A practical approach to non-natural or N-unsubstituted α-arylglycine derivatives: Hf(OTf)4-doped Me3SiCl system-catalyzed aminomethylation of electron-rich arenes with a new type of N,O-acetal

The authors have demonstrated the Hf(OTf)₄-doped Me₃SiCl system-catalyzed aminomethylation of electron-rich aromatic compounds, such as indoles and anilines, with new types of N,O-acetals having a variety of functional groups, such as cyano, ester, bis(trimethylsilyl)amino, diallylamino, and cyclic amino moieties, for the preparation of non-natural aromatic amino acid derivatives. Aminomethylation using an N,O-acetal with a bis(trimethylsilyl)amino group was particularly successful in the direct preparation of an N-unsubstituted α-indolylglycine derivative, which required only a standard aqueous workup.     

Facile and efficient synthesis of polyfunctionalized benzofurans: three-component coupling reactions from an alkynylsilane, an o-hydroxybenzaldehyde derivative, and a secondary amine by a Cu(I)-Cu(II) cooperative catalytic system

The combination of 5 mol % Cu(OTf)₂ and CuCl in the presence of DMAP effectively catalyzed a three-component coupling reaction involving an alkynylsilane, an o-hydroxybenzaldehyde derivative, and a secondary amine. The reaction proceeded via intramolecular 5-exo-dig cyclization, resulting in direct synthesis of the corresponding benzofuran derivatives in moderate to excellent yields.     

Solvation dynamics of coumarin 153 in alcohols confined in silica nanochannels

Solvation dynamics in alcohols confined in silica nanochannels was examined by time-resolved fluorescence spectroscopy using coumarin 153 (C153) as a fluorescent probe. Surfactant-templated mesoporous silica was fabricated inside the pores of an anodic alumina membrane. The surfactant was removed by calcination to give mesoporous silica (Cal-NAM) containing one-dimensional (1D) silica nanochannels (diameter, 3.1 nm) whose inner surface was covered with silanol groups. By treating Cal-NAM with trimethylchlorosilane, trimethylsilyl (TMS) groups were formed on the inner surface of the silica nanochannels (TMS-NAM). Fluorescence dynamic Stokes shifts of C153 were measured in alcohols (ethanol, butanol, hexanol, and decanol) confined in the silica nanochannels of Cal- and TMS-NAMs, and the time-dependent fluorescence decay profiles could be best fitted by a biexponential function. The estimated solvent relaxation times were much larger than those observed in bulk alcohols for both Cal- and TMS-NAMs when ethanol or butanol was used as a solvent, indicating that the mobility of these alcohol molecules was restricted within the silica nanochannels. However, hexanol or decanol in Cal- and TMS-NAMs did not cause a remarkable increase in the solvent relaxation time in contrast to ethanol or butanol. Therefore, it was concluded that a relatively rigid assembly of alcohols (an alcohol chain) was formed within the silica nanochannels by hydrogen bonding interaction and van der Waals force between the surface functional groups of the silica nanochannels and alcohol molecules and by the successive interaction between alcohol molecules when alcohol with a short alkyl chain (ethanol or butanol) was used as a solvent.     

Diffusion of metal complexes inside of silica-surfactant nanochannels within a porous alumina membrane

The present paper describes diffusivities of a series of metal complexes inside of silica-surfactant nanochannels (channel diameter = 3.4 nm), which were formed within a porous alumina membrane by a surfactant-templated method using cetyltrimethylammonium bromide (CTAB) as a template surfactant. The metal complexes used in this study were Fe(CN)6(3-), Ru(NH3)6(3-), ferrocenecarboxylic acid (Fc-COO-), (ferrocenylmethyl)-trimethylammonium (Fc-NMe3+), N,N-(dimethylamminomethyl)ferrocene (Fc-NMe2), and ferrocene methanol (Fc-OH). Apparent diffusion coefficients of these metal complexes were estimated by measuring their mass transports through the silica-surfactant nanochannels. The estimated apparent diffusion coefficients were on the order of 10(-11) cm2 s(-1) for Fe(CN)6(3-) and Ru(NH3)6(3-), and these values were five orders of magnitude smaller than those in a bulk aqueous solution. For the ferrocene derivatives, the apparent diffusion coefficients of charged ferrocene derivatives are almost the same (5.3 x 10(-11) cm2 s(-1) for Fc-COO- and 5.4 x 10(-11) cm2 s(-1) for Fc-NMe3+), whereas neutral ferrocene derivatives (Fc-NMe2 and Fc-OH) show faster diffusion than the charged species. In addition, the apparent diffusion coefficient of Fc-NMe2 (27 x 10(-11) cm2 s(-1)) was about three times larger than that of Fc-OH (10 x 10-11 cm2 s(-1)). The difference in these diffusion coefficients is discussed by considering the mesostructure of the silica-surfactant nanochannels, that is, an ionic interface with cationic head groups of CTA and their counteranions, a hydrophobic interior of the micellar phase, and a silica framework. As a result, it is inferred that the slow diffusivities of the charged metal complexes are due to the electrostatic interaction between the charged species and the ionic interface, whereas less interaction between neutral ferrocenes and the ionic interface causes distribution of metal complexes into the hydrophobic micellar phase, which is a less viscous medium compared to the ionic interface, resulting in the faster diffusivities of the neutral species.     

