Free radical reactions for heterocycle synthesis. Part 7: 2-Bromobenzoic acids as building blocks in the construction of spirobenzolactones and spirobenzolactams

A straightforward 2-step parallel synthesis for structurally diversified spiro compounds is developed. 2-Bromobenzoic acids are used as common building blocks to couple with a series of conjugated enoles or enamines. Sequential intramolecular free radical Michael additions lead to formation of spirobenzolactones, spirobenzolactams, spirobenzolactone-lactams, spiorbenzolactone-thiolactones, spiordilactones, and bridged-spirolactones.     

Isocyanides in the synthesis of nitrogen heterocycles

Isocyanides have long proved themselves to be irreplaceable building blocks in modern organic chemistry. The unique features of the isocyano group make isocyanides particularly useful for the synthesis of a number of important classes of nitrogen heterocycles, such as pyrroles, indoles, and quinolines. Several cocyclizations of isocyanides via zwitterions and radical intermediates as well as transition-metal-catalyzed syntheses of different types of heterocycles have recently been developed. Methods starting from isocyanides often have distinct advantages over alternative approaches to the same heterocycles because of their enhanced convergence, the great simplicity of most of the operations with them, and the great variety of isocyanides readily available for use. Isocyanides have also been used in some enantioselective syntheses of chiral heterocyclic compounds, including natural products as well as precursors thereof.     

New strategies in the synthesis of regioselectively trifluoromethyl- and trifluoromethoxy-substituted arenes as building blocks for biologically active molecules

Regioisomerically pure trifluoromethyl- and trifluoromethoxy-substituted aromatic and heteroaromatic aldehydes and carboxylic acids are valuable building blocks for the synthesis of biologically active molecules. They have been prepared by employing modern organometallic methods. On this basis, a novel access to 2,3-dihydro-5-(trifluoromethoxy)indole was developed which represents an intriguing example of how organometallic and radical chemistry can fecundate each other.     

Free radical reactions of carbohydrate derivatives in the synthesis of carbocyclic compounds. 1. Intramolecular C2–C6 cyclization of monosaccharides — A new route to substituted cyclopentanes

The feasibility of adopting a new approach to the preparation of chiral carbocyclic compounds has been demonstrated by experiment. Synthesis was achieved by way of intramolecular free radical C ₂ –C ₆ cyclization of carbohydrate derivatives, which produced compounds with quaternary C ₂ carbon atom having a strictly defined configuration.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117334 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 650–657, March, 1992.     

Butadienic building blocks from 2-nitrothiophene as precursors of nitrogen heterocycles: intriguing dichotomic behavior

With the goal of their exploitation for the synthesis of heterocycles, sulfides 10 and sulfones 11, derived from the initial ring-opening of 2-nitrothiophene (5) with pyrrolidine/AgNO3 in EtOH, were reacted with diazomethane. Interesting dichotomic behavior was found to yield pyrazolines 17 from 10 and isoxazolines 18 (as the main products) from 11. Intriguingly enough, in the latter case, an unexpected apparent C-C methylene insertion was also observed, leading to the homologous cyclopropanes 19 as secondary products.     

Oxyoxazolidinone as an auxiliary for heterocyclic synthesis. Enantioselective formation of N-unprotected 2-pyrrolidones from selenocarboxylate and allylamines via radical cyclization

Optically active N-unprotected 2-pyrrolidones were prepared in a highly stereoselective manner through radical cyclization reaction of oxyoxazolidinone. Asymmetric induction from the oxyoxazolidinone ring system was generally high and oxazabicyclo[3.3.0]octanones were obtained in good yields. Treatment of the bicyclic compounds with TBAF resulted in the one-step cleavage of C-O and C-N bond, directly giving secondary 2-pyrrolidones in good yields along with recovery of chiral mandelic acid without loss of optical purity. The use of the present procedure gave optically active 4,5-disubstituted N-unprotected 2-pyrrolidone derivatives trans selectively.     

