Dihydropyrrole intermediate

Direct debenzylation of pyrroles 137 using Pd-catalyzed hydrogenation proved unsuccessful, but it was shown that if NH-pyrrole is required, debenzylation was easier to achieve on the dihydropyrrole intermediate 139, using 1-chloroethyl chloroformate. The debenzylated dihydropyrrole 140 can then be aromatized in the usual manner by treatment with DDQ to form 3-SF5-4-(3-thienyl)-AM-pyrrole (141) (Scheme 41). 

R H) then the palladium intermediate can be induced to undergo a variety of other reactions 80JA3583). The catalytic cyclization of 5-tosylamidoalkenes to dihydropyrroles has been achieved similarly (Scheme 7b) 82JA2444). 

Non-enolizable imines such as 9-fluorene imines react with alkynylcarbene complexes to afford mixtures of mesoionic pyrrolium carbonyltungstates and dihydropyrrole derivatives [68] (Scheme 23). Although both compounds can be considered as [3C+2S] cycloadducts, formation of each of them follows a very different pathway. However, the first intermediate of the reaction is common for both compounds and supposes the conjugated addition of the imine to the alkynylcarbene complex to form a zwitterionic intermediate. A cyclisation... 

A novel transformation of iV-alkoxycarbonylprolines to trifluoroacetyl-2,3-dihydropyrroles has been achieved by utilizing trifluoroacetic anhydride. A mesoinic l,3-oxazolium-5-olate is thought to be the probable intermediate in this transformation. 

Methoxyethyltosylamide also participates in the [3 -I- 2] addition reaction with 102, although it does not give any of the expected dihydropyrrole derivative 104. Instead, the major product was found to be pyrrole 105, which presumably results through ready elimination of methanol from the putative intermediate 104. Thus, this addition holds promise for the synthesis of 2-substituted tosylpyrroles (Scheme 29). In addition to 105, a minor product 106 (12%) is also formed in this reaction. 

It of interest to note that the isobutyl group may also be replaced by a heterocyclic ring. The route to this compound, pirprofen (51-6), starts with the direct methylation of unesterihed 4-nitrophenylacetic acid (51-1). The observed selectivity for monoalkylation in this case may reside in the structure of the dianion, whose most stable form is presumably that depicted in (51-2). Catalytic reduction of the product (51-3) gives the corresponding aniline this is then converted to its acetanilide (51-4) with acetic anhydride. Treatment with chlorine followed by hydrolysis gives the chloroaniline (51-5). Double alkylation of this last intermediate with 1,4-dichloro-but-2-ene (depicted as the cis isomer for aesthetic reasons) forms the dihydropyrrole ring. There is thus obtained the NSAID pirprofen (51-6) [52]. 

The homologous azirine (143) with a one-atom bridge gave quite different results.70 Photolysis led to the 3,5-fused bicyclic dihydropyrrole (144). The isomeric azirine (145) also led to (144), although the initial products included dihydropyrrole (146) which apparently converted to (144) as photolysis continued. Azirines (143) and (145) were shown to not interconvert and die postulated two discrete azomethine ylides were trapped with methyl trifluoroacetate. Formation of dihydropyrrole (144) was explained based on a two-step cycloaddition process involving a common diradical intermediate. The observation of (146) from photolysis of (145) but not (143) can be explained based on extinction coefficient differences. Azirine (145) has a high extinction coefficient as does (146). The initial product (146) can then be optically pumped to (144) with a low extinction coefficient. Azirine (143) also has a low extinction coefficient and any (146) that formed from it would be optically pumped to (144) before observa-... 

Despite the isolation of O-vinyloximes from the products of reaction of ketoximes with acetylene, and the demonstration of their conversion to pyrroles by superbase KOH/DMSO (see Section IV.A), the suggested (81MI4) intermediate stages of this rearrangement long remained unproved. The intermediate 4//-2-hydroxy-2,3-dihydropyrroles (94) (Scheme 45) were first isolated by Trofimov et al. (83KGS276). 

As already shown (see Section IV.A), pyrolysis of 0-vinyloximes in the absence of KOH/DMSO does not lead to 4//-2-hydroxy-2,3-dihydropyrroles. It has been assumed (84MI1) that the rearrangement is of specific anionic character and does not necessarily involve the formation of neutral 0, A-divinylhydroxylamines (87,90,93). The intermediate anions (96) are likely to be more active in this case (Scheme 46). 

Two alkyl radicals at position 4 make impossible pyrrolization of the dihydropyrroles 94, while with a hydrogen atom present in this position, the conversion to the corresponding pyrrole (95) happens with ease. A stable representative of these intermediates 4//-4,4-dimethyl-2-hydroxy-... 

As shown above, insertion of alkylidene carbenes is highly regioselective. However, when the normal 1,5-C-H insertion pathway is blocked, 1,4- or 1,6-C-H insertion takes place [Eq. (109)]. Thus, the cyclobutene 121 [192] and the six-membered enol ether 123 [193] were obtained in modest yields. Intramolecular insertion into carbon-carbon double bond provides a method for synthesis of cyclopenten-annulated dihydropyrrole 124, which results from homolytic scission of a methylenecyclopropane intermediate [194]. 

Alkylidene-3-arylamino-2,5-dihydropyrrol-2-ones 721 can rearrange under acidic conditions to form the intermediate 1,3,5-triketoacid equivalent 722, which cyclizes to afford 5,6-fused 2-carbamoylpyran-4-ones (Scheme 178) <2004SL2779>. 

In the presence of Mn(OAc)3 or a Ce(iv) salt, 1,3-dicarbonyl compounds and /3-carbonyl imines react with allylsilanes to give silylmethylated dihydrofurans and dihydropyrroles, respectively.199,200,20011 A proposed mechanism involves the formation of a /3-silylcarbenium ion intermediate via two-electron oxidation and subsequent intramolecular nucleophilic attack (Equation (51)). a... 

Bis(2-lithioallyl)amines 297, a class of non-conjugated dilithio reagents which were formed from 296, were reported by Barluenga and coworkers to react with carboxylic esters affording cyclic alcohols 299 after hydrolysis (Scheme 91)169. A dilithiated dihydropyrrol 298 was generated from 297 via intramolecular carbolithiation of a lithiated double bond and served as the key intermediate. 

Electron transfer has proved to be an efficient way to generate alkylideneaminyl radicals from oxime derivatives. One-electron reduction of 0-2,4-dinitrophenyloximes of phenethyl ketones and y,5-unsaturated ketones gives alkylideneaminyl radical intermediates, which are utilized to synthesize quinoline and dihydropyrrole derivatives. 

As mentioned above, cyanocyclopropanes are frequently used precursors for imines (see equation 30). A recent pyrrolidine synthesis which involves an in situ reduction of the intermediate dihydropyrrole by formic acid follows these lines (equation 33). ... 

The dihydropyrroles are conceivably formed via a nitrile ylide, an intermediate resulting from a reaction between 1-naphthylcarbene and acetonitrile. 

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