Amphiphilic Polymeric Nanoparticles for Photoredox Catalysis in Water

Photoredox catalysis has recently emerged as a powerful synthesis tool in organic and polymer chemistry. In contrast to the great achievements realized in organic solvents, performing photocatalytic processes efficiently in aqueous media encounters several challenges. Here, it is presented how amphiphilic single-chain polymeric nanoparticles (SCPNs) can be utilized as small reactors to conduct light-driven chemical reactions in water. By incorporating a phenothiazine (PTH) catalyst into the polymeric scaffold, metal-free reduction and C−C cross-coupling reactions can be carried out upon exposure to UV light under ambient conditions. The versatility of this approach is underlined by a large substrate scope, tolerance towards oxygen, and excellent recyclability. This approach thereby contributes to a sustainable and green way of implementing photoredox catalysis.     

Chromium-Catalyzed Alkylation of Amines by Alcohols

The alkylation of amines by alcohols is a broadly applicable, sustainable, and selective method for the synthesis of alkyl amines, which are important bulk and fine chemicals, pharmaceuticals, and agrochemicals. We show that Cr complexes can catalyze this C−N bond formation reaction. We synthesized and isolated 35 examples of alkylated amines, including 13 previously undisclosed products, and the use of amino alcohols as alkylating agents was demonstrated. The catalyst tolerates numerous functional groups, including hydrogenation-sensitive examples. Compared to many other alcohol-based amine alkylation methods, where a stoichiometric amount of base is required, our Cr-based catalyst system gives yields higher than 90 % for various alkyl amines with a catalytic amount of base. Our study indicates that Cr complexes can catalyze borrowing hydrogen or hydrogen autotransfer reactions and could thus be an alternative to Fe, Co, and Mn, or noble metals in (de)hydrogenation catalysis.     

Pd-Catalyzed [3+2]-Dehydrogenative Annulation Reactions

The significance of cross dehydrogenative couplings has increased considerably in recent years. This article revisits the [3+2] C−C/N−C, C−C/O−C and C−C/C−C annulation strategy, recently reported by our group, according to a Pd(II) catalyzed dehydrogenative variant. Our original report relied on Pd(0) catalysis, using α,β-unsaturated-γ-oxy carbonyls as bis-electrophiles and resonance-stabilized acetamides or 3-oxoglutarates as C/N and O/C or C/C bis-nucleophiles, respectively. In this more modern and straightforward Pd(II)-catalyzed dehydrogenative approach, β,γ-unsaturated carbonyl derivatives replace α,β-unsaturated-γ-oxy carbonyls as bis-electrophiles. Our study includes experimental optimization and showcases the synthetic versatility in the formation of diverse heterocyclic structures, such as bicyclic lactams, furo-cycloalkanones and bicycloalkane-diones. Furthermore, a mechanism is proposed to elucidate the underlying processes involved in these reactions.     

C−N Coupling through Hydroaminoalkylation on a Single-Atom Rh Heterogeneous Catalyst

C−N coupling is significant for the synthesis of fine chemicals toward various applications. Hydroaminoalkylation of olefins is a tandem reaction of C−N coupling involving first the formation of an aldehyde through hydroformylation of an olefin and then the production of amine through reductive amination of the aldehyde. Here we report a stable, supported catalyst of singly dispersed Rh₁ atoms anchored on TiO₂ (P25) nanoparticles designated as Rh₁/P25. Its high activity for C−N coupling was demonstrated by six hydroaminoalkylations of olefins and amines with selectivity of higher than 90% for producing tertiary amines. The singly dispersed Rh₁O₄ on P25 exhibit activity and selectivity for hydroaminoalkylation comparable or even higher than some reported molecular catalysts. In contrast to molecular catalysts, the Rh-based single-atom Rh heterogeneous catalysis (Rh₁/P25) can be readily separated from reactants and products, reused for multiple runs of hydroaminoalkylation, and recycled with a low cost.     

