Pyrrole oxidative dimerization

The majority of the reactions of pyrrole and its benzologues with radicals result in oxidation or oxidative dimerization. These reactions are discussed in Section 3.05.1.4. 

Lead tetraacetate oxidation of diethyl IV-alkylaminofumarates led to the formation of the unusual dihydropyrrolo[3,2-b ]pyrrole derivatives (343), along with the pyrroles (344) and pyridones (345). In addition, the oxidative dimers (346) and (347) were also isolated (Scheme 119). Although the pyrroles (344) and pyridones (345) can be derived from the dimers (346) and (347), the mechanism of formation of the pyrrolo[3,2-6]pyrroles from three moles of starting material is obscure (77CC854). 

A series of JV-alkylamino fumarates have been oxidized by LTA in the presence of trifluoroacetic acid as a catalyst, leading to mixtures of pyrroles, pyridones and pyrrolo [3,2-fr]pyrroles given in Scheme 4970. In some cases acyclic oxidative dimers were isolated. The enamine molecules in them are linked through their -carbon atoms (Scheme 49). 

A ruthenium-catalyzed three-component reaction between propargylic alcohols, 1,3-dicarbonyl compounds, and primary amines leading to fully substituted pyrroles was developed <07CEJ9973>. Cyclohexa[a]pyrroles ( azabicyclo[4.3.0] systems ) were formed by a three-component sequence involving allenic ketones, primary amines, and acryloyl chloride <07SL431>. An oxidative dimerization sequence involving arylpyruvates in the presence of ammonia was the key step in an approach to the pyrrole natural product, lukianol A <07S608>. 

Oxidation of N-aromatic methanesulfonamides 321 with (diacetoxyiodo)benzene in the presence of thiophene in trifluoroethanol or hexafluoroisopropanol (HFIP) affords the respective coupling products 322 in good yield (Scheme 3.131) [380]. The head-to-tail thiophene dimers 324 can be selectively prepared by the hypervalent iodine oxidation of 3-substituted thiophenes 323 [381,382] and bipyrroles 326 can be regios-electively synthesized by oxidative dimerization of pyrroles 325 with [bis(trifluoroacetoxy)iodo]benzene in the presence of bromotrimethylsilane [383]. Likewise, bithiophenes 328 have been synthesized from 3,4-disubstituted thiophenes 327 using [hydroxy(tosyloxy)iodo]benzene in the presence of bromotrimethylsilane in hexafluoroisopropanol [384]. 

The ligand group can be introduced either on the meso or on the /5-pyrrole position of the porphyrin ring, but the synthesis of the meso-functionalized derivatives is easier and has been more widely exploited. Balch (50-53) reported that the insertion of trivalent ions such as Fe(III) (32) and Mn(III) (33) into octaethyl porphyrins functionalized at one meso position with a hydroxy group (oxophlorins) leads to the formation of a dimeric head-to-tail complex in solution (Fig. 11a) (50,51). An X-ray crystal structure was obtained for the analogous In(III) complex (34), and this confirmed the head-to-tail geometry that the authors inferred for the other dimers in solution (53) (Fig. lib). The dimers are stable in chloroform but open on addition of protic acids or pyridine (52). The Fe(III) octaethyloxophlorin dimer (52) is easily oxidized by silver salts. The one-electron oxidation is more favorable than for the corresponding monomer or p-oxo dimer, presumably because of the close interaction of the 7r-systems in the self-assembled dimer. 

An oxidative radical coupling promoted by tetra-ra-butylammonium cerium(IV) nitrate (TB ACN) between P-aminocinnamate 22 and enamine 23 provided pyrrole-3,4-dicarboxylate 24 <06T2235>. Dimerization of the P-aminocinnamates provided symmetrical pyrroles. 

Pyrroles can also be obtained from aminocrotonates by oxidation. The transformation is actually a dimerization resulting from a two-electron oxidation of the enamine (Scheme 12) (83T793). 1,4-Addition of nitrometh-ane to the vinilogous ester of A A in presence of l,8-diazabicyclo[5.4.0]un-dec-7-ene (DBU) gave a 1 1 diastereomeric mixture of adducts which, upon reduction, spontaneously cyclized into a mixture of pyrrolidinones, formed in a ratio of 8 2 (Scheme 13) (93TL7529). 

In the absence of the iV-oxide, the reaction of 3-aminopyridazino[3,4-i/ pyrimidinediones 33 with imines takes a different course (Equation 17), and cyclization of the intermediate occurs to form a pyrrole ring <2005JHC375>. The reaction with cyclohexylamine in this instance results in the formation of highly fused dimeric products <2003T7669, 2006T652>. 

Anodic oxidation of enamine ketones or esters in CH30H-NaC104 at a graphite anode gives substituted pyrroles in 15-45% yield.101 Formation of the symmetrically substituted pyrroles 47 indicated radical dimerization of radical-cations formed as primary products from 46. This process leads to dications from which the pyrroles can be formed by cyclization and elimination of an amine [Eq. (44)]. 

Owing to the susceptibility of indole, isoindole and pyrrole rings to oxidation (see Section 3.05.1.4) and acid-catalyzed dimerization and polymerization (see Section 3.05.1.2.2), the products of the reactions with nitrating and nitrosating agents are subject to the reaction conditions. 

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