Regio- and Z-Selective Alkyne Hydroamination and Hydrophenoxylation using Tetrafluoro-λ6-Sulfanyl Alkynes under Superbasic,Naked Anion Conditions

Alkyne hydroamination is an effective approach for the production of enamines and enamine-containing N-heterocycles. However, stereoselectivity control is a considerable challenge in this reaction because of the electronic repulsion between an incoming nitrogen lone pair and the alkyne π-system. Herein, we propose a methodology involving β-regio- and Z-selective alkyne hydroamination by using tetrafluoro-λ⁶-sulfanyl (SF₄) alkynes under superbasic, naked anion conditions. The reaction is compatible with a wide variety of N-heterocycles, including indoles, carbazoles, pyrazoles, and imidazoles, and selectively furnishes SF₄-linked Z-vinyl enamines with β-regioselectively. Moreover, the method can be extended to the β- and Z-controlled, base-mediated alkyne hydrophenoxylation with phenols to provide SF₄-linked Z-vinyl ethers in high yields. As the SF₄ unit has attracted attention as a bioisostere for alkynes, p-benzenes, bicyclo[1.1.1]pentyl (BCP) groups, and cubanes in medicinal chemistry, this chemistry represents an effective approach to creating novel drug candidates incorporating SF₄-containing molecules.     

Enantioselective C--C bond formation to sulfonylimines through use of the 2-pyridinesulfonyl group as a novel stereocontroller

Enantioselective C--C bond formation to 2-pyridinesulfonylimines afforded products with good enantioselectivity. Dynamic induction of chirality on the sulfur by coordination of a chiral Lewis acid to the pyridine nitrogen and one of the prochiral sulfonyl oxygens induces enantioselectivity. Since the 2-pyridinesulfonyl group can easily be removed after the reaction, it acts not only as an activating group but also as an efficient stereocontroller.     

Current State of Microflow Trifluoromethylation Reactions

The trifluoromethyl group is a powerful structural motif in drugs and polymers; thus, developing trifluoromethylation reactions is an important area of research in organic chemistry. Over the past few decades, significant progress has been made in developing new methods for the trifluoromethylation of organic molecules, ranging from nucleophilic and electrophilic approaches to transition-metal catalysis, photocatalysis, and electrolytic reactions. While these reactions were initially developed in batch systems, more recent microflow versions are highly attractive for industrial applications owing to their scalability, safety, and time efficiency. In this review, we discuss the current state of microflow trifluoromethylation. Approaches for microflow trifluoromethylation based on different trifluoromethylation reagents are described, including continuous flow, flow photochemical, microfluidic electrochemical reactions, and large-scale microflow reactions.     

Protein adsorption on polymer-modified silica particle surface

Silicon substrate surface and silica particle surface were modified with five kinds of polymers, poly(2-methoxyethyl methacrylate) (pMEMA), poly(2-hydroxyethyl methacrylate) (pHEMA), poly(acrylamide) (pAAm), poly(methyl methacrylate) (pMMA), and poly(styrene) (pSt), using a combined polymerization of surface-initiated polymerization that gives dense polymer chain layers and atom transfer radical polymerization (ATRP) that yields polymers with a narrow molecular weight distribution. Measurements of water contact angle and polymer chain amount on the modified silicon substrate surface and adsorption amounts of proteins (albumin and fibrinogen) on the modified silica particle surface revealed that the amount of polymer on the modified surface greatly affects the suppression of protein adsorption on the surface.