The Asymmetric Buchwald–Hartwig Amination Reaction

Over the past few decades, the Buchwald–Hartwig reaction has emerged as a powerful tool for forging C−N bonds, and has been vital to the pharmaceuticals, materials, and catalysis fields. However, asymmetric Buchwald–Hartwig amination reactions for constructing centered chirality, planar chirality, and axial chirality remain in their infancy owing to limited substrate scope and laggard ligand design. The recent surge in interest in the synthesis of C−N/N−N atropisomers, has witnessed a renaissance in asymmetric Buchwald–Hartwig amination chemistry as the first practical protocol for the preparation of C−N atropisomers. This review highlights reported asymmetric Buchwald–Hartwig amination protocols and provides a brief overview of their chemical practicality.     

One‐Pot Tandem Photoredox and Cross‐Coupling Catalysis with a Single Palladium Carbodicarbene Complex

The combination of conventional transition‐metal‐catalyzed coupling (2 e^? process) and photoredox catalysis (1 e^? process) has emerged as a powerful approach to catalyze difficult cross‐coupling reactions under mild reaction conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates both a Suzuki–Miyaura coupling and photoredox catalysis for C?N bond formation upon visible‐light irradiation. These two catalytic pathways can be combined to promote both conventional transition‐metal‐catalyzed coupling and photoredox catalysis to mediate C?H arylation under ambient conditions with a single catalyst in an efficient one‐pot process.     

Copper-Catalyzed Borylative Couplings with C−N Electrophiles

Copper-catalyzed borylative multicomponent reactions (MCRs) involving olefins and C−N electrophiles are a powerful tool to rapidly build up molecular complexity. The products from these reactions contain multiple functionalities, such as amino, cyano and boronate groups, that are ubiquitous in medicinal and process chemistry programs. Copper-catalyzed MCRs are particularly attractive because they use a relatively abundant and non-toxic catalyst to selectively deliver high-value products from simple feedstocks such as olefins. In this Minireview, we explore this rapidly emerging field and survey the borylative union of allenes, dienes, styrenes and other olefins, with imines, nitriles and related C−N electrophiles.     

Metal-Free Twofold Electrochemical C−H Amination of Activated Arenes: Application to Medicinally Relevant Precursor Synthesis

The efficient production of many medicinally or synthetically important starting materials suffers from wasteful or toxic precursors for the synthesis. In particular, the aromatic non-protected primary amine function represents a versatile synthetic precursor, but its synthesis typically requires toxic oxidizing agents and transition metal catalysts. The twofold electrochemical amination of activated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new C−N bonds of high synthetic value. As a proof of concept, we use our approach to generate a benzoxazinone scaffold that gained attention as a starting structure against castrate-resistant prostate cancer. Further improvement of the structure led to significantly increased cancer cell line toxicity. Thus, exploiting environmentally benign electrooxidation, we present a new versatile and powerful method based on direct C−H activation that is applicable for example the production of medicinally relevant compounds.     

Recent Advances in Iodine-Promoted C−S/N−S Bonds Formation

Sulfur-containing scaffold, as a ubiquitous structural motif, has been frequently used in natural products, bioactive chemicals and pharmaceuticals, particularly C−S/N−S bonds are indispensable in many biological important compounds and pharmaceuticals. Development of mild and general methods for C−S/N−S bonds formation has great significance in modern research. Iodine and its derivatives have been recognized as inexpensive, environmentally benign and easy-handled catalysts or reagents to promote the construction of C−S/N−S bonds under mild reaction conditions, with good regioselectivities and broad substrate scope. Especially based on this, several new strategies, such as oxidation relay strategy, have been greatly developed and accelerated the advancement of this field. This review focuses on recent advances in iodine and its derivatives promoted hybridized C−S/N−S bonds formation. The features and mechanisms of corresponding reactions are summarized and the results of some cases are compared with those of previous reports. In addition, the future of this domain is discussed.     

Chemoselective Intramolecular Formal Insertion Reaction of Rh–Nitrenes into an Amide Bond Over C−H Insertion

The past few decades have witnessed extensive efforts to disclose the unique reactivity of metal–nitrenes, because they could be a powerful synthetic tool for introducing the amine functionality into unactivated chemical bonds. The reactivity of metal–nitrenes, however, is currently mainly confined to aziridination (an insertion into a C=C bond) and C−H amination (an insertion into a C−H bond). Nitrene insertion into an amide C−N bond, however, has not been reported so far. In this work we have developed a rhodium-catalyzed one-nitrogen insertion into amide C−N and sulfonamide S−N bonds. Experimental and theoretical analyses based on density functional theory indicate that the formal amide insertion proceeds via a rhodium-coordinated ammonium ylide formed between the nitrene and the amide nitrogen, followed by acyl group transfer concomitant with C−N bond cleavage. Mechanistic studies have allowed rationalization of the origin of the chemoselectivity observed between the C−H and amide insertion reactions. The methodology presented herein is the first example of an insertion of nitrene into amide bonds and provides facile access to unique diazacyclic systems with an N−N bond linkage.     

