Couple-close construction of non-classical boron cluster-phosphonium conjugates.

Heteropolycyclic molecular systems, which are essential components in the fields of materials and pharmacology, frequently consist of 2D extended organic aromatic rings. Here, we introduce a type of inorganic-organic hybrid 3D conjugates by merging an aromatic boron cluster with a phosphine and a π-conjugated unit. To achieve this, a couple-close synthetic strategy via B-H activation of nido-carboranes with alkynes has been developed, which leads to diverse boron cluster-extended phosphoniums in a twisted structure with high yields under mild conditions. Experimental and theoretical results reveal that the fusion between the boron cluster and the formed borophosphonium heterocycle facilitates electron delocalization throughout the structure. The unusual framework demonstrates distinct properties from bare boron clusters and pure aromatic ring-extended counterparts, such as improved thermal/chemical stability and photophysical properties. Thus, the boron cluster-based 3D conjugates expand the library of aromatic-based heterocyclics, showcasing great potential in functional materials.

Stereoselective Vinylic C-H Addition via Metallaphotoredox Migration.

Geometrically defined allylic alcohols with SE, SZ, RE and RZ stereoisomers serve as valuable intermediates in synthetic chemistry, attributed to the stereoselective transformations enabled by the alkenyl and hydroxyl functionalities. When an ideal scenario presents itself with four distinct stereoisomers as potential products, the simultaneous control vicinal stereochemistry in a single step would offer a direct pathway to any desired stereoisomer. Here, we unveil a metallaphotoredox migration strategy to access stereodefined allylic alcohols through vinylic C-H activation with aldehydes. This method harnesses a chiral nickel catalyst in concert with a photocatalyst to enable a 1,4-Ni migration by using readily accessible 2-vinyl iodoarenes as starting materials. The efficacy of this methodology is highlighted by the precise construction of all stereoisomers of allylic alcohols bearing analogous substituents and the efficient synthesis of key intermediates en route to Myristinin family. Experimental and computational studies have shed light on pivotal aspects including the synergy of metal catalysis and photocatalysis, the driving forces behind the migration, and the determination of absolute configuration in the C-H addition process.

Transforming cyclopropanes to enamides via σ-C-C bond eliminative borylation.

Recent strides in C-H borylation have significantly expanded our toolkit for the preparation of organoboronates. Nevertheless, avenues alternative to obtain these compounds via σ-C-C cleavage, thereby facilitating molecular scaffold editing, remain scarce. Several methodologies have been proposed for hydroboration of cyclopropanes by activating C-C bonds, conventionally relying on noble and hazardous metal catalysts to control reaction outcomes. Here, we present a strategy for crafting stereochemically precise γ-borylenamides through ring-opening of cyclopropanes avoiding any metallic entities. Boryl species, generated through a ternary reaction with BCl3, cyclopropanes, and a tertiary amine, selectively undergo C-C bond eliminative borylation under the directing of N-acyl group, thereby ensuring enhanced selectivity and efficiency along the reaction pathway. Such inherently stereoconvergent approach accommodates precursors of diverse geometries, including cis/trans isomeric blends.

Computational Design of Ligands for the Ir-Catalyzed C5-Borylation of Indoles through Tuning Dispersion Interactions.

The indole moiety is ubiquitous in natural products and pharmaceuticals. C-H borylation of the benzenoid moiety of indoles is a challenging task, especially at the C5 position. We have combined computational and experimental studies to introduce multiple noncovalent interactions, especially dispersion, between the substrate and catalytic ligand to realize C5-borylation of indoles with high reactivity and selectivity. The successful computational predictions of new ligands should be suitable for ligand design in other transition-metal catalyzed reactions.

Metallaphotoredox deuteroalkylation utilizing thianthrenium salts.

