4- Acylindole derivatives

The synthesis of 4-acylindole derivatives, including (245), by the Diels-Alder cycloaddition between the 2-(2-phenylsulfinylvinyl)pyrrole (242) and electron-deficient alkynes such as (243), has been reported [187]. The initial cycloadduct (244) spontaneously aromatized under the reaction conditions to give (245) (Scheme 5.78). 

Diacetylpyrrole is also formed (77JOC3952). The analogous reaction of indoles with carboxylic acids in the presence of trifluoroacetic anhydride and phosphoric acid also gives the 3-acylindoles (derived from the carboxylic acid) in high yield, but without the concomitant formation of the 3-trifluoroacetyl derivatives (80H(14)1939). 

The acetal linker 1.33 (90), obtained from suitably protected aminophenol (three steps from 2-nitro-5-methoxytoluene) and hydroxy PS resin, was activated by acetal hydrolysis to give acylindole derivatives which could be cleaved and diversified to give... 

Ban s general entry to the Strychnos and Aspidospema alkaloids makes ingenious use of a novel photoisomerization of 1-acylindole derivatives to 3-acylindolenines. When applied to the tryptamine derivative (132), the derived indolenine (133) spontaneously rearranged, with formation of the indole-amide (134) in 80% yield (Scheme 22). Obvious stages then led to (135), which... 

The structure of ervinidine was determined as 68 on the basis of the above information and the rationale that follows. The two carbonyls of the lactam and the ketone were placed adjacent to each other in order to account for the facile loss of 28 mu, as shown in Scheme 1, and from the same intermediate the important fragment at m/e 168 is produced. An alternative initial fragmentation (Scheme 1) leads to the ions at 228, 214, and 154 mu. Lithium aluminum hydride afforded the aspidospermine derivative 69 by cyclization. One of the problems associated with this particular structure is the possibility that it would not exist as described but rather as the 3-acylindole derivative 70. In this event, the carbonyl at 1720 cm-1 would be assigned to the ester group and that at 1690 cm-1 to the 3-acylindole function. The C-20 stereochemistry was not determined. 

The intermolecular variant of the above reaction between W-methylphthalimide (74) and a series of W-acylindole derivatives 75a-f was next examined [37, 38]. Compounds 75a and 75d-f produced the corresponding more sterically hindered oxetanes 76a and 76d-f in which the aromatic rings of the isoindolone and indoline moieties overlap (Scheme 19). Interestingly, in the cases of 75b, c, the initially formed oxetanes 76b-d were converted to a variety of products, presumably via the hydrolysis of the oxetanes, followed by ring opening of the indoline ring and subsequent reactions to produce 78-81. 

The authors next focused their attention on the potential use of 3-acylindoles bearing suitable functionality in a subsequent cyclization step [47]. Thus, 6-aryl-ll H-indolo[3,2-c]quinolines 37 were prepared in one-pot process through a straightforward palladium-catalyzed carbonylative cyclization of o-(o -aminophenylethynyl)tri-fluoroacetanilide with aryliodides followed by the cyclization of the resultant 3-acylindole derivative (Scheme 13.21). 

One route to 0-vinyl derivatives involves LiPdCl4-calalysed exchange with vinyl acetate[l]. Rearrangement and cyclization occur concurrently to give 1-acylindoles. 

Thallation of 3-acylindoles gives the 4-thallated products, which can be converted to both the 4-nitro and 4-azido derivatives in copper(II)-promoted processes (89H(29)643). The nitro compound is formed by heating the organothallium intermediate with sodium nitrite and copper sulfate in DMF at 100°C. This methodology has been used in a total synthesis of indolactam-V (90T6623). 

Although it is more usual to obtain the halogenoacyl derivatives of pyrrole and indole by direct acylation (see Section 3.05.1.2.6), it is possible to carry out electrophilic halogena-tion of acylindoles <79HC(25-3)357). 3,4-Diacetyl-l,2,5-trimethylpyrrole has also been reported to react with phenyltrimethylammonium tribromide to give the 3,4-bis(bromoacetyl) derivative, which cyclizes in the presence of a zinc-copper catalyst to yield 4,5,6,7-tetrahydro-l,2,3-trimethyl-4,7-dioxoisoindole (74CC1034). 

The lithium derivatives of 1-substituted pyrroles and indoles provide another general route of access to 2-acyl pyrroles and indoles. The ketones can be obtained directly by reaction with aryl nitriles or acid halides but, at least for 1-benzenesulfonylindole, a two-step procedure involving reaction with an aldehyde followed by oxidation of the carbinol to the ketone is frequently more convenient (equation 179) (73JOC3324, 75JOC2613). This method is probably the most general route to 2-acylindoles, although many have also been prepared by direct Fischer cyclization (see Section 3.06.3.4.2). 

Generation of 3-indolylacyl radicals from the selenoesters 149, using either /j-Bu3SnH or tris(trimethylsilyl)silane (TTMSS) followed by reaction with various alkenes, offers a route to 3-acylindoles 150. On the other hand, the use of n-Bu Sn2 under irradiation gave cyclopent[6]indole derivatives such as 151 via a cascade involving initial addition of the acyl radical to the alkene, and a subsequent oxidative cyclization at the indole C-2 <02JOC6268>. 

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