Copper-Catalyzed Decarboxylation Cross-Coupling Cascade Reaction for Synthesis of Fused Dihydro-benzoxazinones.

A protocol for a tandem copper-catalyzed intermolecular decarboxylation cross-coupling cascade between o-bromobenzoic acids and proline or piperic acid has been disclosed. The developed protocol allows access to a variety of synthetically useful fused benzoxazinones scaffolds with high efficiency and good functional group compatibility. A mechanistically sequential approach for the decarboxylation and dehydration coupling process was presented.

Silver-Catalyzed Radical Umpolung Cross-Coupling of Silyl Enol Ethers with Activated Methylene Compounds: Access to Diverse Tricarbonyl Derivatives.

A silver-catalyzed protocol for the intermolecular radical umpolung cross-coupling protocol of silyl enol ethers with activated methylene compounds is disclosed. The protocol exhibits excellent functional group tolerance, enabling the expedient preparation of a variety of tricarbonyl compounds. Preliminary mechanistic investigations suggest that the reaction proceeds through a process involving free radicals in which silver oxide has a dual role, acting as both a catalyst and a base.

Construction of Phenanthridinone Skeletons through Palladium-Catalyzed Annulation.

Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.

Synthesis of pyrimidine-fused skeletons through copper-catalyzed consecutive Sonogashira coupling and aminocyclization.

A copper-catalyzed sequence involving a Sonogashira coupling reaction and 5-exo-dig aminocyclization between a terminal alkyne and a 2-(2-bromophenyl)pyrimidine analog based on six-membered rings is presented. This protocol provides a controlled and modular approach to access a variety of synthetically useful pyrimidine-fused skeletons with high efficiency, broad substrate scope, and excellent functional group compatibility. Under acidic conditions, the (Z)-configuration of products spontaneously converts into (E)-9-benzylidene-1,9-dihydro-11H-pyrazolo[4',3':4,5]pyrimido[2,1-a]isoindol-11-ones.

[Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway].

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Modular synthesis of 3-substituted isocoumarins via silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes.

A method involving silver-catalyzed aerobic oxidation/6-endo heterocyclization of ortho-alkynylbenzaldehydes to yield 3-substituted isocoumarins is described. The developed protocol allows convenient access to a range of synthetically useful 3-substituted isocoumarins and related fused heterocyclolactones in good to high yields, using silver tetrafluoroborate as the catalyst, and atmospheric oxygen as the terminal oxidant and the source of endocyclic oxygen. Mechanistic studies suggest the involvement of a free-radical pathway.

Silver-Assisted [3 + 2] Annulation of Nitrones with Isocyanides: Synthesis of 2,3,4-Trisubstituted 1,2,4-Oxadiazolidin-5-ones.

A silver-assisted method for [3 + 2] annulation of nitrones with isocyanides has been developed. The developed protocol allows access to a variety of 2,3,4-trisubstituted 1,2,4-oxadiazolidin-5-one derivatives as single diastereomers in good to excellent yields using silver oxide as the catalyst and molecular oxygen as the terminal oxidant. A plausible mechanism involving a nucleophilic addition/cyclization/protodeargentation/oxidation pathway is proposed on the basis of experimental results.

Silver-Mediated Synthesis of Substituted Benzofuran- and Indole-Pyrroles via Sequential Reaction of ortho-Alkynylaromatics with Methylene Isocyanides.

A silver-mediated reaction between 2-ethynyl-3-(1-hydroxyprop-2-yn-1-yl)phenols or 2-ethynyl-3-(1-hydroxyprop-2-yn-1-yl)anilines and methylene isocyanides has been developed. A sequential 5-endo-dig cyclization and [3 + 2] cycloaddition process is proposed. This synthetic strategy is atom- and step-efficient and applicable to a broad scope of substrates, allowing the synthesis of valuable substituted benzofuran- and indole-pyrroles in moderate to high yields.

Synthesis of Substituted 4 H-Thiochromen-4-imines via Copper-Catalyzed Cyclization Cascades of o-Bromobenzothioamides with Terminal Alkynes.

A series of ( E)- N-aryl-4 H-thiochromen-4-imines has been conveniently obtained through a cascade reaction between o-bromobenzothioamides and terminal alkynes. This novel approach probably involved an initial generation of benzothietane-2-imine intermidates via an intramolecular Ullmann reaction under CuI/L-proline cocatalysis and alkaline conditions followed by imine alkynylation, ring opening, and cyclization sequences to provide the unexpected 4 H-thiochromen-4-imines rather than isothiochromans.

An efficient synthesis of 16H-dibenzo[2,3:6,7][1,4]oxazepino[5,4-b]quinazolin-16-ones via an Ullmann reaction catalyzed by CuI.

CuI functions as a mild Lewis acid catalyst to promote the condensation and cyclization reaction of 2-amino-N-(2-hydroxyphenyl)benzamide and 2-bromobenzaldehyde to build the quinazoline moiety first. With the addition of Cs2CO3, it also can catalyse the subsequent intramolecular Ullmann type reaction to give 16H-dibenzo[2,3:6,7][1,4]oxazepino[5,4-b]quinazolin-16-ones in good yields.

