3- Nitroindole derivatives

Gribble and Kishbaugh [31] also reported the Diels-Alder reactions of phenyl-sulfonyl- (i.e., 51) or ethoxycarbonyl-protected 3-nitroindole derivatives (i.e., 55) with Danishefsky s diene (52) (Scheme 15). While the cycloaddition reaction with the sulfonyl-protected indole resulted in a mixture of the exo Diels-Alder adduct 53 and the carbazole product 54 (resulting from a subsequent acid hydrolysis of 53), the corresponding reaction with the ethoxycarbonyl-protected indole produced solely the 2-hydroxycarbazole derivative 56 in high yield. 

A transannular 4 + 2-cycloaddition initiates the tandem 4 + 2/3+2-cycloaddion cascade of 1,3,4-oxadiazoles (1) to yield cycloadduct intermediates (2) used for the synthesis of analogues of vinblastine (Scheme 1)." The multi-component 4+ 2/3+2-domino cycloaddition reactions of 3-nitroindole derivatives with vinyl ethers and acrylates were studied computationally and experimentally. The 4+2-reaction follows a classical concerted asynchronous process while the 3 + 2-addition involves an electron donation by an electron-deficient reaction partner. ... 

Wojciechowski K, Makosza M (1989) Reactions of organic anions. Part 158. Vicarious nucleophilic substitution of hydrogen in 5- and 6-nitroindole derivatives. Synthesis 106-109... 

Similarly, the ethoxycarbonyl-protected 2-nitroindole derivative 57a also participated in Diels-Alder reactions with Danishefsky s diene (52), as well as Rawal s diene (59), to produce the 3-hydroxycarbazole products 58a and 60a in synthetically useful yields (Scheme 16). However, the sulfonyl-protected analog 57b did... 

Similar heterocyclizations were shown to proceed between wta-nitroanilines and carbanions of alkanenitriles to produce 2-amino-4-(and -6-)nitroindoles. For example, the reaction of weta-nitroaniline with acetonitrile leads to 2-amino-4-nitroindole, while 6-nitroindole derivative is formed in the reaction with phenylace-tonitrile (Scheme 58) [171]. 

Gonzalez-Fuentes, M. A., B. R. Diaz-Sanchez, A. Vela, and F. J. Gonzdlez. Radical grafting of carbon surfaces by oxidation of 5-nitroindole derived anions. J. Electroanal. 

Indole can be nitrated with benzoyl nitrate at low temperatures to give 3-nitroindole. More vigorous conditions can be used for the nitration of 2-methylindole because of its resistance to acid-catalyzed polymerization. In nitric acid alone it is converted into the 3-nitro derivative, but in a mixture of concentrated nitric and sulfuric acids 2-methyl-5-nitroindole (47) is formed. In sulfuric acid, 2-methylindole is completely protonated. Thus it is probable that it is the conjugate acid which is undergoing nitration. 3,3-Dialkyl-3H-indolium salts similarly nitrate at the 5-position. The para directing ability of the immonium group in a benzenoid context is illustrated by the para nitration of the conjugate acid of benzylideneaniline (48). 

In the previous review (91YGK205, 99H1157), we reported that l-hydroxy-4-nitroindole forms active ester derivatives by reaction with carboxylic acids, which can be applied to acylation of various nucleophiles. To expand the scope of the reaction and obtain novel fungicidal compounds, an attempt has been made to prepare derivatives of wasabi phytoalexin 109 (98P1959). 

In the presence of DCC, 140 is allowed to react with both l-hydroxy-5-nitroindole (36) and 1-hydroxy-1,2,3-benzotriazole (141). Interestingly, their corresponding active esters, 142 and 143, are obtained in excellent yields as stable crystalline compounds. Both compounds are found to react with variety of nucleophiles, such as alcohols and amines, to produce 144 and 145 in good to excellent yields, as can be seen from the typical examples shown in Scheme 22 (2001H2361). As aresult, it becomes possible to produce various kinds of derivatives of wasabi phytoalexin utilizing 142 and 143. 

The 3-nitroindoles show interesting reactivity toward the anion of ethyl isocyanoacetate iV-sulfonyl derivatives give the pyrrolo[3,3-b indole ring system lEq. 10.38. " On the other hand, iV-alkoxycarbonyl derivatives give the normal product, the pyrrolo[3,4-li indole ring system fEq, 10,39, ... 

This procedure illustrates the synthesis of 4-nitroindoles the present method can easily be extended to the 2-alkyl derivatives (using other ortho esters), 5-, 6- and/or 7-substituted derivatives and 1-alkyl derivatives (from... 

NTII was prepared by reacting naltrexone with (4-nitrophenyl)hydrazine to form 5 -nitroindole (142) which was reduced by catalytic hydrogenation over Raney nickel to the 5 -amino derivative (143). Treatment with thio-phosgene yielded NTII [203]. 

Enantioselective Friedel-Crafts alkylation of A -benzylpyrrole and 5-nitroindole with benzoylhydrazones 504 promoted by a simple strained silacycle reagent 505 gives 2- and 3-derivatives 506 and 507, respectively (Scheme 102) <2005JA2858>. Indole itself provides the corresponding product with significantly reduced enantioselectivity (ee 24%). 

The corresponding reaction of 2-alkenyl-3-alkadienyM-nitropyrrole 1156 also leads to 3-nitroindoles 1158 (21-90%) via intermediate 1157, however, now together with 3-nitrotetrahydroindole derivatives 1159 (Scheme 225) <1998T1913>. The latter compounds are formed by a tandem 6jt-electrocyclization-intramolecular Diels-Alder reaction, and are the predominant (or only) products when nitrobenzene is replaced by triglyme (70-78% yield). 

The 3-proton of 2-ethoxycarbonyl-4-nitroindole absorbs, as might be expected, at unusually low field (1.91r). In the 7-nitro derivative the deshielding is not so pronounced (2.71t).57... 

The 5-nitroindole (121), benzimidazole and 5-nitro- and 6-nitro-ben-zimidazole as their 5 -triphosphates are all incorporated opposite each of the natural nucleotides by DNA Pol a and Klenow fragment with efficiencies up to 4000-fold better than a natural mismatch.Pol a preferentially incorporated each opposite pyrimidines, whilst Klenow preferentially incorporated them opposite purines. Both polymerases incorporated the triphosphates opposite an abasic site up to 140-fold more efficiently than dATP, whilst T4 DNA polymerase incorporated (121) 1000-fold more efficiently than dATP. Incorporation of the 5 -triphosphate derivative of the related indole nucleoside opposite... 

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