Pyrrole ring, reduction

Reduction of isoindoles with dissolving metals or catalytically occurs in the pyrrole ring. Reduction of indolizine with hydrogen and a platinum catalyst gives an octahydro derivative. With a palladium catalyst in neutral solution, reduction occurs in the pyridine ring but in the presence of acid, reduction occurs in the five-membered ring (Scheme 38). Reductive metallation of 1,3-diphenylisobenzofuran results in stereoselective formation of the cw-1,3-dihydro derivative (Scheme 39) (80JOC3982). 

This synthesis of the pyrrole ring system, due to Knorr, consists in the condensation of an a-aminoketone with a 1,3-diketone or the ester of a p-keto-acid, a-Aminoketones are unstable in the free state, readily undergoing self-condensation consequently they must be prepared, by the reduction of an a-nitroso (or oximino) ketone, in the presence of the 1,3-diketone or p-ketoester, to ensure rapid interaction. 

A special technique was necessary to obtain good yields of ethyl pyrrole-3-acetate from ethyl pyrrole-3-glyoxalate. Reduction over W-7 Raney Ni in 50% aq ethanol was accompanied by major ring reduction and tarring. By use of a two-phase system, toluene and 50% aq ethanol, these side reactions could be curtailed. Apparently the desired product was removed effectively from the aqueous layer into the toluene as soon as it was formed (26). 

Partial and total reduction of A -methylpyrrole was achieved with zinc [433], and of a pyrrole derivative to a dihydropyrrole derivative with phos-phonium iodide [287] (p. 34, 35). The pyrrole ring is not reduced by sodium. 

Reduction of the pyrrole ring in benzopyrrole (indole) is discussed on p. 56 [430]. 

Lactonization of the suitable hydroxy acids or their derivatives is the most common synthetic method for benzoxepinenones with fused pyrrole rings. Therefore, reduction of the formyl group in the ester aldehyde 121 with sodium borohydride gives a mixture of alcohol 122 (80% yield) and lactone 123 (19%). Further heating of the open-chain product 122 in refluxing ethanol affords cyclic lactone 123 quantitatively (Scheme 25 (1998T11079)). 

The pyrrole ring can also be constructed starting from an 7V-vinyl-2-halobenzoic amide. The /V-(2-iodobcnzoyl)-1,4-dihydropyndine derivative shown in 3.19. underwent palladium catalysed ring closure to give a condensed isoindolone derivative. The use of formic acid as co-solvent led to the reduction of the intermediate palladium complex formed in the insertion step, instead of / -hydride elimination. The transfer of the stereochemical information from the starting material to the product was poor.25... 

A variety of pyrrole ring closure reactions are conveniently formulated as proceeding via nitrene intermediates, although it is doubtful whether a free nitrene is involved. Pyrolysis of o-nitrobiphenyls with iron(II) oxalate (61T(16)80), or reduction under milder conditions with triethyl phosphite (65JCS4831) or tris(trimethylsilyl) phosphite (79TL375), leads to the carbazole, as does the pyrolysis or photolysis of 2-azidobiphenyls (Scheme 3) (75JA6193). 

When the reactions of pyrroles and indoles with aldehydes are catalyzed by hydriodic acid, the initially formed carbinols or azafulvenes are reduced to yield the corresponding alkylpyrroles and alkylindoles (68CJC3291,70CJC139). The reductive alkylation of the pyrrole ring, using a range of aliphatic and aromatic aldehydes and ketones, may also be accomplished with phosphonium iodide, with hydrochloric acid and zinc amalgam, or with tin(II) bromide in hydrobromic acid. 

Copper chromite tends to catalyze the reduction of the heterocyclic ring and any readily reduced substituents, whereas rhodium on alumina is an effective catalyst for the hydrogenation of the pyrrole ring under very mild conditions (B-77MI30505, B-77MI30507,79CJC1977). 

Reduction of the carbonyl groups at the 2-position of the pyrrole ring and at the 3-position of the indole ring with LAH or diborane generally leads to the formation of the corresponding alkyl derivatives, due to the facile nucleophilic displacement of the hydroxy group of the carbinols by the mechanism depicted in Scheme 69 (see Section 3.05.2.2). Predictably,... 

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