Elucidating the Mechanism of Electrooxidative Allene Dioxygenation: Dual Role of Tetramethylpiperidine -Oxyl (TEMPO).

The cumulated π system of a nonsymmetric allene contains three distinct unsaturated carbons that imbue it with unique reactivity toward radicals as compared to its alkene and alkyne counterparts. Despite the synthetic potential of these versatile building blocks, electrochemical transformations of allenes have been historically underexplored. Myriad strategies for easy access to allenes, coupled with the resurgence of interest in sustainable oxidative transformations of hydrocarbons, prompted our efforts to conduct an in-depth investigation of a rare example of an electrochemical TEMPO-mediated allene dioxygenation.

Recycling of Rare Earth Elements: From E-Waste to Stereoselective Catalytic Reactions.

Raw mixtures of Rare Earths Elements, REE, recovered by E-waste, were used as catalysts to promote the (stereoselective) synthesis of highly valuable compounds. YO, the major species that is recovered by the E-waste, can be easily converted into the catalytically active Y(OTf) that is able to efficiently promote the Michael addition of indoles to benzylidene malonates and the stereoselective Diels-Alder cycloaddition between cyclopentadiene and 4-(S)-3 acryloyl 4-tert-butyl 2-oxazolidinone. Additionally, the raw mixtures were immobilissed onto silica and used to construct packed reactors, resulting in values for Productivity and Space-Time Yields that were significantly higher than those of the corresponding batch conversions.

Silver-catalyzed direct conversion of epoxides into cyclopropanes using N-triftosylhydrazones.

Epoxides, as a prominent small ring O-heterocyclic and the privileged pharmacophores for medicinal chemistry, have recently represented an ideal substrate for the development of single-atom replacements. The previous O-to-C replacement strategy for epoxides to date typically requires high temperatures to achieve low yields and lacks substrate range and functional group tolerance, so achieving this oxygen-carbon exchange remains a formidable challenge. Here, we report a silver-catalyzed direct conversion of epoxides into trifluoromethylcyclopropanes in a single step using trifluoromethyl N-triftosylhydrazones as carbene precursors, thereby achieving oxygen-carbon exchange via a tandem deoxygenation/[2 + 1] cycloaddition.

Electrifying Friedel-Crafts Intramolecular Alkylation toward 1,1-Disubstituted Tetrahydronaphthalenes.

In this work, we successfully employed electrochemical conditions to promote a Hofer-Moest, intramolecular Friedel-Crafts alkylation sequence. The reaction proceeds under mild conditions, employing carboxylic acids as starting materials. Notably, the electrochemical process performed in batch was adapted to a continuous flow electrolysis apparatus to provide a significant improvement.

Iridium Acylnitrenoid-Initiated Biomimetic Cascade Cyclizations: Stereodefined Access to Polycyclic δ-Lactams.

Ring-fused azacyclic compounds are important building units in the synthesis of biorelevant natural products, pharmaceutical agents, and molecular materials. Herein, we present a new approach to these condensed azacycles by a biomimetic cascade cyclization of arylalkenyl dioxazolones. This cascade reaction was found to proceed with excellent stereoselectivity and a high functional group tolerance.

Asymmetric [2+1] cycloaddition of difluoroalkyl-substituted carbenes with alkenes under rhodium catalysis: Synthesis of chiral difluoroalkyl-substituted cyclopropanes.

Herein, we report a novel strategy for the synthesis of chiral difluoroalkyl-substituted cyclopropanes through enantioselective [2 + 1] cyclopropanation of alkenes and difluoroalkyl-substituted carbenes under rhodium catalysis, wherein the newly designed α, α-difluoro-β-carbonyl ketone -triftosylhydrazones are used as the difluoroalkyl-substituted carbenes precursors. This approach represents the first asymmetric cyclopropanation of alkenes with difluoroalkyl carbenes, featuring high yield, high enantioselectivity, and broad substrate scope. Gram-scale synthesis and further interconversion of diverse functional groups demonstrate the usefulness of this protocol in the preparation of diverse functionalized chiral difluoroalkyl-substituted cyclopropanes.

Chemoselective carbene insertion into the N-H bonds of NH·HO.

The conversion of inexpensive aqueous ammonia (NH·HO) into value-added primary amines by N-H insertion persists as a longstanding challenge in chemistry because of the tendency of Lewis basic ammonia (NH) to bind and inhibit metal catalysts. Herein, we report a chemoselective carbene N-H insertion of NH·HO using a TpAg-catalyzed two-phase system. Coordination by a homoscorpionate Tp ligand renders silver compatible with NH and HO and enables the generation of electrophilic silver carbene.

