Cu(II)-Catalyzed [3 + 1 + 1 + 1] Cyclization of 1,3-Diketones and 2-Naphthols Using N,N-Dimethylethanolamine as a Dual Carbon Synthon for the Synthesis of 2H-Chromenes.

Reactions with diverse C1 synthons to realize homologation were well explored. However, homologations occurring twice with one C1 synthon in a reaction were less reported. We disclose herein a Cu(II)-catalyzed novel and efficient synthesis of 2H-chromenes from 2-naphthols, 1,3-diketones, and N,N-dimethylethanolamine (DMEA) as a dual carbon synthon. Various 2H-chromenes with different functional groups are constructed in moderate to good yields. This is the first report that DMEA acts as a dual C1 synthon.

Regioselective C3Alkylation of Indoles for the Synthesis of Bis(indolyl)methanes and 3-Styryl Indoles.

Herein, we describe an efficient transition-metal-free regioselective C3alkylation of indoles for the synthesis of bis(indolyl)methanes and 3-styryl indoles. Nitrobenzene is employed as the oxidant to oxidize the alcohols in the presence of a strong base and the reaction avoids the use of transition metals such as Ru and Mn. The protocol provides a favorable route to access biologically active compounds such as arundine, vibrindole A, and turbomycin B.

Metal-free construction of dihydropyrazino[2,3-b]indoles from 2-aminoacetophenones, isocyanates and 1,2-diamines.

A Brønsted acid/iodine co-mediated approach to construct dihydropyrazino[2,3-b]indoles in 2-MeTHF as a green solvent at room temperature was established. A wide range of diversely substituted dihydropyrazino[2,3-b]indoles (42 examples, 61-85% yields) were synthesized under mild conditions, even on a gram scale. This protocol features organocatalysts, an eco-friendly solvent, mild conditions, readily accessible substrates, broad substrate scope and simple work-up.

Palladium-Catalyzed C-H Allylation/Annulation Reaction of Amides and Allylic Alcohols: Regioselective Construction of Vinyl-Substituted 3,4-Dihydroisoquinolones.

A palladium-catalyzed highly regioselective C-H allylation/annulation reaction of N-sulfonyl amides with secondary or tertiary allylic alcohols has been developed to construct 3,4-dihydroisoquinolones bearing a synthetically valuable vinyl substituent. This cascade cyclization approach of allylic alcohols involving C-H allylation has not been reported previously. The commercially available allylic alcohol substrates, the only by-product of water, and the used terminal oxidant of O2 provide environmentally benign advantages.

Cu(II)-catalyzed domino construction of spironaphthalenones by dearomatization of ß-naphthols and using N,N-dimethylaminoethanol as a C1 synthon.

Herein, a Cu(II)-catalyzed facile construction of synthetically valuable spiro compounds from ß-naphthols in air is reported, in which N,N-dimethylaminoethanol (DMEA) serves as an efficient and unique C1 synthon. This transformation proceeds through an ortho-quinone methide (o-QM) formation/Michael addition/dearomatization sequence, affording various spiro(naphthalenenaphtho)furan-2-ones in moderate to excellent yields.

I2-mediated coupling of quinazolinone enamines with 2-aminopyridines: a new strategy to access spiroquinazolinones.

Herein, we report a novel, rapid and efficient route to the spiroquinazolinone framework via an umpolung strategy mediated by molecular iodine. A library of functionalized spiroquinazolinone iodide salts was synthesized in moderate to good yields under ambient, metal-free and mild conditions. The current methodology opens up a new efficient and concise strategy for the construction of spiroquinazolinones.

Optical Imaging Opportunities to Inspect the Nature of Cytosolic Iron Pools.

The chemical nature of intracellular labile iron pools (LIPs) is described. By virtue of the kinetic lability of these pools, it is suggested that the isolation of such species by chromatography methods will not be possible, but rather mass spectrometric techniques should be adopted. Iron-sensitive fluorescent probes, which have been developed for the detection and quantification of LIP, are described, including those specifically designed to monitor cytosolic, mitochondrial, and lysosomal LIPs. The potential of near-infrared (NIR) probes for in vivo monitoring of LIP is discussed.

