Indoles benzoquinones

Birch reduction of indole with lithium metal in THF in the presence of trimethylsilyl chloride followed by oxidation with p-benzoquinone gave l,4-bis(trimethylsilyl)indoIe (106). This is readily converted in two steps into l-acetyl-4-trimethylsilylindole. Friedel-Crafts acylation of the latter compound in the presence of aluminum chloride yields the corresponding 4-acylindole (107) (82CC636). 

At least two pathways have been proposed for the Nenitzescu reaction. The mechanism outlined below is generally accepted." Illustrated here is the indolization of the 1,4-benzoquinone (4) with ethyl 3-aminocrotonate (5). The mechanism consists of four stages (I) Michael addition of the carbon terminal of the enamine 5 to quinone 4 (II) Oxidation of the resulting hydroquinone 10 to the quinone 11 either by the starting quinone 4 or the quinonimmonium intermediate 13, which is generated at a later stage (HI) Cyclization of the quinone adduct 11, if in the cw-configuration, to the carbinolamine 12 or quinonimmonium intermediate 13 (IV) Reduction of the intermediates 12 or 13 to the 5-hydroxyindole 6 by the initial hydroquinone adduct 7 (or 8, 9,10). 

The directing influence of the trifluoromethyl group also competes with that of the strongly electron-donating methoxyl group. Thus 2-methoxy-5-trifluoromethyl-l,4-benzoquinone (26) was treated with ethyl 3-aminocrotonate (5) to furnish 25% of each of the two possible isomeric indoles 27 and 28. °... 

The best yields of 5-hydroxyindoles are obtained when equimolar amounts of the quinone and enamine are used. An excess of enamine gives rise to non-indolic products derived from reaction of two enamine units and one quinone unit or the product which results from the initial Michael addition of the enamine to the quinone. Use of excess quinone has been reported less frequently, but limited studies indicate no advantage. When 2,5-dichloro-l,4-benzoquinone (32) was treated with a 50% excess of ethyl 3-... 

Studies on the Bischler-Napieralski cyclization of A -acetyltryptamine in the presence of indole have led to the isolation of numerous products, among which the indolocarbazole 186 could be found in 3.5% yield. This outcome was rationalized as a result of the intermediacy of a spiroindolenine species formed under these conditions [89H(28)175]. During detailed studies on the polymerization of indole, formation of a low yield of the related indolo[3,2-h]carbazole 187 was discovered in the product mixture originating from the treatment of indole with p-toluenesulfonic acid at elevated temperature [88JCS(P1)2387]. In an investigation of the condensation of p-benzoquinone with 4-substituted anilines, an indolo[3,2-h]carbazole derivative has been reported to be formed in 2% yield (80JOC1493). 

Ethyl tram-5 a,9 a-dihydro-1 H- -benzazepine-1 -carboxy late (2), a photorearrangement product of ethyl 3,3a,7a,7b-tetrahydro-l//-cycIobut[6]indole-3-carboxylate (1), on treatment with tet-rachloro-l,2-benzoquinone in benzene undergoes oxidation to the l//-l-benzazepine 3.109... 

Reactions of 2-(2-nitrovinyl)-l,4-benzoquinone with furans, indoles, and endocyclic enol ethers form angular, fused heterocyclic quinoid ring systems (see Eq. 8.13).23... 

Dimethyl 2-(17/-indol-2-yl)but-2-enedioate, easily available by reaction of 4,7-dihydroindole with dimethyl acet-ylenedicarboxylate followed by oxidation with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ), treated with PTAD provided compound 703, which was thermaly isomerized to 704 (Scheme 111) <2006JOC7793>. 

Ketcha and Wilson reported the solid-phase version of the classic Nenitzescu indole synthesis in a process involving initial acetoacetylation of ArgoPore-NH2 resin with diketene to afford a polymer bound acetoacetamide <00TL6253>. Formation of the corresponding enaminone 102 via condensation with primary amines in the presence of trimethylorthoformate followed by addition of 1,4-benzoquinones 103 leads to formation of polymer bound 5-hydroxyindole-3-carboxamides 104 which could be cleaved from the resin using TFA yielding the indoles 105. 

