Metal-free Conditions Research Articles

Multicomponent Heterogeneous Semiconductor Photocatalytic Sulfinylsulfonylation of Alkenes with Alkyl Iodides and SO2.

A multicomponent heterogeneous semiconductor photocatalytic sulfinylsulfonylation of alkenes with alkyl iodides and SO2 was displayed under mild metal-free conditions by using boron carbonitride (BCN) as the alternative photocatalyst. This approach has resulted in the production of a wide range of structurally diverse sultine products in moderate to high yields, using readily available starting materials including alkyl iodides and olefins with broad functional group tolerance. The method is also suitable for the late-stage functionalization of complex bioactive molecules. A radical-polar crossover cyclization (RPCC) process was proposed based on mechanistic studies.

Direct one-pot synthesis of tetrazole derivatives from aldehydes under metal-free conditions.

Direct one-pot synthesis of tetrazole derivatives from aldehydes under metal-free conditions.

Light-Induced Transformations of Donor-Donor Diazo Compounds Derived from N-Sulfonylhydrazones.

The donor-donor carbene chemistry field is underdeveloped and often relies on harsh reaction conditions, utilizing either thermal or oxidative process with or without transition-metal catalysts. In this review, we discussed the synthesis and transformation of donor-donor diazo compounds from N-sulfonylhydrazones in the presence of light and base. The N-sulfonylhydrazones are easily accessible from the corresponding carbonyl compounds and sulfonyl hydrazides through condensation. The in situ generated N-sulfonyl anion in the presence of base would undergo the N-S bond cleavage with the aid of light to generate the donor-donor diazo compounds. The donor-donor diazo compounds showed various reactivity in the presence of light for the C-C and C-X bond formation, cyclopropanation reactions, and synthesis of nitrogen, oxygen-containing heterocyclic compounds, which all are discussed under metal-free conditions.

Site-Selective γ-Trihalomethylation and γ-Dihalomethylidenation of Silyl Dienol Ethers under Organophotoredox Catalysis.

We report a general remote tribromo- and trichloromethylation process using CBr4 and CBrCl3 as ready available sources of trihalomethyl radicals. This method operates under mild and metal-free photocatalyzed conditions and enables the access to γ-trihalomethylated enals with complete regioselectivity in up to 71% isolated yield. Importantly, this protocol is easily adapted to the selective one-pot synthesis of the corresponding γ-dihalomethylidenated enals in up to 49% overall yield. Mechanistic studies are in favor of a radical chain propagation initiated by an oxidative quenching of the photocatalyst.

Light-Driven Organocatalyzed Controlled Radical Copolymerization of (Perfluoroalkyl)ethylenes and Vinyl Esters/Amides.

Fluoropolymers of well-defined structures exhibit significant potential in a broad range of high-tech applications. However, the controlled synthesis of fluoropolymers from easily available monomers remains difficult. In this work, we report the development of an organocatalyzed controlled radical copolymerization of (perfluoroalkyl)ethylenes (PFAEs) and unconjugated vinyl monomers (UCMs) under light irradiation, which has enabled on-demand access toward side-chain fluorinated polymers under metal-free conditions. This method furnishes a large variety of polymers with diverse fluoroalkyl and ester/amide as pendent groups, tunable molar masses, and low dispersities (ca. Đ = 1.1-1.3), and adjustable fractions of PFAE and UCM units. Obtained fluoropolymers exhibit good chain-end fidelity and activity, allowing chain-extension polymerizations to prepare block copolymers of complicated compositions. Furthermore, the PFAE copolymers exhibit outstanding light transmission and low refractive index.

Highly Regioselective Dehydrogenative Hydrazination of Tropones.

Direct C(sp2)-H bond functionalization of the tropone skeleton constitutes an atom-economical strategy to access substituted tropones that exist in some bioactive compounds. Herein, we report a convenient method for the preparation of 2-hydrazinotropones via C(sp2)-H bond functionalization. A variety of tropones participated in the dehydrogenative hydrazination reaction with hydrazine, delivering structurally diverse 2-hydrazinotropones in moderate to good yields with extremely high regioselectivity. This method is featured by operational simplicity and metal-free reaction conditions, thereby tolerating various functional groups.

