Search

Environmentally friendly acid-catalyzed ynamide N–Csp bond cleavage, skeletal rearrangement and chemo-, regio- and stereospecific functionalization with nucleophiles are of great interest in synthetic chemistry. However, such transformations present remarkable regio- and stereospecific challenges due to the biased carbon–carbon (α and β) triple bonds in ynamides. Herein, we developed a greener and faster acid-catalyzed ynamide N–Csp bond fission, skeletal rearrangement and stereospecific functionalization with nucleophilic anisole derivatives to produce thermodynamically unstable challenging cis-alkene tethered indole scaffolds in a very short reaction time (5–10 min). The key features of this transformation are its transition-metal-free nature, broad scope, ease of handling, simple setup, mild reaction conditions, atom/step/time economy, and the gram-scale experiment. Most importantly, 13C-isotope labeling experiments in mechanistic studies confirmed the alkyne-carbon position in the rearrangement process. The green chemistry metrics evaluation and EcoScale score (75 on a scale of 0–100) indicate that our transformation is safer, environmentally friendly, and economically feasible. [ABSTRACT FROM AUTHOR]

We synthesized tetrasubstituted olefins regioselectively and stereoselectively from ynamides and internal alkynes with sulfonyl iodides under blue LEDs in few minutes. The key features are being metal-free, easy to handle, simple, broad in scope, and environmentally friendly. Furthermore, a gram-scale experiment was conducted, and the synthesized corresponding sulfonyl-iodinated products were smoothly altered into various other products. [ABSTRACT FROM AUTHOR]

Herein, we have developed metal and oxidant-free visible light-promoted alkene vs. alkyne regio- and chemoselective radical cascade cyclization of electronically unbiased 1,6-enynes with chalcogens to synthesize substituted pyrrolidines bearing chalcogens. The reaction generated three new bonds, namely, C–SO2, C–C, and C–Se under extremely mild conditions. Furthermore, we achieved regio- and chemoselective mono-addition of aromatic thiophenols with unactivated 1,6-enynes. The key features of this protocol are broad substrate scope, environment-friendly conditions, operational simplicity, atom economy, and amenability to gram-scale synthesis. The mechanistic studies corroborate that the reaction proceeds via a radical pathway. [ABSTRACT FROM AUTHOR]

The development of a method for performing radical initiated intramolecular cascade cyclization of 1,n-enynes provided a competent protocol for producing structurally diverse complex heterocycles. Herein, we demonstrate I2/TBHP promoted, solvent controlled, regio- and chemoselective 5-exo-trig or 6-endo-trig radical cyclization of electronically unbiased 1,n-enynes to synthesize nitrogen-containing heterocycles. These metal-free protocols confer access to synthetically robust piperidine motif-bearing iodinated-homoallylic alcohol and pyrrolidine fused cyclopropane rings. The key factor in these methods is operational simplicity, and the environmentally friendly reaction system works under exceedingly mild conditions. Furthermore, the source of hydroxyl groups in the tertiary alcohols is indirectly confirmed with H218O labeled studies. Based on mechanistic studies, all of these cyclizations were initiated through single electron oxidation. The products with active C–I bonds present opportunities for further transformations. [ABSTRACT FROM AUTHOR]

The FeCl3-promoted ring size-controlled oxidative activation of o-alkynylanilines opens up a complementary appealing protocol for poly-N-heterocycle synthesis. When electron-poor π-alkyne iron species combine with cyclic enamines obtained from cyclohexanone and β-tetralone, they undergo a regioselective 6-exo-dig cyclization to afford the corresponding dibenzo[b,j][1,10]phenanthrolines and 12-benzoylated dihydrobenzo[a]acridine skeletons. Later, these acridine motifs become completely unsaturated due to dehydrogenative aromatization via the aza-allyl oxidation intermediate. We obtained all quaternary carbon centre pseudoindoxyls through the Mannich-type alkylation of 2,3-dihydro-1H-inden-1-one with cyclic ketimines generated from the in situ intramolecular nucleophilic cyclization of o-alkynylanilines. [ABSTRACT FROM AUTHOR]

Oximes have been identified as reusable templates for the synthesis of ureas and carbamates by an in situ generation of carbamoyl oximes under metal-free conditions. The recovered oxime has been utilised for three trials in the synthesis of urea derivatives without any loss in the yield and efficiency. In addition, this template approach could override the usage of hazardous and less stable isocyanates as substrates. [ABSTRACT FROM AUTHOR]

Aerobic oxidative tandem conversion of PEG-400 to acetyl radical via C-C and C-O bond cleavages followed by silver-catalyzed menisci-type addition to the C3 position of quinoxalin-2(1H)-one is described. This reaction involves the in situ formation of the acetyl radical from PEG-400 via a sequence of acetaldehyde, 2-oxopropanal and, 2-oxopropanoic acid formation and successive oxidative cleavage to form the acetyl radical. This protocol uses cheap, readily available and environmentally-friendly PEG-400 as the acetyl source and solvent. The in situ generated acetyl radicals from PEG-400 have been coupled to a broad range of electron-deficient quinoxalin-2(1H)-one compounds in a menisci-type reaction.

The FeCl 3 -promoted ring size-controlled oxidative activation of o-alkynylanilines opens up a complementary appealing protocol for poly-N-heterocycle synthesis. When electron-poor π-alkyne iron species combine with cyclic enamines obtained from cyclohexanone and β-tetralone, they undergo a regioselective 6-exo-dig cyclization to afford the corresponding dibenzo[b,j][1,10]phenanthrolines and 12-benzoylated dihydrobenzo[a]acridine skeletons. Later, these acridine motifs become completely unsaturated due to dehydrogenative aromatization via the aza-allyl oxidation intermediate. We obtained all quaternary carbon centre pseudoindoxyls through the Mannich-type alkylation of 2,3-dihydro-1H-inden-1-one with cyclic ketimines generated from the in situ intramolecular nucleophilic cyclization of o-alkynylanilines.