3- Acyl indoles

If, instead of an ester, the Japp-Klingemann reaction is done with a salt of a P-ketoadd, decarboxylation occurs and the eventual product is a 2-acyl-indole. 

Table 15.3 gives some examples of reductive deoxygenation of 2-acyl and 3-acyl indoles. 

The enamine-imine tautomerism of the indolenine system gives rise to rearrangement reactions of interest in indole alkaloid chemistry. Thus the synthesis of dihydroburnamicine (625) utilized the rearrangement of an acetoxyindolenine to an a-hydroxyalkyl indole, presumably through an intermediate enamine. Similarly 2,3-dialkyl indoles undergo oxidations to 2-acyl indoles (626-631). 

Changing the functionality on the alicyclic ring from an amine to a carboxylic acid leads to a compound that shows antiallergic activity, acting possibly by means of inhibition of the release of allergic mediators. Thus, condensation of acylated indole with cyclohexanone carboxylic acid affords directly oxarbazole (29). ... 

ALKYLATED AND 3 ACYLATED INDOLES FROM A COMMON PRECURSOR 3-BENZYLINDOLE AND 3-BENZOYLINDOLE... 

Lithiumalanat reduziert auch 3-Formyl- und 3-Acyl-indole zu den Alkyl-indolen, wenn das Stickstoff-Atom nicht methyliert ist14,15 z.B. ... 

For a general, simple high yield indole synthesis from anilines and methylthioacetaldehyde etc. see JACS 95,588,591,2718,6508 (1973). For indoles from N-( /3 -hydroxy-ethyl aniline esters see BSC 2485(1973). For a 2-acyl-indoles in one step from orthoamino-ketones and alpha-haloketones or 2-carboxyindoles from sulfonamides of ortho-aminocarbonyls see JOC 38,3622-24(1972). Indole and 5-Br-indole in 4 steps from beta-naphthol see Chem. Het. Cpds. (Russ.) 753(1973). Indole-JOC 37,3622(1972). 

TV-Acyl indoles derived from amides have been employed for the conversion of lactones into protected hydroxyacids. Thus, (chloromethyl)alumi-num 2-(2-propenyl)anilide reacts (120) with 1,4- and 1,5-lactones, as for example per-O-terZ-butyldimethylsilyl-D-ribono-1,4-lactone (104), to afford hydroxyamides. After protection of the free hydroxyl group, these amides were converted by ozonolysis into TV-acyl indoles, 105, which were readily saponified to the acid 106. 

Yamamoto, H. 1-Acyl-indoles. II. A new syntheses of 1-(p-chlorobenzoyl)-5-methyoxy-3-indolyacetic acid and its polymorphism, Chem. Pharm Bull. 1968, 16, 17 ibid 1968, 16, 647. 

Table 15.3 gives some examples 3-acyl indoles. 

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. 

Syntheses of 2-substituted indoles from (2-aminobenzyl)triphenylphosphonium salts have been achieved either by cyclization with carboxylic acid anhydrides in the presence of triethylamine, or acyl chlorides in 2,6-lutidine <02TL2885>. In a related study, the acylated indoles 65 have been prepared from the phosphonium salts 66 in a process involving extrusion of a one-carbon fragment. A mechanistic rationale for these findings was also provided by the authors <02TL8893>. 

N-Acylated indoles are converted into tricyclic compounds 211 in the presence of samarium diiodide (2.5 eq.) along with hexamethylphosphoramide (10 eq.) and phenol (2.0 eq.) as proton source <20030L4305>. 

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>. 

N-Acylated indoles 1520 furnished tricyclic compounds 1521 in the presence of samarium diiodide (2.5 equiv) in tetrahydrofuran along with an excess of hexamethylphosphoramide (10 equiv) and phenol (2 equiv) as proton source (Equation 311) <20030L4305>. Whereas methyl ketone 1520 (R = Me) smoothly cyclized to compound 1521 (in 73% yield), the corresponding aldehyde 1520 (R = H) provided compound 1521 only in low yield (28%). 

Polycyclic products 1523, 1524,1526, and 1528 were formed with essentially perfect diastereoselectivity and good to excellent yields when the reactions of N-acylated indoles 1522, 1525, and 1527 were performed in the absence of HMPA (Scheme 291, Equations 312 and 313) <20030L4305>. 

Phosphine oxide anions are often superior to ylids in olefmation reactions, and the anion of 68, made with lithium di-isopropyl-amide (LDA), has none of the disadvantages of the ylid 67. We have made 41 a range of vinyl ethers 70 this wayc, and as part of a synthesis of stiychnos alkaloids43, we were able41 to convert the acyl indole 71 into the aldehyde 72... 

The conversion of gardnerine (1) to ochropine (39), a 2-acyl indole alkaloid isolated from the stem bark of Ochrosia poweri 175. was also carried out to establish structure 39 for the latter alkaloid. The reaction sequence is shown in Scheme 10. The nitrile function of 43 was converted to the carbomethoxy grouping by methanolysis. C-D ring cleavage with BrCN gave an epimeric mixture of C-3 hydroxyls which was then subjected to Cornforth oxidation to furnish 46. Decyanation of 46 and... 

For a similar reason the carbonyl group of benzopiperi-dones or of 3-acyl-indoles behaves chemically more like an amidic carbonyl then like a ketonic one. hi 2-methoxy-jpflrfl-benzoquinone the reactivity of the methoxy group is... 

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