This Minireview examines a selection of case studies that showcase distinctive and enabling electrochemical approaches that have allowed for the generation and reaction of carbocation intermediates under mild conditions. Particular emphasis is placed on the progress that has been made in this area of organic synthesis and polymer chemistry over the past decade.

A general phase-transfer catalyst (PTC) mediated enantioselective alkylation of N-acylsulfenamides is reported. Essential to achieving high selectivity was the use of the triethylacetyl sulfenamide protecting group along with aqueous KOH as the base under biphasic aqueous conditions to enable the reaction to be performed at -40 °C. With these key parameters, enantiomeric ratios up to 97.5:2.5 at the newly generated chiral sulfur center were achieved with an inexpensive cinchona alkaloid derived PTC. Broad scope and excellent functional group compatibility was observed for a variety of S-(hetero)aryl and branched and unbranched S-alkyl sulfenamides. Moreover, to achieve high selectivity for the opposite enantiomer, a pseudoenantiomeric catalyst was designed and synthesized from inexpensive cinchonidine. Given that sulfoximines are a bioactive pharmacophore of ever-increasing interest, selected product sulfilimines were oxidized to the corresponding sulfoximines with subsequent reductive cleavage affording the free-NH sulfoximines in high yields. The utility of the disclosed method was further demonstrated by the efficient asymmetric synthesis of atuveciclib, a phase I clinical candidate for which only chiral HPLC separation had previously been reported for isolation of the desired (R)-sulfoximine stereoisomer.

Sulfur(VI)-based functional groups are popular scaffolds in a wide variety of research fields including synthetic and medicinal chemistry, as well as chemical biology. The growing interest in sulfur(VI)-containing molecules has motivated the scientific community to explore new methods to synthesize and modify them. Here, photocatalysis plays a key role granting access to new types of reactivity under mild reaction conditions. In this Perspective, we present a selection of works reported in the last six years focused on the photocatalytic assembly and reactivity of sulfones, sulfonamides, and sulfoximines. We addressed the key synthetic intermediates for each transformation, while discussing limitations and strength points of the protocols. Future directions of the field are finally presented.

In recent years, the increasingly severe pollution of heavy metals has posed a significant threat to the environment and human safety. Heavy metal ions are highly non-biodegradable, with a tendency to accumulate through biomagnification. Consequently, accurate detection of heavy metal ions is of paramount importance. As a new type of synthetic nanomaterials, single-atom nanozymes (SANs) boast exceptional enzyme-like properties, setting them apart from natural enzymes. This unique feature affords SANs with a multitude of advantages such as dispersed active sites, low cost and variety of synthetic methods over natural enzymes, making them an enticing prospect for various applications in industrial, medical and biological fields. In this paper, we systematically summarize the synthetic methods and catalytic mechanisms of SANs. We also briefly review the analytical methods for heavy metal ions and present an overall overview of the research progress in recent years on the application of SANs in the detection of environmental heavy metal ions. Eventually, we propose the existing challenges and provide a vision for the future.

Combining simple amines with the bench-stable sulfinylamine Tr-NSO allows in situ preparation of reactive alkyl sulfinylamines, which when combined with alkyl radicals generated by photocatalytic decarboxylation, provides N-alkyl sulfinamides. The reactions are broad in scope and tolerate a wide variety of functional groups on both the acid and amine components. The sulfinamide products are used to prepare a selection of challenging S(VI) products. The method provides a convenient way to use reactive and unstable alkyl sulfinylamines.

Organophosphorus(V) fluorides have a long and tumultuous history, with early applications as toxins and nerve agents reflecting their poisonous past. Behind these very real safety considerations, there is also growing potential in a wide range of fields, from chemical biology to drug development. The recent inclusion of organophosphorus(V) fluorides in click chemistry exemplifies the promise these compounds possess and brings these molecules to the brink of a resurgence. In this Perspective, we delve into the history of P(V)-F compounds, discuss the precautions needed to work with them safely, and explore recent advancements in their synthesis and application. We conclude by discussing how this field can continue on a path toward innovation.

A modular synthesis of sulfondiimidoyl fluorides - the double aza-analogues of sulfonyl fluorides - allowing variation of the carbon and both nitrogen-substituents is reported. The chemistry uses readily available organometallic reagents, commercial sulfinylamines, simple electrophiles, and N-fluorobenzenesulfonimide (NFSI), as the starting materials. The reactions are broad in scope, efficient, and scalable. We show that the sulfondiimidoyl fluoride products can be combined with amines to provide sulfondiimidamides, and with organolithium reagents to provide sulfondiimines, and that reactivity in these transformations can be modulated by variation of the N-substituents.

Quinoxaline molecule has gathered a great attention in medicinal chemistry due to its vide spectrum of biological activities and emerged as a versatile pharmacophore in drug discovery and development. Its structure comprises bicyclic ring of benzopyrazine and displays a range of pharmacological properties including antibacterial, antifungal, antiviral, anticancer and anti-inflammatory. This review summarizes the different strategies for the synthesis of quinoxalines and their anti-inflammatory properties acting through different mechanisms. Structure activity relationships have also been discussed in order to determine the effect of structural modifications on anti-inflammatory potential. These analyses illuminate critical structural features required for optimal activity, driving the design and synthesis of new quinoxaline analogues with better anti-inflammatory activities. The anti-inflammatory properties of quinoxalines are attributed to their inhibitory action on expression of several inflammatory modulators such as cyclooxygenase, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NFB) and p38 mitogen activated protein kinase (p38 MAPK). Activators of nuclear factor erythroid 2-related factor 2 (NRF2) and agonistic effect on opioid receptors have also been discussed. Hence, this review may provide a future template for the design and development of novel quinoxaline derivatives acting through different molecular targets as potential anti-inflammatory agents with better efficacy and safety profile.

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The 2,2-difluoroethyl group is an important lipophilic hydrogen bond donor in medicinal chemistry, but its incorporation into small molecules is often challenging. Herein, we demonstrate electrophilic 2,2-difluoroethylation of thiol, amine and alcohol nucleophiles with a hypervalent iodine reagent, (2,2-difluoro-ethyl)(aryl)iodonium triflate, via a proposed ligand coupling mechanism. This transformation offers a complementary strategy to existing 2,2-difluoroethylation methods and allows access to a wide range of 2,2-difluoroethylated nucleophiles, including the drugs Captopril, Normorphine and Mefloquine.

Dichloromethane, as a readily available and inexpensive C1 synthon is proposed as a powerful building block for cyclopropanation of alkenes under mild conditions. Herein, we report a highly efficient and versatile dual photoredox system, involving a nickel aminopyridine coordination complex and a photocatalyst, for the cyclopropanation of aromatic olefins using dichloromethane, under visible-light irradiation. The cyclopropanation protocol has been successfully applied at gram scale. Mechanistic studies suggest a Ni(II) pyridyl radical complex as the key intermediate for the homolytic cleavage of the Csp3-Cl bond, generating a chloromethyl radical that is captured by the olefin coupling partner. Our findings also highlight the versatility of this methodology. By directing the radical/polar crossover process, we were able to selectively drive the reaction towards either the formation of cyclopropyl derivatives or the corresponding non-cyclic alkyl chloride products. The methodology also successfully apply to geminal dichloroalkanes, including the formation of spiro[2,2] compounds. Moreover, our methodology extends to the synthesis of deuterium-labelled cyclopropanes, demonstrating its utility in isotopic labelling and broadening its applicability in chemical synthesis and drug development.