Chemospecific C3- and C2-Olefinations of Isatins by TfOH-Promoted Tandem Aldol-Grob and Semiacetalization-Grob Fragmentations.

A novel method for TfOH-promoted chemospecific C3- and C2-olefinations of isatins is developed, which offers the first examples of Grob fragmentation using isatins and amides as substrates.

Tandem Synthesis of 2-Azaspiro[4.5]deca-1,6,9-trien-8-ones Based on Tf2O-Promoted Activation of N-(2-Propyn-1-yl) Amides.

Structurally novel 2-azaspiro[4.5]deca-1,6,9-trien-8-ones were synthesized from N-(2-propyn-1-yl) amides and 1,3,5-trimethoxybenzenes by a tandem method consisting of a Tf2O-promoted amide activation and a TfOH-promoted Friedel-Crafts ipso-cyclization. The method offered the first example of using N-(2-propyn-1-yl) amides as substrates in both Tf2O-promoted secondary amide activation and the synthesis of azaspiro[4.5]deca-6,9-diene-8-ones.

Mechanistic Insights into Tf2O-Promoted Electrophilic Activation of 2-Propynamides and a New Synthesis of 2,4-Disubstituted Quinolines.

Direct evidence explaining why 2-propynamides have never been used as substrates in Tf2O-promoted electrophilic activations was obtained. Furthermore, a new method for the synthesis of structurally special 2,4-disubstituted quinolines was developed, by which the substituent at position 2 of quinolines can be diversified easily.

Bischler-Napieralski Synthesis of Polycyclic N-Heteroaromatics Based on Tf2O-Promoted Electrophilic Activation of N-Aryl-2-Propynamides.

2-Propynamides have been never used as substrates in classic and Tf2O-promoted Bischler-Napieralski reactions. In this article, a novel tandem synthesis of benzo[a]acridines is developed from N-aryl-2-propynamides and alkynes consisting of a Tf2O-promoted intermolecular Bischler-Napieralski reaction and a TfOH-promoted intramolecular Friedel-Crafts reaction.

Tandem Synthesis of 1,3-Disubstituted Naphthalenes via TfOH-Promoted Directed-Aldol and Friedel-Crafts Reactions.

A TfOH-promoted tandem synthesis of 1,3-disubstituted naphthalenes is developed via a directed-aldol reaction and a Friedel-Crafts reaction. Two new C-C bonds and one new benzene ring are created efficiently in one pot due to the discovery of a TfOH-promoted highly chemoselective directed-aldol reaction between two different ketones with α-hydrogens.

Bischler-Napieralski Synthesis of 6-Alkynyl Phenanthridines Based on Tf2O-Promoted Electrophilic Activation of N-Aryl-2-propynamides.

An efficient method for the synthesis of 6-alkynyl phenanthridines was developed. The method offered the first example to use 2-propynamides as substrates in the Bischler-Napieralski reaction and to create alkynylnitrilium triflates as new active intermediates in organic synthesis.

General Synthesis of Fully Substituted 4-Aminooxazoles from Amides and 1,4,2-Dioxazol-5-ones Based on Amide Activation and Umpolung Process.

A general and efficient synthesis of fully substituted 4-aminodixazoles was developed based on the strategies of amide activation and umpolung reaction. In this method, 1,4,2-dioxazol-5-ones were introduced as a rare type of umpolung reagent bearing a nucleophilic N-atom that could be used well together with the activating agent Tf2O. Because 1,4,2-dioxazol-5-ones played triple roles as an umpolung reagent, a substrate, and a weak base, the method proceeded smoothly under extremely convenient conditions.

General Synthesis of α-Alkyl Ynones from Morpholine Amides and 1-Copper(I) Alkynes Promoted by Triflic Anhydride.

The first general method for the synthesis of α-alkyl ynones was developed based on the strategy of electrophilic activation of amides. Its distinctive advantages are attributed to the use of air-stable "bare" 1-copper(I) alkyne as a mild nucleophile without any exogeneous ligand.

A Method for Bischler-Napieralski-Type Synthesis of 3,4-Dihydroisoquinolines.

