Cross-Coupling Between Aryl Halides and Aryl Alkynes Catalyzed by an Odd Alternant Hydrocarbon.

Catalytic cross-coupling between aryl halides and alkynes is considered an extremely important organic transformation (popularly known as the Sonogashira coupling) and it requires a transition metal-based catalyst. Accomplishing such transformation without any transition metal-based catalyst in the absence of any external stimuli such as heat, photoexcitation or cathodic current is highly challenging. This work reports transition-metal-free cross-coupling between aryl halides and alkynes synthesizing a rich library of internal alkynes without any external stimuli. A chemically double-reduced phenalenyl (PLY)-based molecule with the super-reducing property was employed for single electron transfer to activate aryl halides generating reactive aryl radicals, which subsequently react with alkyne. This protocol covers not only various types of aryl, heteroaryl and polyaryl halides but also applies to a large variety of aromatic alkynes at room temperature. With a versatile substrate scope successfully tested on more than 75 entries, this radical-mediated pathway has been explained by several control experiments. All the key reactive intermediates have been characterized with spectroscopic evidence. Detailed DFT calculations have been instrumental in portraying the mechanistic pathway. Furthermore, we have successfully extended this transition-metal-free catalytic strategy for the first time towards solvent-free cross-coupling between solid aryl halide and alkyne substrates.

Redox-Neutral Decarboxylative Cross-Coupling of Oxamates with Aryl Bromides.

Dual nickel-photoredox-enabled direct synthesis of amides through cross-coupling of cesium oxamates with aryl bromides has been developed. This methodology's key advantages are mild reaction conditions, utilizing organic dye as a photocatalyst, employing readily available starting chemicals as coupling partners, and late-stage carbamoylation of pharmaceutically relevant molecules. DFT studies suggested that the nickel catalytic cycle proceeds via a radical addition pathway prior to the oxidative insertion.

Exploiting N-Centered Umpolung Reactivity of α-Iminomalonates for the Synthesis of N-Sulfenylimines and Sulfonamides.

An efficient and interesting N-centered umpolung method has been disclosed to construct beneficial S-N bonds, furnishing N-sulfenylimines, which can readily be converted into the corresponding sulfonamide derivatives in a one-pot sequential operation. N-Sulfenylimines are potent intermediates in organic synthesis, whereas sulfonamides are of major molecular interest due to their rich biological activities and wide applicability in medicinal chemistry. Owing to the simple reaction conditions and setup, this protocol displays a broad and versatile substrate scope, resulting in excellent functional group tolerability toward the synthesis of both N-sulfenylimines and sulfonamides. A density functional theory (DFT) computed and experimentally supported convenient mechanism has been proposed for this unique method.

Regioselective 1,2-Alkylboration of Benzylidenecyclopropanes: Access to Csp3-Enriched Cyclopropyl Boronic Esters.

We describe a novel, regioselective alkylboration of versatile (hetero)benzylidenecyclopropanes with ß-H-containing alkyl iodides and bis(pinacolato)diboron enabled by copper catalysis. This three-component method allows for consecutive B-Csp3 and Csp3-Csp3 bond formation to access Csp3-enriched diverse tertiary cyclopropyl boronic esters with broad functionality tolerance, and the so-formed C-B bond is amenable to further structural diversification. Radical clock experiment, Hammett analysis, and DFT calculation suggest a mechanism of polar, rather than radical manifold, and SN2-type C-C bond formation was found to be the rate-limiting step instead of migratory alkene insertion.

Redox-Neutral Radical Cascade Cyclization of N-Arylacrylamides with Unactivated Alkyl and Aryl Chlorides.

Herein, we report the first metal-free, redox-neutral strategy for radical cascade alkylative radical addition, cyclization of N-arylacrylamides with unactivated alkyl chlorides to give corresponding 3,3-disubstituted oxindoles in moderate to good yields. This transformation's salient features are the utilization of an organo photocatalyst, mild reaction conditions, and broad substrate scope. Moreover, this methodology is suitable for hetero cycle derived acrylamides and further allowed to utilize aryl chlorides for radical cyclization reaction. Finally, DFT studies allow us to shed light on the reaction mechanism.

Amine-rich Nickel(II)-Xerogel as a Highly Active Bifunctional Metallo-organo Catalyst for Aqueous Knoevenagel Condensation and Solvent-free CO2 Cycloaddition.

