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Dynamic covalent bonds are useful tools in a wide range of applications. Although various reversible chemical reactions have been studied for this purpose, the requirement for harsh conditions, such as high temperature and low or high pH, to activate generally stable covalent bonds limits their potential applications involving biomolecules or household utilization. Here, we report the design, synthesis, characterization, and dynamic covalent bonding properties of 1,2-disubstituted 1,2-dihydro-1,2,4,5-tetrazine-3,6-dione (TETRAD). Hetero-Diels-Alder reactions of TETRAD with furan derivatives and their retro-reactions proceeded rapidly at room temperature under neutral conditions, enabling a chemically induced sol-gel transition system.

Due to its mild reaction conditions and unique chemoselectivity, hydrogen atom transfer (HAT) hydrogenation represents an indispensable method for the synthesis of complex molecules. Its analog using deuterium, deuterium atom transfer (DAT) deuteration, is expected to enable access to complex deuterium-labeled compounds. However, DAT deuteration has been scarcely studied for synthetic purposes, and a method that possesses the favorable characteristics of HAT hydrogenations has remained elusive. Herein, we report a protocol for the photocatalytic DAT deuteration of electron-deficient alkenes. In contrast to the previous DAT deuteration, this method tolerates a variety of synthetically useful functional groups including haloarenes. The late-stage deuteration also allows access to deuterated amino acids as well as donepezil-d2. Thus, this work demonstrates the potential of DAT chemistry to become the alternative method of choice for preparing deuterium-containing molecules.

Ruthenium(II)-catalyzed enantioselective C–H functionalization reactions of sulfoximines with sulfoxonium ylides are described. The combination of [RuCl2(p-cymene)]2 and a pseudo-C 2-symmetric binaphthyl monocarboxylic acid furnished the S-chiral products in 76:24 to 92:8 er.

Photosensitization of organometallics is a privileged strategy that enables challenging transformations in transition-metal catalysis. However, the usefulness of such photocatalyst-induced energy transfer has remained opaque in iron-catalyzed reactions despite the intriguing prospects of iron catalysis in synthetic chemistry. Herein, we demonstrate the use of iron/photosensitizer-cocatalyzed cycloaddition to synthesize polyarylpyridines and azafluoranthenes, which have been scarcely accessible using the established iron-catalyzed protocols. Mechanistic studies indicate that triplet energy transfer from the photocatalyst to a ferracyclic intermediate facilitates the thermally demanding nitrile insertion and accounts for the distinct reactivity of the hybrid system. This study thus provides the first demonstration of the role of photosensitization in overcoming the limitations of iron catalysis.

Herein, we report visible light-promoted single nickel catalysis for diverse carbon-heteroatom couplings under mild conditions. This mild, general, and robust method to couple diverse nitrogen, oxygen, and sulfur nucleophiles with aryl(heteroaryl)/alkenyl iodides/bromides exhibits a wide functional group tolerance and is applicable to late-stage modification of pharmaceuticals and natural products. On the base of preliminary mechanistic studies, a Ni

Resolvins are pro-resolving lipid mediators with highly potent anti-inflammatory effects. Because of their polyunsaturated structures, however, they are unstable to oxygen as a drug prototype. To address this issue, we designed and synthesized CP-RvE3 as oxidatively stable congeners of RvE3 by replacing the

Molecular dynamics (MD) simulations on the molten state of Li2SO4-Na2SO4 have been performed to investigate the structure and the transport properties. In MD, the screened Born-Mayer type pair-pote...

A previously unreported heterodetic cyclic peptide, homophymamide A (1), was isolated from a Homophymia sp. marine sponge. The structure of homophymamide A was determined to be a lower homologue of anabaenopeptins by spectroscopic analysis, chemical degradation, and chemical synthesis. Analysis of the acidic hydrolysate showed that the racemization of Lys took place, leading us to pose a cautionary note on the configurational assignment of peptides that contain a ureido bond.

Oshimalides A (1) and B (2) were isolated from a Luffariella sp. marine sponge. The absolute configurations of the stereogenic centers in the cyclohexenone ring were determined by the modified Mosher's analysis of the reduction product. The absolute configuration of the stereogenic center in the dihydropyran ring was assigned by analysis of the 1H NMR data of the vicinal diols which were prepared by AD-mix reagents stereoselectively.

Myrindole A, a bis-indole alkaloid, was isolated from the deep-sea sponge Myrmekioderma sp. The high degree of unsaturation of the molecule complicated the assignment of its structure by standard 2D-NMR experiments but was ultimately achieved by a combination of 1H-15N-HMBC and 1,n-ADEQUATE experiments as well as the comparison of measured and calculated CD spectra. Myrindole A showed antimicrobial activity against Gram-positive and Gram-negative bacteria.

Enantioselective C(sp3)–H functionalization reactions using high-valent group 9 metal catalysts with cyclopentadienyl ligands have been achieved by the introduction of appropriate chiral carboxylic...

The transition-metal-free 211At-astatination of spirocyclic aryliodonium ylides via a nucleophilic aromatic substitution reaction is described. This method enables the preparation of 211At-radiolabeled compounds derived from multi-functionalized molecules and heteroarenes in good to excellent radiochemical yields.

