Regioselective synthesis of heterocyclic scaffold by aryl radical cyclization

Regioselective synthesis of a number of coumarin‐annulated pentacyclic heterocycles have been achieved by tri‐n‐butyltin hydride‐mediated aryl radical cyclization. The products are formed as a mixture of cis‐ and trans‐ forms which were successfully separated by careful silica gel flash chromatography.     

Regioselective synthesis of quinolone-annulated sulfur heterocycles by aryl radical cyclization

The tin hydride-mediated cyclizations of a number of sulfides and sulfones under mild, neutral conditions, have been investigated accompanied by some amount of β-scission product for sulfides. The sulfides were derived from 4-mercaptoquinolone and 2-bromobenzyl bromides by phase transfer catalyzed reaction and the corresponding sulfones were prepared by treatment of the sulfides with m-CPBA at room temperature. The sulfides and the corresponding sulfones were then reacted with ⁿBu₃SnH-AIBN to give regioselective quinolone-annulated sulfur heterocycles.     

A radical cyclization between enol silyl ethers and aryl or alkenyl bromide moieties

Enol silyl ethers bearing aryl or alkenyl bromide moieties at their appropriate positions undergo radical cyclization in the presence of Bu₃SnH and AIBN to yield the corresponding 5- and 6-membered cycloalkanols in good yields.     

Synthesis of heterocyclic compounds using radical reactions and evidence for the formation of spiro radical intermediates

Synthesis of novel heterocycles using radical reactions have been described. Reaction mechanism of their formation is also presented.     

Nonconventional carbon additions to azomethines. aryl amination/indoline synthesis by direct aryl radical addition to azomethine nitrogen

[reaction: see text]. The generality of a new method for aryl amination has been defined. Ketimines derived from o-bromophenethylamine cyclize to the N-substituted indoline when treated with nBu3SnH and a radical initiator. The pH-neutral conditions tolerate base- and acid-sensitive functionality. The observed regioselectivity is nonconventional for addition reactions involving carbon radicals and carbon-heteroatom pi-bonds.     

Ti(III)-mediated radical cyclization of β-aminoacrylate containing epoxy alcohol moieties: synthesis of highly substituted azacycles

Ti(III)-mediated radical cyclization of β-aminoacrylate containing 2,3-epoxy alcohol moieties led to the formation of highly substituted piperidine and pyrrolidine rings. The pyrrolidine ring system was then transformed into an indolizidine framework present in many natural products.     

Antitumor,cytotoxic, and antioxidant evaluation of six heterocyclic compounds containing different heterocycle moieties

Heterocyclic compounds with different heterocycle moieties, namely benzoxazinone, benzimidazole, quinazolinone, and benzofuranone heterocyclic rings, were synthesized, characterized, and evaluated for their anticancer activity against human hepatocellular carcinoma cell line (HepG2) using sulforhodamine B (SRB) and dimethylthiazol-diphenyltetrazolium bromide (MTT) assays. Also, their cytotoxic activities were tested against human epithelioid carcinoma (Hela) cell line in comparison with normal cell, amniotic epithelial (WISH) cell line, as an in vitro toxicity estimation model. The results showed clearly that 2-(2-benzyl-4-oxoquinazolin-3(4H)-yl)acetohydrazide 4 is the most potent antioxidant and anticancer agents. Although, 3-amino-2-benzylquinazolin-4(3H)-one 5 is less potent anticancer agent against Hela but it is more safe against normal cell (WISH).     

Review of synthesis and various biological activities of spiro heterocyclic compounds comprising oxindole and pyrrolidine moities

Spirocyclic compounds isolated from plant and animal origins have important applications in medicinal chemistry. Spiro compounds having cyclic structures fused at a central carbon are of recent interest because of their interesting conformational features and their structural implications for biological systems. Spiro heterocycles like spiropyrrolidines and oxindole moieties have been found to play fundamental roles in biological processes and have exhibited diversified biological activity and pharmacological and therapeutical properties. In view of these facts we decided to present a representative synthetic scheme and various biological activities of the heterocycles like spiropyrrolidines and oxindole moieties derivatives, especially in relation to microbial infections like cancer and tubercular, viral, HIV, bacterial, and fungal infections.     

Regioselective synthesis of substituted 1-indanols, 2,3-dihydrobenzofurans and 2,3-dihydroindoles by electrochemical radical cyclization using an arene mediator

Electrochemical reduction of haloarenes carrying 2-(1-hydroxybut-3-enyl), 2-allyloxy or N-allyl-N-methylamino group in the presence of phenanthrene as a mediator generated the corresponding aryl radicals and gave the corresponding 5-exo cyclization products in good yields. Higher regio- and stereoselectivities than those of usual radical cyclization using AIBN-Bu₃SnH were achieved.     

Syntheses and polymerization of (meth)acrylates containing spiro ortho ester moieties

Acrylates and methacrylates bearing pendant spiro ortho ester groups ( 3 ) were prepared by the reaction of (meth)acrylic acid with bromomethyl spiro ortho esters ( 2 ) in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU). These monomers were copolymerized with styrene (St) at 60°C in the presence of α,α'-azobisisobutyronitrile (AIBN) to give the corresponding copolymers with M?_n 6000-17000 and their compositions were in proportion to the feed ratios. Similarly, the copolymerization of 3 with acrylonitrile (AN) was carried out at 60°C to obtain the corresponding copolymers with the similar compositions to the feed ratios. Two kinds of 3 -St copolymers with different compositions were treated with BF₃OEt₂ in refluxing methylene dichloride affording the crosslinked polymers quantitatively. Slight expansion in volume was observed during the crosslinking.     

