A Quantitative Study of the Halogenophilic Nucleophilic Substitution (S2X) Reaction and Chalcogenophilic Nucleophilic Substitution (S2Ch) Reaction.

Halogenophilic nucleophilic substitution (S2X) has a distinctly different reaction pathway compared to the bimolecular nucleophilic substitution reaction (S2), but they can lead to the same reaction product. However, their differences can be distinguished by studying stereoselective reactions in which both reaction pathways are possible. Herein, we utilize the stereospecific nature of S2 and the presence of a pro-chiral anion intermediate in S2X to conduct a quantitative study in which both S2 and S2X reactions exist.

Asymmetric N-oxidation catalyzed by bisguanidinium dinuclear oxodiperoxomolybdosulfate.

N-oxides play a pivotal role in natural products and emerging drug design, while also serving as valuable ligand scaffolds in organometallic chemistry. Among heteroatom oxidations, the conversion of amines to N-oxides is a critical and challenging facet. We present here a highly enantioselective N-oxidation methodology for both cyclic and acyclic amines.

Enantioselective Reduction and Sulfenylation of Isoflavanone Derivatives via Bisguanidinium Hypervalent Silicate.

In this work, we describe an enantioselective reduction and sulfenylation of isoflavanone derivatives by an ion pair strategy. The chiral cationic catalyst bisguanidinium () is capable of chiral induction in catalytic systems. Silane hydride works as a reductant and helps to form an anionic hypervalent silicate complex and intermediates with substrates to pair with chiral catalyst.

Structural investigations on the mitochondrial uncouplers niclosamide and FCCP.

There has been renewed interest in using mitochondrial uncoupler compounds such as niclosamide and carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) for the treatment of obesity, hepatosteatosis and diseases where oxidative stress plays a role. However, both FCCP and niclosamide have undesirable effects that are not due to mitochondrial uncoupling, such as inhibition of mitochondrial oxygen consumption by FCCP and induction of DNA damage by niclosamide. Through structure-activity analysis, we identified FCCP analogues that do not inhibit mitochondrial oxygen consumption but still provided good, although less potent, uncoupling activity.

Conjugating uncoupler compounds with hydrophobic hydrocarbon chains to achieve adipose tissue selective drug accumulation.

One potential approach for treating obesity is to increase energy expenditure in brown and white adipose tissue. Here we aimed to achieve this outcome by targeting mitochondrial uncoupler compounds selectively to adipose tissue, thus avoiding side effects from uncoupling in other tissues. Selective drug accumulation in adipose tissue has been observed with many lipophilic compounds and dyes.

A chiral pentanidium and pyridinyl-sulphonamide ion pair as an enantioselective organocatalyst for Steglich rearrangement.

Enantioselective ion pair catalysis has gained significant attention due to its ability to exert selectivity control in various reactions. Achiral counterions have been found to play crucial roles in modulating reactivity and selectivity. The modular nature of an ion pair catalyst allows rapid alterations of the achiral counterion to achieve optimal outcomes, without the need to modify the more onerous chiral component.

Applications of Vanadium, Niobium, and Tantalum Complexes in Organic and Inorganic Synthesis.

Organometallic catalysis is a powerful strategy in chemical synthesis, especially with the cheap and low toxic metals based on green chemistry principle. Thus, the selection of the metal is particularly important to plan relevant and applicable processes. The group VB metals have been the subject of exciting and significant advances in both organic and inorganic synthesis.

Asymmetric Synthesis of S(IV) and S(VI) Stereogenic Centers.

Sulfur can form diverse S(IV) and S(VI) stereogenic centers, of which some have gained significant attention recently due to their increasing use as pharmacophores in drug discovery programs. The preparation of these sulfur stereogenic centers in their enantiopure form has been challenging, and progress made will be discussed in this Perspective. This Perspective summarizes different strategies, with selected works, for asymmetric synthesis of these moieties, including diastereoselective transformations using chiral auxiliaries, enantiospecific transformations of enantiopure sulfur compounds, and catalytic enantioselective synthesis.