In addition to examining the vinylation of l-methyl-2-indolecarboxaldehyde with methyl acrylate (Pd(OAc>2/HOAc/AgOAc) to give methyl ( )-3-(2-formyl-l-methyl-3-indoiyl)-acrylate in 60% yield, Pindur found that similar reactions of methyl 3-(l-methyl-2-indolyl)-acrylate afford bis(carbomethoxy)carbazoles albeit in low yield [85]. Fujiwara discovered that the combination of catalytic Pd(OAc)2 with benzoquinone and t-butylhydroperoxide serves to couple indole with methyl acrylate to give methyl ( )-3-(3-indolyl)acrylate in 52% yield [86]. 

Michael additions to quinones. In the presence of TrC104, enol silyl ethers undergo 1,4-addition to benzoquinone to give adducts that cyclize to benzofurans.1 A similar reaction with diimidoquinones produces indole derivatives. 

A general and efficient synthesis of 5-oxygenated indoles 126 and 128 has been reported by Kita et al. (92H503). The method involves intramolecular imine formation from p-benzoquinones 125 and p-benzoquinone monoacetals 127 bearing the 2-aminoethyl side chain. Compounds 125 and 127 are prepared by the oxidation of 124 with IBTA in acetonitrile in the presence of water and methanol, respectively (Scheme 35). 

As an extension of the Nenitzescu indole synthesis, p-benzoquinone (521) was condensed with various electron-withdrawing anilines 522 in the presence of trifluoroacetic acid (TFA) to give 6-hydroxycarbazoles 523. Besides the low )deld of... 

In an analogous process o-allylanilines were converted into indole derivatives by Hegedus (3.66.). Since the process is initiated by a palladium(II) catalyst and produces palladium(O) as product, recycling of the catalyst had to be ensured by the addition of stoichiometric amounts of an oxidant (e g. benzoquinone).83... 

Bcnzofuran-4,7-dioncs have been synthesized regioselectively by [3 + 2] photoaddition of 2-hydroxy-1,4-benzoquinones with a range of alkenes (equation 185)664. The reaction occurs in 30-60% yield and is a useful method for the synthesis of the benzofuran ring system, which is important in natural products like acamelin665. Substituted naphthoquinones may also be used in this reaction666,667 and this has lead to a very simple two-step synthesis of maturinone. In a similar reaction, a [3 + 2] photoaddition reaction of 2-amino-1,4-naphthoquinones with electron-rich alkenes gave 13-82% yields of 2,3-dihydro-177-bcn/ /]indole-4,9-diones in a single-step process which involved photolysis followed by oxidation (equation 186)668,669. 

Masked o-benzoquinones, as the most accessible type of cyclohexa-2,4-dienones, are of immense synthetic potential [187-193]. At both room temperature and reflux, the dienones 263 generated in situ from commercially available 2-methoxyphenols 262 by adding (diacetoxyiodo)benzene (DAIB, 1 equiv.) at 0 °C in MeOH underwent unusual Michael addition to indoles (2, 19, 264) followed by aromatization of the adducts to give highly functionalized 2-arylindoles 265a-c in excellent yields (Scheme 57) [193]. 

Asterriquinone, the pigment isolated earlier from Aspergillus terreus, proves to be one of eleven closely related pigments, based on a bisindolyl-p-benzoquinone skeleton substituted at positions 1, 2 or 7 of the indole rings by isoprene or... 

The first step is to make an indole by Pd(II)-catalysed cyclization in the presence of benzoquinone as reoxidant. The nucleophilic nature of the 3-position of the indole (Chapter 43) was exploited to introduce the required iodine functionality. Rather than direct iodination, a high yielding two-step procedure involving mercuration followed by iodination was employed. The more reactive iodide was then involved in a Heck coupling with an unsaturated side chain in the absence of phosphine... 

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