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Scheme 34 Additive-driven Rh-catalyzed [4 + 1]/[4 + 2] annulations of N-arylphthalazine-1,4-dione.
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Phthalazinones and their higher congeners are commonly prevalent structural motifs that occur in natural products, bioactive molecules, and pharmaceuticals. In the past few decades, transition-metal-catalyzed reactions have received an overwhelming response from organic chemists as challenging organics and heterocycles could be built with ease. Cur...
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... We chose ethanol with the intention of also exploring the activation of the CÀ H bond in the À CH 2 À group. The activation of the CÀ H bond is well established in the literature and is defined as the β-CÀ H mechanism [23][24][25][26] and in this work we explore the mechanism of breaking the CÀ H bond of ethanol. ...
Thin gold nanowires (NWs) are materials that could be used as support in different chemical reactions. Using density functional theory (DFT) it was shown that NWs that form linear atomic chains (LACs) are suitable for stimulating chemical reactions. To this end, the oxidation reaction of ethanol supported on the LACs of Au−NWs was investigated. Two types of LACs were used for the study, one pure and the other with an oxygen impurity. The results showed that the oxygen atom in the LAC fulfills important functions throughout the reaction pathway. Before the chemical reaction, it was observed that the LAC with impurity gains structural stability, that is, the oxygen acts as an anchor for the gold atoms in the LAC. In addition, the LAC was shown to be sensitive to disturbances in its vicinity, which modifies its nucleophilic character. During the chemical reaction, the oxidation of ethanol occurs through two different reaction paths and in two stages, both producing acetaldehyde (CH3CHO). The different reaction pathways are a consequence of the presence of oxygen in the LAC (oxygen conditions the formation of reaction intermediates). In addition, the oxygen in the LAC also modifies the kinetic behavior in both reaction stages. It was observed that, by introducing an oxygen impurity in the LAC, the activation energy barriers decrease ∼69 % and ∼97 % in the first and second reaction stages, respectively.
Photoinduced ruthenium‐catalyzed ortho‐benzoxylation through organophosphine ligand is unveiled. The in situ generation of the organophosphine‐ruthenium complex facilitates ligand‐to‐metal charge transfer (LMCT) under visible light, promoting the site‐selective ortho‐benzoxylation at room temperature. The broad scope of aryl, aliphatic, and heterocyclic carboxylic acids are key attractions of this methodology. EPR and UV‐Vis analysis support a LMCT process between a photoexcited organophosphine and Ru‐complex under blue‐light irradiation. Comprehensive mechanistic investigation highlights the role of light, ligands, oxidants, the LMCT process, and the unique reactivity of the directing group.
The present work documents construction of C4‐cyanoalkylated phthalazinones under visible light‐mediated conditions. The three‐component reaction involving aryl hydrazines, 2‐formylbenzoic acids and cyclobutanone oxime esters with organic dye Eosin Y as photocatalyst, features initial formation and subsequent cyanoalkylation of phthalazin‐1(2H)‐one in one pot. The reaction is notable for mild conditions, operational simplicity, wide substrate scope and good yields of the products. The phthalazinone products were further converted into other valuable organic derivatives. image
Amidines are a vital class of bioactive compounds and often necessitate multiple components for their synthesis. Therefore, exploring efficient and sustainable methodologies for their synthesis is indispensable. Herein, we disclose an alternative and greener method for synthesizing an unexplored new class of amidines through the photochemical synergistic effect of copper/nitroxyl radical catalysis. This approach facilitates site‐selective radical amination of unactivated imine C(sp²)−H bond in C,N,N‐cyclic imines over favored selectivity via halogen‐atom transfer (XAT). This greener method ticks 11 out of 12 green chemistry metrics (GCM), effectively sidestepping the need for oxidants, bases, ligands, multistep processes, and harsh conditions, distinguishing it from conventional methods described in previous studies. Kinetic, spectroscopic, and computational tools have been employed to elucidate the synergistic effect of Cu/nitroxyl radical, the role of light, XAT, the influence of substituents, and the order of the reaction in the catalytic cycle.
β-Enaminone transformation strategies are widely employed in the synthesis of numerous biologically active drugs and natural products, highlighting their significance in medicinal chemistry. In recent years, various strategies have been developed for synthesizing several five- and six-membered heterocycles, as well as substituted polyaromatic scaffolds, which serve as crucial synthons in drug development, from β-enaminones. Among these approaches, site-selective transformations of β-enaminones via C-H activation and annulation have been particularly well explored. This review summarizes the most recent literature (over the past eight years) on β-enaminone transformations for developing bioactive scaffolds through site-selective C-H bond functionalization and annulation.
A direct ortho‐Csp²‐H acylalkylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with unsubstituted and substituted allyl alcohols is achieved in high yields through Rh(III)‐catalyzed C−H bond activation process. The additional employment of Cu(OAc)2⋅2H2O as an oxidant detour the reaction towards [4+1] annulation, producing 13‐(2‐oxopropyl)‐13H‐indazolo[1,2‐b]phthalazine‐6,11‐diones in moderate yields. Interestingly, Lawesson's reagent‐mediated conditions accomplished intramolecular cyclization in ortho‐(formylalkylated)‐2,3‐dihydrophthalazine‐1,4‐diones to produce diazepino[1,2‐b]phthalazine‐diones in moderate yields. Furthermore, allyl alcohol showcased distinct reactivity in presence of different additives to produce ortho‐allylated, oxidative and non‐oxidative [4+2] annulated products.
An operationally simple and expeditious protocol for Ru(II)-catalyzed ortho-C(sp2)–H hydroxyalkylation of phthalazinones using commercially available ethyl glyoxalate in 2-Me-THF is reported. This greener approach involves the imine nitrogen on the phthalazinones as a directing group to effect the regioselective hydroxyalkylation. Ample examples of biologically relevant hydroxyalkylated phthalazinones were prepared, and relevant controlled studies were performed to decipher the reaction mechanism.
Visible‐light photoredox‐catalyzed metal‐free one‐pot tandem regioselective synthesis of C4‐phosphorylated phthalazin‐1(2H)‐ones from arylhydrazines, 2‐formylbenzoic acids with diarylphosphine oxides is described. This three‐component transformation occurs smoothly under mild conditions, providing regiospecific access to various phosphorylated products in 73–91% yield. The efficacy of the current catalysis arises from the use of organic 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene (4CzIPN) as the photocatalyst and cheap K2S2O8 as the oxidant.
Heterocyclics are the crucial scaffolds present in pharmaceuticals, natural products, biologically active compounds and agrochemicals. Consequently, the development of simple and practical methods for constructing heterocyclics has always been a fascinating field in organic synthesis. Recently, 2‐acylbenzoic acids, highly reactive and versatile synthons, have been broadly applied in the construction of heterocycles due to their multiple reaction sites. In this review, we summarized recent progress in the application of 2‐acylbenzoic acids for the synthesis of heterocycles including phthalides, isochromanones, isoindolines, phthalazinones, and quinolones. The substrate scopes, proposed mechanisms, and product application of different types of reactions are discussed.
