Metal-Free Highly Regioselective 1,4-Sulfonyliodination of 1,3-Enynes.

Herein, a novel, practical, and green synthetic method using readily available 1,3-enynes with sulfonyl hydrazides and I2 through tert-butyl hydroperoxide (TBHP)-mediated 1,4-sulfonyliodination has been developed for synthesizing various tetrasubstituted allenyl iodides under metal-free conditions. Notably, the proposed method exhibits a broad substrate scope, operational simplicity, tolerance to air, high functional-group tolerance, satisfactory yields, and excellent regioselectivity as well as involves the use of cost-effective reagents such as green oxidants.

Copper-Catalyzed 1,1-Alkylmonofluoroalkylation of Terminal Alkynes with Diazo Compounds and 2-Fluoro-1,3-dicarbonyl Compounds: Access toward (E)-ß-Monofluoroalkyl-ß,γ-unsaturated Esters or Ketones.

An efficient copper-catalyzed three-component 1,1-alkylmonofluoroalkylation of terminal alkynes, diazo compounds, and 2-fluoro-1,3-dicarbonyl compounds for the synthesis of (E)-ß-monofluoroalkyl-ß,γ-unsaturated esters or ketones has been developed. The methodology features a broad substrate scope, an inexpensive and easily available catalytic system, and excellent selectivity with good yields. The mechanism of the tandem Cu-catalyzed cross-coupling and nucleophilic addition of allenes has been investigated.

Ligand-free copper-catalyzed regio- and stereoselective 1,1-alkylmonofluoroalkylation of terminal alkynes.

The copper-catalyzed highly regio- and stereoselective 1,1-alkylmonofluoroalkylation of terminal alkynes with α-chloroacetamides and dialkyl 2-fluoromalonate or 2-fluoro-N,N-dialkyl-3-oxobutanamide without an external ligand has been realized. With this novel methodology, (E)-ß-monofluoroalkyl-ß,γ-unsaturated amides containing quaternary C-F centers can be easily constructed in good to excellent yields.

Copper-catalyzed 1,1-arylalkylation of terminal alkynes with diazo esters and organoboronic acids.

A novel copper-catalyzed 1,1-arylalkylation of terminal alkynes with diazo esters and organoboronic acids is described. With this methodology, (E)-ß-aryl-ß,γ-unsaturated esters can be easily constructed in good to excellent yields directly from readily available and inexpensive traditional coupling reagents.

Copper-Catalyzed Regio- and Stereoselective 1,1-Dicarbofunctionalization of Terminal Alkynes.

The copper-catalyzed highly regio- and stereoselective 1,1-dicarbofunctionalization of terminal alkynes is realized for the first time. Using a removable, bidentate 8-aminoquinoline auxiliary, the three-component, selective 1,1-arylalkylation of alkynes with α-haloacetamides and organoboronic acids by the addition of both alkyl and aryl groups to the terminal carbon of alkynes was achieved. Mechanistic investigations suggest that the reaction likely proceeds via the copper-catalyzed cross-coupling of terminal alkynes with α-haloamides, rearrangement, transmetalation, syn-carbocupration, and protonolysis.

Cu-Catalyzed atom transfer radical addition reactions of alkenes with α-bromoacetonitrile.

A practical, simple, and efficient copper-catalyzed atom transfer radical addition reaction of alkenes with α-bromoacetonitrile is realized. With this methodology, various γ-bromonitriles and ß,γ-unsaturated nitriles were efficiently constructed.

Ruthenium-Catalyzed ortho/meta-Selective Dual C-H Bonds Functionalizations of Arenes.

The first example of transition-metal-catalyzed ortho/meta-selective dual C-H functionalizations of arenes in one reaction is described. In this transformation, ortho-C-H chlorination and meta-C-H sulfonation of 2-phenoxypyri(mi)dines were achieved simultaneously under catalysis by [Ru(p-cymene)Cl2]2. The other reactant, namely, an arylsulfonyl chloride, played the role of both a sulfonation and chlorination reagent. More importantly, the arylsulfonyl chloride was also an oxidant in the process. Mechanistic studies indicated that six-membered ruthenacycles were the key intermediate in the reaction.

Cu-Catalyzed Aminodifluoroalkylation of Alkynes and α-Bromodifluoroacetamides.

The copper-catalyzed highly regioselective aminodifluoroalkylation of alkynes and α-bromodifluoroacetamides was realized for the first time. With this method, 3,3-difluoro-1H-pyrrol-2(3H)-ones were constructed in a single step from various alkynes and α-bromodifluoroacetamides substrates without using any extra oxidant.

A novel metal-free amidosulfenylation of alkenes leading to ß-azolyl sulfides.

A novel and environmentally benign method for C-S and C-N bond formation by the direct amidosulfenylation of alkenes has been developed under metal-free conditions. Various alkenes and azoles were transformed into the corresponding ß-azolyl sulfides in ionic liquids. The wide substrate scope, good functional group tolerance, and ease of operation make this reaction attractive for the synthesis of nitrogen- and sulfur-containing molecules.

A novel metal-free method for the selenocyanation of aromatic ketones to afford α-carbonyl selenocyanates.

A new method has been developed for the selenocyanation of aromatic ketones. This reaction avoids the need to use pre-prepared α-halo ketones, providing rapid access to α-carbonyl selenocyanates. We also investigated the mechanism for this reaction and found that it proceeds via sequential radical iodination and nucleophilic substitution reactions.