Highly electrophilic silver carbenes.

Catalytic carbene transfer reactions are fundamental transformations in modern organic synthesis, which enable direct access to diverse structurally complex molecules. Despite diazo precursors playing a crucial role in catalytic carbene transfer reactions, most reported methodologies take into account only diazoacetates or related compounds. This is primarily because diazoalkanes, unless they contain a resonance stabilizing group, are more susceptible to violent exothermic decomposition.

A New Benzothiazolthiazolidine Derivative, 11726172, Is Active , , and against Nonreplicating Cells of Mycobacterium tuberculosis.

Tuberculosis (TB) still poses a global menace as one of the deadliest infectious diseases. A quarter of the human population is indeed latently infected with Mycobacterium tuberculosis. People with latent infection have a 5 to 10% lifetime risk of becoming ill with TB, representing a reservoir for TB active infection.

Carbodefluorination of fluoroalkyl ketones via a carbene-initiated rearrangement strategy.

The C-F bond cleavage and C-C bond formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical and efficient route to partially fluorinated compounds.

Oxo-Rhenium-Mediated Allylation of Furanoside Derivatives: A Computational Study on the Mechanism and the Stereoselectivity.

Properly substituted tetrahydrofuran (THF) rings are important building blocks in the synthesis of many natural metabolites. Having reliable procedures to control the stereoselectivity at the THF core while decorating it with different substituents is a fundamental requirement to achieve and fulfill the complexity of nature. We recently reported a new chemical approach to control the stereochemistry in the alkylation and arylation of furanoside derivatives by using a rhenium(V) complex to form an intermediate oxo-carbenium species able to react with proper soft nucleophiles.

-Triftosylhydrazones: A New Chapter for Diazo-Based Carbene Chemistry.

Over recent decades, -sulfonylhydrazones have attracted significant attention in academic and industrial contexts owing to their ease of preparation, versatile reactivity, high stability, and practicality. In particular, the use of -sulfonylhydrazones as precursors for diazo compounds has paved the way for innovative and original organic reactions that are otherwise difficult to achieve. Three key developments are noteworthy in the history of -sulfonylhydrazone chemistry: (1) Bamford and Stevens initially disclosed the application of -tosylhydrazones as a diazo source in 1952; (2) Aggarwal and co-workers investigated -tosylhydrazone salts as diazo precursors for sulfur ylide-mediated asymmetric epoxidation and aziridination in 2001; and (3) Barluenga, Valdés and co-workers first reported Pd-catalyzed cross-coupling reactions with -tosylhydrazones in 2007, thus introducing the direct use of -tosylhydrazones in carbene transfer reactions.

Direct gem-Difluoroalkenylation of X-H Bonds with Trifluoromethyl Ketone N-Triftosylhydrazones for Synthesis of Tetrasubstituted Heteroatomic gem-Difluoroalkenes.

The direct gem-difluoroalkenylation of X-H bonds represents the most straightforward approach to access heteroatomic gem-difluoroalkenes that, as the isostere of the carbonyl group, have great potency in drug discovery. However, the construction of tetrasubstituted heteroatomic gem-difluoroalkenes by this strategy is still an unsolved problem. Here, we report the first direct X-H bond gem-difluoroalkenylation of amines and alcohols with trifluoromethyl ketone N-triftosylhydrazones under silver (for (hetero)aryl hydrazones) or rhodium (for alkyl hydrazones), thereby providing a most powerful method for the synthesis of tetrasubstituted heteroatomic gem-difluoroalkenes.

A Carbene Strategy for Progressive (Deutero)Hydrodefluorination of Fluoroalkyl Ketones.

Hydrodefluorination is one of the most promising chemical strategies to degrade perfluorochemicals into partially fluorinated compounds. However, controlled progressive hydrodefluorination remains a significant challenge, owing to the decrease in the strength of C-F bonds along with the defluorination. Here we describe a carbene strategy for the sequential (deutero)hydrodefluorination of perfluoroalkyl ketones under rhodium catalysis, allowing for the controllable preparation of difluoroalkyl- and monofluoroalkyl ketones from aryl- and even alkyl-substituted perfluoro-alkyl ketones in high yield with excellent functional group tolerance.

Synthetic exploration of sulfinyl radicals using sulfinyl sulfones.

Sulfinyl radicals - one of the fundamental classes of S-centered radicals - have eluded synthetic application in organic chemistry for over 60 years, despite their potential to assemble valuable sulfoxide compounds. Here we report the successful generation and use of sulfinyl radicals in a dual radical addition/radical coupling with unsaturated hydrocarbons, where readily-accessed sulfinyl sulfones serve as the sulfinyl radical precursor. The strategy provides an entry to a variety of previously inaccessible linear and cyclic disulfurized adducts in a single step, and demonstrates tolerance to an extensive range of hydrocarbons and functional groups.

