Indoles naphthoquinones

Heteroaromatics such as furan, thiophene, and even the 2-pyridone 280 react with acrylate to form 281(244-246]. Benzene and heteroaromatic rings are introduced into naphthoquinone (282) as an alkene component[247]. The pyrrole ring is more reactive than the benzene ring in indole. 

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

Srinivasan found that the typical stoichiometric Pd(OAc)2 conditions effect cyclization of 2-(N-arylaminomethyl)indoles to aryl-fused p-carbolines in low yield [e.g., 51 to 52] [73]. Similar to the chemistry observed with N-(phenylsulfonyl)pyrrole, 1,4-naphthoquinone also undergoes Pd(OAc)2 oxidative coupling with A-(phenylsulfonyl)indole to give 53 in 68% yield [74],... 

The solid state photochemical reaction of indole with 1,4-naphthoquinone yielded 5H-dinaphtho(2,3-a 2, 3 -c)carbazole-6,ll,12,17-tetrone in addition to 2-(3-indolyl)-1,4-naphthoquinone which was also the only product in the solution photoreaction. Solventless thermochemical reactions of indole with phenanthrenequinone in the presence or absence of zinc chloride gave 10-(lH-indol-3-yl)-9-phenanthrenol and 9,10-dihydro-9-(lH-indol-3-yl)-10-(3H-indol-3-ylidene)-9-phenanthrenol or 10,10-di-lH-indol-3-yl-9(10H)-phenanthrenone, respectively. All of these products were only obtained in trace amounts in corresponding solution reactions, and are different from the adduct 10-hydroxy-10-(lH-indol-3-yl)-9(10H)-phenanthrenone obtained in the solution photoreaction (Wang et al., 1998). 

Other ring types prepared from thioureas include those of Petersen and Hcitzer, who prepared the naphthoxathiolones 233 (X = 0, Y = OH)411 from 2-(2-methylpropanal-2-yl)-l,4-naphthoquinone and 233 (X = NH, Y = H)412 starting with a tctrahydrobenz[gr]indol-5-one, each through reaction with thiourea in hydrochloric acid. Kaushal and Narang413 prepared a series of dihydrothiazolo[4,5-c]cinnolines... 

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. 

Sulfur-substituted 3-vinylpyrroles generated from A -methyl-3-thioace-tylpyrrole have been used to accomplish the synthesis of functionalized indoles by Diels-Alder cycloaddition. In the reactions with MA, NPMI, and naphthoquinone the [4 + 2]-cycloadducts were obtained with low to moderate yields and directly transformed to the corresponding indoles by treatment with DDQ (91CPB489). 

Acylated indoles, in their enol form (54), are formed by heating the phenyliodo-nium ylide of 2-hydroxy-1,4-naphthoquinone in the presence of some indoles.58 The intermediacy of an o ,a ,-dioxoketene (55) is suggested. The same reactants (with the exception of indole itself) form 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a Cu(II)-catalysed reaction. 

Several protocols using multi-component reactions to prepare multisubstituted furans were reported. One procedure was that using acetylenedicarboxylate, isocyanides, triphenylphosphine and an aromatic carboxylic acid <07SL1610>. The others include the reaction of acetylenedicarboxylate, isocyanides and nicotinic acid <07S2637>, of dibenzoylacetylene, amines and diketene <07T8083>, of alkyl isocyanides, aromatic aldehydes and 3-cyanoacetyl indoles <07TL8987>, and of naphthoquinone, isocyanides and aldehydes <07T10269>. 

Thermal decomposition of phenyliodonium ylide of 2-hydroxy-l,4-naphthoquinone (lawsone) 403 in the presence of indole derivatives 402 (GH2CI2, reflux, 4-7 h) affords 3-acylated indoles existing in their enol forms 404, through a ring contraction and ot,ot -dioxoketene formation reaction (Scheme 87) <2005JOC8780>. 

