Reduction of isoindoles

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). 

Redox measurements (see Table VIII) on several isoindole derivatives indicate that this system should be particularly susceptible to reduction. In practice, reduction of isoindoles (and, presumably, also... 

Peak Potentials and Estimated Lifetimes of Ion Radicals in Electrochemical Oxidation—Reduction of Isoindoles ... 

Isoindolines comprise a group of well-characterized and easily synthesized substances, and being at the next stable reduction state below that of isoindoles, they constitute suitable precursors for synthesis of the latter. In principle, either oxidation or elimination from isoindolines should lead to isoindoles however, in view of the susceptibility of isoindoles to further oxidation, elimination has been preferred, and in all cases reported the leaving group has been placed on nitrogen rather than carbon. 

The perhydroisoindole system can be prepared by high-pressure hydrogenation of the isoindole over nickel on alumina at elevated temperatures. The use of Raney nickel with dioxane in the reduction of l,3-diphenyl-2-methylisoindole (47) gives the perhydro product (96), accompanied by the isoindoline (97). An alternative route to partially hydrogenated isoindoles has been described in Section III, D. 

Electrolytic reduction of phthalimide and of phthalimidines which are at an oxidation level above that of isoindole, proceeds through the isoindole to the isoindoline stage, which is then stable to further... 

A study of the electrochemical oxidation and reduction of certain isoindoles (and isobenzofurans) has been made, using cyclic voltammetry. The reduction wave was found to be twice the height of the oxidation wave, and conventional polarography confirmed that reduction involved a two-electron transfer. Peak potential measurements and electrochemiluminescence intensities (see Section IV, E) are consistent vidth cation radicals as intermediates. The relatively long lifetime of these intermediates is attributed to steric shielding by the phenyl groups rather than electron delocalization (Table VIII). 

Mercury-sensitized irradiation of 1,2,3-triphenylisoindole (65) in the presence of oxygen gives a peroxide (103). This peroxide is relatively stable compared with the peroxide (104) derived from similar oxidation of 1,3-diphenylisobenzofuran and can be reconverted to the isoindole (65) by pyrolysis or by treatment with zinc and acetic acid. Reduction of 103 under mild conditions affords o-dibenzoylbenzene (46) and aniline. Aerial oxidation of 47 gives 46 and methylamine, presumably via a peroxide intermediate similar to 103. °... 

The isoindolobenzazepine 380 obtained readily from prechilenine (139), 13-hydroxyoxyberberine (134), or oxybisberberine (130) (223), was recently isolated and named as chilenine (225). On reduction with zinc in hydrochloric acid-acetic acid 380 gave chilenamine (458) along with the hydroxylated product 459 (Scheme 94). Reduction of 380 followed by methylation and elimination of methanol gave pictonamine (460). On treatment with sodium hydroxide in aqueous methanol, 380 was converted to the isoindole 461, exposure of which to trifluoroacetic acid promoted cyclization and decarboxylation to afford the isoindoloisoquinoline neuvanine (462) (226). Its structure was revised (227) from the one originally proposed 463 (228). 

Reduction of N-phenylphthalimide in dry acetonitrile containing an excess of chlorotrimethylsilane gave the l,3-bis(trimethylsilyloxy)isoindole in a two-electron reaction.391... 

Indole-2-carboxylic esters undergo reduction with magnesium in methanol to give the 2,3-dihydroindole (indoline). Dissolving metals reduce the heterocyclic ring of isoindoles. 

Polarographic studies and ESR spectroscopic measurements have been made on the radicals formed on reduction of 2ff-benzo[/]isoindole-4,9-quinones (167).556-558 It is found that the nitrogen and heterocyclic methyl splittings in 167 are approximately proportional to the sum of the Hammett constants for the substituents R1, R2, and R3.556... 

A fundamental chemical tactic in the synthetic manipulation of heterocycies by organic chemists is the reduction of the heterocyclic ring. This chapter will review advances in the partial and complete reduction of pyrroles, furans, thiophenes and their benzo analogs, indoles, benzo[Z>]furans and benzo[Z>]thio-phenes. As appropriate, coverage will include the reduction of those benzo analogs of lesser interest isoindole, carbazole, benzo[c]furan (isobenzofuran), dibenzofuran and dibenzothiophene. 

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