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.

Modular Synthesis of Tetrasubstituted Pyrroles via an Annulative Migration Reaction of Allenyl Ketones and p-Toluenesulfonylmethyl Isocyanide.

The metal-free cyclization of allenyl ketones and p-toluenesulfonylmethyl isocyanide (TosMIC), promoted by Cs2CO3, provides a convenient access to tetrasubstituted pyrroles in which an acyl group undergoes 1,2-migration. This tandem Michael addition/annulative migration synthetic strategy is general and high-yielding for various substituted allenyl ketones. Moreover, a phosphoryl or ester moiety is also a suitable functionality to enable such migration.

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.

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.

Rhodium(III)-Catalyzed Sequential Cyclization of N-Boc Hydrazones with Propargylic Monofluoroalkynes via C-H Activation/C-F Cleavage for the Synthesis of Spiro[cyclobutane-1,9'-indeno[1,2-a]indenes].

An effective rhodium(III) catalysis for the construction of valuable tetracyclic compounds is described herein. This domino process involving the C-H activation/[3 + 2] annulation/intramolecular Friedel-Crafts reaction sequences of simple and readily available N-Boc hydrazones and propargylic monofluoroalkynes afforded fused tetracyclic spiro[cyclobutane-1,9'-indeno[1,2-a]indenes] in moderate to good yields, featuring three C-C bond formation. Moreover, control experiments indicated that the C-H activation might be involved in the rate-determining step.

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.

Identification and Speciation of Nanoscale Silver in Complex Solid Matrices by Sequential Extraction Coupled with Inductively Coupled Plasma Optical Emission Spectrometry.

Nanoscale silver (n-Ag) including silver nanoparticles (Ag-NPs), silver chloride nanoparticles (AgCl-NPs), and silver sulfide nanoparticles (Ag2S-NPs) and their corresponding ionic counterpart, namely, dissolved Ag, may coexist in soils. X-ray absorption near edge spectroscopy (XANES) is used to elucidate the speciation of n-Ag in soils, whereas it possesses drawbacks like high costs, rare availability of the instrument, and providing semiquantitative data. We developed a new method for the identification and speciation of n-Ag in soils and sediments based on a sequential extraction technique coupled with inductively coupled plasma optical emission spectrometry. Extraction conditions were first evaluated, establishing the optimal extraction procedure; Ag-NPs, AgCl-NPs, and dissolved Ag in soil were simultaneously extracted by using an aqueous solution of 10 mM tetrasodium pyrophosphate, followed by selective isolation and quantification via AgCl-NPs dissolution (4.45 M aqueous ammonia), centrifugation (Ag-NPs), and detection. The Ag2S-NPs remaining in the soil were then extracted with Na2S solution at pH 7.0 through selective complexation. Optimal recoveries of Ag-NPs, AgCl-NPs, Ag2S-NPs, and dissolved Ag were 99.1 ± 2.4%, 112.0 ± 3.4%, 96.4 ± 4.0%, and 112.2 ± 4.1%, respectively. The method was validated to investigate the speciation of n-Ag in soils and sediments, exhibiting the distribution of Ag-NPs, AgCl-NPs, Ag2S-NPs, and dissolved Ag in each sample, wherein Ag2S-NPs, the major species of n-Ag, accounted for 35.42-68.87% of the total Ag. The results of n-Ag speciation in soil are comparable to those obtained through the linear combination fitting of XANES. This method thus is a powerful, yet convenient, substitute for XANES to understand the speciation of n-Ag in complex solid matrices.

Transition-Metal-Free Arylation and Alkylation of Diarylmethyl p-Tolyl Sulfones with Zinc Reagents.

The transition-metal-free synthesis of unsymmetrical and highly functionalized triarylmethanes through arylation of the situ generated o-QMs from diarylmethyl p-tolyl sulfones with aryl zinc reagents is described. Alkyl zinc reagents are also well tolerated in this reaction. Additionally, the straightforward synthesis of the analogue of the antituberculosis agent A and the key precursor of the anti-breast-cancer agent B are achieved by this strategy.

Catalyst-Controlled Chemodivergent Modification of Indoles with 2-Furylcarbinols: Piancatelli Reaction vs Cross-Dehydrative Coupling Reaction.

A divergent synthetic strategy to functionalize the indole nucleus with readily available 2-furylcarbinols was developed. It was found that the 3-(4-oxo-2-cyclopentenyl)indoles were obtained in moderate to good yields (up to 89%) through Piancatelli reaction catalyzed by ZnCl2, whereas employment of Brønsted acid TFA afforded directly coupled product 3-(2-furyl)indoles in moderate to good yields (up to 87%) via the deprotonation-rearomatization route.

Strain-Promoted Nitration of 3-Cyclopropylideneprop-2-en-1-ones and the Application for the Synthesis of Pyrroles.

The tunable nucleophilic nitration of 3-cyclopropylideneprop-2-en-1-ones with cheap sodium nitrite is described. This transformation proceeds with the assistance of a strained cyclopropane ring and allows for a divergent route to various synthetically useful ß,γ-dinitro or γ-mononitro adducts in high yields with exclusive regio- and stereoselectivity. Additionally, a wide array of valuable functionalized N-unprotected pyrroles is achieved from the resulting ß,γ-dinitro compounds via reductive cyclization strategy.

Base-mediated diastereoselective [4 + 3] annulation of in situ generated ortho-quinone methides with C,N-cyclic azomethine imines.

