Pyrrole ring expansion

FIGURE 6.28 Reaction scheme of the lowest energy pathway of methylene pyrrole ring expansion. All the energy values are calculated relative to the reactant. 

Photolysis of pyridazine IV-ethoxycarbonylimide results in the formation of the pyrrole derivative (56). The rearrangement is postulated to proceed via a diaziridine, followed by ring expansion to the corresponding 1,2,3-triazepine derivative and rearrangement to a triazabicycloheptadiene, from which finally a molecule of nitrogen is eliminated (Scheme 19) (80CPB2676). 

Furan, 2,5-dialkoxy-2-( 1 -hydroxyalkyl)-2,5-dihydro-ring expansion, 1, 425 Furan, 2,5-dialkoxytetrahydro-pyrrole synthesis from, 4, 330 Furan, 2,4-dialkyl-synthesis, 4, 661, 685 Furan, 2,5-dialkyl-... 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

With monochlorocarbene, pyrrole and indole underwent ring expansion to pyridine and quinohne, respectively, and 2,3-dimethyl-indole similarly gave 2,4-dimethylquinohne. ... 

The concept of expansion of the porphyrin macrocycle by formally inserting additional carbon atoms between the pyrrole rings was first considered and synthetically realized by LeGoff/ He also suggested a nomenclature for these macrocyclic systems using the word platyrin which... 

Cis- and rranx-cyclopropane-1,2-diamines (both primary and secondary) react with a range of aldehydes, R CHO, to give pyrroles under very mild conditions. NMR has been used to identify the intermediates. The key steps involve ring expansion of the monoiminium ion (22), via an azomethine ylid (23), to yield a dihydropyrrolium ion (24). 

Irradiation of the pyridinium dicyanomethylide (324) in benzene gives the substituted pyrrole (325), by the postulated route shown (Scheme 242) which originates from the singlet excited ylide. 7,7-Dicyanoazanorcaradiene presumably arises by N—C bond fission in the triplet which produces a dicyanocarbene (of dubious multiplicity) which is trapped by the solvent benzene (67CR(C)(264)1307). Photolysis of the imino-ylide (326) in benzene (equation 200) follows the same pathways initially but the two products result from ring expansions,... 

An example of the synthetic utility of the oxidative cleavage of the pyrrole C-2 to C-3 bond is the ring expansion of bicyclic pyrroles (127) to lactams (128) (83S390). 

Porphyrin synthesis can be enhanced by metal template methods using several strategies, including tetramerization of pyrrole derivatives (equation 45),251 dimerization of dipyrrolomethenes (equation 46)252 and cyclization of 1,19-dideoxybiladiene-ac derivatives (equation 47).252 These derivatives can also be induced to undergo direct base-catalyzed template cyclization to octa-dehydrocorrins of different chromophores depending on the 1,19-substituents (Scheme 61).253-255 The cationic complex (99) can be transformed by thermal ring expansion processes to porphyrin derivatives (Scheme 62).253... 

A rather unique synthetic example based on the well-known pyrrole-pyridine carbene insertion reaction involves the following ring expansion.16... 

A useful expansion of the pyrrole-ring annelation methodology was found when 3-alkynyl-6,8-dimethylpyrimido[4,5-< ]pyridazine-5,7(6//,8//)-dione reacts with an amine and silver permanganate pyridine complex. It was postulated that first amination at the C4-position takes place, followed by an intramolecular cyclization into the pyrrolopyridazinopyrimidine derivative (Scheme 35). A similar reaction was reported with 6-alkynyl-l,3-dimethylpyrimido[4,5-Z]pyrazinedione (03MI3). 

However, studies on the scope of this sequence revealed that the substrate has to be an N-tosyl sulfonamide and that certain boronic acids are not trans-metallated but rather give rise to the formation of the pyrrole 21 or a pyridine derivative 22 (Scheme 7). The peculiar outcome as a carbopalladation-Suzuki sequence is rationalized by co or dinative stabilization of the insertion intermediate 18 by the sulfonyl oxygen atom, as represented in structure 19, now suppressing the usual /3-hydride elimination. If the transmetallation is rapid the Suzuki pathway is entered leading to product 17. However, if the transmetallation is slow, as for furyl or ferrocenyl boronic acid, either /i-hydride elimination or a subsequent cyclic carbopalladation occurs. The former leads to the formation of the diene 20 that is isomerized to the pyrrole 21. The latter furnishes the cyclopropylmethyl Pd species 23, which rearranges with concomitant ring expansion to furnish piperidyl-Pd intermediate 24 that suffers a -hydride elimination to give the methylene tetrahydro pyridine 22. 

Of lesser relevance to this discussion are halogenation methods involving the modification of the carbon skeleton (synthesis and degradation). The Hunsdiecker reaction, as applied to certain heterocyclic acids, has had limited application for the synthesis of halogen derivatives. The preparation of 3-bromo-4,6-dimethyl-2-pyridone from the silver salt of the respective 3-carboxylic acid by treatment with bromine in carbon tetrachloride is a rare example of success.13 The interaction of carbenes with heterocycles also has been employed infrequently, but recent advances in carbene generation may reactivate this approach.14 The Ciamician-Dennstedt ring expansion of pyrrole to / -halopyridines is a case in point18 [Eq. (4)] ... 

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