Indolylmagnesium bromide

Preparation of bromoindoles by replacement of metallic substituents have included oxidation of indolylmagnesium bromide by p-nitrobenzoic acid to give 3-bromoindole (67BSF1294), thallation procedures (illustrated in Scheme 18 also applied to the synthesis of chloroindoles) [85H(23)3113 86H(24)3065 87CPB3146, 87H(26)2817 89H(29)1163], and the use of lithium derivatives. The thallation reactions provide access particularly to 4- and 7-bromoindoles. Quenching the protected 2-lithium derivative of indole with 1,2-dibromotetrachloroethane gave an 87% yield of 2-bromoindole (92JOC2495). 

Of all the palladium-catalyzed coupling reactions, the Kumada coupling has been applied least often in indole chemistry. However, this Grignard-Pd cross-coupling methodology has been used to couple l-methyl-2-indolylmagnesium bromide with iodobenzene and a-bromovinyltrimethylsilane to form l-methyl-2-phenylindole and l-methyl-2-(l-trimethyl-... 

Kametani (71JOC1291) used a completely different approach to the synthesis of 29 (and correspondingly 7b, 30 and 31). The reaction between 3-indolylmagnesium bromide and 3-ethyl-4-carbomethoxypyridine N-oxide gave a mixture of 3-pyiidylindoles 32a and 32b, separated chromatographically and converted into the corresponding methiodides with subsequent catalytic... 

Faul et al. reported an improved synthesis of arcyriarubin A (349) by reaction of indolylmagnesium bromide (1358) with dichloromaleimide (1366). Following Hill s route, 349 was transformed to staurosporinone (293) in three steps and 47% overall yield (see Scheme 5.225). This approach provides, so far, the shortest access to staurosporinone (293) with the best overall yield (771) (Scheme 5.228). 

In the following year, this method was also applied to the total synthesis of tjipanazole FI (371) (784). For this synthesis, the required bisindole 1444 was obtained starting from 5-chloroindole (1440) in three steps and 47% overall yield. Acylation of 1440 with oxalyl chloride led to the glyoxylic acid chloride 1441. Transmetalation of indolylmagnesium bromide with zinc chloride, followed by addition of the acid chloride, provided the ot-diketone 1443. Exhaustive reduction of 1443 with lithium aluminum hydride (LiAlFl4) afforded the corresponding bisindolylethane 1444. Executing a similar reaction sequence as shown for the synthesis of tjipanazole F2 (372) (see Scheme 5.243), the chloroindoline (+ )-1445 was transformed to tjipanazole FI (371) in two steps and 50% overall yield (784) (Scheme 5.244). 

A-Alkylation, -acylation and -sulfonation are also promoted by a polar solvent, such as HMPA (hexamethylphosphoric triamide).This acts to solvate the ions (promoting dissociation), but in a non-polar solvent like diethyl ether or tetrahydrofuran (THF), attack by most carbon electrophiles upon indolylmagnesium bromide proceeds at C-3 (Scheme 7.9). 

Treatment of 4-methoxy-2-oxazolidinone 86 with indolylmagnesium bromide 87, followed by A-protection with a ferf-butoxycarbonyl (Boc) group affords NJd -di-Boc-4-(3-indolyl)-2-oxazolidinone 88. Subsequent treatment with A-bromosuc-cinimide (NBS) in the presence of azobisisobutyronitrile (AIBN) followed by electrochemical reduction yields the protected 4-(3-indolyl)-2(3//)-oxazolone 90 (Fig. 5.23). The Boc groups are easily removed by pyrolysis."" "" ... 

C-Alkylation of pyrroles and indoles can be mediated by alumina in association with the appropriate halide. 3-Indolyl sugar derivatives have been obtained by alkylation reactions of indolylmagnesium bromide. This type of alkylation has been extended to ring-fused indoles 105 and yields 3//-indole derivatives 106 in good yields. 

Treatment of indolylmagnesium bromide cf. Section 9.9.1 with phosgene under reflux in diethyl ether gave, after work-up, a mixture of the following compounds [177] ... 

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