Deuterium labeling compounds play a crucial role in organic and pharmaceutical chemistry. The synthesis of such compounds typically involves deuterated building blocks, allowing for the incorporation of deuterium atoms and functional groups into a target molecule in a single step. Unfortunately, the limited availability of synthetic approaches to deuterated synthons has impeded progress in this field. Here, we present an approach utilizing alkyl-substituted thianthrenium salts that efficiently and selectively introduce deuterium at the α position of alkyl chains through a pH-dependent HIE process, using D2O as the deuterium source. The resulting α-deuterated alkyl thianthrenium salts, which bear two deuterium atoms, exhibit excellent selectivity and deuterium incorporation in electrophilic substitution reactions. Through in situ formation of isotopically labelled alkyl halides, these thianthrenium salts demonstrate excellent compatibility in a series of metallaphotoredox cross-electrophile coupling with (hetero)aryl, alkenyl, alkyl bromides, and other alkyl thianthrenium salts. Our technique allows for a wide range of substrates, high deuterium incorporation, and precise control over the site of deuterium insertion within a molecule such as the benzyl position, allylic position, or any alkyl chain in between, as well as neighboring heteroatoms. This makes it invaluable for synthesizing various deuterium-labeled compounds, especially those with pharmaceutical significance.

Asymmetric 2,3-Addition of Sulfinylamines with Arylboronic Acids Enabled by Nickel Catalysis.

Sulfinamides have been widely used in organic synthesis, with research on their preparation spanning more than a century. Despite advancements in catalytic methodologies, creating sulfur stereocenters within these molecules remains a significant challenge. In this study, we present an effective and versatile method for synthesizing a diverse range of S-chirogenic sulfinamides through catalytic asymmetric aryl addition to sulfinylamines. By utilizing a nickel complex as a catalyst, this process exhibits impressive enantioselectivity and can incorporate various arylboronic acids at the sulfur position. The resulting synthetic sulfinamides are stable and highly adaptable, allowing for their conversion to a variety of sulfur-containing compounds. Our study also incorporates detailed experimental and computational studies to elucidate the reaction mechanism and factors influencing enantioselectivity.

Hydrodeuteroalkylation of Unactivated Olefins Using Thianthrenium Salts.

Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered the synthesis of corresponding products. In this study, we introduce a nickel-catalyzed system that facilitates the synthesis of various deuterium-labeled alkanes through the hydrodeuteroalkylation of d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional deuterated alkyl reagents, alkyl thianthrenium (TT) salts can effectively and selectively introduce deuterium at α position of alkyl chains using D2O as the deuterium source via a single-step pH-dependent hydrogen isotope exchange (HIE). Our method allows for high deuterium incorporation, and offers precise control over the site of deuterium insertion within an alkyl chain. This technique proves to be invaluable for the synthesis of various deuterium-labeled compounds, especially those of pharmaceutical relevance.

Chromium- and Metal-Reductant-Free Asymmetric Nozaki-Hiyama-Kishi (NHK) Reaction Enabled by Metallaphotoredox Catalysis.

Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki-Hiyama-Kishi (NHK) reaction is a widely used method for the synthesis of allylic alcohols, it suffers from drawbacks such as the use of toxic chromium salts, high amounts of metal reductants, and poor enantiocontrol. To address these limitations, we present a novel approach involving a metallaphotoredox-catalyzed asymmetric NHK reaction for the production of chiral allylic alcohols. This method marries alkenyl (pseudo)halides with aldehydes, leveraging a synergistic blend of a chiral nickel catalyst and a photocatalyst. This innovative technique enables both oxidative addition and insertion just using nickel, diverging significantly from the conventional NHK reaction pathway mediated by nickel and chromium salts. The adoption of this methodology holds immense promise for crafting a spectrum of intricate compounds, particularly those of significance in pharmaceuticals. Detailed experimental investigations have shed light on the metallaphotoredox process, further enhancing our understanding and enabling further advancements.

Late-Stage Diversification of Phosphines by C-H Activation: A Robust Strategy for Ligand Design and Preparation.

