Synthesis of heterocycles via ligand-free palladium catalyzed reductive Heck cyclization

Synthesis of five and six membered heterocycles, indolines, 2,3-dihydrobenzofurans, chromans, isochromans, 1,2,3,4-tetrahydroquinolines, and 1,2,3,4-tetrahydroisoquinolines, in 70-99% yield by a ligand-free palladium catalyzed reductive Heck cyclization of phenyl bromides and chlorides, under mild conditions, is reported. Water was found to be essential for these reactions.     

Efficient synthesis of the 3-benzazepine framework via intramolecular Heck reductive cyclization

A microwave-assisted protocol based on reductive Heck reaction was developed for regio- and stereoselective construction of the 3-benzazepine core.     

A model study for constructing the DEF-benzoxocin ring system of menogaril and nogalamycin via a reductive Heck cyclization

A novel reductive Heck cyclization approach was developed in order to construct a model DEF-benzoxocin ring system that is present in nogalamycin, menogaril, and related anthracycline antitumor antibiotics.     

Direct synthesis of fused indoles by gold-catalyzed cascade cyclization of diynes

A direct, concise, and atom-economical synthetic method for the generation of fused indoles, using a gold-catalyzed cascade cyclization of diynes, has been developed. The reaction gave various fused indoles, such as aryl-annulated[a]carbazoles, dihydrobenzo[g]indoles, and azepino- or oxepinoindole derivatives in good to excellent yields, through an intramolecular cascade 5-endo-dig hydroamination followed by a 6- or 7-endo-dig cycloisomerization, without producing theoretical byproduct. Three of the resulting indoles exhibited potent antifungal activities against T. mentagrophytes and T. rubrum, demonstrating the practical application of the described cascade reaction for drug discovery.     

Task-specific ionic liquid-catalyzed efficient couplings of indoles with 1,3-dicarbonyl compounds: an efficient synthesis of 3-alkenylated indoles

Direct alkenylation of indoles at the 3-position with 1,3-dicarbonyl compounds under Brønsted acidic ionic liquid catalysis has been developed. The yields were excellent, and the catalyst can be reused at least six times without noticeable loss of catalytic activity.     

Direct electroreductive preparation of indolines and indoles from diazonium salts

[reaction: see text] Indolines and indoles are prepared for the first time by direct electrochemical reduction of arenediazonium salts.     

Palladium-catalyzed intramolecular Heck dearomative gem-difluorovinylation of indoles

A palladium-catalyzed dearomative reaction of indoles has been developed through a domino Heck/gem-difluorovinylation sequence. By taking advantage of a difluorocarbene precursor (ClCF₂COONa), the palladium difluorocarbene ([Pd] CF₂) species was formed smoothly. Then, a migratory insertion/β-H elimination process enabled access to polycyclic indolines containing 1,1-difluoroethylene units in acceptable yields with a broad substrate scope, which also showed dearomative gem-difluorovinylation for the first time. Remarkably, the superb diversified transformations allowed the product to install various functional groups.

Dearomative gem-difluorovinylation was reported for the first time and provided a new way to construct complex organofluorine compounds rapidly.     

An efficient synthesis of indoles via a CuMgAl-LDH-catalyzed cyclization of 2-alkynylsulfonanilides

A highly efficient method for the synthesis of indoles has been successfully developed via a CuMgAl-LDH-catalyzed intramolecular annulation reaction of 2-alkynylsulfonanilides. This CuMgAl-LDH catalyst features facile preparation, recovery, and reuse at least seven times without a marked loss in the catalytic activity, as well as the unique dual activation. Moreover, the crystal structures and Hirshfeld surface analysis of typical indole compounds were also presented.     

Mild and efficient cyclization reaction of 2-ethynylaniline derivatives to indoles in aqueous medium

Results of the optimized cyclization reaction of 2-ethynylaniline derivatives to indoles catalyzed by copper(II) salts are described. The reactions can be carried out in a mixture of H₂O and MeOH in the presence of 1-ethylpiperidine at room temperature. These conditions can be applied to a bulky substrate, which is difficult to be cyclized efficiently by existing reaction conditions. Furthermore, this reaction condition was applied to a catalyst recycling reaction system.     

Synthesis of novel KDR kinase inhibitors through catalytic reductive cyclization of o-nitrobenzylcarbonyl compounds

An efficient synthesis of o-nitrobenzylcarbonyl compounds is demonstrated through the Swern-type oxidation of readily accessible phenethanol analogues. Reductive cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H-indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase inhibitor 1 in quantitative yield. The examination of the reductive cyclization reaction and optimization of conditions is described.     

Improved procedure for the reductive phenylation and cyclization of nitroarenes

The reductive phenylation of nitroarenes was improved by using iron pentacarbonyl (IPC) as a reducing reagent. The method was applied to the synthesis of ellipticine and dibenzazocine derivatives.     

Ammonium formate-based one-pot reductive Heck reactions for the construction of cyclic sulfonamides

A modified method is reported for the conversion of unsaturated sulfonamides into their cyclic saturated counterparts. This method utilises a single palladium catalyst for an intramolecular Heck reaction and subsequent transfer hydrogenation, which is achieved in one-pot following the addition of ammonium formate. Accordingly, a range of fourteen structural variations are reported and under optimal conditions the adducts were generated in typically good to excellent yields. Notably, discrimination of differentially substituted dienes can be accomplished in the case of compounds 28 and 29 and the process was only observed to fail with the more sterically hindered precursor 32.     

Theoretical evidence for oxygenated intermediates in the reductive cyclization of nitrobenzenes

Deoxygenation of nitroaromatics is a classic synthetic method for the construction of nitrogen heterocycles. The generally accepted mechanism involves exhaustive deoxygenation to a singlet nitrene. We present theoretical evidence for an alternative, 6pi-electron 5-atom electrocyclization of nitroso-styrenes, -stilbenes, and -biphenyls to nitronates. A downstream 1,5-H shift and tautomerization leads to N-hydroxy heterocycles. [reaction: see text]     

The intramolecular reductive cyclization of cyclic enones

The reductive cyclization (electrohydrocyclization reaction) of tethered cyclic enones has been investigated under electrochemical, metal-mediated, and photochemical conditions. The tricyclic products are generally formed with excellent stereoselectivity, particularly if at least one of the enones is β,β-disubstituted.     

Copper-catalyzed domino intramolecular cyclization: a facile and efficient approach to polycyclic indole derivatives

A mild and efficient Cu(2)O-catalyzed domino intramolecular C-N coupling/C-Y (Y = O, S, N) bond formation was successfully achieved. Thus oxazino[3,2-a]indole, thiazino[3,2-a]indole and indolo[2,1-b]quinazoline derivatives were facilely assembled from readily accessible gem-dibromovinyl systems. The protocol is general and practical, affording a variety of the indole-incorporated products in good to excellent yields even under air atmosphere.     

Total synthesis of (-)-galanthamine and (-)-lycoramine via catalytic asymmetric hydrogenation and intramolecular reductive Heck cyclization

A synthetic strategy featuring efficient ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryloxy cyclic ketone via dynamic kinetic resolution and palladium-catalyzed intramolecular reductive Heck cyclization has been developed for the asymmetric total synthesis of (-)-galanthamine (20.1%, 12 steps) and (-)-lycoramine (40.2%, 10 steps).