An efficient [4 + 3] annulation of 2-(1-tosylalkyl)phenols with C,N-cyclic azomethine imines via in situ generation of ortho-quinone methides (o-QMs) under mild basic reaction conditions is disclosed, furnishing biologically interesting seven-membered heterocyclic compounds with moderate to good yields and excellent diastereoselectivities. A gram-scale reaction is performed to demonstrate the potential in industrial application and two transition states are proposed to rationalize the outstanding diastereoselectivity.

1-Hydroxybenzotriazole-Assisted, N-Heterocyclic Carbene Catalyzed ß-Functionalization of Saturated Carboxylic Esters: Access to Spirooxindole Lactones.

A 1-hydroxybenzotriazole-assisted, N-heterocyclic carbene catalyzed direct ß-functionalization of saturated carboxylic esters is disclosed. This formal [3 + 2] annulation reaction of carboxylic esters with isatins affords optically pure spirooxindole lactones (on gram scale) bearing two vicinal stereogenic centers. A dual role of HOBt is proposed based on controlled experiments to rationalize the enhancement of diastereoselectivity and enantioselectivity.

Lewis Acid Catalyzed Regiospecific Cross-Dehydrative Coupling Reaction of 2-Furylcarbinols with ß-Keto Amides or 4-Hydroxycoumarins: A Route to Furyl Enols.

Lewis acid catalyzed directly dehydrative carbon-carbon bond formation reaction of 2-furylcarbinols with ß-keto amides provides a straightforward method for regioselective synthesis of (Z)-furyl enols. Moreover, this Lewis acid catalyzed cross-coupling reaction can be extended to an interesting heterocyclic version featuring a functionalized 3-furyl-4-hydroxycoumarin synthesis.

Spontaneous dimerization of allenes in situ: an efficient synthesis of substituted 1,2-dimethylenecyclobutanes with high regio- and stereoselectivities.

An intermolecular [2+2] cycloaddition reaction for the synthesis of 1,2-dimethylenecyclobutane derivatives from the commercially available starting materials aryl acetylenes, nBuLi, formamides, and trimethylsilyl cyanide (TMSCN) has been achieved. This reaction displays high regio- and stereoselectivities due to the captodative effect. The mechanism of the reaction has been investigated by the deuterium labeling experiments and DFT calculations.

Copper-free arylation of 3,3-disubstituted allylic halides with triazene-softened aryl Grignard reagents.

A copper-free allylic arylation reaction between 3,3-disubstituted allylic halides and triazene-softened aryl Grignard reagents has been developed. This protocol presents a direct and efficient way to construct both α- or γ-isomers with high regioselectivity under environmentally benign conditions. Various functional groups can be tolerated in the reaction and the products are of high value for multiple synthetic applications. The α- and γ-isomers can be converted to the corresponding 3H-indole and indole derivatives in multigram scale respectively.

Brönsted acid-mediated intramolecular cyclization of biaryl triazenes for the synthesis of fluorenes and 9,10-dihydro-phenanthrenes.

The efficient synthesis of fluorenes from biaryl triazenes is successfully developed. Up to 27 examples of biaryl triazenes are converted into their corresponding fluorene derivatives in the presence of CF3COOH (4.0 equiv). Mechanism research indicates that the reaction undergoes concerted processes, and pentacoordinate carbocations may be involved in these reactions.

Hydroxyphosphinylation reaction of 3-cyclopropylideneprop-2-en-1-ones via C-P σ-bond cleavage.

An unexpected hydroxyphosphinylation of 3-cyclopropylideneprop-2-en-1-ones with phosphines has been observed. This method provides a unique regio- and stereoselective synthesis of highly functionalized 1-dialkylphinyl-3-oxo-(1Z)-alkenyl cyclopropanols with important potentials. The reaction displays an unusual mechanistic feature--a highly selective cleavage of C-P σ bonds in phosphines.

Cu(I)-catalyzed domino reaction of 3-cyclopropylideneprop-2-en-1-ones.

CuCl-catalyzed cyclization-dimerization reactions of 3-cyclopropylideneprop-2-en-1-ones provide an interesting route to benzofuran-7(3aH)-one derivatives with one highly strained three-membered ring and one four-membered ring via intramolecular cycloisomerization, sequential bimolecular [4 + 2] cycloaddition, opening of the oxa-bridge, and ring contraction. Furthermore, the reaction was monitored by NMR experiments to unveil some key intermediates.

Palladium/Silver Cocatalyzed Divergent Dimerization of 2H-Azirines for Regioselective Synthesis of Tetrasubstituted Pyrroles and Pyrimidines.

The unprecedented dimerizations of 2H-azirines have been developed under the catalysis of palladium and silver. Upon changing the reaction conditions, the fully aryl-substituted pyrrole and pyrimidine derivatives were furnished in moderate yields with regiospecificity, respectively. Control experiments uncovered distinct catalytic effects of two transition metals, and the proposed catalytic cycles plausibly rationalized the chemodivergence and regioselectivity.

Synthesis of Trisubstituted Furans via Copper(I)-Catalyzed Strain-Driving Cycloisomerization/Annulative Fragmentation.

The in situ formed furan-fused cyclobutenes via Cu(I)-catalyzed cycloisomerization of readily available allenyl ketones bearing a cyclopropyl moiety are a highly reactive and powerful species, which undergo annulative fragmentation with terminal ynones to afford a wide variety of functional furans in moderate to high yields. This ring-distortion protocol features an unprecedented strain-controlled cycloisomerization/Diels-Alder/retro-Diels-Alder (CDRD) sequence under mild conditions.