ConspectusThe advent of the twenty-first century marked a golden era in the realm of synthetic chemistry, exemplified by groundbreaking advancements in the field of C-H activation, which is a concept that quickly transitioned from mere academic fascination to an essential element within the synthetic chemist's toolkit. This methodological breakthrough has given rise to a wealth of opportunities spanning a wide range of chemical disciplines. It has facilitated the late-stage diversification of elaborate organic frameworks, encompassing the spectrum from simple methane to complex polymers, thus refining the lead optimization process and easing the production of diverse molecular analogues. Among these strides forward, the development of phosphorus(III)-directed C-H activation stands out as an increasingly significant and inventive approach for the design and synthesis of ligands, substantially redefining the contours of synthetic methodology.Phosphines, renowned for their roles as ligands and organocatalysts, have become fundamentally important in modern organic chemistry. Their efficiency as ligands is significantly affected by coordination with transition metals, which is essential for their involvement in catalytic processes, influencing both the catalytic activity and the selectivity. Historically, the fabrication of phosphines predominantly relied on synthesis employing complex, multistep procedures. Addressing this limitation, our research has delved into ligand design and synthesis through innovative catalytic P(III)-directed C-H activation strategies. In this Account, we have explored a spectrum of procedures, including direct arylation using metal catalysis, and ventured further into domains such as C-H alkylation, alkenylation, aminocarbonylation, alkynylation, borylation, and silylation. These advances have enriched the field by providing efficient methods for the late-stage diversification of biaryl-type monophosphines as well as enabled the C-H activation of triphenylphosphine and its derivatives. Moreover, we have successfully constructed libraries of diverse axially chiral binaphthyl phosphine ligands, showcasing their potency in asymmetric catalysis. Through this Account, we aim to illuminate the exciting possibilities presented by P(III)-directed C-H activation in propelling the boundaries of organic synthesis. By highlighting our pioneering work, we hope to inspire further developments in this promising field of chemistry.

Enantioselective Rhodium-Catalyzed C-H Arylation Enables Direct Synthesis of Atropisomeric Phosphines.

Atropisomeric phosphines hold considerable significance in asymmetric catalysis, yet their synthesis presents a formidable challenge owing to intricate multistep procedures. In this context, a groundbreaking methodology has been presented for their preparation. This innovative approach entails an atroposelective rhodium-catalyzed C-H activation employing aryl and heteroaryl halides, chelated by a P(III) center. The essence of this strategy lies in its ability to directly construct chiral phosphine ligands in a single step, thereby exhibiting exceptional efficiency in terms of atom and redox economy. Illustrative examples serve to demonstrate the immense potential of in situ-formed ligands in asymmetric catalysis. Mechanistic experiments have further provided invaluable insights into this transformation.

P(III)-Directed Asymmetric C-H Arylation toward Planar Chiral Ferrocenes by Palladium Catalysis.

Planar chiral ferrocenyl phosphines have been employed as highly valuable ligands in metal-catalyzed asymmetric reactions. However, their preparation remains a formidable challenge due to the requirement for intricate, multistep synthetic sequences. In addressing this issue, we have developed a groundbreaking enantioselective C-H activation strategy facilitated by P(III) directing groups, enabling the efficient construction of planar chiral ferrocenyl phosphines in a single step. Our innovative approach entails the combination of a palladium catalyst, a parent ferrocenyl phosphine, and a chiral phosphoramidite ligand, leading to exceptional reactivity and enantioselectivity. Remarkably, these novel ligands exhibit remarkable efficacy in silver-catalyzed asymmetric 1,3-dipolar cycloadditions. We carried out a combination of experimental and computational studies to obtain a more comprehensive understanding of the reaction pathway and the factors contributing to enantioselectivity.

A Green Environmental Protection Photocatalytic Molecular Reactor for Aerobic Oxidation of Sulfide to Sulfoxide.

The design and synthesis of metal-organic frameworks (MOFs) as photocatalytic molecular reactors for varied reactions have drawn great attention. In this work, we designed a novel photoactive perylenediimides-based (PDI) carboxylate ligand N,N'-di(3',3",5',5"-tetrakis(4-carboxyphenyl))-1,2,6,7-tetrachloroperylene-3,4,9,10-tetracarboxylic acid diimide (Cl-PDI-TA) and use it to successfully synthesize a novel Zr(IV)-based MOF 1 constructed from [Zr6 O8 (H2 O)8 ]8+ clusters bridged by Cl-PDI-TA ligands. Structural analysis revealed that Zr-MOF 1 manifests a 3D framework with (4,8)-connected csq topology and possesses triangular channels of ~17 Šand mesoporous hexagonal channels of ~26 Šalong c-axis. Moreover, the synthesized Zr-MOF 1 exhibits visible-light absorption and efficient photoinduced free radical generation property, making it a promising photocatalytic molecular reactor. When Zr-MOF 1 was used as a photocatalyst for the aerobic oxidation of sulfides under irradiation of visible light, it could afford the corresponding sulfoxides with high yield and selectivity. Experimental results demonstrated that the substrate sulfides could be fixed in the pores of 1 and directly transformed to the products sulfoxides in the solid state. Furthermore, the mechanism for the photocatalytic transformation was also investigated and the results revealed that the singlet oxygen (1 O2 ) and superoxide radical (O2 ⋅- ) generated by the energy transfer and electron transfer from the photoexcited Zr-MOF to oxidants were the main active species for the catalytic reactions. This work offers a perceptive comprehension of the mechanism in PDI-based MOFs for further study on photocatalytic reactions.

