Indoles 3- nitroindoles from

The Barton-Zard pyrrole synthesis <1990T7587> was applied in the syntheses of pyrrolo[3,4- ]indoles 423 from 3-nitroindoles 422. Treatment of appropriate alkyl 3-nitroindole-l-carboxylates 422a-c with ethyl isocyanoacetate and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the corresponding pyrrolo[3,4- ]indole 423a-c (Equation 12) <1997CC1873, 1999S1117>. 

A neat synthesis of 4-nitroindole depends on an acyladon-deacyladon sequence from 2-methyl-3-nitroaniline, as shown in Eq. 10.53. On the other hand, treatment of iV-protected indoles v/ith acetyl nitrate generated in sini at bw temperanire gives the correspondmg... 

The previously unknown 2-nitroindoles have been conveniently prepared from o-nitroben-zaldehyde via the Sundberg indole synthesis fEq 10 61 ... 

Gribble et al. (110,111) found that mtinchnones react smoothly with 2- and 3-nitroindoles to afford pyrrolo[3,4-h]indoles 200 and 201 (Table 10.5). In the case of unsymmetrical mtinchnones the regiochemistry, which can be very clean, does not follow simple FMO theory and probably results from a combination of electronic, steric, and dipole interactions. The structures of regioisomers were established... 

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. 

Several additional examples of the Nordlander indole synthesis are tabulated in Table 1 [13-19]. It is obvious that some of these entries could have easily been included in the Bischler chapter because both reactions involve similar if not identical precursor synthesis and acid-catalyzed cyclizations. For example, the snbstrate in Entry 5 was prepared from the corresponding ethyl bromopyruvate. The example in Entry 3 is one of several similar Nordlander indolizations that yield heavily snbstituted nitroindoles. Likewise, the chemistry depicted in Entry 6 was applied to the preparation of several... 

Gribble and Pelkey adapted the Barton-Zard pyrrole synthesis [84] to 3-nitroindoles and ethyl isocyanoacetate (and tosylmethyl isocyanide) to give 2,4-dihydropyrrolo [3,4-T [indoles (Scheme 15, equation 1) [85, 86], In complementary work, Gribble and cowoikers synthesized pyrrolo[3,4-fc]indoles from the 1,3-dipolar cycloaddition of 2- and 3-nitroindoles with miinchnones (1,3-oxazo-lium-5 elates) (eqnations 2, 3) [87, 88]. The mesoionic miinchnones were generated in situ from the appropriate Af-benzyl-Af-acylamino acids. Gribble and Kishbaugh... 

Nevertheless, there are several other oxidation (dehydrogenation) routes to indoles from indolines. In a series of papers, Somei and colleagues used sodium tungstate to synthesize A-hydroxyindole derivatives from the corresponding indolines (Scheme 11, equations 1 and 2) [64, 103-107]. The simple l-hydroxy-6-nitroindole [106] and 4-, 6-, and 7-ethoxy-l-methoxyindoles were synthesized in similar fashion [107]. Pedras and coworkers employed the Somei method to prepare the natural phytoalexin methyl l-methoxyindole-3-carboxylate [108], and McNab and... 

Nguyen and Kurth reported a microwave-assisted synthesis of 3-nitroindole 119 from aryl enamine 118 under palladium-catalyzed conditions. Mild compared to standard nitration conditions, these reactions are tolerant of aryl, heteroaryl, alkyl, and halogen moieties. In addition, esters or nitriles can be used in place of the nitro group to deliver the corresponding 3-functionalized indoles (130L362). 

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