A new method for the Bischler-Napieralski-type synthesis of 3,4-dihydroisoquinolines was developed by a Tf2O-promoted tandem annulation from phenylethanols and nitriles. Its success was mainly due to the fact that a phenonium ion was formed in the process and practically functioned as a stable and reactive primary phenylethyl carbocation.

Metal-Free Method for Direct Synthesis of Functionalized ß-Ketoenamines.

A new method for direct synthesis of ß-ketoenamines was developed by a BF3·OEt2-catalyzed cyclization of 1-iodoalkyne and α-keto acid followed by an amine-mediated ring-opening in one pot. Its metal-free conditions allowed the easy synthesis of those products bearing the transition metal-sensitive functional groups. Its three-component process achieved wide range of functionalized products.

A general two-step one-pot synthesis process of ynones from α-keto acids and 1-iodoalkynes.

A general two-step one-pot synthesis process of ynones was developed by cycloaddition of α-keto acids and 1-iodoalkynes followed by a ring-opening reaction. Its easy conditions and novel mechanism endowed it with two distinctive advantages: iodine-atom bonded to C(sp2) remained intact and α-keto acids became a part of the triple bonds in ynones.

N-Sulfonyl acetylketenimine as a highly reactive intermediate for the synthesis of N-sulfonyl amidines.

A highly reactive intermediate N-sulfonyl acetylketenimine was generated from a 3-butyn-2-one participating CuAAC/ring-opening method. Its high reactivity due to bearing two EWGs allowed us to offer the first example of a reaction between ketenimine and amide to synthesize N-sulfonyl amidines efficiently.

Silver-catalyzed decarboxylative acylation of quinoxalin-2(1H)-ones with α-oxo-carboxylic acids.

A novel silver-catalyzed decarboxylative acylation of α-oxo-carboxylic acids was developed, by which various 3-acyl quinoxalin-2(1H)-ones were synthesized by direct C-H bond acylation of quinoxalin-2(1H)-ones. In this method, α-oxo-carboxylic acids served as efficient acylating reagents to in situ generate the required active acyl radical. Its excellent chemoselectivity allowed the molecular diversity of 3-acyl quinoxalin-2(1H)-ones to be achieved by convenient functionalizations of both N1- and C3-positions.

Tandem Synthesis of α-Diazoketones from 1,3-Diketones.

A highly efficient synthesis of α-diazoketone was achieved by simply stirring the mixture of 1,3-diketone, TsN3, and MeNH2 in EtOH. It was a tandem reaction including a novel primary amine-catalyzed Regitz diazo transfer of 1,3-diketone and a novel primary amine-mediated C-C bond cleavage of 2-diazo-1,3-diketone.

Ruthenium-Catalyzed Synthesis of Fused Tricyclic 1H-2,3-Dihydropyrimido[1,2-a]quinolines in One Step.

A novel ruthenium-catalyzed intramolecular cyclization of a nitrile and an azetidine was developed to achieve a one-step synthesis of the fused tricyclic 1H-2,3-dihydropyrimido[1,2-a]quinoline, which is the core skeleton for more than 100 natural pyoverdines and is also responsible for their fluorescence.

In-situ Generated and Premade 1-Copper(I) Alkynes in Cycloadditions.

The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was discovered in 2002, which has become the most remarkable example for "click chemistry" to date. In CuAAC reaction, 1-copper(I) alkyne has been recognized to be a key intermediate. However, many contradictory experimental results for this intermediate were reported in literature. For example, only the in-situ generated 1-copper(I) alkyne was used, while the premade 1-copper(I) alkyne proved to be inefficient under the standard conditions. The kinetic studies indicated that CuAAC reaction had a strict second-order dependence on Cu(I) and the DFT studies demonstrated that 1-copper(I) alkyne intermediate should be a dinuclear copper(I) complex. But these results were inconsistent with the structure of the premade 1-copper(I) alkyne. Although hundreds of structurally different ligands were reported to significantly enhance the efficiency of CuAAC reaction, their functions were assigned to prevent the oxidation and the disproportionation of Cu(I) ion. Based on the investigation of the references and our works, we proposed that the in-situ generated 1-copper(I) alkyne in CuAAC reaction is not identical with the premade 1-copper(I) alkyne. The ligands may play dual roles to activate the 1-copper(I) alkyne by blocking the polymerization of the in-situ formed 1-copper(I) alkynes and dissociating the polymeric structures of the premade 1-copper(I) alkynes. As a result, we first disclosed that carboxylic acids can function as such activators and a novel carboxylic acid-catalyzed CuAAC strategy was developed, which has been proven to be the most convenient and highly efficient CuAAC method to date. Furthermore, highly efficient and regioselective methods for the syntheses of 1,4,5-trisubstituted 1,2,3-triazoles were developed by using the premade 1-copper(I) alkynes as substrates, in which the novel function of the premade 1-copper(I) alkynes as excellent dipolarophiles was first disclosed and applied. In this article, a series of works reported by our group for the in-situ generated and the premade 1-copper(I) alkynes in cycloadditions are reviewed.