Guanidinium Hypoiodite-Catalyzed Intramolecular Oxidative Coupling Reaction of Oxindoles with β-Dicarbonyls.

Spiro[indoline-3,4'-piperidine] is a fundamental motif present in various biologically active compounds. Here, we report an intramolecular oxidative coupling reaction of oxindoles with β-dicarbonyls in the presence of a guanidinium hypoiodite catalyst, providing spiro-coupling products in moderate to excellent yields. Furthermore, a chiral hypoiodite catalyst derived from the chiral guanidinium organocatalyst is effective for the challenging asymmetric carbon-carbon bond-forming reaction, affording optically active spiro[indoline-3,4'-piperidines].

Organobase-Catalyzed Umpolung of Amides: The Generation and Transfer of Carbamoyl Anion.

A novel organobase-catalyzed umpolung reaction of amides was disclosed. This method provides an efficient method to generate and transfer carbamoyl anions. In this transformation, some of the inherent disadvantages of carbamoyl metal were avoided.

A quantitative study exploring the acceptance of the eHealth model for mental wellness among digital workers.

eHealth makes use of information and communication technologies (ICT) to improve health. In the digital age, the use of eHealth applications and other health-related applications has gained popularity, particularly during the COVID-19 pandemic. As a result of the pandemic, many uncertainties have arisen, causing stress and affecting the mental health of many skilled workers in the digital industry, particularly in the ICT, computing, and creative media industries.

Direct S2 or S2X Manifold─Mechanistic Study of Ion-Pair-Catalyzed Carbon(sp)-Carbon(sp) Bond Formation.

Density functional theory (DFT) is used in this work to predict the mechanism for constructing congested quaternary-quaternary carbon(sp)-carbon(sp) bonds in a pentanidium-catalyzed substitution reaction. Computational mechanistic studies were carried out to investigate the proposed S2X manifold, which consists of two primary elementary steps: halogen atom transfer (XAT) and subsequent S2. For the first calculated model on original experimental substrates, XAT reaction barriers were more kinetically competitive than an S2 pathway and connect to thermodynamically stable intermediates.

Synthesis of chiral sulfinate esters by asymmetric condensation.

Achiral sulfur functional groups, such as sulfonamide, sulfone, thiol and thioether, are common in drugs and natural products. By contrast, chiral sulfur functional groups are often neglected as pharmacophores, although sulfoximine, with its unique physicochemical and pharmacokinetic properties, has been recently incorporated into several clinical candidates. Thus, other sulfur stereogenic centres, such as sulfinate ester, sulfinamide, sulfonimidate ester and sulfonimidamide, have started to attract attention.

A Descriptor for Accurate Predictions of Host Molecules Enabling Ultralong Room-Temperature Phosphorescence in Guest Emitters.

Although doping can induce room-temperature phosphorescence (RTP) in heavy-atom free organic systems, it is often challenging to match the host and guest components to achieve efficient intersystem crossing for activating RTP. In this work, we developed a simple descriptor ΔE to predict host molecules for matching the guest RTP emitters, based on the intersystem crossing via higher excited states (ISCHES) mechanism. This descriptor successfully predicted five commercially available host components to pair with naphthalimide (NA) and naphtho[2,3-c]furan-1,3-dione (2,3-NA) emitters with a high accuracy of 83 %.

Restriction of Twisted Intramolecular Charge Transfer Enables the Aggregation-Induced Emission of 1-(,-Dialkylamino)-naphthalene Derivatives.

Understanding the mechanisms of aggregation-induced emission (AIE) is essential for the rational design and deployment of AIEgens toward various applications. Such a deep mechanistic understanding demands a thorough investigation of the excited-state behaviors of AIEgens. However, because of considerable complexity and rapid decay, these behaviors are often not experimentally accessible and the mechanistic comprehension of many AIEgens is lacking.

In silico characterization and prediction of thiourea-like neutral bidentate halogen bond catalysts.