Organic Photoredox Catalytic Difluoroalkylation of Unactivated Olefins to Access Difluoro-Containing Tetrahydropyridazines.

Herein, we disclose a readily available phenothiazine derivative as an organocatalyst, which upon excitation with 371 nm light acquires a strongly reducing power and serves to induce the radical cascade difluoromethylation/cyclization reaction of N-homoallylacetohydrazides. A variety of CF2COR-tetrahydropyridazines have been obtained in moderate to excellent yields. This catalytic platform proceeds under metal-free conditions with a wide substrate scope and broad functional group compatibility, which unlocks the new reactivity of phenothiazine derivatives and adds significant synthetic value to N-heterocycles.

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts.

Diaryliodonium salts have become widely recognized as arylating agents in the last two decades. Both, symmetrical and unsymmetrical forms of these salts serve as effective electrophilic arylating reagents in various organic syntheses. The use of diaryliodoniums in C-C and carbon-heteroatom bond formations, particularly under metal-free conditions, has further enhanced the popularity of these reagents. In this review, we concentrate on various arylation reactions involving carbon and other heteroatoms, encompassing rearrangement reactions in the absence of any metal catalyst, and summarize advancements made in the last five years.

Brook-Oxidation Reaction of Acylsilanes: General Access to α-Ketoamides and α-Ketothioamides.

A novel chemoselective Brook-oxidation reaction of acylsilanes initiated by the carbamoyl anion has been successfully developed for the first time. This method enables the synthesis of diverse α-ketoamides and α-ketothioamides under transition metal-free and strong oxidant-free conditions with high yields and high chemoselectivity. It also demonstrates tolerance toward a wide range of functional groups. The synthetic utility of this process is underscored by its successful application in the synthesis of an orexin receptor antagonist from acylsilane, highlighting its potential for the development of novel therapeutic agents and further exploration in synthetic chemistry.

Organocatalytic Asymmetric Construction of 2,6-Diazabicyclo-[2.2.2]octanes by Harnessing the Potential of an 3-Oxindolium Ion Intermediate.

Due to its structural complexity and intrinsic sensitivity of bridged aminal junction, 2,6-diazabicyclo[2.2.2]octane (2,6-DABCO) has remained a highly desirable target in synthetic chemistry. However, the asymmetric access to this unit is still insufficient and hampered by the need for meticulously created functionalities for intricate double aza-cyclizations. Herein, we have developed a novel enantio- and diastereoselective protocol to access polycyclic chiral 2,6-DABCOs under metal-free conditions. This domino process involves the amine-catalyzed [4+2] annulation between glutaraldehyde and 2-arylindol-3-ones, followed by an acid-mediated Pictet-Spengler reaction/intramolecular aza-cyclization cascade sequence with tryptamine by trapping of in situ generated 3-oxindolium ion intermediate for the first time. Overall, 2,6-DABCOs fused with medicinally relevant scaffolds were isolated with good yield and excellent stereoselectivity by constructing five new bonds and four stereocenters in a one-pot operation.

Selective Access to 2‐Phenylquinazolin‐4(3H)‐Ones and 2,3‐Dihydroquinazolin‐4(1H)‐Ones from Same Precursors in Organic Salts Derived DES

AbstractA binary mixture of organic salts, also known as ionic liquids, [C12mim][Br]:[MPIM][HCOO] denoted as BmIL1 has been explored as bifunctional catalyst for the selective synthesis of 2‐phenylquinazolin‐4(3H)‐ones and 2,3‐dihydroquinazolin‐(1H)‐ones from same precursors under metal, ligand and additive free conditions. The methodology has been extended to the synthesis of 2‐phenylquinazolin‐4(3H)‐ones via another pathway from different precursors under the same catalytic system. Greener synthesis of existing drugs reestablished the multifunctionality of BmIL1. Gram scale synthesis of both the products, DFT calculations and sc‐XRD data add significance to the developed protocol. Moreover, high atom economy and eco score values justify the sustainability of the methodology.

