High Step Economy Research Articles

One-Step Visible Light Photoredox-Catalyzed Purine C8 Alkoxylation with Alcohol.

A cross-dehydrogenation coupling reaction between purines and alcohols, induced by visible light, using an acridinium photocatalyst and air as the sole oxidant, to synthesize a series of C8-alkoxy purine derivatives was developed. This protocol is a green and novel method to construct the C8-O bond on a purine ring with high step and atom economy.

Metal-Free Temperature-Controlled Intermolecular [3 + 2] Annulation to Access Benzo[d]thiazole-2(3H)-thiones and Benzo[d]thiazol-2(3H)-ones.

A facile access to benzo[d]thiazole-2(3H)-thiones and benzo[d]thiazol-2(3H)-ones has been developed through a temperature-controlled intermolecular [3 + 2] annulation of N,N-disubstituted arylhydrazines with CS2 in the presence of DMSO. This protocol can obviate the prefunctionalization of the starting materials. This direct C-S/C-N bond formation reaction was performed in the absence of any external catalysts, transition metals, bases, ligands, and oxidants with high step economy.

Copper catalyzed C-N-bond formation and synthesis of Imidazopyridinone derivatives

The formation of the C–N bond is critical because it allows for the incorporation of nitrogen into organic molecules. Despite significant advances in this area, the formation of the C–N bond continues to be a challenge for organic chemists owing to the need of severe reaction conditions or costly catalysts in many cases. As a result, developing alternate, milder, and less expensive C–N bonding techniques is a challenge. Herein, a series of novel imidazopyridinone derivatives (8a-8e) were synthesized via copper-mediated C–¬N bond-forming reaction. This reaction takes place under mild conditions with high efficiency, step economy, and tolerance for a wide range of functional groups. All synthesized new compounds were analyzed by 1H NMR, 13C NMR and mass spectrometry.

DBU-promoted synthesis of novel heterocyclic [4.3.3] propellanes from α‑cyanoketones and cyclic α-diketones

An effective base-catalyzed Knoevenagel, Michael and intramolecular/Paal-Knorr cyclization strategy for the construction of heterocyclic [4.3.3] tetrahydro epoxyetheno benzo-furan propellanes (TEBFs) from cyclic α-diketones and α‑cyanoketones is reported through single-step reaction. The reaction proceeds under mild reaction conditions and shows excellent chemo and distereoselectivity in the absence of any external transition metal and ligands. The one-pot two-component procedure also shows the merits of straightforward reaction conditions, simple operation, using available feedstock, wide substrate scope, and high atom and step economy. This reaction provides facile access to highly substituted fused tetrahydro furo-furan propellanes, which can be used in the field of chemical and pharmaceutical research.

Copper-Catalyzed Phosphorylation of N,N-Disubstituted Hydrazines: Synthesis of Multisubstituted Phosphorylhydrazides as Potential Anticancer Agents.

An efficient copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction for the synthesis of multisubstituted phosphorylhydrazides from N,N-disubstituted hydrazines and hydrogen phosphoryl compounds is accomplished. The reaction proceeds under mild conditions without the addition of any external oxidants and bases. This work reported here represents a direct P(═O)-N-N bond formation with the advantages of being operationally simple, good functional group tolerance, and high atom and step economy. Furthermore, the selected compounds exhibit potential inhibitory activity against tumor cells, which can be used in the field of screening of anticancer agents as new chemical entities.

Asymmetric Synthesis of Chiral Aza-macrodiolides via Iridium-Catalyzed Cascade Allylation/Macrolactonization.

Iridium-catalyzed cascade allylation/macrolactonization between vinylethylene carbonate (VEC) and isatoic anhydride derivatives was successfully developed, readily generating a wide range of C2-symmetric chiral macrodiolides bearing 14-membered rings in moderate to good yields with excellent diastereoselectivities and enantioselectivities (generally 99% ee). Control experiments revealed that racemic VEC as the precursor of electrophilic iridium-π-allyl species underwent kinetic resolution process. This expedient protocol features easily available substrates, excellent stereoselective control, and high step economy.