Peroxodisulfate-mediated selenoamination of alkenes yielding amidoselenide-containing sulfamides and azoles.

A new protocol for C-Se and C-N bond formation by the direct difunctionalization of alkenes is reported. The protocol is operationally simple, has a wide substrate scope, and uses readily available amino sources. This reaction represents a significant addition to the limited number of intermolecular selenide difunctionalization reactions of alkenes and would find practical application in the synthesis of nitrogen- and selenium-containing molecules.

Metal-free methylation of a pyridine N-oxide C-H bond by using peroxides.

Metal-free methylation of a pyridine N-oxide C-H bond was developed using peroxide as a methyl reagent under neat conditions. Pyridine N-oxide derivatives with various groups (e.g., Cl, NO2, and OCH3) were all suitable substrates, and the desired products were obtained in moderate to excellent yields under standard conditions. Moreover, the methylation can be performed with a good yield on the gram-scale experiment. Tentative mechanistic studies show that the methylation is a classical radical process.

Regioselective, Molecular Iodine-Mediated C3 Iodination of Quinolines.

A novel and convenient method has been developed for the regioselective iodination of quinolines at their C3 position under metal-free conditions. Iodinated quinolines, which are popular building blocks in organic and medicinal chemistry, can be prepared in gram quantities and good yields using this method and further derivatized to give increasingly complex compounds. Preliminary mechanistic studies have shown that this reaction most likely occurs via a radical intermediate.

Copper(II)-catalyzed electrophilic amination of quinoline N-oxides with O-benzoyl hydroxylamines.

Copper acetate-catalyzed C-H bond functionalization amination of quinoline N-oxides was achieved using O-benzoyl hydroxylamine as an electrophilic amination reagent, thereby affording the desired products in moderate to excellent yields. Electrophilic amination can also be performed in good yield on a gram scale.

Direct N-methylation reaction using DMSO as one-carbon bridge: convenient access to heterocycle-containing ß-amino ketones.

A novel oxidative C-S bond cleavage reaction of DMSO for dual C-C and C-N bond formation is described. A series of acetyl heteroarenes could be selectively converted into the corresponding ß-amino ketones, which are frequently found in biologically active compounds and pharmaceuticals. DMSO acted in this reaction not only as the solvent but also as a one-carbon bridge.

Regioselective C-H imidation of five-membered heterocyclic compounds through a metal catalytic or organocatalytic approach.

An efficient method for the synthesis of 2-amino and ß-amino five-membered heterocyclic derivatives that are closely related to a variety of biologically active natural products is described. Regioselectivity was achieved through a metal catalytic or organocatalytic approach. Preliminary studies on the reaction mechanism suggest a radical imidation pathway; however, further studies are needed to verify the mechanism.

nBu4NI-catalyzed oxidative imidation of ketones with imides: synthesis of α-amino ketones.

nBu4NI-Catalyzed oxidative imidation of ketones and imides for the synthesis of α-amino ketones were realized for the first time. The methodology is characterized by its wide substrate scope even for acetone with readily available phthalimide, saccharin and succinimide, which opens a new pathway for direct imidation of ketones.

Investigation on the mechanism of water-assisted palladium-catalyzed benzylic C-H amination by N-fluorobenzenesulfonimide.

A combination of computational and experimental methods was carried out to elucidate the mechanism of palladium-catalyzed water-assisted benzylic C-H amination with N-fluorobenzenesulfonimide (NFSI), which involved the oxidative addition of Pd(II) to Pd(IV)-species as a rate-limiting step, followed by water-assisted concerted metalation-deprotonation (CMD) of the Pd(IV) complex and water-assisted reductive elimination (RE) processes, and then a nucleophilic addition process to generate the final product and complete the catalytic cycle. The stability of the Pd(IV) complex could be ascribed to the suitable ligands with strong σ-donors and resistance to decomposition, as well as being sufficiently bulky because the water-clusters assembled the ligands through hydrogen bonds to act as one multidentate ligand. Calculation results suggested that water also plays a crucial role as a proton transferring bridge in water-assisted CMD and RE processes. The corresponding experimental findings substantiate the expectation. Additionally, NFSI was found to act as both the oxidant and the nitrogen source to facilitate the reaction, while the steric effect of the bulky -N(SO2Ph)2 group contributed to circumventing the o-C-H amination. In this reaction, we investigated a novel spiro-cyclopalladation intermediate, formed by the reaction of the Pd(IV) centre with pristine-carbon instead of ortho-carbon, which might be valuable for our understanding and further development of transition metal catalyzed C-H functionalization.

Reductive amination of tertiary anilines and aldehydes.

An unprecedented oxidant-mediated reductive amination of tertiary anilines and aldehydes without external reducing agents was developed via the nucleophilic attack of the oxygen atom of the carbonyl group to in situ generated iminium ions, in which tertiary anilines were used as both nitrogen source and reducing agent for the first time.

Copper-catalyzed annulation of amidines for quinazoline synthesis.

An efficient Cu-catalyzed synthesis of quinazolines via the C-N bond formation reactions between N-H bonds of amidines and C(sp(3))-H bonds adjacent to sulfur or nitrogen atoms in the commonly used solvents, such as DMSO, DMF, DMA, NMP or TMEDA, followed by intramolecular C-C bond formation reactions was developed for the first time.