Boron-Mediated Selective C-H Hydroxylation of 1-Phenyl-1H-Pyrazoles.

A novel strategy for boron-mediated C-H hydroxylation of 1-phenyl-1H-pyrazoles is presented. The protocol exhibits high efficiency and site exclusivity, offering the corresponding phenols in moderate to excellent yields with wide functional group tolerance under simple and metal-free conditions. Moreover, the hydroxylated products show good derivatization applications. This route provides a convenient and practical way to obtain functionalized 1-phenyl-1H-pyrazoles.

Bulky Phosphazenium Salt Controlling Chemoselective Terpolymerization of Epoxide, Anhydride and CO2: From Well-Defined Block to Truly Random Copolymers.

Copolymers with precise compositions and controlled sequences are great appealing for high-performance polymeric materials, but their synthesis is very challenging. In this study, tetrakis[tris(dimethylamino)phosphoranylidenamino] phosphonium chloride (P5Cl) and triethylboron (TEB) were chosen as the binary catalyst to synthesize both well-defined block and truly random poly(ester-carbonate) copolymers via the one-pot/one-step terpolymerization of epoxide/anhydride/CO2 under metal-free conditions. The bulky nature of phosphazenium cation not only led to loose cation-anion pairs and enhanced the reactivity, but also provided the chain-end an appropriate protection and improved the controllability. In particular, P5Cl/TEB with a molar ratio of 1/0.5 showed an extraordinary chemoselectivity for ring-opening alternating copolymerization (ROAC) of cyclohexene oxide (CHO) and phthalic anhydride (PA) first and then ROAC of CHO/CO2. Thus, well-defined block polyester-polycarbonate copolymers were synthesized by CHO/PA/CO2 terpolymerization. The chemoselectivity was easily tuned and the ROAC of CHO/PA and ROAC of CHO/CO2 occurred simultaneously with P5Cl/TEB=1/2, producing truly random poly(ester-carbonate) copolymers from CHO/PA/CO2. In addition, this P5Cl/TEB catalyst and the strategy to regulate its chemoselectivity are versatile for various anhydrides, epoxides and initiators. Thus, poly(ester-carbonate) copolymers with varying sequences, compositions, and topologies are successfully synthesized, making it possible to compare their properties and to expand their applications.

Divergent Regioselective Synthesis of Functionalized 1,2,3-1H-Triazoles from Nitriles and Arylazides Under Metal-Free and/or Solvent-Free Conditions.

Highly selective and divergent syntheses, which are crucial in both organic synthesis and medicinal chemistry, involve significant advancements in compound accessibility. By modifying α-cyano esters into α-cyano ketones, the synthesis pathway broadens to include a diverse range of 4-CN, 5-amino, and 5-arylamino derivatives of 1,2,3-triazoles, which are achieved notably through the Dimroth rearrangement. This versatility extends further with the potential for a triple cascade reaction, leading to the production of carboximidamide compounds, which are facilitated by the Cornforth rearrangement. Advancements in compound accessibility not only expand the repertoire of synthesized molecules but also open new avenues for potential pharmacological agents. Building on these findings, we have developed an innovative and efficient method for the divergent synthesis of functionalized 1,2,3-triazoles. This method strategically utilizes α-cyanocarbonyls and arylazides by harnessing their reactivity and compatibility to orchestrate a variety of molecular transformations. By optimizing these substrates, our goal is to simplify synthetic routes, improve product yields, and accelerate the discovery and development of new chemical entities with promising biological activities.

Iodine(III)-Mediated Keto-oximation of O-Alkynyl Hydroxylamines: ARoute to 3-Acyl Isoxazolines and 1,2-Oxazines.

