Pyrroles transformations

Comparing the [l,5]-sigmatropic hydrogen shifts in pyrrole and phosphole, at the MP2/6-31G level, Bachrach has shown that the more stable tautomeric form is, respectively, IH -pyrrole and 2//-phosphole2d. The activation enthalpies were computed to be 186 kJmoG1 for 1H-pyrrole to 2H-pyrrole transformation and only 67 kJmoG1... 

Synthesis of Folate Antimetabolites A Furan to Pyrrole Transformation... 

The adsorption of pyrrole on a series of different oxides and zeolites showed that the shift of the NH infrared vibration to lower values could be used as a measure of the increased basic strength of the sites (65). Infrared spectra can be recorded 10-15 min. after pyrrole is contacted with the zeolite. This is a great advantage over calorimetry for instance which requires a long time to reach equilibrium, which may favor the pyrrole transformation. 

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). 

The TV-protected pyrrole (212) can be palladated, but not lithiated, in the 3-position to give the stable complex (213) this is readily converted into the 3-methoxycarbonylpyrrole (214) (82JOM(234)l23). The use of palladium derivatives thus further increases the range of transformations made possible through the intermediacy of metallo groups. 

The rearrangement of thiophenes to the isomeric pyrroles has proven synthetically useful (Schemes 98a and 98b). In the absence of a suitable internal nucleophilic nitrogen, so-called degenerate ring transformations may occur (Schemes 98c and 98d). 

Similar transformations are based upon 1,2-thiazine 2,2-dioxides (5-sultones), easily obtained by treating a,/3- or /3,y-unsaturated ketones with acetic anhydride and sulfuric acid. These compounds can be converted subsequently into furans, thiophenes or pyrroles (Scheme 115). 

The thermal transformations observed with these systems can be rationalized in terms of an equilibration of the 1-azirine with a transient vinylnitrene which subsequently rearranges to the 2,5-disubstituted pyrrole (56). 

In a series of papers in late 1884 and early 1885, Paal and Knorr demonstrated that several 1,4-dicarbonyls could be transformed into furans, pyrroles, and thiophenes. Paal first discovered this transformation and used it to prepare di-, tri-, and tetrasubstituted furans. For example, dicarbonyl 3 yielded disubstituted furan 4 upon treatment with weak acid. 

Interestingly, when utilizing a secondary amide, these reactions are limited by the simultaneous formation of the corresponding pyrrole as exemplified in the transformation of 46 to thiophene 47 and pyrrole 48... 

In a similar manner, metapyridophanes 18 can be prepared by reaction of sodium trichloroacetate with pyrrole 17 (Scheme 8.3.5). The transformation can also be achieved with phenyl(bromodichloromethyl)mercury, albeit in lower yield. 

Total syntheses of pyrrole alkaloids, furanoterpenes, macrolide antibiotics, and carbohydrates based on transformations catalyzed by transition metals 99SL1523. 

It has been found that the fusion of the pyrazole with the pyrrole ring is difficult, probably for steric reasons. All attempts to cyclize 3-amino- and 5-amino-4-acetylenylpyrazole have failed. For example, upon prolonged heating of 5-amino-4-acetylenylpyrazole 68 in DMF in the presence of Cul and (or) CuC=CPh, side transformations andresinification occurred. The side processes were suppressed by acylation of the amino group and substitution of DMF by inert cyclohexane. However, 80-90% of the starting compounds was recovered after heating acylamine... 

First we consider diacetylene transformations leading to fundamental heterocycles (pyrroles, thiophene, selenophene, tellurophenes, pyrazoles, isoxazoles, pyridines, pyrimidines). Then cyclization reactions involving 1-heterobut-l-en-3-ynes, 4-heterobut-3-en-2-ones, and 4-heterobut-3-yn-2-ones (91UK103 92KGS867 00UK642) as diacetylene equivalents are discussed. 

DBU IS most widely employed as the base m the Barton-Zard reaction Stronger nonionic bases such as PrMeNCH-,CH-j,N and the phosphazene base Csiipplied by Flukai are more effective to induce pyrrole formadon in the reaction of nitroalkenes v/ith isocyano esters than DBU Sterically hindered nitroalkenes are converted into the corresponding pyrroles using these bases, as shovm in Eq 10 35, but DBU is not effective in this transformation... 

This general method has been used by Parham and coworkers4 to transform indenes into /3-halonaphthalenes. Other references in the literature indicate that tins method is also useful for the conversion of pyrroles to -substituted pyridines and of indoles to j8-lialoquinolines.3... 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

A two-step procedure was required for the preparation of a diverse set of pyrrole-3-carboxylic acid derivatives. The diketone 15 was prepared using a functional homologation of a 6-ketoester 14 with different aldehydes followed by oxidation with PCC. The Paal-Knorr reaction was carried out in AcOH in a sealed tube under microwave irradiation (180 °C, 5-10 min) to give differently substituted pyrroles with a COOMe group in position 3 (Scheme 5). This group was further transformed to expand the diversity of the products prepared with this method [32]. 

Tetrasubstituted pyrroles were also obtained in a coupled domino process carried out under solvent-free conditions on silica gel (Scheme 9). The process involved the transformation of the alkynoate 27 into the 1,3-oxazoUdine 28 that could be further rearranged (through loss of one molecule of water)... 

One-electron oxidation of the vinylidene complex transforms it from an Fe=C axially symmetric Fe(ll) carbene to an Fe(lll) complex where the vinylidene carbon bridges between iron and a pyrrole nitrogen. Cobalt and nickel porphyrin carbene complexes adopt this latter structure, with the carbene fragment formally inserted into the metal-nitrogen bond. The difference between the two types of metalloporphyrin carbene, and the conversion of one type to the other by oxidation in the case of iron, has been considered in a theoretical study. The comparison is especially interesting for the iron(ll) and cobalt(lll) carbene complexes Fe(Por)CR2 and Co(Por)(CR2) which both contain metal centers yet adopt... 

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