Enantioselective C–H alkylation of ferrocene carboxamides with diazomalonates using an achiral Cp*Ir(III)/chiral carboxylic acid is described. The combination of an achiral Cp*Ir(III) complex and a binaphthyl-based chiral carboxylic acid provided planar chiral alkylated ferrocenes in good yields with moderate to good enantioselectivity (up to 94 : 6 er).

State-of-the-art photoredox/nickel dual catalysis is a powerful strategy for the rapid assembly of complex scaffolds but requires expensive and highly reactive photosensitizers to shuttle energy or electrons. Single nickel catalysis, which performs dual roles of light-harvesting and organometallic catalysis, avoids these issues associated with photocatalysts. Herein, we report visible light-promoted single nickel catalysis for diverse carbon-heteroatom couplings under mild conditions. This mild, general, and robust method to couple diverse nitrogen, oxygen, and sulfur nucleophiles with an aryl(heteroaryl)/alkenyl iodides/bromides exhibits a wide range of functional group tolerance and is applicable to late-stage modification of pharmaceuticals and natural products. Based on preliminary mechanistic studies, a NiI/NiIII cycle was proposed via the generation of active NiI complexes that appear from homolysis of NiII-I rather than NiII-aryl bond.

An enantioselective [4+3] cyclization via C(sp

Among sulfoximine derivatives containing a chiral sulfur center, benzothiadiazine-1-oxides are important for applications in medicinal chemistry. Here, we report that the combination of an achiral cobalt(III) catalyst and a pseudo-C

Organosilanes are synthetically useful reagents and precursors in organic chemistry. However, the typical inertness of unactivated Si-C(sp3) bonds under conventional reaction conditions has hampered the application of simple tetraalkylsilanes in organic synthesis. Herein we report the chemoselective cleavage of Si-C(sp3) bonds of unactivated tetraalkylsilanes using iodine tris(trifluoroacetate). The reaction proceeds smoothly under mild conditions (-50 °C to room temperature) and tolerates various polar functional groups, thus enabling subsequent Tamao-Fleming oxidation to provide the corresponding alcohols. NMR experiments and density functional theory calculations on the reaction indicate that the transfer of alkyl groups from Si to the I(III) center and the formation of the Si-O bond proceed concertedly to afford an alkyl-λ3-iodane and silyl trifluoroacetate. The developed method enables the use of unactivated tetraalkylsilanes as highly stable synthetic precursors.

The enantioselective C-H alkylation of 8-ethylquinolines with enones or acrolein using a RhIII catalyst and a chiral carboxylic acid is described. Under mild reaction conditions, a binaphthyl-based chiral carboxylic acid enables the enantioselective cleavage of the 8-ethylquinoline C(sp3)-H bond. The obtained results demonstrate the utility of the combination of a high-valent group 9 metal catalyst and a chiral carboxylic acid for the enantioselective C(sp3)-H activation and the subsequent C-C bond formation.

The development of robust and reactive chiral catalysts is a fundamental aim in asymmetric catalysis, and crucial for providing efficient methods for synthesizing chiral molecules. Chiral paddle-wheel bimetallic complexes provide a highly tunable chiral environment in rhodium-catalysed asymmetric carbene/nitrene transfer reactions and Lewis acid-catalysed reactions. Chiral paddle-wheel complexes having other transition metals as the reactive metal centre, however, have not yet been identified in asymmetric catalysis. Here, we report the synthesis, structures and high catalytic performances of chiral paddle-wheel diruthenium complexes. The cationic chiral diruthenium complex [Ru2((S)-BPTPI)4]+ exhibited remarkable reactivity as a Lewis acid catalyst for asymmetric hetero-Diels–Alder reactions, achieving a turnover number of up to 1,880,000 with high enantioselectivity (>90% e.e.). The chiral diruthenium complexes also exhibited good reactivity and high enantioselectivity in C–H amination and cyclopropanation reactions under oxidizing conditions, indicating their high tolerance towards oxidation. Our results reveal the chiral paddle-wheel diruthenium scaffold as a promising platform for asymmetric catalysis. The development of chiral catalysts is of fundamental importance in asymmetric catalysis. Now, chiral paddle-wheel diruthenium complexes are reported that are stable under oxidizing conditions and effective in asymmetric C–C and C–N bond-forming reactions with turnover numbers of up to 1,880,000.

Proton conductor inorganic acid Cs2(HSO4)(H2PO4) is investigated by molecular dynamics (MD) simulation in its molten and glass states using the screened Born–Mayer (BM) type potentials. The glass f...

In the past decade, synthetic chemists have discovered the outstanding generality and potential of visible-light-driven photoredox catalysis, which converts visible light into chemical energy, realizing numerous transformations of small molecules. The current state-of-the-art strategy in photoredox catalysis, combining photoredox and transition-metal catalysis, has received considerable attention in organometallic chemistry. In parallel with the rapid development of nickel/photoredox and copper/photoredox catalysis, cobalt/photoredox catalysis has emerged as a distinct new option in this area. This short review covers the general strategy, characteristics compared with other metallaphotoredox systems, and future perspectives of cobalt/photoredox catalysis. To our knowledge, this is the first review encompassing the general combination of cobalt and photoredox catalysis in synthetic chemistry.