A general synthesis of 2-substituted-5-aminooxazoles: building blocks for multifunctional heterocycles

Condensation of unsubstituted isocyanoacetamides with aldehydes and ketones, or their derived iminium ions, leads to 2-substituted-5-aminooxazoles, which are useful compounds for drug discovery programs.     

Free radical reactions of carbohydrate derivatives in the synthesis of carbocyclic compounds

The benzyloxy group at C(4) of the pyranose ring in 3,4-disubstituted and 3-deoxy carbohydrate derivatives affects the direction of intramolecular free-radical C(2)-C(6) cyclization. A possible mechanism of the formation of the tetrahydrofuran ring was proposed.For Part 3, see Ref. 1.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 767–773, April, 1995.The present work was partially supported by the Russian Foundation for Basic Research (project No. 93-03-5834) and the International Science Foundation (Project No. MOM 000).     

Recent advances in 4-hydroxycoumarin chemistry. Part 2: Scaffolds for heterocycle molecular diversity

The present paper aims to review the synthetic applicability of 4-hydroxycoumarin in heterocyclic synthesis during the period from 1996 up to now. This compound can be used as building blocks for five, six, and seven-membered heterocycles as well as fused rings.     

1-Bromo-2-trifluoroacetylcyclobutenes as novel building blocks for the construction of trifluoromethyl substituted heterocycles. Part 2: Synthesis of trifluoromethyl substituted thiophenes, condensed with cyclobutene moieties

This paper describes a novel synthetic approach to 2-cyano-3-trifluoromethylthiophenes fused with cyclobutene rings with variable spiro conjunctions. The reaction of substituted 1-bromo-2-trifluoroacetylcyclobutenes with mercaptoacetonitrile results in the substitution of bromine with S-center to afford the corresponding nitriles in high yields, which form the target thiophenes by subsequent treatment of lithium 2,2,6,6-tetramethylpiperidide and acetic anhydride.     

Ring-closure reactions through intramolecular displacement of the phenylselenonyl group by nitrogen nucleophiles: a new stereospecific synthesis of N-tosyl and N-benzoyl-1,3-oxazolidin-2-ones from beta-hydroxyalkyl phenyl selenides

A new and convenient method for the stereospecific synthesis of variously substituted 1,3-oxazolidin-2-ones from the easily available beta-hydroxyalkyl phenyl selenides is presented. After transformation into the N-tosyl or N-benzoyl carbamates, the selenides were oxidized to the corresponding selenones. The key step of the process is the ring-closure reaction, which occurs by stereospecific intramolecular nucleophilic substitution of the selenone group by the nitrogen atom of the carbamate. Enantiomerically pure 1,3-oxazolidin-2-one derivatives can be easily prepared by using enantiomerically pure beta-hydroxyalkyl phenyl selenides as starting materials.     

2-Aryl-3,4-dihydropyrans as building blocks for organic synthesis: ring-opening reactions with nucleophiles

An electrophilic ring-opening reaction of 2-aryl-3,4-dihydropyran with many nucleophiles, such as thiophenols, thiols, benzenesulfinic acid, resorcin, 2-methylfuran, benzamide and allyltrimethylsilane, was developed. In the presence of an appropriate catalyst, a product that contains not only a moiety of the nucleophile but also a fragment of 1,3-dicarbonyl compound was obtained.     

1-Bromo-2-trifluoroacetylcyclobutenes as novel building blocks for the construction of trifluoromethyl substituted heterocycles. Part 3: Synthesis of trifluoromethylsubstituted pyridines, condensed with cyclobutene moieties

This paper describes a general synthetic approach to 3-cyano-4-trifluoromethylpyridines fused with cyclobutene rings with variable spiro conjunctions. The reaction of various 1-bromo-2-trifluoroacetylcyclobutenes with ammonia results in the substitution of bromine with an NH₂ group leading to corresponding enaminoketones in high yields, which, in turn, form the target pyridines by treatment with diethyl ethoxymethylencyanophosphonate in the presence of sodium hydride.