B−B Cleavage and Ring-Expansion of a 1,4,2,3-Diazadiborinine with N-Heterocyclic Carbenes

A 1,4,2,3-diazadiborinine derivative was found to form Lewis adducts with strong two-electron donors such as N-heterocyclic and cyclic (alkyl)(amino)carbenes. Depending on the donor, some of these Lewis pairs are thermally unstable, converting to sole B,N-embedded products upon gentle heating. The products of these reactions, which have been fully characterized by NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction, were identified as B,N-heterocycles with fused 1,5,2,4-diazadiborepine and 1,4,2-diazaborinine rings. Computational modelling of the reaction mechanism provides insight into the formation of these unique structures, suggesting that a series of B−H, C−N, and B−B bond activation steps are responsible for these “intercalation” reactions between the 1,4,2,3-diazadiborinine and NHCs.     

Asymmetric Synthesis of Axially Chiral C−N Atropisomers

Molecules with restricted rotation around a single bond or atropisomers are found in a wide number of natural products and bioactive molecules as well as in chiral ligands for asymmetric catalysis and smart materials. Although most of these compounds are biaryls and heterobiaryls displaying a C−C stereogenic axis, there is a growing interest in less common and more challenging axially chiral C−N atropisomers. This review offers an overview of the various methodologies available for their asymmetric synthesis. A brief introduction is initially given to contextualize these axially chiral skeletons, including a historical background and examples of natural products containing axially chiral C−N axes. The preparation of different families of C−N based atropisomers is then presented from anilides to chiral five- and six-membered ring heterocycles. Special emphasis has been given to modern catalytic asymmetric strategies over the past decade for the synthesis of these chiral scaffolds. Applications of these methods to the preparation of natural products and biologically active molecules will be highlighted along the text.     

Synthesis of β-Diamine Building Blocks by Photocatalytic Hydroamination of Enecarbamates with Amines,Ammonia and N−H Heterocycles

3-Amino-substituted saturated nitrogen heterocycles are an important subclass of β-diamines, appearing in a number of clinical agents. Herein, we report a unified approach to these products based upon the regioselective photoredox-mediated hydroamination of enecarbamates. The amine coupling partner can encompass diverse amine types under a single set of reaction conditions, including primary alkyl amines, ammonia, aryl and heteroaryl amines, and N−H heterocycles. The method enables the synthesis of a wide range of pharmaceutically relevant building blocks.     

Iron-Catalyzed Oxidative C−O and C−N Coupling Reactions Using Air as Sole Oxidant**

We describe the oxygenation of tertiary arylamines, and the amination of tertiary arylamines and phenols. The key step of these coupling reactions is an iron-catalyzed oxidative C−O or C−N bond formation which generally provides the corresponding products in high yields and with excellent regioselectivity. The transformations are accomplished using hexadecafluorophthalocyanine−iron(II) (FePcF₁₆) as catalyst in the presence of an acid or a base additive and require only ambient air as sole oxidant.     

Electrochemical C−H Amidation of Heteroarenes with N-Alkyl Sulfonamides in Aqueous Medium

The construction of C−N bonds by free radical reactions represents a powerful synthetic approach for direct C−H amidations of arenes or heteroarenes. Developing efficient and more environmentally friendly synthetic methods for C−H amidation reactions remains highly desirable. Herein, metal-free electrochemical oxidative dehydrogenative C−H amidations of heteroarenes with N-alkylsulfonamides have been accomplished. The catalyst- and chemical-oxidant-free C−H amidation features an ample scope and employs electricity as the green and sole oxidant. A variety of heteroarenes, including indoles, pyrroles, benzofuran and benzothiophene, thereby underwent this C(sp²)−H nitrogenation. Cyclic voltammetry studies and control experiments provided evidence for nitrogen-centered radicals being directly generated under metal-free electrocatalysis.     