PhIO-Mediated Oxidative C═C Bond Cleavage and Reassembly toward Highly Functionalized Oxazolones.

An efficient PhIO-mediated oxidative C═C bond cleavage and reassembly of enaminone toward oxazolone with high regioselectivity has been reported. DFT calculations revealed that the reaction proceeded through an oxygen atom transfer, C═C bond cleavage, alkylthio migration, and reassembly cascade. This strategy is highlighted by high atom and step economy with formation of five bonds in one pot and generation of a high-valued oxazolone skeleton under mild conditions.

Synthesis of \u03b1,\u03b2-unsaturated ketones through nickel-catalysed aldehyde-free hydroacylation of alkynes

α,β-Unsaturated ketones are common feedstocks for the synthesis of fine chemicals, pharmaceuticals, and natural products. Transition metal-catalysed hydroacylation reactions of alkynes using aldehydes have been recognised as an atom-economical route to access α,β-unsaturated ketones through chemoselective aldehydic C–H activation. However, the previously reported hydroacylation reactions using rhodium, cobalt, or ruthenium catalysts require chelating moiety-bearing aldehydes to prevent decarbonylation of acyl-metal-hydride complexes. Herein, we report a nickel-catalysed anti-Markovnikov selective coupling process to afford non-tethered E-enones from terminal alkynes and S-2-pyridyl thioesters in the presence of zinc metal as a reducing agent. Utilization of a readily available thioester as an acylating agent and water as a proton donor enables the mechanistically distinctive and aldehyde-free hydroacylation of terminal alkynes. This non-chelation-controlled approach features mild reaction conditions, high step economy, and excellent regio- and stereoselectivity.

Electrochemical Ring-Opening Dicarboxylation of Strained Carbon-Carbon Single Bonds with CO2: Facile Synthesis of Diacids and Derivatization into Polyesters.

Diacids are important monomers in the polymer industry to construct valuable materials. Dicarboxylation of unsaturated bonds, such as alkenes and alkynes, with CO2 has been demonstrated as a promising synthetic method. However, dicarboxylation of C─C single bonds with CO2 has rarely been investigated. Herein we report a novel electrochemical ring-opening dicarboxylation of C─C single bonds in strained rings with CO2. Structurally diverse glutaric acid and adipic acid derivatives were synthesized from substituted cyclopropanes and cyclobutanes in moderate to high yields. In contrast to oxidative ring openings, this is also the first realization of an electroreductive ring-opening reaction of strained rings, including commercialized ones. Control experiments suggested that radical anions and carbanions might be the key intermediates in this reaction. Moreover, this process features high step and atom economy, mild reaction conditions (1 atm, room temperature), good chemoselectivity and functional group tolerance, low electrolyte concentration, and easy derivatization of the products. Furthermore, we conducted polymerization of the corresponding diesters with diols to obtain a potential UV-shielding material with a self-healing function and a fluorine-containing polyester, whose performance tests showed promising applications.

Base‐Promoted Three‐Component Cyclization and Coupling Strategy for the Synthesis of Substituted 3‐Aryl‐5‐thio‐1,3,4‐thiadiazole‐2‐thiones

AbstractAn effective base‐promoted cyclization and coupling strategy for the construction of substituted 3‐aryl‐5‐thio‐1,3,4‐thiadiazole‐2‐thiones from phenylhydrazines, olefins and CS2 is developed through employing CS2 as a sulfur feedstock. The reaction proceeds under mild reaction conditions in the absence of any external catalysts, transition metals and ligands. The one‐step three‐component procedure also shows the merits of simple operation, using available starting materials, wide substrate scopes, and high atom and step economy. This reaction provides facile access to substituted 3‐aryl‐5‐thio‐1,3,4‐thiadiazole‐2‐thiones, which could be used in the field of drug research.

Esters as Both Alkylating and Acylating Reagents: PCl3‐Promoted Friedel‐Crafts Reaction in One‐Pot

AbstractAn efficient PCl3‐promoted Friedel‐Crafts reaction using esters as both alkylating and acylating reagents has been developed. By using a PCl3/I2 combination, various esters underwent Friedel‐Crafts alkylation and acylation reactions with arenes in one‐pot, readily producing two kinds of products aromatic ketones and alkyl aromatics by one step in good yields. The Friedel‐Crafts alkylation and acylation of arene with 4‐formylbenzoate derivatives in one‐pot have also been achieved. This novel strategy features high step economy, low‐cost, metal‐free and simple reaction conditions.