Nickel-Catalyzed Asymmetric Propargyl-Aryl Cross-Electrophile Coupling.

Performing asymmetric cross-coupling reactions between propargylic electrophiles and aryl nucleophiles is a well-established method to build enantioenriched benzylic alkynes. Here, a catalytic enantioselective propargyl-aryl cross-coupling between two electrophiles was achieved for the first time in a stereoconvergent manner. Propargylic chlorides were treated with aryl iodides as well as heteroaryl iodides in the presence of a chiral nickel complex, and manganese metal was used as a stoichiometric reductant, allowing for the construction of a propargyl C-aryl bond under mild conditions. An alternative dual nickel/photoredox catalytic protocol was also developed for this cross-electrophile coupling in the absence of a metal reductant. The potential utility of this conversion is demonstrated in the facile construction of stereoenriched bioactive molecule derivatives and medicinal compounds based on the diversity of acetylenic chemistry. Detailed experimental studies have revealed the key mechanistic features of this transformation.

Atroposelective hydroarylation of biaryl phosphines directed by phosphorus centres.

Prized for their ability to generate chemical complexity rapidly, catalytic carbon-hydrogen (C-H) activation and functionalization reactions have enabled a paradigm shift in the standard logic of synthetic chemistry. Directing group strategies have been used extensively in C-H activation reactions to control regio- and enantioselectivity with transition metal catalysts. However, current methods rely heavily on coordination with nitrogen and/or oxygen atoms in molecules and have therefore been found to exhibit limited generality in asymmetric syntheses. Here, we report enantioselective C-H activation with unsaturated hydrocarbons directed by phosphorus centres to rapidly construct libraries of axially chiral phosphines through dynamic kinetic resolution. High reactivity and enantioselectivity are derived from modular assembly of an iridium catalyst with an endogenous phosphorus atom and an exogenous chiral phosphorus ligand, as confirmed by detailed experimental and computational studies. This reaction mode significantly expands the pool of enantiomerically enriched functional phosphines, some of which have shown excellent efficiency for asymmetric catalysis.

Merging Visible Light Photocatalysis and P(III)-Directed C-H Activation by a Single Catalyst: Modular Assembly of P-Alkyne Hybrid Ligands.

Metal-catalyzed C-H activation strategies provide an efficient approach for synthesis by minimizing atom, step, and redox economy. Developing milder, greener, and more effective protocols for these strategies is always highly desirable to the scientific community. In this study, the utilization of a single rhodium complex enabled the visible-light-induced late-stage C-H activation of biaryl-type phosphines with alkynyl bromides, employing inherent phosphorus atoms as directing groups. This chemistry combines P(III)-directed C-H activation with visible light photocatalysis, under exogenous photosensitizer-free conditions, offering a unique platform for ligand design and preparation. Furthermore, this study also explores the asymmetric catalysis and coordination chemistry of the resulting P-alkyne hybrid ligands with specific transition metals. Experimental results and density functional theory calculations demonstrate the mechanistic intricacies of this transformation.

Metal-Free Stereoconvergent C-H Borylation of Enamides.