Highly Stereoselective Glycosylation Reactions of Furanoside Derivatives via Rhenium (V) Catalysis.

A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3--1,4- systems.

Fluorocyclization of Allyl Alcohols and Amines to Access 3-Functionalized Oxetanes and Azetidines.

An efficient method to prepare 3-functionalized oxetanes and azetidines has been realized by fluorocyclization of readily available 2-azidoallyl/2-alkoxyallyl alcohols and amines. Notably, this is the first example applying the fluorocyclization strategy to construct four-membered heterocycles. The pendant electron-donating group (-N or -OR) plays a crucial role in polarizing the C═C double bond and facilitating the cyclization process, as verified by DFT and experimental studies.

Transition Metal Promoted Cascade Heterocycle Synthesis through C-H Functionalization.

Sequential, domino and tandem reactions could be defined as a sequence of synthetic transformations that occur one after the other, in the same reaction flask. This Review highlights recent advances at the overlap of two worlds: transition-metal mediated C-H activation as a trigger of cascade reaction, for the heterocycles synthesis. To shed some light on this intricate "middle-earth", focus was put on the reaction mechanism rather than the type of metal or the chronological order of the reaction.

Overriding ortho selectivity by template assisted meta-C-H activation of benzophenones.

An orthogonal selectivity for distal meta-C-H activation of benzophenone is acheived by overriding the inherent proximal ortho-selectivity through a template assisted metalation approach. This strategy has been successfully utilized in Pd-catalyzed regioselective C-C and C-Si bond formation.

Difluoroacetaldehyde N-Triftosylhydrazone (DFHZ-Tfs) as a Bench-Stable Crystalline Diazo Surrogate for Diazoacetaldehyde and Difluorodiazoethane.

Despite the growing importance of volatile functionalized diazoalkanes in organic synthesis, their safe generation and utilization remain a formidable challenge because of their difficult handling along with storage and security issues. In this study, we developed a bench-stable difluoroacetaldehyde N-triftosylhydrazone (DFHZ-Tfs) as an operationally safe diazo surrogate that can release in situ two low-molecular-weight diazoalkanes, diazoacetaldehyde (CHOCHN ) or difluorodiazoethane (CF HCHN ), in a controlled fashion under specific conditions. DFHZ-Tfs has been successfully employed in the Fe-catalyzed cyclopropanation and Doyle-Kirmse reactions, thus highlighting the synthetic utility of DFHZ-Tfs in the efficient construction of molecule frameworks containing CHO or CF H groups.

Recent advances in cobalt-catalysed C-H functionalizations.

Ready availability, low cost and low toxicity of cobalt salts have redirected the attention of researchers away from noble metals, such as Pd, Rh, and Ir, towards Co in the field of C-H functionalization. In this context, the examples of Co-catalysed functionalization have exponentially grown over the last few decades. This present review focuses on the most recent developments on Co-catalysed C(sp)-H and C(sp)-H functionalizations.

Cobalt-Catalyzed C(sp)-H Allylation of Biphenyl Amines with Unbiased Terminal Olefins.

Unactivated olefins usually react poorly in conventional alkenylation reactions. Their introduction via C-H activation is limited to aromatic acids. Herein, we disclose a C-H functionalization protocol of aromatic amines with unactivated olefins, which shows exclusive allylic selectivity for the distal ring of the biphenyl system by exploiting a readily available cobalt(II) catalyst.

BODIPY-Labeled Cyclobutanes by Secondary C(sp )-H Arylations for Live-Cell Imaging.

Arylated cyclobutanes were accessed by a versatile palladium-catalyzed secondary C(sp )-H activation, exploiting chelation assistance by modular triazoles. The C-H arylation led to cyclobutane natural product derivatives in a highly regioselective fashion, setting the stage for the easy access to novel fluorogenic boron-dipyrrin (BODIPY)-labeled probes for live-cell imaging.

Direct meta-C-H Perfluoroalkenylation of Arenes Enabled by a Cleavable Pyrimidine-Based Template.

The development of efficient and mild methods for the synthesis of organofluorine compounds is of foremost interest in various fields of chemistry. A direct pyrimidine-based selective meta-C-H perfluoroalkenylation of arenes involving several commercially available perfluoroolefins is described. The synthetic versatility of the protocol is demonstrated by an extensive substrate scope including different benzylsulfonyl, alkylarene and phenylacetic acid scaffolds.