Despite their unique potential as rare 1,1-dipole synthons, allyl sulfones are rarely used in target-oriented syntheses, likely due to the lack of a general catalytic method for their branch-selective allylic substitution. Herein, we identified allyl 4-chlorophenyl sulfone as a versatile linchpin for both base-mediated α-derivatization and subsequent cobalt-catalyzed allylic substitution. The sequential transformations allow for highly regioselective access to branched allylic substitution products with a variety of aliphatic side chains. The photoredox-enabled­ ­cobalt catalysis is indispensable for achieving high yields and regioselectivity­ for the desulfonylative substitution in contrast to traditional metal-catalyzed protocols, which lead to inferior outcomes in the corresponding transformations.

Transition-metal-catalyzed C-H functionalization reactions with Cp*MIII catalysts (M=Co, Rh, Ir) have found a wide variety of applications in organic synthesis. Albeit the intrinsic difficulties in achieving catalytic stereocontrol using these catalysts due to their lack of additional coordination sites for external chiral ligands and the conformational flexibility of the Cp ligand, catalytic enantioselective C-H functionalization reactions using the Group 9 metal triad with Cp-type ligands have been intensively studied since 2012. In this minireview, the progress in these reactions according to the type of the chiral catalyst used are summarized and discussed. The development of chiral Cpx ligands the metal complexes thereof, artificial metalloenzymes, chiral carboxylate-assisted enantioselective C-H activations, enantioselective alkylations assisted by chiral carboxylic acids or chiral sulfonates, and chiral transient directing groups are discussed.

An extensively N-methylated linear nonapeptide heptavalinamide A (1) was isolated from the marine cyanobacterium Symploca sp. collected at Kabira Reef of Ishigaki Island, Okinawa. The amino acid sequence of 1 was assigned by interpretation of 2D NMR and MS/MS data. The absolute configurations of the constituent amino acids were determined by the application of Marfey's method. A method to assign the configuration of N,N-dimethylvaline by LCMS is discussed.

Intramolecular hydroarylation of alkenes through hydrogen atom transfer (HAT) represents a robust method to prepare benzo-fused heterocycles. However, the reported methods have limitations in a variety of accessible cyclic scaffolds. Here we report a dual cobalt- and photoredox-catalyzed HAT hydroarylation of alkenes that is characterized by higher efficiency in the synthesis of a δ-lactam compared to established protocols. The proposed mechanism is supported by experiments and DFT calculations.

Despite the rapid progress in C-C bond-forming reactions using Katritzky salts, their deaminative allylation remains a challenge. Inspired by the metallaphotoredox-catalyzed allylic substitution regime, here, we report the deaminative allylation of Katritzky salts via cobalt/organophotoredox dual catalysis. This cross-electrophile coupling enables regioselective allylation using a variety of allylic esters, overcoming the substrate limitations of reported protocols. Mechanistic studies indicate the involvement of a pi-allyl cobalt complex as a radicalophile that mediates C-C bond formation.

The production of bioactive metabolites is increasingly recognized as an important function of host-associated bacteria. An example is defensive symbiosis that might account for much of the chemical richness of marine invertebrates including sponges (Porifera), 1 of the oldest metazoans. However, most bacterial members of sponge microbiomes have not been cultivated or sequenced, and therefore, remain unrecognized. Unequivocally linking metabolic functions to a cellular source in sponge microbiomes is, therefore, a challenge. Here, we report an analysis pipeline of microfluidic encapsulation, Raman microscopy, and integrated digital genomics (MERMAID) for an efficient identification of uncultivated producers. We applied this method to the chemically rich bacteriosponge (sponge that hosts a rich bacterial community) Theonella swinhoei, previously shown to contain ‘Entotheonella’ symbionts that produce most of the bioactive substances isolated from the sponge. As an exception, the antifungal aurantosides had remained unassigned to a source. Raman-guided single-bacterial analysis and sequencing revealed a cryptic, distinct multiproducer, ‘Candidatus Poriflexus aureus’ from a new Chloroflexi lineage as the aurantoside producer. Its exceptionally large genome contains numerous biosynthetic loci and suggested an even higher chemical richness of this sponge than previously appreciated. This study highlights the importance of complementary technologies to uncover microbiome functions, reveals remarkable parallels between distantly related symbionts of the same host, and adds functional support for diverse chemically prolific lineages being present in microbial dark matter., PNAS Nexus, 1 (1), ISSN:2752-6542

The C–H bond addition reaction of 2-phenylpyridine derivatives with α,β-unsaturated carboxylic acids catalyzed by Cp*Rh(III)/BH3·SMe2 is reported. Activation of C–H bonds with the rhodium catalyst and activation of α,β-unsaturated carboxylic acids with the boron catalyst cooperatively work, and a BINOL-urea hybrid ligand significantly improved the reactivity. With the optimized hybrid catalytic system, various β-disubstituted carboxylic acids were obtained under mild reaction conditions.