Heterocyclic compounds anionic cyclization

The foregoing examples show that the nucleophilic attack to nitroarenes at the o>T/ o-position followed by cyclization is a general method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion derived from ethyl isocyanoacetate as the reactive anion for the preparation of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyrimidines depending on the structure of nitroarenes (Eqs. 9.56 and 9.57).89 The synthesis of pyrroles is discussed in detail in Chapter 10. 

The synthesis of oxygen- and nitrogen-containing heterocyclic compounds by anionic cyclization of unsaturated organolithium compounds has been reviewed recently. " Broka and Shen reported the first intramolecular reaction of an unstabilized a-amino-organolithium compound using reductive lithiation of an A,5-acetal derived from a homoaUylic secondary amine (Scheme 21). Just one example was reported treatment with lithium naphthalenide gave the pyrrolidine product, predominantly as the cis isomer. 

Thus the synthesis of heterocyclic compounds with one or more heteroatoms along with perfluoroalkyl groups is possible if the fluorinated molecule has a multiple bond and if an anionic center may be generated at the heteroatom or carbon atom of the functional group in intramolecular nucleophilic cyclization reactions. These new approaches point to the specific effect of fluorine atoms and to the important role of the electronic effects in... 

In contrast to the 5-endo-trig anionic cyclization reactions, rarely observed, there are several examples in which 5-endo-dig processes are involved. Hence 2,3-disubstituted benzofurans, benzothiophenes and indoles 374 have been synthesized starting from triflu-oroethyl ethers, thioethers and anilines 373, respectively, and alkyllithium compounds. A 5-endo-dig carbolithiation reaction on 375, generated by two successive eliminations, one substitution and one ortho-lithiation reactions, is proposed to account for the formation of the corresponding 2-lithiated heterocycles. Further reaction of these intermediates with electrophiles affords compounds 374 (Scheme 98)159. In the case of thioether 373 (X = S) a bromine substituent must be present at the ortho position. 

Numerous carbo- and heterocyclic compounds of various sizes have been prepared by HR-type monocyclization. Cyclopropanes are formed only when neopentylpalladium intermediates are formed in the absence of anions. Intramolecular carbopalladation of the alkenyl triflate 201 generates the neopentylpalladium 202, and its 3-exo cyclization and jd-H elimination afford the cyclopropane 203 [95]. Intermolecular carbopalladation of the alkyne 204 generates 205. Its 5-exo cyclization provides the neopentylpalladium 206, which undergoes 3-exo cyclization to construct the three-membered ring 207. Finally y3-H elimination gives rise to the cyclopropane 208 [96]. 

The main use of this reaction is for the synthesis of bowl-shaped polycyclic aromatic hydrocarbons and fullerenes [325], Exploring the boundaries of these reactions resulted in the synthesis of compounds of different geometry, tt-electron structure, aromaticity, and with the presence of heteroatoms [324]. Various cross-conjugated enediynes exert anionic cycloaromatization to form fulvene and fulvalene anions and even heterocycles. In accordance with the concept of aromaticity, the anionic Bergman type cyclization is preferred to the classical Bergman cycloaromatization of linear enediynes. This anionic cyclization differs considerably from the classical Bergman cyclization and related cycliza-tions, as well as from other dianionic cyclizations [326]. 

Nitrobenzoylamino)-2,2-dimethylpropanamide (143 R = Me) reacts in methanol-DMSO solution with sodium methoxide to yield 5,5-dimethyl-2-(4-nitrophenyl)imidazol-4(5//)-one (144 R = Me). The 4-methoxyphenyl derivative and the parent phenyl derivative react similarly, as do compounds in which variation of the 2-substitutent (R = Pr , Ph, 4-O2NC6H4) was made. The mechanism of the cyclization probably involves initial formation of the anion of the alkanamide (145), which adds to the carbonyl group of the benzamido moiety to yield the tetrahedral oxyanion (146) proton transfer and dehydration then yield the heterocycle (144). The kinetics of hydrolysis in water at 70 °C and pH 2-11 of A-glycidylmorpholine (147) have been reported. ... 

Reissert compounds, 9, I 24, 187 Ring closure of ortlio-substituted t-anilines, heterocycles by, 14, 211 Ring-opening of flve-membered heteroaromatic anions, 41, 41 Ring synthesis of heteroaromatic nitro compounds, 25, 113 Ring transformations and cyclizations on reaction of azines with bifunctional nucleophiles, 43, 301 of five-membered heterocycles, 56, 49... 

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