Atom and step economical synthesis of acyclic quaternary centers via iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes.

Quaternary benzylic centers are accessed with high atom and step economy by Ir-catalyzed alkene hydroarylation. These studies provide unique examples of the use of non-polarized 1,1-disubstituted alkenes in branch selective Murai-type hydro(hetero)arylations. Detailed mechanistic studies have been undertaken, and these indicate that the first irreversible step is the demanding alkene carbometallation process. Structure-reactivity studies show that the efficiency of this is critically dependent on key structural features of the ligand. Computational studies have been undertaken to rationalize this experimental data, showing how more sterically demanding ligands reduce the reaction barrier via predistortion of the reacting intermediate. The key insight disclosed here will underpin the ongoing development of increasingly sophisticated branch selective Murai hydroarylations.

Base-promoted cyclization reaction of o-isothiocyanato arylacetylenes and aroylacetonitriles: easy access to benzo[d][1,3]thiazines.

A green and efficient synthesis of benzo[d][1,3]thiazines through a base-promoted cyclization reaction of o-isothiocyanato arylacetylenes with aroylacetonitriles has been developed. This protocol features high step economy and efficiency, and tolerates various functional groups. The reaction was scalable and applied for the post-modification of drugs.

Oxidative Cross‐Coupling Reactions between Two Nucleophiles†

Comprehensive SummaryOxidative cross‐coupling reactions between two nucleophiles have become one of the most important tools to construct chemical bonds in organic synthesis methodology. Directly using hydrocarbons to synthesize valuable chemicals is an ideal and economical process because hydrocarbons are cheap, abundant and readily available. The account covered a brief introduction about our efforts on the development of oxidative cross‐coupling reactions. We discovered this reaction model by the cross‐coupling of two organometallic reagents. Related mechanisms were revealed by the characterization of reaction intermediates and the study of reaction kinetics through operando spectroscopy, such as in‐situ IR (infrared), EPR (electron paramagnetic resonance), Raman and XAS (X‐ray absorption) spectroscopy. Representative applications, such as oxidative cross‐coupling reactions with H2 evolution, exhibited their high atom economy and step economy. What is the most favorite and original chemistry developed in your research group?Oxidative Cross‐Coupling – The chemistry between two “nucleophiles”.How do you get into this specific field? Could you please share some experiences with our readers?My first contact with palladium chemistry was the halopalladation of acetylene in 1998. Then I worked on palladium enolate and found it could initiate a transmetalation reaction. Until 2006, I found that desyl chloride (a halogenated hydrocarbon) showed different reactivity with organometallic reagents due to the halophilic and oxyphilic properties, thus we achieved the cross‐coupling between two organometallic reagents. At that moment, we started the research about “Oxidative Cross‐coupling Reactions – the chemistry between two nucleophiles.What is the most important personality for scientific research?Hard‐working, passion and ambition (安钻迷).What are your hobbies? What are your favorite book(s)?Sports. Jin Yong's martial arts novels, Morrison's Organic Chemistry, Electronic Interpretation of Organic Chemistry.

Copper-Catalyzed Intermolecular Enantioselective Radical Oxidative C(sp3 )-H/C(sp)-H Cross-Coupling with Rationally Designed Oxazoline-Derived N,N,P(O)-Ligands.

The intermolecular asymmetric radical oxidative C(sp3 )-C(sp) cross-coupling of C(sp3 )-H bonds with readily available terminal alkynes is a promising method to forge chiral C(sp3 )-C(sp) bonds because of the high atom and step economy, but remains underexplored. Here, we report a copper-catalyzed asymmetric C(sp3 )-C(sp) cross-coupling of (hetero)benzylic and (cyclic)allylic C-H bonds with terminal alkynes that occurs with high to excellent enantioselectivity. Critical to the success is the rational design of chiral oxazoline-derived N,N,P(O)-ligands that not only tolerate the strong oxidative conditions which are requisite for intermolecular hydrogen atom abstraction (HAA) processes but also induce the challenging enantiocontrol. Direct access to a range of synthetically useful chiral benzylic alkynes and 1,4-enynes, high site-selectivity among similar C(sp3 )-H bonds, and facile synthesis of enantioenriched medicinally relevant compounds make this approach very attractive.