Application of N,N-Dimethylethanolamine as a One-Carbon Synthon for the Synthesis of Pyrrolo[1,2-a]quinoxalines, Quinazolin-4-ones, and Benzo[4,5]imidazoquinazolines via [5 + 1] Annulation.

The synthesis of N-heterocycles composes a significant part of synthetic chemistry. In this report, a Cu(II)-catalyzed green and efficient synthesis of pyrrolo[1,2-a]quinoxaline, quinazolin-4-one, and benzo[4,5]imidazoquinazoline derivatives was developed, employing N,N-dimethylethanolamine (DMEA) as a C1 synthon. Green oxidant O2 is critical in these transformations, facilitating the formation of a key intermediate─a reactive iminium ion. The method conducted under mild conditions is compatible with a diversity of functional groups, providing an appealing alternative to the previously developed protocols.

Photocatalytic C-H Activation and Amination of Arenes with Nonactivated N-Hydroxyphthalimides Involving Phosphine-Mediated N-O Bond Scission.

Herein, we reported a metal-free photoredox/phosphine-catalyzed C-H amination of arenes. This allows for concise synthesis of highly functionalized N-arylphthalimides from readily available N-hydroxyphthalimides directly, without the preparation of activated N-hydroxyphthalimide intermediates. Mechanistic studies reveal that the radical is produced via phosphine-mediated N-O bond scission.

Employing Visible-Light Photoredox Catalysis in Multicomponent-Multicatalyst Reactions: One-Pot Synthesis of Spiroquinazolin-2-(thi)ones.

The multicomponent-multicatalyst reaction ((MC)2R) and visible-light catalysis have emerged as green and powerful strategies for achieving ideal syntheses. Here, we report the first example of a visible-light-induced approach toward spiroquinazolin(thi)ones. This (MC)2R features an eco-friendly energy source and solvent, metal-free catalysts, step- and atom-economy, a relay catalysis strategy, air as green oxidant, mild conditions, and easily accessible starting materials.

I2-Promoted In Situ Cyclization-Rethiolation Reaction: Synthesis of 2-Aliphatic- or Aromatic-Substituted Indolizines.

An efficient I2-promoted one-pot one-step three-component reaction for the synthesis of sulfhydryl indolizines from methyl ketones, 2-pyridylacetate derivatives, and sulfonyl hydrazides via an in situ cyclization-rethiolation strategy has been developed. This protocol shows excellent substrate compatibility, including for chain and cyclic aliphatic methyl ketones, natural product pregnenolone acetate, and phosphorus-containing methyl ketones, affording a series of valuable aliphatic-substituted indolizines in good yields.

Facile construction of C,N-disulfonated 5-amino pyrazoles through an iodine-catalyzed cascade reaction.

A green and facile synthesis of previously unreported C,N-disulfonated 5-amino pyrazoles was established through an iodine-catalyzed cascade reaction of easily accessible sulfonyl hydrazides, ß-ketonitriles, and sodium sulfinates. Diverse C,N-disulfonated 5-amino pyrazoles could be obtained in 38-88% yields. This methodology features green and mild conditions, broad substrate scope, and effortless work-up.

Efficient synthesis of spiro diheterocycles via multi-component dicyclization reaction.

A facile synthetic protocol for the preparation of spiro diheterocycles from easily available 2'-aminoacetophenones, isocyanates and 1,4-benzoquinones or quinone monoimines under mild conditions has been developed. This multi-component transformation is characterized by efficient construction of two heterocycles and one valuable quaternary carbon in one pot via an in situ cyclization-respiroannulation strategy. Moreover, this reaction showed a broad substrate scope, and generated diverse five-membered oxaspiros.

Construction of a Pyrimidine Framework through [3 + 2 + 1] Annulation of Amidines, Ketones, and N,N-Dimethylaminoethanol as One Carbon Donor.