Enamides, functional derivatives of enamines, play a significant role as synthetic targets. However, the stereoselective synthesis of these molecules has posed a longstanding challenge in organic chemistry, particularly for acyclic enamides that are less thermodynamically stable. In this study, we present a general strategy for constructing ß-borylenamides by C-H borylation, which provides a versatile platform for generating the stereodefined enamides. Our approach involves the utilization of metalloid borenium cation, generated through the reaction of BBr3 and enamides in the presence of two different additives, avoiding any exogenous catalyst. Importantly, the stereoconvergent nature of this methodology allows for the use of starting materials with mixed E/Z configurations, thus highlighting the unique advantage of this chemistry. Mechanistic investigations have shed light on the pivotal roles played by the two additives, the reactive boron species, and the phenomenon of stereoconvergence.

Tunably strained metallacycles enable modular differentiation of aza-arene C-H bonds.

The precise activation of C-H bonds will eventually provide chemists with transformative methods to access complex molecular architectures. Current approaches to selective C-H activation relying on directing groups are effective for the generation of five-membered, six-membered and even larger ring metallacycles but show narrow applicability to generate three- and four-membered rings bearing high ring strain. Furthermore, the identification of distinct small intermediates remains unsolved. Here, we developed a strategy to control the size of strained metallacycles in the rhodium-catalysed C-H activation of aza-arenes and applied this discovery to tunably incorporate the alkynes into their azine and benzene skeletons. By merging the rhodium catalyst with a bipyridine-type ligand, a three-membered metallacycle was obtained in the catalytic cycle, while utilizing an NHC ligand favours the generation of the four-membered metallacycle. The generality of this method was demonstrated with a range of aza-arenes, such as quinoline, benzo[f]quinolone, phenanthridine, 4,7-phenanthroline, 1,7-phenanthroline and acridine. Mechanistic studies revealed the origin of the ligand-controlled regiodivergence in the strained metallacycles.

Facile preparation of organosilanes from benzylboronates and gem-diborylalkanes mediated by KOtBu.

Methods to efficiently synthesize organosilanes are valuable in the fields of synthetic chemistry and materials science. During the past decades, boron conversion has become a generic and powerful approach for constructing carbon-carbon and other carbon-heteroatom bonds, but its potential application in forming carbon-silicon remains unexplored. Herein, we describe an alkoxide base-promoted deborylative silylation of benzylic organoboronates, geminal bis(boronates) or alkyltriboronates, allowing for straightforward access to synthetically valuable organosilanes. This selective deborylative methodology exhibits operational simplicity, broad substrate scope, excellent functional group compatibility and convenient scalability, providing an effective and complementary platform for the generation of diversified benzyl silanes and silylboronates. Detailed experimental results and calculated studies revealed an unusual mechanistic feature of this C-Si bond formation.

Enantioselective Reductive (Hetero)Arylation of Cyclic N-Sulfonyl Imines by Cobalt Catalysis.

Transition-metal-catalyzed enantioselective addition of aryl organometallic reagents to imines has emerged as one of the most powerful tools for the formation of optically active diarylmethylamines. Here, we report the first asymmetric reductive (hetero)arylations of imines using aryl and heteroaryl halides enabled by a chiral cobalt-bisphosphine catalyst. This approach shows good functional group compatibility and complements the reported strategy without use of organometallic reagents. Mechanistic investigations supported that aryl-cobalt, instead of an arylzinc reagent, was formed in situ in this reductive aryl-addition event.

Stereospecific nickel-catalyzed [4+2] heteroannulation of alkynes with aminophosphanes.

Enantioenriched phosphorus compounds play crucial roles in many fields ranging from catalyst to materials science to drug development. Despite advances in the construction of phosphacycles, incorporation of a P-chirogenic center into heterocycles remains challenging. Here, we report an effective method for the preparation of phosphacycles through nickel-catalyzed [4+2] heteroannulation of internal alkynes with aminophosphanes derived from o-haloanilines. Notably, chiral 2-λ5-phosphaquinolines can be prepared from P-stereogenic substrates via NH/PH tautomeric equilibrium without loss of stereochemical integrity. The strategy is found to exhibit a broad scope in terms of both reaction components, enabling modular construction of libraries of 2-λ5-phosphaquinolines with different steric and electronic properties for fine-tuning photophysical properties, where some of these compounds showed distinct fluorescence with high quantum yields. A series of mechanistic studies further shed light on the pathway of the heteroannulation and reasons for stereospecificity.