Pyrrole anions, reaction with carbon

Phenyl-l-azirine (42a) reacts with acetophenone in the presence of the dimethylsulfinyl carbanion to give 2,4-diphenylpyrrole (150).65 This reaction probably involves initial attack of the enolate anion on the carbon-nitrogen double dond, to give intermediate 147 and 148 which ring-opens to 149 and loses hydroxide ion giving pyrrole (150). A similar reaction of ethyl benzoylacetate with 2-phenyl-l-azirine yields 3-benzoyl-4-phenyl-2-oxopyrroline (151). 

In the reaction with acetic anhydride in an inert solvent, pyrrole gives a mixture of 1- and 2-acetyl derivatives.139 The substitution at the 2-carbon seems to involve the neutral molecule of pyrrole, whereas that at nitrogen probably involves the dissociated anion. In fact, the C/N isomer ratio is decreased by adding sodium acetate (which favors ionization) and increased by adding acetic acid (which opposes it). 

Systematic investigations of the reaction of pyrroles with carbon disulfide in the superbase system KOH/DMSO [537-541] have shown that pyrrole anions, generated in this system, attack CS2 (20°C-25°C, 2 h) exclusively or mainly by the position 2 to afford pyrrole-2-carbodithioates. The latter, after alkylation with alkylhalides (20°C-25°C, 2 h), give the corresponding pyrrole-2-carbodithionic acid esters in 46%-75% yields (Scheme 2.71, Table 2.9) [537-540]. The only exception is unsubstituted pyrrole, which gives only pyrrole-l-carbodithioate [540]. 

Trofimov, B.A., L.N. Sobenina, A.I. Mikhaleva et al. 2000. Reaction of pyrrole anions with carbon disulfide. Synthesis of pyrrole-3-carbodithioates. Tetrahedron 56 7325-7329. 

Kobychev, V.B., N.M. Vitkovskaya, I.L. Zaitseva et al. 2001. Ab initio quantum chemical study of the reaction of pyrrole anions with carbon disulfide. Zh Strukt Khim 42 (4) 645-653. 

There are some recent examples of this type of synthesis of pyridazines, but this approach is more valuable for cinnolines. Alkyl and aryl ketazines can be transformed with lithium diisopropylamide into their dianions, which rearrange to tetrahydropyridazines, pyrroles or pyrazoles, depending on the nature of the ketazlne. It is postulated that the reaction course is mainly dependent on the electron density on the carbon termini bearing anionic charges (Scheme 65) (78JOC3370). 

Feldman reported a route to dihydropyrroles, pyrroles, and indoles via the reaction of sulfonamide anions with alkynyliodonium triflates <96JOC5440>. Thus, upon nucleophilic addition of the anion of 91 to the p-carbon of the alkynyliodonium salt, the alkylidene carbene 92 is generated which can the undergo C-H insertion to the desired product 93. 

As discussed in Section 3.3.1.6.1, pyrroles are weak acids. The resulting ions react exceedingly readily, even with weak electrophilic reagents at either carbon (30) or nitrogen (31) this behavior is similar to that of the ambident anion from acetoacetic ester which shows alternative reactions (32, 33). 

Several classes of carbon nucleophiles have been successfully used in these systems, reflecting the utility of Reissert chemistry for derivatizing azines via carbon-carbon bond formation. Apart from cyanide anion, other classes of carbon nucleophiles have been explored. For instance, addition of indole (51) to A-acyla-zinium salts proceeds selectively at the a-position (Scheme 9). Pyrrole, quinolines and isoquinolines all behave similarly [73-76]. A related reaction, yielding adduct 70 (Scheme 12b) has also been described. In this case, azine activation is promoted by Vilsmeier reagents (generated by reaction of amides with POCI3) [77]. p-Dicarbonyls are reactive inputs in this chemistry, and dialkyl malonates 53... 

Some typical reactions of 1,1 -difluoroethene with nucleophiles are summarized in Scheme 2.18. Alkoxides [3], trialkylsilyl anion [4], ester enolates [5], and diphenylphosphinyl anion [6] attack the gem-difluorinated carbon of 5. However, it is noteworthy that nucleophilic substitution and proton abstraction are in some cases competitive, and thus s -butyl lithium abstracts the (3 -vinylic proton predominantly to generate vinyllithium. The lithium species can be trapped with an aldehyde, providing difluoroallyl alcohol, which is then hydrolyzed to a, (3-unsaturated carboxylic ester (11) [ 7 ] (Scheme 2.19). Some synthetically useful examples are shown in Schemes 2.20 and 2.21. Tetrathiafulvalene derivative (14) is prepared from difluorinated derivative (13) [8]. An elegant intramolecular version was demonstrated by Ichikawa, which provided a range of cyclized compounds (17), including dihydrofurans, thiophenes, pyrroles, and cyclopentenes, and also corresponding benzo derivatives (20) [2]. 

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