Metallogels formed from supramolecular interactions of low-molecular-weight gelators (LMWGs) combine the qualities of heterogeneous catalysts and offer the advantages of multifunctionality owing to the facile installation of desired task-specific moieties on the surface and along the channels of the gels. We discuss the applications of a triazole-based Ni(II) gel-derived xerogel (NiXero) having a high density of Ni(II)-nodes and appended primary amines as a recyclable heterogeneous catalyst for Knoevenagel condensation of aldehyde and malononitrile in water and the solvent-free cycloaddition of CO2 to form a series of cyclic carbonates with near-quantitative conversion of the respective epoxides, with low catalyst loading (0.59 mol %), high catalyst stability, and recyclability. The structural advantages of NiXero, due to the concurrent presence of bifunctional Lewis acid-base sites on the channels, open Ni(II) nodes, Ntriazole, pendant -NH2 and its chemical stability, are conducive to the cooperative heterogeneous catalytic activity under mild conditions. This work emphasizes the effective amalgamation of metals with purpose-built ligand systems for the construction of metallogels and their utility as heterogeneous catalysts for desired organic transformations.

Dynamic Kinetic Stereoselective Glycosylation via RhII and Chiral Phosphoric Acid-Cocatalyzed Carbenoid Insertion to the Anomeric OH Bond for the Synthesis of Glycoconjugates.

Chemical synthesis of glycoconjugates is essential for studying the biological functions of carbohydrates. We herein report an efficient approach for the stereoselective synthesis of challenging α-linked glycoconjugates via a RhII /chiral phosphoric acid (CPA)-cocatalyzed dynamic kinetic anomeric O-alkylation of sugar-derived lactols via carbenoid insertion to the anomeric OH bond. Notably, we observed excellent anomeric selectivity, excellent diastereoselectivity, broad substrate scope, and high efficiency for this glycosylation reaction by exploring various parameters of the cocatalytic system. DFT calculations suggested that the anomeric selectivity was mainly determined by steric interactions between the C2-carbon of the carbohydrate and the phenyl group of the metal carbenoid, while π/π interactions with the C2-OBn substituent on the carbohydrate substrate play a significant role for diastereoselectivity at the newly generated stereogenic center.

Photocatalytic Hydro Tri/Difluoromethylation of Alkenes with Bench Stable Tri/Difluoromethylating Reagents.

Herein, we demonstrate the synthesis and characterization of bench stable tri/difluoromethylating reagents and their potential applications in redox neutral hydro tri/difluoromethylation of alkenes enabled by visible light. The new tri/difluoromethylating reagents are obtained on a gram-scale through simply cyclocondensation of commercially available anthranilamide with phenyltrifluoro or difluoromethyl ketone. Preliminary mechanistic studies indicated that a canonical photoredox catalytic cycle is being operative. DFT studies support this and further reveal that deprotonation occurs before radical cleavage. DFT studies also show that the better yield with HCF2 reagent is attributed to the favorable expulsion of the corresponding radical moiety.

Ruthenium-Catalyzed Selective α-Alkylation of ß-Naphthols using Primary Alcohols: Elucidating the Influence of Base and Water.

Functionalized arenes and arenols have diverse applications in chemical synthesis and material chemistry. Selective functionalization of arenols is a topic of prime interest. In particular, direct alkylation of arenols using alcohols is a challenging task. In this report, a ruthenium pincer catalyzed direct α-alkylation of ß-naphthol using primary alcohols as alkylating reagents is reported. Notably, aryl and heteroaryl methanols and linear and branched aliphatic alcohols underwent selective alkylation reactions, in which water is the only byproduct. Notably, catalytically derived α-alkyl-ß-naphthol products displayed high absorbance, emissive properties, and quantum yields (up to 93.2 %). Dearomative bromination on α-alkyl-ß-naphthol is demonstrated as a synthetic application. Mechanistic studies indicate that the reaction involves an aldehyde intermediate. DFT studies support this finding and further reveal that a stoichiometric amount of base is required to make the aldol condensation as well as elementary steps required for regeneration of catalytically active species. In situ-generated water molecule from the aldol condensation reaction plays an important role in the regeneration of an active catalyst.

Reduced-Phenalenyl-Based Molecule as a Super Electron Donor for Radical-Mediated C-N Coupling Catalysis at Room Temperature.

We demonstrate that an in situ generated di-reduced phenalenyl (PLY) species accumulates sufficiently high energy and acts as a super electron donor to generate aryl radicals from aryl halides to accomplish Buchwald-Hartwig-type C-N cross-coupling reactions at room temperature. This catalytic protocol does not require any external stimuli such as heat, light, or cathodic current. This protocol shows a wide variety of substrate scope covering different genres of aryl and heteroaryl halides with various aromatic as well as aliphatic amines and late-stage functionalization of the well-known natural products. The control experiments, along with extensive density functional theory (DFT) calculations, unveil that the aryl radical is generated by a single electron transfer from the di-reduced PLY to the aryl halide substrate. The aryl radical acts as an electrophile and binds with amine, leading to the chemically driven radical-mediated C-N cross-coupling under transition-metal-free conditions.

Nickel-Catalyzed Dearomative Arylboration of Indoles: Regioselective Synthesis of C2- and C3-Borylated Indolines.