Dioxane-involving reaction for the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines catalyzed by AgOTf.

Dioxane was found to be involved in the reaction of 2-(arylethynyl)benzaldehydes and 3-aminopyrazine-2-carbohydrazide, and underwent a ring-opening reaction catalyzed by AgOTf. This domino type procedure provided an efficient method for the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields via the loss of a molecule of 3-aminopyrazine-2-carboxamide.

Cu(OAc)2-Catalyzed Aerobic Oxidative Dehydrogenation Coupling: Synthesis of Heptacyclic Quinolizino[3,4,5,6-kla]perimidines.

A Cu(OAc)2-catalyzed domino tricyclization between naphthalene-1,8-diamine and 2-(phenylethynyl)benzaldehyde is described, enabling aerobic oxidative dehydrogenation coupling to access heptacyclic quinolizino[3,4,5,6-kla]perimidines. In this reaction, the formation of three new rings and four new bonds was achieved in a functional-group-compatible fashion, allowing a facile method toward fused aza-heterocycles containing both quinolizine and perimidine moieties.

Consecutive Sonogashira Coupling and Hydroamination Cyclization for the Synthesis of Isoindolo[1,2-b]quinazolin-10(12H)-ones Catalyzed by CuI/l-Proline.

A consecutive Sonogashira coupling reaction, acetylene hydroamination cyclization of 2-(2-bromophenyl)quinazolin-4(3H)-ones and terminal alkynes, is described catalyzed by CuI/l-proline in the presence of Cs2CO3. This procedure provided a facile method for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-one derivatives in good yields.

N-Heterocyclic Carbene-Catalyzed [4 + 2] Cyclization of Saturated Carboxylic Acid with o-Quinone Methides through in Situ Activation: Enantioselective Synthesis of Dihydrocoumarins.

An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] synthesis of dihydrocoumarins was realized from saturated carboxylic acids and o-quinone methides via an in situ activation strategy. This protocol results in excellent diastereoselectivity and enantioselectivity and good yields and uses readily available and inexpensive starting materials.

An efficient synthesis of 6-arylbenzo[4,5]imidazo[2,1-a]isoquinolines via sequential α-arylation of carbonyl and deacylation catalyzed by CuI.

Dibenzoyl methane was found to undergo α-arylation of carbonyl and deacylation reaction with 2-(2-bromophenyl)-1H-benzo[d]imidazoles catalyzed by CuI in the presence of Cs2CO3, and provided an efficient synthesis of 6-arylbenzo[4,5]imidazo[2,1-a]isoquinolines via subsequent intra-molecular nucleophilic addition and dehydration.

Copper-catalyzed synthesis of arylcarboxamides from aldehydes and isocyanides: the isocyano group as an N1 synthon.

An interesting radical coupling reaction of aromatic aldehydes with isocyanides was disclosed for the synthesis of amides catalyzed by copper. According to the experimental results and mechanistic study, the isocyano group acted as an N1 synthon rather than exhibiting the carbene-like reactivity, exploiting a new reactivity profile of isocyanides.

Iodine-catalyzed synthesis of dibenzo[b,h][1,6]naphthyridine-11-carboxamides via a domino reaction involving double elimination of hydrogen bromide.

An iodine-catalyzed reaction of 2-aminobenzamides and mucobromic acid was described and utilized to synthesize a variety of 6-oxo-5,6-dihydrodibenzo[b,h][1,6]naphthyridine-11-carboxamide derivatives in refluxing THF. As the two bromine atoms in mucobromic acid were found missing in the dibenzonaphthyridine products, a domino-type reaction mechanism involving a double elimination of hydrogen bromide was proposed.

Enantioselective assembly of spirocyclic oxindole-dihydropyranones through NHC-catalyzed cascade reaction of isatins with N-hydroxybenzotriazole esters of α,ß-unsaturated carboxylic acid.

An NHC-catalyzed formal [4 + 2] reaction of isatins with N-hydroxybenzotriazole ester of α,ß-unsaturated carboxylic acids bearing γ-H to construct spirocyclic oxindole-dihydropyranones featuring a chiral tetrasubstituted carbon stereogenic center was developed. The high enantioselectivity, the ready availability of the raw materials, the facile assembly, and the potential biological significance of the final products make this protocol an attractive alternative for the synthesis of spirocyclic heterocycles.

CuI-catalyzed C-N bond formation and cleavage for the synthesis of benzimidazo[1,2-a]quinazoline derivatives.

A copper(I)-catalyzed domino reaction of N-(2-benzimidazolyl)-2-aminobenzamide and 2-halogenated benzaldehyde has been studied. The procedure is based on a sequential CuI-catalyzed Ullmann reaction (C-N bond formation) and two bond cleavage reactions and provides an efficient strategy for the synthesis of benzimidazo[1,2-a]quinazolines catalyzed by CuI/L-proline.

General Approach to Amides through Decarboxylative Radical Cross-Coupling of Carboxylic Acids and Isocyanides.

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.