Diastereoselective Syntheses of Spiro[indoline-3,4'-pyridin]-2-yl Carbamates via AgOTf/Ph3P-Catalyzed Tandem Cyclizations of Tryptamine-Ynesulfonamides.

Spiro[indoline-3,4'-piperidine] is a significant structural scaffold in numerous polycyclic indole alkaloids with a variety of bioactivities. In this study, a synthetic strategy was developed to access spiro[indoline-3,4'-pyridin]-2-yl carbamate via an AgOTf/PPh3-catalyzed tandem cyclization of tryptamine-ynesulfonamides. The unique feature of this strategy is the efficient intermolecular capturing of the in situ generated spiroindoleninium intermediates with carbamates, leading to the diastereoselective syntheses of spiro[indoline-3,4'-pyridin]-2-yl carbamate derivatives. A broad scope of this cyclization was demonstrated by a variety of tryptamine-ynesulfonamide substrates and several carbamates. A plausible mechanism of this reaction was proposed.

Solid-State Radical C-H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials.

The application of piezoelectricity for the generation of trifluoromethyl (CF3 ) radicals is reported together with the development of a method for the mechanochemical C-H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C-H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.

Iridium(I)-Catalyzed C-H Borylation in Air by Using Mechanochemistry.

Mechanochemistry has been applied for the first time to an iridium(I)-catalyzed C-H borylation reaction. By using either none or just a catalytic amount of a liquid, the mechanochemical C-H borylation of a series of heteroaromatic compounds proceeded in air to afford the corresponding arylboronates in good-to-excellent yields. A one-pot mechanochemical C-H borylation/Suzuki-Miyaura cross-coupling sequence for the direct synthesis of 2-aryl indole derivatives is also described. The present study constitutes an important milestone towards the development of industrially attractive solvent-free C-H bond functionalization processes in air.

N-Fluorobenzenesulfonimide as a highly effective Ag(i)-catalyst attenuator for tryptamine-derived ynesulfonamide cycloisomerization.

N-Fluorobenzenesulfonimide (NFSI) was identified for the first time as a highly effective Ag(i)-catalyst attenuator in the annulation of a tryptamine-derived ynesulfonamide to azepino[4,5-b]indole derivatives. Substrate tolerances were examined thoroughly and a plausible mechanism was proposed. The interaction between the Ag(i) catalyst and NFSI was probed by density functional theory (DFT) calculations. This study provided a highly efficient method to synthesize azepino[4,5-b]indole derivatives.

Copper(i)-catalysed stereoselective debromoborylation of aliphatic 1,1-dibromo-1-alkenes with bis(pinacolato)diboron.

A stereoselective debromoborylation of aliphatic 1,1-dibromo-1-alkenes to prepare (Z)-1-bromo-1-alkenylboronate esters using copper(i) catalysts was developed. The debromoborylation of various aliphatic 1,1-dibromo-1-alkenes in the presence of a copper(i) catalyst and bis(pinacolato)diboron proceeded smoothly to produce (Z)-1-bromo-1-alkenylboronate esters in good yields with only Z geometry.

Mechanochemical synthesis of magnesium-based carbon nucleophiles in air and their use in organic synthesis.

Since the discovery of Grignard reagents in 1900, the nucleophilic addition of magnesium-based carbon nucleophiles to various electrophiles has become one of the most powerful, versatile, and well-established methods for the formation of carbon-carbon bonds in organic synthesis. Grignard reagents are typically prepared via reactions between organic halides and magnesium metal in a solvent. However, this method usually requires the use of dry organic solvents, long reaction times, strict control of the reaction temperature, and inert-gas-line techniques. Despite the utility of Grignard reagents, these requirements still represent major drawbacks from both an environmental and an economic perspective, and often cause reproducibility problems. Here, we report the general mechanochemical synthesis of magnesium-based carbon nucleophiles (Grignard reagents in paste form) in air using a ball milling technique. These nucleophiles can be used directly for one-pot nucleophilic addition reactions with various electrophiles and nickel-catalyzed cross-coupling reactions under solvent-free conditions.

Redox reactions of small organic molecules using ball milling and piezoelectric materials.

Over the past decade, photoredox catalysis has harnessed light energy to accelerate bond-forming reactions. We postulated that a complementary method for the redox-activation of small organic molecules in response to applied mechanical energy could be developed through the piezoelectric effect. Here, we report that agitation of piezoelectric materials via ball milling reduces aryl diazonium salts. This mechanoredox system can be applied to arylation and borylation reactions under mechanochemical conditions.

Access to Benzo[a]carbazoles and Indeno[1,2-c]quinolines by a Gold(I)-Catalyzed Tunable Domino Cyclization of Difunctional 1,2-Diphenylethynes.

The cyclization order of the difunctional 1,2-diphenylethynes was precisely tuned under the catalysis of gold by changing the nitrogen substitution of the substrates, leading to the facile preparation of benzo[a]carbazole and indeno[1,2-c]quinoline derivatives. The mechanisms of these domino cyclizations were probed by control experiments, and an insight into the selectivity of the cyclization was gained by density functional theory (DFT) calculations. This research represents a unified and common method to access benzo[a]carbazoles and indeno[1,2-c]quinolines.