An efficient, facile, and eco-friendly synthesis of pyrimidine derivatives has been developed. It involves a [3 + 2 + 1] three-component annulation of amidines, ketones, and one carbon source. N,N-Dimethylaminoethanol is oxidized through C(sp3)-H activation to provide the carbon donor. One C-C and two C-N bonds are formed during the oxidative annulation process. The reaction shows good tolerance to many important functional groups in air, making this methodology a highly versatile alternative, and significant improvement to the existing methods for structuring a pyrimidine framework, especially 4-aliphatic pyrimidines.

Transition Metal-Free De Novo Synthesis of Sulfonated Pyrazoles from Sulfonyl Hydrazides, 1,3-Diketones, and Sodium Sulfinates at Room Temperature.

A transition metal-free method for de novo construction of diverse sulfonated pyrazoles from readily available sulfonyl hydrazides, 1,3-diketones, and sodium sulfinates was established under mild conditions. Pyrazoles bearing two different sulfonyl groups were obtained in one step. The method features a diversity of substituents of the pyrazole products and a remarkably simple work-up.

Environmentally Benign Synthesis of Quinoline-Spiroquinazolinones by Iron-Catalyzed Dehydrogenative [4 + 2] Cycloaddition of Secondary/Tertiary Anilines and 4-Methylene-quinazolinones.

We report an efficient iron-catalyzed cross-dehydrogenative coupling [4 + 2] annulation of secondary/tertiary anilines with quinazolinones to generate quinoline-spiroquinzolinones. The reaction proceeds smoothly with a relatively broad variety of functional groups, a cheap transition metal catalyst (FeCl3), and environmentally friendly oxidant (H2O2/O2) under mild reaction conditions. Creatively, N-methylanilines are employed for the first time for the cycloaddition as both methyl and methylene sources attached to the N atom of tetrahydroquinolines.

Oxidant/Solvent-Controlled I2-Catalyzed Domino Annulation for Selective Synthesis of 2-Aroylbenzothiazoles and 2-Arylbenzothiazoles under Metal-Free Conditions.

A simple and practical domino protocol for the selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothiazoles catalyzed by I2 is developed under metal-free conditions. The reaction outcomes are exclusively controlled by the reaction oxidant/medium. With DMSO employed as both the solvent and the oxidant, an oxidation of aromatic methyl ketones takes precedence over the condensation with 2-aminobenzenethiols. On the other hand, when the reaction was carried out in PhNO2 or in 1,4-dioxane containing PhNO2, the condensation of aromatic methyl ketones with 2-aminobenzenethiols has priority to form imines which is followed by an oxidation of the methyl group from ketones to afford 2-arylbenzothiazoles as a sole product. The PhNO2/I2 co-catalytic system is proposed first time.

I2-Catalyzed Three-Component Consecutive Reaction for the Synthesis of 3-Aroylimidazo[1,2-a]-N-Heterocycles.

A convenient one-pot, three-component reaction has been developed for the synthesis of 3-aroylimidazo[1,2-a]-N-heterocycles from aryl ketones and 2-amino-N-heterocycles using dimethyl sulfoxide as a methylene donor. The reaction proceeds smoothly catalyzed by I2 in the presence of K2S2O8 and affords the desired products in moderate to good yields. This protocol offers significant superiority in accessing biologically active 3-aroylimidazo[1,2-a]-N-heterocycles with various substitution patterns.

Expeditious Approach to Indoloquinazolinones via Double Annulations of o-Aminoacetophenones and Isocyanates.

A novel procedure for a one-pot cascade reaction of o-aminoacetophenones and aryl/aliphatic isocyanates catalyzed/oxidized by the [Pd]/[Ag] system was developed. The reaction involves two C-N bond and one C-C bond formations during the double annulation process and the desired indoloquinazolinones and derivatives were afforded up to 81% yields from readily available substrates with a tolerance of a broad variety.

Sustainable Four-Component Annulation for the Synthesis of 2,3,4,6-Tetraarylpyridines.

A one-pot, four-component annulation of 2,3,4,6-tetraarylpyridines from aromatic aldehydes, methyl ketones, diaryl ethanones, and ammonium acetate is described. The reaction features high functional group compatibility in air under solvent-free conditions without any additive and only water as the nontoxic byproduct, providing a strategy for the facile, economical, and eco-friendly construction of multiaryl-substituted pyridines from simple and readily available reactants.