Indole dearomatization is an important strategy to access indolines: a motif present in a variety of natural products and biologically active molecules. Herein, a method for transition-metal catalyzed regioselective dearomative arylboration of indoles to generate diverse indolines is presented. The method accomplishes intermolecular dearomatization of simple indoles through a migratory insertion pathway on substrates that lack activating or directing groups on the C2- or C3-positions. Synthetically useful C2- and C3-borylated indolines can be accessed through a simple change in N-protecting group in high regio- and diastereoselectivities (up to >40:1 rr and >40:1 dr) from readily available starting materials. Additionally, the origin of regioselectivity was explored experimentally and computationally to uncover the remarkable interplay between carbonyl orientation of the N-protecting group on indole, electronics of the C2-C3 π-bond, and sterics. The method enabled the first enantioselective synthesis of (-)-azamedicarpin.

Rhodaelectro-catalyzed chemo-divergent C-H activations with alkylidenecyclopropanes for selective cyclopropylations.

Herein, we report on selectivity control in C-H activations with alkylidenecyclopropanes (ACPs) for the chemo-selective assembly of cyclopropanes or dienes. Thus, unprecedented rhodaelectro-catalyzed C-H activations were realized with diversely decorated ACPs with a wide substrate scope and electricity as the sole oxidant.

Electrochemical B-H Nitrogenation: Access to Amino Acid and BODIPY-Labeled nido-Carboranes.

Electrocatalyzed oxidative B-H nitrogenations of nido-carborane (nido-7,8-C2 B9 H12- ) with N-heterocycles have been established, enabling the preparation of various N-substituted nido-carboranes without chemical oxidants or metal catalyst under ambient conditions. The electrolysis manifold occurred with high levels of efficiency as well as chemo- and position- selectivity, employing sustainable electricity as the sole oxidant. The strategy set the stage for a user-friendly access to novel amino acid and fluorogenic boron-dipyrrin (BODIPY)-labeled nido-carborane hybrids.

Recyclable Ruthenium Catalyst for Distal meta-C-H Activation.

We disclose the unprecedented hybrid-ruthenium catalysis for distal meta-C-H activation. The hybrid-ruthenium catalyst was recyclable, as was proven by various heterogeneity tests, and fully characterized with various microscopic and spectroscopic techniques, highlighting the physical and chemical stability. Thereby, the hybrid-ruthenium catalysis proved broadly applicable for meta-C-H alkylations of among others purine-based nucleosides and natural product conjugates. Additionally, its versatility was further reflected by meta-C-H activations through visible-light irradiation, as well as para-selective C-H activations.

Photo-Induced Ruthenium-Catalyzed C-H Arylations at Ambient Temperature.

Ambient temperature ruthenium-catalyzed C-H arylations were accomplished by visible light without additional photocatalysts. The robustness of the ruthenium-catalyzed C-H functionalization protocol was reflected by a broad range of sensitive functional groups and synthetically useful pyrazoles, triazoles and sensitive nucleosides and nucleotides, as well as multifold C-H functionalizations. Biscyclometalated ruthenium complexes were identified as the key intermediates in the photoredox ruthenium catalysis by detailed computational and experimental mechanistic analysis. Calculations suggested that the in situ formed photoactive ruthenium species preferably underwent an inner-sphere electron transfer.

Insights into Ruthenium(II/IV)-Catalyzed Distal C-H Oxygenation by Weak Coordination.

C-H hydroxylation of aryl acetamides and alkyl phenylacetyl esters was accomplished via challenging distal weak O-coordination by versatile ruthenium(II/IV) catalysis. The ruthenium(II)-catalyzed C-H oxygenation of aryl acetamides proceeded through C-H activation, ruthenium(II/IV) oxidation and reductive elimination, thus providing step-economical access to valuable phenols. The p-cymene-ruthenium(II/IV) manifold was established by detailed experimental and DFT-computational studies.

Azaruthena(II)-bicyclo[3.2.0]heptadiene: Key Intermediate for Ruthenaelectro(II/III/I)-catalyzed Alkyne Annulations.

A ruthenium-catalyzed electrochemical dehydrogenative annulation reaction of imidazoles with alkynes has been established, enabling the preparation of various bridgehead N-fused [5,6]-bicyclic heteroarenes through regioselective electrochemical C-H/N-H annulation without chemical metal oxidants. Novel azaruthenabicyclo[3.2.0]heptadienes were fully characterized and identified as key intermediates. Mechanistic studies are suggestive of an oxidatively induced reductive elimination pathway within a ruthenium(II/III) regime.

Regioselective B(3,4)-H arylation of o-carboranes by weak amide coordination at room temperature.

Palladium-catalyzed regioselective di- or mono-arylation of o-carboranes was achieved using weakly coordinating amides at room temperature. Therefore, a series of B(3,4)-diarylated and B(3)-monoarylated o-carboranes anchored with valuable functional groups were accessed for the first time. This strategy provided an efficient approach for the selective activation of B(3,4)-H bonds for regioselective functionalizations of o-carboranes.