In synthetic organic chemistry, sodium hydride (NaH) has been utilized almost exclusively as a routine Brønsted base, while NaH has not been considered to work as a hydride donor. Recently, our group has serendipitously found that NaH can function as a unique hydride donor by its solvothermal treatment with sodium iodide (NaI) or lithium iodide (LiI) in tetrahydrofuran (THF) as a solvent. This discovery led to the development of unprecedented reductive molecular transformations such as hydrodecyanation of α-quaternary benzyl cyanides, controlled reduction of amides into aldehydes, dearylation of arylphopsphine oxides, and hydrodehalogenation of haloarenes. Moreover, this concise protocol allows for the use of NaH as enhanced Lewis acid and Brønsted base, enabling directed aromatic C-H sodiation, nucleophilic amination of methoxy arenes, and C2-amination of pyridines (the Chichibabin amination).
Hydrogen (H2) is an environmentally friendly energy source that produces only water through combustion and is a useful reducing agent in organic chemistry. However, according to the law, it needs to be strictly stored, transported, and managed in pressure vessels. Although H2 is mainly produced industrially by the steam reforming of methane (CH4), this is not environmentally friendly owing to the emissions of carbon dioxide (CO2) as well as the energy input from the endothermic reaction. Herein, hydrogen generation is achieved from water (H2O and D2O), alkane, and diethyl ether (Et2O) without CO2 emissions through the mechanochemical collision of stainless-steel balls using a planetary ball mill machine. Furthermore, in situ generated H2 can be directly utilized as a reductant for various reducible functionalities, such as alkynes, alkenes, ketones, nitro groups, and aromatic halides. In addition, D2 derived from D2O promotes a reductive deuteration to provide the corresponding deuterated products. When using Et2O as a hydrogen source, a reduction of arene can be achieved. In this paper, the hydrogen generation from water, alkanes, and Et2O, subsequent hydrogenation, and the role of stainless-steel balls are summarized.
Aliphatic polyketones are structurally flexible compounds that can induce and fix various conformations using ketone-related molecular interactions and reactions, such as hydrogen-bonding interactions and nucleophilic additions, respectively. These characteristics are advantageous to create structurally diverse molecules. However, difficulty in synthesis and reaction control of aliphatic polyketones depends on the ketone sequence. Recently, a new ketone sequence comprising alternating 1,3- and 1,4-diketone subunits was developed using stepwise oligomerization of an acetylacetone derivative. This sequence allowed preparation of the polyketone chains as their discrete forms with fixed chain length. Thus, various compounds including chromophores and coordination assemblies were generated through chemo-, regio-, and stereoselective transformations. This account focuses on the recent developments in molecular synthesis using aliphatic polyketone chains bearing an alternating 1,3- and 1,4-diketone sequence.
Our four recent synthetic studies of polycyclic terpenoids using the intramolecular aldol type cyclization reaction are described. (i) Asymmetric total synthesis of tricyclic diterpenoid spirocurcasone using an intramolecular aldol condensation to construct the bicyclic ring system. (ii) Total synthesis of tricyclic sesquiterpenoid albaflavenone using sequential intramolecular aldol condensations to construct its tricyclic framework. (iii) Total synthesis of paralemnolide A using an intramolecular Reformatsky-Honda reaction to construct the tricyclic framework. (iv) Synthetic study of marine diterpenoid aberrarone using a repeated 1,4-addition followed by intramolecular aldol reaction protocol to construct the tetracyclic framework.
Membrane protein integration is a vital event in cells. We identified a novel factor involved in this process in Escherichia coli, which we named MPIase after its function. A combination of spectroscopic analyses and synthetic work has revealed that MPIase is a glycolipid despite its enzyme-like activity. MPIase has a long glycan chain composed of repeating trisaccharide units and an anchor composed of a pyrophosphate and a diacylglycerol. To determine the mechanism of activity, we synthesized a trisaccharyl pyrophospholipid termed mini-MPIase-3, a minimal unit of MPIase, and its derivatives. Structure-activity relationship studies demonstrated that the glycan part of MPIase prevents the aggregation of substrate proteins. Moreover, MPIase embedded in the membrane alters the physicochemical properties of membranes to facilitate proteins to interact with the inner part of the membrane.