Preorganization is a common strategy to align halogen bond (XB) donors to form two or more halogen bonds simultaneously. Previous approaches have utilized various non-covalent interactions such as steric interactions, ππ stacking, and hydrogen bond interactions. However, some of the introduced aligning interactions may compete with halogen bond interactions if the donors are employed in catalysis.

Molybdenum/Tungsten-Based Heteropoly Salts in Oxidations.

Oxidation represents one of the most important and practical chemical transformations for both organic synthesis, material science and pharmaceutical area. Among the existing strategies, molybdenum/tungsten-based heteropoly salts involved oxidations with low-cost and environmentally benign terminal oxidant and thus have attracted considerable attention in recent years. In this review, we have summarized the recent development of heteropoly salts utilized in oxidations, mainly the peroxomolybdates and peroxotungstates.

Enantioselective transition metal catalysis directed by chiral cations.

Enantioselective transition metal catalysis directed by chiral cations is the amalgamation of chiral cation catalysis and organometallic catalysis. Thus far, three strategies have been revealed: ligand scaffolds incorporated on chiral cations, chiral cations paired with transition metal 'ate'-type complexes, and ligand scaffolds incorporated on achiral anions. Chiral cation ion-pair catalysis has been successfully applied to alkylation, cycloaddition, dihydroxylation, oxohydroxylation, sulfoxidation, epoxidation and C-H borylation.

Catalytic Reductive Cross Coupling and Enantioselective Protonation of Olefins to Construct Remote Stereocenters for Azaarenes.

A novel enantioselective protonation protocol that is triggered by reductive cross coupling of olefins is reported. When under cooperative photoredox and chiral hydrogen-bonding catalytic conditions and using a terminal reductant, various α-branched vinylketones with diverse vinylazaarenes could provide important enantioenriched azaarene derivatives containing tertiary stereocenters at their remote δ-position with high yields and enantioselectivities. This reaction system is also suitable for α-branched vinylazaarenes, thus successfully assembling elusive 1,4-stereocenters.

Enantioselective Addition-Alkylation of α,β-Unsaturated Carbonyls via Bisguanidinium Silicate Ion Pair Catalysis.

Silicon hydrides, alkynylsilanes, and alkoxylsilanes were activated by fluoride in the presence of bisguanidinium catalyst to form hypervalent silicate ion pairs. These activated silicates undergo 1,4-additions with chromones, coumarins, and α-cyanocinnamic esters generating enolsilicate intermediates, for a consequent stereoselective alkylation reaction. The reduction-alkylation reaction proceeded under mild conditions using polymethylhydrosiloxane, a cheap and environmentally friendly hydride source.

Golden Jubilee of Singapore National Institute of Chemistry (1970-2020): Celebrating its Partnership with Wiley-VCH.

This year Singapore National Institute of Chemistry (SNIC) is celebrating its golden jubilee (1970-2020). Wiley-VCH has been a steadfast partner accompanying the rapid rise of chemistry research in Singapore. In celebration of this golden jubilee, we highlight 50 significant papers published in Angewandte Chemie by scholars currently based in Singapore, covering the widest possible spectrum of chemistry research.

Kinetic and Dynamic Kinetic Resolution of Racemic Tertiary Bromides by Pentanidium-Catalyzed Phase-Transfer Azidation.

We have developed a method to afford enantiomerically enriched tertiary azides and bromides through pentanidium-catalyzed kinetic resolution (KR) of racemic tertiary bromides under base-free conditions. We found that the absence of water is crucial to attain a high selectivity factor (s). On the other hand, new experimental observations and DFT modeling led us to propose that enantioconvergent azidation of tertiary bromides proceeded through dynamic kinetic resolution (DKR).

Recent Advances in Chiral Guanidine-Catalyzed Enantioselective Reactions.

Chiral guanidines have been widely used as Brønsted base catalysts and phase transfer catalysts in enantioselective reactions. Due to their amendable structure and powerful catalytic ability, they have attracted much interest. Several new catalysts containing a guanidinium moiety have been reported over the past decade and many promising outcomes have been achieved.