Enantioselective heterocyclic synthesis of spiro chromanone-thiochroman complexes catalyzed by a bifunctional indane catalyst

Novel asymmetric domino reactions of benzylidenechroman-4-ones and 2-mercaptobenzaldehydes for efficient construction of spiro chromanone-thiochroman complexes were accomplished with high yields and excellent selectivities via a novel bifunctional indane catalyst.     

1,3-dipolar cycloaddition as a method for synthesis of fullerene C60 derivatives containing heterocyclic moieties

We generalize literature data and our own experimental data on using 1,3-dipolar cycloaddition reactions for synthesis of fullerene C₆₀ derivatives containing annelated heterocyclic moieties.M. V. Lomonosov Moscow State University, Moscow 119899, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 291–297, March, 1998.     

Regioselective synthesis of azetidines or pyrrolidines by selenium-induced cyclization of secondary homoallylic amines

Azetidines or pyrrolidines can be regioselectively obtained by selenocyclization of homoallylic amines, according to the double bond substitution.     

Total synthesis of mappicine ketone (nothapodytine B) by means of sulfur-directed 5-exo-selective aryl radical cyclization onto enamides

Enamides 5, on treatment with Bu(3)SnH-AIBN, underwent aryl radical cyclization in a 5-exo manner to give 1-[bis(phenylthio)methyl]dihydroisoindoles 6, which were partially desulfurized with Bu(3)SnH-AIBN to give 1-mono(phenylthio)methyl congeners 7. Formation of 6 from 5 may be explained by the presence of two phenylthio groups at the terminus of the N-vinylic bond of 5, since enamide 8a having no phenylthio group underwent aryl radical cyclization in a 6-endo manner. Compound 7d (R = CF(3)) was transformed into sulfoxide 16, which was treated with (CF(3)CO)(2)O and then with 10% NaOH to give a model compound 20 of mappicine ketone (MPK) (1) through aldol condensation of aldehyde 18. An attempt to synthesize MPK using this method with sulfoxide 28 prepared from 25, however, was unsuccessful, and, instead, photochemical cyclization of enamide 38 prepared from 25 furnished MPK.     

Stereoselective synthesis of substituted 2,5-diazabicyclo[2.2.1]heptanes by iodine-mediated cyclization of optically pure compounds containing the 4,5-diamino-1,7-octadiene and 1,2-diamino-4-alkene moieties

3,7-endo-Disubstituted 2,5-diazabicyclo[2.2.1]heptanes were obtained by iodo-cyclization of N,N′-di[(S)-1-phenylethyl]-(E,E)-4,5-diamino-1,8-diphenyl-1,7-octadiene and substituted N,N′-di[(S)-1-phenylethyl]-1,2-diamino-4-alkenes. Removal of only one N-substituent of the bridged piperazines was achieved by reduction with ammonium formate and Pd/C. Unexpected cleavage of the skeleton of vinyl-substituted bridged piperazines was observed using hydrogen, leading to substituted 3-aminopyrrolidines.     

Synthesis of functionalized compounds containing pyridazine and related moieties

3‐Aminopyridazines 17 and 3‐hydrazinopyridazines 18 were used as building blocks for the preparation of various types of functionalized, pyridazine ring containing compounds. 3‐Aminopyridazines were employed in the synthesis of 3‐(6‐chloroimidazo[1,2‐b]pyridazin‐2‐yl)alanines 26, 27 and for the preparation of 3‐amino‐4H‐pyrimido[1,2‐b]pyridazin‐4‐ones 103 , intermediates in the ‘ring switching’ synthesis of alkyl 1‐pyridazin‐3‐yl‐1,2,3‐triazole‐4‐carboxylates 106 .On the other hand, hydrazinopyridazines 18 were employed in a two‐step preparation of 3‐functionalized 1,2,4‐triazolo[4,3‐b]pyridazines via condensation with functionalized aldehydes and their enamino analogs followed by oxidative cyclization of the intermediate hydrazones. In this manner, 1,2,4‐triazolo[4,3‐b]pyridazin‐3‐yl substituted alanines 29, 30 , polyols 33, 39–48 , C‐nucleosides 49, 50 , and terpenes 58, 62, 64–69 were prepared. In another general approach, 3‐hydrazinopyridazines 18 were treated with functionalized enaminones as 1,3‐dielectrophiles to give the 1‐(substituted pyridazin‐3‐yl)‐1H‐pyrazole derivatives containing an ester 72, 73, 75, 76 , alanine 79, 84, 85, 87 , 2‐phenylethylamine 97, 99 , and β‐amino alcohol functional element 98, 100 . In the reaction of 4‐oxohomoglutamate 82 with hydrazine hydrate and methyl hydrazine, chiral functionalized tetrahydropyridazinones 88a,b were obtained.     

Synthesis of heterocyclic compounds by the cyclization of isatin and its derivatives (review)

Published data on the synthesis of heterocyclic compounds formed as the result of the recyclization of isatin and its derivatives are classified and summarized.Academician A. N. Kosygin Moscow State Textile Academy, Moscow. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 291–323, March, 1996. Original article submitted September 14, 1995.