Macrolactamization is one of the most important peptide-modifying reactions. However, chemical macrocyclization is often hampered by several technical problems such as epimerization at the C-terminal residue, and a requirement for high dilution conditions, as well as for protective groups. In contrast, natural cyclopeptides are biosynthesized by efficient cyclases under mild conditions, suggesting these enzymes have potential as biocatalysts. However, the versatility of natural cyclases has not been fully exploited, mainly due to their strict substrate specificity. During the course of our synthetic and biosynthetic studies on surugamides, we have discovered a new family of cyclases showing broad substrate specificity. The new cyclase SurE, which is homologous to penicillin binding protein, offloads two assembly lines of non-ribosomal peptide synthetase, and remarkably, catalyzes the head-to-tail macrolactamization of two distinct peptides, thereby offering a new platform for the development of biocatalysts for macrolactamization.
The fluorescence properties, e.g., fluorescence intensity, of fluorescent sensors can change due to covalent derivatization or noncovalent complexation with a target chemical species (i.e., molecules and ions) or by variations in circumstantial physical parameters (e.g., temperature and viscosity). The internal charge transfer (ICT) character and photoinduced electron transfer (PET) efficiency can be used to tune the fluorescence switching mechanism, facilitating the development of new fluorescent sensors. In addition, the utilization of an environment-sensitive (i.e., polarity- and hydrogen bonding-sensitive) fluorophore in stimulus-responsive macromolecules to design novel fluorescent sensors has been proposed. Based on this concept, highly sensitive fluorescent polymeric thermometers and (extremely sensitive) digital fluorescent pH sensors have been developed. These thermometers are being used to measure the temperature of live cells in biological and medical studies. This concept has also allowed nanoscale proton mapping near membranes, which exemplifies the downsizing of targets for fluorescent sensing from a micrometer-scale to a nanometer-scale.
In this account we describe our recent development of rapid syntheses of π-extended azacorannulenes. The key to successful synthesis is the use of polycyclic aromatic azomethine ylides, which exhibit extremely high reactivity in sequential 1,3-dipolar cycloadditions with alkenes and alkynes followed by oxidation to form fused pyrroles. This efficient construction of the polycyclic pyrrole structure has led to the rapid synthesis of various π-extended azacorannulenes, which are characterized by their extended π-surface and highly curved, bowl-shaped structures. The present study provides useful insights toward the bottom-up synthesis and property elucidation of heteroatom-containing fullerenes and their fragment molecules.
Recently dinuclear complexes have attracted attention as catalysts for olefin polymerization. This account describes the synthesis and catalytic behavior of dinuclear Pd, Ni, Co, and Fe complexes with cyclic ligands. The two metal centers of the dinuclear complexes are located in close proximity owing to the rigid, cyclic ligands. These dinuclear complexes show higher catalytic activity, and/or produce polymers with higher molecular weight than the corresponding mononuclear complexes. The dinuclear catalysts were shown to have higher thermal stability during polymerization. They also enable the synthesis of branched ethylene/acrylate copolymer with acrylate units incorporated into the main chain, and the selective incorporation of non-conjugated dienes in the copolymerization with ethylene, reactions which could not be achieved using their mononuclear analogues.
Despite their intriguing structure and potential applications, the synthesis of structurally uniform carbon nanohoops has been a significant challenge until recently. The first synthesis of cycloparaphenylenes (CPPs), which are representative carbon nanohoops, nearly a decade ago considerably enhanced the availability of various carbon nanohoops, but the final products are usually only prepared on a mg scale. This review describes our endeavors to increase the availability of CPPs and their derivatives in large quantities. The three key reactions are 1) the one-pot, stereoselective two-fold addition of aryllithium to 1,4-benzoquinones to give U-shaped cyclization precursors, 2) subsequent nickel- or platinum-mediated selective cyclization, and 3) H2SnCl4-mediated reductive aromatization. This straightforward and high-yielding synthetic route provides gram quantities of various CPPs and their derivatives. Preliminary results on the applications of CPPs in electronic devices and the elucidation of CPP reactivity are also discussed.