Synthesis of N-Sulfonyl Arylaldimines Developed by Retesting an Old Process.

By simply heating the mixture of an arylaldehyde and a sulfonylisocyanate in a solvent or in neat form under catalyst- and additive-free conditions, the desired N-sulfonylimine was produced with the release of carbon dioxide. The method is characterized by its unique clean efficiency, convenience, and scalability, but it was reported to fail half a century ago.

[Crosslinking sodium hyaluronate gel with different ratio of molecular weight for subcutaneous injection: animal experimental study and clinical trials subcutaneous injection].

OBJECTIVE: To investigate the biocompatibility and degradation rate of crosslinking sodium hyaluronate gel with different ratio of molecular weight, so as to choose the effective, safe and totally degraded hyaluronate gel for aesthetic injection. METHODS: (1) Compound colloid was formed by cross-linking the divinyl sulphone and sodium hyaluronate with different molecular weight (4 x 10(5), 8 x 10(5), 10 x 10(5), 12 x 10(5)). (2) Healthy level KM mice was randomly divided into two groups to receive hyaluronic acid gel or liquid injection. Each group was subdivided into three subgroup to receive hyaluronic acid with different molecular weight. The biocompatibility and degradation rate, of hyaluronate were observed at 7, 90, 180 days after injection. At the same time, different molecular weight of sodium hyaluronate gel is sealed or exposed respectively under the low temperature preservation to observe its natural degradation rate. (3) The most stable colloid was selected as aesthetic injector for volunteers to observe the aesthetic effect. RESULTS: The sodium hyaluronate gel with molecular of 4 x 10(5) was completely degraded 90 days later. The sodium hyaluronate gel with molecular of 8 x 10(5) was completely degraded 180 days later. The sodium hyaluronate gel with molecular of 10 x 10(5) was degraded to 90.0% after 180 days. The sodium hyaluronate liquid can be degraded completely within 7 days. The colloid could be kept for at least 12 months when sealed under low temperature, but was totally degraded when exposed for I d. Sodium hyaluronate gel with molecular 10 x 10(5) was confirmed to be kept for at least 6 months in animal experiment and clinical trials. CONCLUSIONS: Under the same condition of material ratio, the higher the molecular weight is, the lower the degradation rate is. But the liquidity of gel is not good for injection when molecular weight is too large. It suggests that Sodium hyaluronate gel with molecular 10 x 10(5) maybe the best choice in cosmetic injections.

Tandem Synthesis of 3-chloro-4-iodoisoxazoles from 1-copper(I) alkynes, dichloroformaldoxime, and molecular iodine.

A tandem synthesis for structurally novel 3-chloro-4-iodoisoxazoles was developed by simply mixing 1-copper(I) alkynes, dichloroformaldoxime, and molecular iodine together. The combination of 1-copper(I) alkyne and molecular iodine was well used as a synthetic equivalent of 1-iodoalkyne without the need for tedious preparation, purification, and storage of 1-iodoalkyne.

Tandem synthesis of 3-halo-5-substituted isoxazoles from 1-copper(I) alkynes and dihaloformaldoximes.

A tandem synthesis of 3-halo-5-substituted isoxazoles has been developed from 1-copper(I) alkynes and dihaloformaldoximes under base-free conditions. Thus, 1,3-dipolar cycloaddition and all its drawbacks can now be avoided completely.