The same reactants afford 3-(3-indolyl)-2-hydroxy-l,4-naphthoquinones 405 in a copper-catalyzed reaction (CH2CI2, 00(0+3803)2, rt, overnight). In case the more electron-rich position 3 in the indole ring is substituted, as in 3-methylindole, the reaction takes place from position 2, but the yield of the corresponding derivative is very low (7%) (Equation 95). The thermal reaction of reagent 403 with 1-methylpyrrole afforded the expected acylation product 407 in high yield (Equation 96) <2005J008780>. 

A variety of heterocyclic compounds of the indole and benzofuran type can be made via photoaddition of alkenes to 2-amino- or 2-hydroxy-1,4-naphthoquinone. These products, described by H. Suginome probably derive from an intramolecular trapping reaction of the intermediary 1,4-biradicals or 1,4-zwitterions. 

The reaction of 3-aminoprop-2-enoates with 1,4-naphthoquinone affords 5-hydroxy-benzo[g]indoles and hence offers access to pyrano[3,2-e]benzo[g]indoles that become strongly red coloured on irradiation with half-lives similar to the analogous 5,6-dimethylnaphtho-[l,2-b]pyran 14 (Scheme 19) <00WOP31080>. 

A Michael adduct, reminiscent in structure of the first intermediate in the Gates synthesis of morphine, has been obtained as a catechol derivative en route to conversion to an indole. 3-Nitro-6-ethoxycarbonyl-1,2-naphthoquinone with ethyl acetoacetate in dioxan containing zinc chloride was refluxed for 5-10 minutes, allowed to stand for 20 minutes, the nitro compound reduced with zinc dust to the amino compound which cyclised after a final oxidation step to an indole,... 

Velezheva and coworkers described the Lewis acid-catalyzed Nenitzescu indolization using zinc iodide in dichloromethane (Scheme 9, equation 1 and 43-45) [23], later improved to the use of zinc chloride (equations 2, 3) [24]. Boruah and colleagues employed a Lewis acid-catalyzed microwave-modified Nenitzescu indolization to prepare 3-amino-5-hydroxybenzo[ ]indoles (Scheme 9, equation 4, and 46-47) [25]. Boron trifluoride etherate was superior to other Lewis adds studied (TiCl, AICI3, ZnClj, InCy. The reaction presumably proceeds by a Michael addition of the carbonyl component, in the form of a p-hydroxyenamine to the naphthoquinone, and the urea serves as a controlled-release source of ammonia. 

Suginome and coworkers discovered the novel [3+2] regioselective photoaddilion of 2-amino-1,4-naphthoquinones with electron-rich alkenes to afford lH-benz[/] indole-4,9-diones (Schane 16, equation 1) [112]. Likewise, amino-1,4-benzoquinones with alkenes gave lH-indole-4,7-diones (equation 2). If the initial photoproducts could not indolize by loss of alcohoL then the corresponding dihydro compounds were isolated. Parker and Mindt found that qui-none monoimides were smoothly photocyclized to the respective 5-hydroxyindoles (equation 3) [113]. 

From a solution containing scatole, indole may be precipitated as the naphthoquinone derivative and each of the substances in question can then be determined... 

A number of miscellaneous methods for forming carbon-carbon bonds are of interest. Carbene-chromium complexes were involved in the synthesis of deoxyfrenolicin, the important step being conversion into the naphthoquinone (Scheme 32). Silylated tricarbonylarenechromium(0) complexes of indole may... 

Reaction with 2-Aminoquinones. Acyl and carbox3miethyl radicals generated using Mn(OAc)3 react with 2-aminoquinones in a fashion similar to that of their naphthoquinone counterparts. In case of 2-arylainino-l,4-benzoquinones, sequential radical addition/cycUzation occurs to afford the corresponding acridine derivatives (eq 34). The yield is lowered in the presence of an electron-withdrawing group on the aniline. Benzo[/]-indole-4,9-diones and their derivatives can be obtained exclusively with... 

Finally, copper(II) catalysis was reported to be efficient in the formation of complex indolizine templates constructed Irom pyridine via a three-component reaction. When an excess of pyridine is reacted with equimolar amount of 1,4-naphthoquinone and dimethyl butynedioate (1 equiv) in the presence of copper(II) chloride under aerobic conditions, benzo[/]pyrido[l,2-a]indole-6,ll-dione is formed in 93% yield (eq 39). 

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