Copper‐Catalyzed Intermolecular Enantioselective Radical Oxidative C(sp3)−H/C(sp)−H Cross‐Coupling with Rationally Designed Oxazoline‐Derived N,N,P(O)‐Ligands

AbstractThe intermolecular asymmetric radical oxidative C(sp3)−C(sp) cross‐coupling of C(sp3)−H bonds with readily available terminal alkynes is a promising method to forge chiral C(sp3)−C(sp) bonds because of the high atom and step economy, but remains underexplored. Here, we report a copper‐catalyzed asymmetric C(sp3)−C(sp) cross‐coupling of (hetero)benzylic and (cyclic)allylic C−H bonds with terminal alkynes that occurs with high to excellent enantioselectivity. Critical to the success is the rational design of chiral oxazoline‐derived N,N,P(O)‐ligands that not only tolerate the strong oxidative conditions which are requisite for intermolecular hydrogen atom abstraction (HAA) processes but also induce the challenging enantiocontrol. Direct access to a range of synthetically useful chiral benzylic alkynes and 1,4‐enynes, high site‐selectivity among similar C(sp3)−H bonds, and facile synthesis of enantioenriched medicinally relevant compounds make this approach very attractive.

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2

Dual Functionalization of Alkynes Utilizing the Redox Characteristics of Transition Metal Catalysts

AbstractTri‐ and tetrasubstituted alkene scaffolds are prominent building blocks in many bioactive natural products, drug molecules, and key intermediates in various synthetic transformations. The dual functionalization of alkynes promises an easy introduction of functional groups across the triple bond with a high step and atom economy, exemplifying a class of reactions to construct tri‐ and tetrasubstituted alkene scaffolds. This review discusses the versatility and advances in the transition metal‐catalyzed redox dual functionalization of alkynes, their unique mechanistic features, and the synthetic applications of the methodology. This collection focuses on the formation of simultaneous C−C/C−X bonds involving various oxidation states of the metals in the catalytic cycle. Apart from the classical redox reactivity, radical‐mediated functionalizations are also discussed in detail.

Dirhodium(II)/Xantphos-Catalyzed Relay Carbene Insertion and Allylic Alkylation Process: Reaction Development and Mechanistic Insights.

Although dirhodium-catalyzed multicomponent reactions of diazo compounds, nucleophiles and electrophiles have achieved great advance in organic synthesis, the introduction of allylic moiety as the third component via allylic metal intermediate remains a formidable challenge in this area. Herein, an attractive three-component reaction of readily accessible amines, diazo compounds, and allylic compounds enabled by a novel dirhodium(II)/Xantphos catalysis is disclosed, affording various architecturally complex and functionally diverse α-quaternary α-amino acid derivatives in good yields with high atom and step economy. Mechanistic studies indicate that the transformation is achieved through a relay dirhodium(II)-catalyzed carbene insertion and allylic alkylation process, in which the catalytic properties of dirhodium are effectively modified by the coordination with Xantphos, leading to good activity in the catalytic allylic alkylation process.

Synthesis of Imidazoles and Oxazoles via a Palladium-Catalyzed Decarboxylative Addition/Cyclization Reaction Sequence of Aromatic Carboxylic Acids with Functionalized Aliphatic Nitriles.

We herein report an efficient approach for the assembly of multiply substituted imidazoles and oxazoles in a single-step manner. These transformations are based on a decarboxylation addition and annulation of readily accessible aromatic carboxylic acids and aliphatic nitriles and exhibit good functional group compatibility and a high step economy. The reaction is scalable, and as-prepared products could be transformed into practical skeletons. Importantly, the late-stage derivatization of Momelotinib highlights the potential utility of this methodology.