Electrosynthesis, driven by renewable energy, is a powerful method for accessing useful chemical reactivity in a sustainable fashion. Typically, electrochemical reactions have been carried out using direct current (DC), where electrons flow in a single direction. In contrast, utilization of alternating current (AC) has been largely unexplored in synthetic electrochemistry despite its wide applications in our daily life. This could stem from a historical perception regarding the lack of unique reactivity/selectivity that would result from using such a waveform, as well as the absence of readily available instrumentation to remove the engineering barrier for mass adoption. A breakthrough in this area is the introduction of rapid alternating polarity (rAP), which alternates the polarity of an electrode in the millisecond timescale. This mode of current delivery, now implemented in the widely employed potentiostat, ElectraSyn2.0, enables access to unique reactivity and selectivity in organic synthesis that are challenging or currently impossible to achieve by any known method (chemical or electrochemical). The remarkable chemoselectivity and simplicity of rAP open new vistas in modern synthetic electrochemistry.

Carbon-hydrogen (C-H) bonds are ubiquitous in complex natural products. Over the past three decades, many methods to convert C-H bonds distal from functional groups, which were generally considered inert, have been developed. These advances now enable selective peripheral functionalizations at a late-stage. The direct engagement of traditionally unreactive C-H bonds in reactions expands chemical space by reducing functional group interconversions. As such, C-H functionalization serves as a powerful tool in medicinal and agrocultural chemistry as well as in the total synthesis of natural products where diversification to a broad array of compounds from a common intermediate is often desired. In this Account, we detail the thought processes and design principles that relied on emerging methods for C-H functionalization to prepare a wide range of bridged, polycyclic, natural products in the cephalotane and longibornane families from a common intermediate in each case.

Development and applications of the Ru-MACHO family of ruthenium complexes are described. The parent Ru-MACHO was originally developed for catalytic reduction of esters by molecular hydrogen, which not only provides an environmentally benign and safe protocol, but also achieves a wide range of substrate scope. The reaction with methyl lactate was demonstrated on an industrial scale, producing 2,200 kg of 1,2-propanediol with high optical purity. In addition to hydrogenation of esters, the Ru-MACHO family catalyzes a variety of reactions, including hydrogenation of nitriles and sugars, dehydrogenation of alcohols, N-monomethylation of aromatic amines, and formal deoxygenative hydrogenation of lactams.

Carboxylic acids are one of the most important functional groups found in various feedstocks. Their significance lies in their pivotal role as key intermediates in selective transformations during organic synthesis. Despite the existence of various decarboxylative transformation reactions such as Kolbe dimerization, these methods still exhibit certain limitations that present opportunities for further improvement. In this account, we present our recent studies on the application of photocatalytic decarboxylative transformation that allows the divergent transformation of carboxylic acids.

The impressive structural diversity of polycyclic arenes (PCAs) comprised of pentagon, hexagon, heptagon, and octagon rings has continued to drum up interest in the fields of synthetic chemistry and materials science owing to their tunable electronic properties in relation to their unique planar, twisted, and curved π-surface conformations. Although an array of synthetic strategies have been developed to construct both known and new PCA scaffolds in the past decades, flexible and expedient strategies for creating PCAs with differently sized rings embedded are rare. We describe herein our recent studies on the tandem oxidative ring expansion (TORE) strategy for the construction of structurally diverse PCAs involving intra- and intermolecular TORE reactions for hexagon-embedded PCAs, and intramolecular TORE reactions for O- or S-incorporated heptagon-embedded PCAs and octagon-embedded PCAs.

The ubiquitin-proteasome system (UPS) regulates cellular protein degradation to maintain protein homeostasis (proteostasis). The UPS mainly consists of three steps, ubiquitination, deubiquitination, and protein degradation. In the ubiquitination process, a series of enzymes, the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), catalyze the formation of a polyubiquitin chain on target proteins. Prior to the degradation of the polyubiquitinated proteins by the proteasome, deubiquitination enzymes remove this polyubiquitin chain and cleave it into monoubiquitin molecules. The UPS plays a key role in controlling proteostasis and multiple signaling pathways. Dysfunction of the UPS has been implicated in the development of various diseases, including cancer, neurodegenerative diseases, and autoimmune diseases. Therefore, UPS inhibitors that disrupt protein degradation are promising as drug leads. In our study, we searched for natural products (NPs) that inhibit UPS-dependent proteolysis using dual-reporter HeLa cells expressing Ub^G76V-green fluorescent protein (GFP) and the oxygen-dependent degradation domain of HIF1α fused to luciferase (ODD-Luc). Here we report our research on NPs that inhibit the UPS using these cell-based reporter assays.

Carbon-nitrogen bond formation with ammonia or its equivalent has been a major research field in organic chemistry since the discovery of Wöhler’s urea synthesis. Given the versatility of nitrogen-doped organic molecules in natural products, pharmaceuticals, agrochemicals and materials, many such transformations have been conceived during the last 200 years. While the focus has shifted more and more to developing new catalysts rather than reagents to achieve this goal, over the last couple of years we have been intrigued by the possibility of inventing new ammonia equivalents which suit modern catalytic synthesis. We review herein our recent study triggered by this renewed interest in reagent design, which has led to the discovery and application of N-(fluorosulfonyl)carbamates as a new class of aminating reagents.

This paper introduces our recent research on metallo-supramolecular polymers (MSPs) and the electrochromic (EC) device fabrication, including (1) control of metal sequence in one-dimensional (1D) MSPs, (2) design of two-dimensional (2D) MSPs, (3) three-dimensional (3D) hyperbranched MSPs, (4) EC devices (ECDs) with MSPs and (5) our trial for ECD applications. MSPs are a kind of coordination polymers and obtained by complexation of metal ions with multitopic organic ligands. MSPs show EC properties in the film state, activated by the electrochemical redox of the metal ions. The EC changes are caused by the reversible appearance and disappearance of the metal-to-ligand charge transfer (MLCT) absorption in the metal complex moieties of MSPs. ECDs with MSPs have great potential for the future’s smart window applications and spreading.

In recent years, the use of various elements has been attracting large attention in drug discovery and materials science. Particularly, organoborons and organosilicons are promising candidates owing to their high stability and relatively low toxicity. However, there are still limitations in the available chemical structures and hence development of novel skeletal-constructing methods is an urgent task in synthetic chemistry. Based on precise designs of boron and silicon ate complexes through an integration of theoretical and experimental chemistry, we have developed novel boration and silylation reactions.

Bisphenol A (BPA) is a component used in the manufacture of polycarbonate plastics and epoxy resins around the world; however, it is also well-known as one of the most notorious endocrine-disrupting chemicals. To avoid using BPA as an ingredient, various BPA derivatives and related compounds have been synthesized and the use of these for making polymers has grown significantly; however, the safety of these BPA derivatives, also known as next-generation bisphenols, has not been fully evaluated. We hypothesized that the bisphenol moiety is a privileged structure for binding to nuclear receptors. Here, we summarize the binding ability of next-generation bisphenols to estrogen receptors and show that halogen-containing bisphenols act as coactivator binding inhibitors for estrogen receptor β.