An intramolecular iodine(III)-mediated keto-oximation of O-alkynyl hydroxylamines offers rapid and straightforward access to 3-acyl Δ2-isoxazolines and 1,2-oxazines. This approach features mild, metal-free, and aerobic reaction conditions with good functional group tolerance. Moreover, the synthetic utility of this method is demonstrated by the synthesis of unique structural motifs such as isoxazolidine, 3-vinyl isoxazoline, and 2,5-diphenylpyrazine derivatives by the conversion of 3-acyl Δ2-isoxazolines, thereby showcasing its efficiency and applicability in synthetic chemistry.

Transition-metal-free nucleophilic substitution of alkenyl boronic acids with propargylic mesylates sp3-carbon electrophiles

We developed a highly versatile transition metal-free Suzuki type cross-coupling protocol. Alkenyl/aryl boronic acids could couple smoothly with propargylic mesylates Csp3 electrophiles in the presence of mild bases. The counterion in the base plays a crucial role for the reactivity. Our metal-free condition is orthogonal towards the classic transition metal catalysed Suzuki reactions.

TFA-Catalyzed cascade annulation of thioamides with aromatic hydrazides/amines: an internal oxidant-triggered protocol to diverse N-heterocycles

An internal oxidant-triggered highly efficient protocol for the synthesis of diverse N-heterocycles (benzothiazoles, benzoxazoles, quinazolines, and 1,3,4-oxadiazoles) by TFA-catalyzed cascade annulation of thioamides with aromatic hydrazides or ortho-functionalized arylamines is described. In this transformation, thioamides act as a “C1” source as well as an internal oxidant, constructing a C=N double bond and a C-X (O/S/N) bond. The protocol is characterized by simple operation, metal-free conditions, broad substrate scope, good yields, and gram-scale synthesis. In addition, products can be further modified by Buchwald-Hartwig amination reactions, to a series of novel fluorescent compounds, which exhibit significant fluorescence performance with large Stokes shifts.

Base-Mediated Annulation of ortho-Iminophenols and ortho-Vinylphenols with MBH Carbonates of Isatins: Straightforward Access to Dihydrobenzofuran and Benzofuran Derivatives.

We have developed a convenient synthetic protocol for efficient construction of significant dihydrobenzofuran and benzofuran scaffolds by Lewis base-mediated annulation reaction ortho-iminophenols and ortho-vinylphenols with MBH carbonates of isatins under mild and metal-free conditions. The selective generation of different kinds of dihydrobenzofuran and benzofuran derivatives was successfully achieved by employing different substituted isatin-derived MBH carbonates with ortho-N-tosyliminophenols and ortho-vinylphenols. The features included broad substrate scopes, excellent functional group compatibility, high molecular diversity, and atomic economy.

Visible-light-induced radical difluoromethylation/cyclization of biarylvinyl azides: Facile access to CF2H-labelled phenanthridines

The direct difluoromethylation/cyclization of biarylvinyl azides with easily accessible [bis(difluoroacetoxy)iodo]benzene is achieved by visible-light-mediated radical difluoromethylation/iminyl cyclization process under mild conditions. The reaction initiates the decarboxylation of difluoromethyl carboxylic acids through light-induced the homolytic cleavage of [bis(difluoroacetoxy)iodo]benzene and affords a series of difluoromethyl functionalized phenanthridines in moderate to good yields. This strategy has the advantages of simple and readily available materials and transition metal-free conditions, thus boding well for the widespread applications of this method in medical and synthetic chemistry.

Alkyl Sulfonium Salts Enabled Radical Thiocyanohydroxylation of Alkenes.

Herein, we report a novel and practical strategy for alkyl sulfonium salts mediating radical thiocyanohydroxylation of alkenes. This reaction features metal-free and mild conditions, generation of noncarbon radicals from the readily available alkyl sulfonium salts, easy handling, and excellent functional group compatibility. A diverse range of activated and unactivated alkenes worked well to deliver various β-thiocyanato alcohols.