Recent Progress in Asymmetric Ion-Pairing Catalysis with Ammonium Salts

Quaternary ammonium salts play an important role in asymmetric catalysis. In this Minireview, how asymmetric ion-pairing catalysis with ammonium ions has been utilized in organic synthesis is explained, particularly in the design of novel catalytic cycles. This includes the use of chiral ammonium-based catalysts for the construction of challenging stereogenic centers. Ammonium-derived electrophilic reagents, typically formed in situ and in the context of phase-transfer catalysis (PTC), have also been utilized in asymmetric bond-forming reactions. Furthermore, ammonium salts have been employed as substrates in several stereocontrolled C−N bond cleavage processes, leading to enantioenriched products by using novel asymmetric induction modes. In addition, merging ammonium ion-pairing catalysis with other catalytic approaches has also emerged as a new platform for achieving previously less straightforward reactions, thereby allowing new synthetic applications.     

Carbene-Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3)−H Bonds

The development of catalyst-controlled methods for direct functionalization of two distinct C−H bonds represents an appealing approach for C−C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp³)−H bonds employing readily available aldehyde as “acyl source” involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp³)−H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential in the oxidative radical N-heterocyclic carbene catalysis to give a ketyl radical and C(sp³) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C−C formations in high efficiency under a metal- and light-free catalytic conditions. Moreover, the prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.     

General Synthesis of Secondary Alkylamines by Reductive Alkylation of Nitriles by Aldehydes and Ketones

The development of C−N bond formation reactions is highly desirable due to their importance in biology and chemistry. Recent progress in 3d metal catalysis is indicative of unique selectivity patterns that may permit solving challenges of chemical synthesis. We report here on a catalytic C−N bond formation reaction—the reductive alkylation of nitriles. Aldehydes or ketones and nitriles, all abundantly available and low-cost starting materials, undergo a reductive coupling to form secondary alkylamines and inexpensive hydrogen is used as the reducing agent. The reaction has a very broad scope and many functional groups, including hydrogenation-sensitive examples, are tolerated. We developed a novel cobalt catalyst, which is nanostructured, reusable, and easy to handle. The key seems the earth-abundant metal in combination with a porous support material, N-doped SiC, synthesized from acrylonitrile and a commercially available polycarbosilane.     

Chromium‐Catalyzed Alkylation of Amines by Alcohols

The alkylation of amines by alcohols is a broadly applicable, sustainable, and selective method for the synthesis of alkyl amines, which are important bulk and fine chemicals, pharmaceuticals, and agrochemicals. We show that Cr complexes can catalyze this C?N bond formation reaction. We synthesized and isolated 35 examples of alkylated amines, including 13 previously undisclosed products, and the use of amino alcohols as alkylating agents was demonstrated. The catalyst tolerates numerous functional groups, including hydrogenation‐sensitive examples. Compared to many other alcohol‐based amine alkylation methods, where a stoichiometric amount of base is required, our Cr‐based catalyst system gives yields higher than 90 % for various alkyl amines with a catalytic amount of base. Our study indicates that Cr complexes can catalyze borrowing hydrogen or hydrogen autotransfer reactions and could thus be an alternative to Fe, Co, and Mn, or noble metals in (de)hydrogenation catalysis.     

Recent Advances in Carbon-Nitrogen/Carbon-Oxygen Bond Formation Under Transition-Metal-Free Conditions

Carbon-heteroatom bond formation under transition-metal free conditions provides a powerful synthetic alternative for the efficient synthesis of valuable molecules. In particular, C−N and C−O bonds are two important types of carbon-heteroatom bonds. Thus, continuous efforts have been deployed to develop novel C−N/C−O bond formation methodologies involving various catalysts or promoters under TM-free conditions, which enables the synthesis of various functional molecules comprising C−N/C−O bonds in a facile and sustainable manner. Considering the significance of C−N/C−O bond construction in organic synthesis and materials science, this review aims to comprehensively present selected examples on the construction of C−N (including amination and amidation) and C−O (including etherification and hydroxylation) bonds without transition metals. Besides, the involved promoters/catalysts, substrate scope, potential application and possible reaction mechanisms are also systematically discussed.