved with diaryliodonium salts on the basis of base-dependent chemoselectivity. In the presence of ,-diethylaniline in fluorobenzene, pyridin-2-ones were very selectively converted to -arylated products in high yields. On the other hand, the -arylation reactions smoothly proceeded with the use of quinoline in chlorobenzene, leading to high yields and selectivities.

Shono-Type Oxidation for Functionalization of N-Heterocycles.

The development of facile synthetic methods for stereodefined aliphatic cyclic amines is an important research field in synthetic organic chemistry since such scaffolds constitute a variety of natural products and biologically active compounds. N-Acyl cyclic N,O-acetals which prepared by electrochemical oxidation of the corresponding cyclic amines have proven to be useful and versatile precursors for the synthesis of such skeletons. In this Personal Account, we introduce our efforts toward the development of synthetic strategies for the diastereo- and/or enantioselective synthesis of cyclic amines by using electrochemically prepared cyclic N,O-acetals.

Copper-Catalyzed Enantioselective Synthesis of Oxazolines from Aminotriols via Asymmetric Desymmetrization.

A copper-catalyzed enantioselective transformation of tris(hydroxymethyl)aminomethane-derived aminotriols was developed to provide multisubstituted oxazolines with a tetrasubstituted carbon center. The present transformation consisted of sequential reactions involving mono-sulfonylation of aminotriols, subsequent intramolecular cyclization to afford prochiral oxazoline diols, and sulfonylative asymmetric desymmetrization of resultant oxazoline diols. In addition, the kinetic resolution process would be involved in the sulfonylative asymmetric desymmetrization step, which would amplify the enantiopurities of the desired products.

Anodic Oxidation for the Stereoselective Synthesis of Heterocycles.

Stereodefined aliphatic heterocycles are one of the fundamental structural motifs observed in natural products and biologically active compounds. Various strategies for the synthesis of these building blocks based on transition metal catalysis, organocatalysis, and noncatalytic conditions have been developed. Although electrosynthesis has also been utilized for the functionalization of aliphatic heterocycles, stereoselective transformations under electrochemical conditions are still a challenging field in electroorganic chemistry.

Computational study of the competitive binding of valproic acid glucuronide and carbapenem antibiotics to acylpeptide hydrolase.

The efficacy of the antiepileptic drug VPA is decreased by co-administered carbapenems (CBPMs). The mechanism of CBPM selective inhibition of acylpeptide hydrolase (APEH) hydrolysis of VPA-glucuronide (VPA-G) to VPA is unclear due to the lack of APEH structural information. Here we performed homology modeling of the three-dimensional structure of APEH and subsequent docking simulations with a modeled structure to understand this mechanism.

Deuterodechlorination of Aryl/Heteroaryl Chlorides Catalyzed by a Palladium/Unsymmetrical NHC System.

The catalytic deuterodechlorination of aryl/heteroaryl chlorides was developed with a palladium/unsymmetrical NHC system, and the precisely controlled introduction of deuterium into a variety of aryl/heteroaryl compounds was achieved with a high level of efficiency, selectivity, and deuteration degree. This method was also successfully applied to the transformation of bioactive agents even in a gram-scale synthesis. The crystal structure analysis of Pd-NHC complexes led to the observation of Pd-arene interaction.

Molecular-shape selectivity by naphthalimido-modified silica stationary phases: Insight into the substituents effect of naphthalene on shape recognition and π-π interactions via electrostatic potential.

This report describes the molecular-shape selectivity of four naphthalimido-modified silica (NIM) stationary phases. To investigate the selectivity, several alkylbenzenes and polycyclic aromatic hydrocarbons (PAHs) were tested using capillary electrochromatography (CEC) with each NIM stationary phase. Results revealed that nitro group-substituted NIM phases had outstanding molecular-shape recognition ability toward PAHs; a strong negative correlation existed between the k' value and L/B ratio that is opposite those observed for C18 phases, in addition, one possessed 10-fold greater molecular-shape recognition ability compared to existing stationary phases.

Palladium-catalyzed synthesis of heterocycle-containing diarylmethanes through Suzuki-Miyaura cross-coupling.

The heterocycle-containing diarylmethane synthesis from chloromethyl(hetero)arenes with (hetero)arylboron reagents was attained using the palladium/ether-imidazolium chloride system. This coupling process tolerated a diverse range of heteroaromatic moieties with sufficient catalytic activity to achieve the efficient synthesis of various diheteroarylmethanes in good to excellent yields.

Ether-imidazolium carbenes for Suzuki-Miyaura cross-coupling of heteroaryl chlorides with aryl/heteroarylboron reagents.

Easily accessible and handled ether-imidazolium chlorides were developed as ligand precursors. The coupling reactions of heteroaryl chlorides with aryl/heteroarylboronic acids and esters were catalyzed by the palladium/ether-imidazolium chloride system with high substrate tolerance to give various heterobiaryls in good to excellent yields.

Development of efficient catalytic arylation of aldehydes with thioether-imidazolinium carbene ligands.

Effective methods of ligand design have been highly sought due to the significant roles of ligands in controlling metal catalyses. In particular, easy-to-handle ligands to realize high reaction efficacy, substrate tolerance, and environmental friendliness are desirable. Novel bidentate ligands containing N-heterocyclic carbene and thioether moieties were developed based on findings of hemilabile coordination, whose precursors were crystalline solids stable enough to handle and store in the air.

Electrochemical deallylation of alpha-allyl cyclic amines and synthesis of optically active quaternary cyclic amino acids.

Electrochemical oxidation of alpha-allylated and alpha-benzylated N-acylated cyclic amines by using a graphite anode easily affords the corresponding alpha-methoxylated products with up to 76 % yield. Ease of oxidation was affected by the type of electrode, the size of cyclic amine, and the nature of the protecting group. This method was successfully applied to the synthesis of optically active N-acylated alpha-alkyl-alpha-amino acid esters with up to 99 % ee.

Efficient synthesis of 3-arylphthalides using palladium-catalyzed arylation of aldehydes with organoboronic acids.

The synthesis of 3-arylphthalides via palladium-catalyzed arylation of aldehydes with organoboronic acids was achieved using the thioether-imidazolinium carbene ligand in good to excellent yields and was carried out using 1.0 mol % of the catalyst with high substrate tolerance.

Steric tuning of the amidomonophosphane-rhodium(I) catalyst in asymmetric addition of arylboroxines to N-phosphinoyl aldimines.

Highly enantioselective rhodium-catalyzed addition of arylboroxines to N-phosphinoylaldimines was realized by the steric tuning of a diphenylphosphorus moiety to a di(o-tolyl)phosphorus moiety of a chiral amidomonophosphane. The presence of MS 4 A in a 5:1 solvent mixture of dioxane-propanol was essential to afford the corresponding diarylmethylamines in high yield.