3-allyl indoles

Aniline, N-alkyl-o-allyl-indole synthesis from, 4, 321 Aniline, N-allyl-... 

Formylation of the V-allyl indole derivatives 311 (obtained by allylation of the indole 310) afforded l-allyl-7-formyl-indole 312. Subsequent condensation of 7-formyl indole derivatives 312 with ethyl acetate in presence of sodium ethoxide gave 313 (89S322). Reaction of 312 with N-methylhydroxylamine hydrochloride afforded the cycloadduct, tetracyclic... 

Aniline, JV-alkyl-o-allyl-indole synthesis from, 4, 321 Aniline, N-allyl-indole synthesis from, 4, 326 Aniline, AT-allyl-o-bromo-indole synthesis from, 4, 327 Aniline, N-allyl-o-iodo-indole synthesis from, 4, 327 Aniline, o-bromo-in indole synthesis, 4, 340 Aniline, o-halo-cyclization, 4, 340 Aniline, m-nitro-in indole synthesis, 4, 338 Aniline black, 3, 197 Anilines... 

Allylic alcohols can also allylate indole in the presence of triethylborane and a Pd catalyst [94]. This system is capable of allylating a number of nucleophiles and is believed to proceed through a 7t-allylic-Pd intermediate. The borane functions as a Lewis acid, activating the allylic alcohol towards oxidative addition [95]. With unsymmetrical alcohols, a mixture of the allylic regioisomers is observed. The reaction proceeds satisfactorily with both electron-releasing and electron-withdrawing C-ring substiments. With 3-methylindole the indolenine is isolated. 

The aza-Claisen rearrangement also occurs in N-allylic indoles 142 [104]. 

In addition, allylboron dichloride, generated in situ from allylstannanes and boron trichloride, smoothly allylates indol. An ate -like boron intermediate has been proposed to explain the excellent regioselectivity observed. The chemistry has been applied in the total synthesis of Tryprostatin B (Scheme 23.37). 9... 

Platinum(II) chloride-catalysed reaction of allenes R R C=C=CHR with N-protected indoles (In) in THF with added MeOH proceeds at 70 C over 20 h and affords products of geminal bisindolylation, that is, R R CH-CH2C(3-In)2R. By contrast, gold(I) complexes catalyse monoindolylation, giving rise to allyl indoles... 

Another hitherto unobserved type of rearrangement which may have synthetic and biogenetic implications has been found by Casnati et al. (77). 3-Alkyl-l-allyl-indoles rearrange under acid catalysis by trifluoro-acetic acid to give 2-allyl derivatives. A 3-protonated species seems to be the most probable intermediate for this new type of rearrangement, which was clearly shown to occur intramolecularly. 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Indol-2-ylcopper reagents can also be prepared from 2-lithioindoles and they have some potential for the preparation of 2-substituted indoles. 1-Methyl-indol-2-ylcopper can be prepared by reaction of 2-lithio-l-methylindole with CuBr[10]. It reacts with aryl iodides to give 2-aryl-1-methylindoles. Mixed cyanocuprate reagents can be prepared using CuCN[ll], The cyan-ocuprate from 1-methylindole reacts with allyl bromide to give 2-allyl-l-methylindole. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Table 11.1 lists some of the reaction conditions which have given prepara-tively useful yields of 3-alkylation. Entries 1-3 are typical alkylations using a magnesium salt and an alkyl halide. Even 2,3-disubstituted indoles are alkylated at C3 under these conditions (Entry 7). Entry 5 represents a more recently developed method in which an allylic alcohol and indole react in the... 

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

A 20% excess of ethylmagnesium bromide was prepared from magnesium (6.5 g) in ether (80 ml) by adding ethyl bromide (30 g) in ether (30 ml). Indole (25.8 g) in benzene (50 ml) was then added slowly with stirring and stirring was continued for 20 min after addition was complete. A solution of allyl bromide (29.2 g) in benzene (20 ml) was then added slowly. The mixture was stirred overnight and then diluted with ether and the product isolated and purified by distillation (22.7 g, 70% yield). 

Vilsmeier-Haack formylation, 4, 222 Indole, dimethyl- C NMR, 4, 172 Indole, 1,2-dimethyl-bis-allylation, 4, 357 Indole, 1,3-dimethyl-nitration, 4, 211 reactions... 

Bromination of the diphenyl indole derivative 316 with bromine in DMF or trimethylammonium bromide afforded the 7-bromo derivative 317. Reaction with allyl bromide or its derivatives gave A-allyl derivatives 318 that upon cyclization with palladium acetate gave 7,9-dimethoxy-l,2-diphenylpyrrolo[3,2,l-// ]quinoline derivatives 319 (92T7601) (Scheme 57). 

Metathesis of N-tosylated ene-amides and yne-amides has been less extensively investigated. An example of the RCM of ene-amides is a new indole synthesis developed by Nishida [79] metathesis precursor 96 (prepared by ruthenium-catalyzed isomerization of the corresponding allyl amide) is cy-clized to indole 97 in the presence of 56d (Eq. 13). 

A concise total synthesis of the indole alkaloid dihydrocorynantheol (101) (Scheme 19), that features two RCM steps and a zirconocene-catalyzed carbo-magnesation [68], is a further example of Martin s interest in applying RCM as a key reaction for the construction of alkaloid frameworks [69]. The first RCM step was applied to bis-allyl amide 96. The resulting intermediate 97 was directly subjected to carbomagnesation and subsequent elimination to deliver 98 in 71% yield from 96. Amide 98 was then transformed into acrylamide 99 in... 

A novel approach to 3-substituted indolines and indoles via the anionic cyclization of 2-bromo-lV,lV-diallyanilines has been developed simultaneously by Bailey <96JOC2596> and Liebeskind <96JOC2594>. Thus, treatment of 2-bromo-lV,lV-diallylanilines 78 with 2 equivalents of BuLi at -78 °C leads to the formation of the intermediate 79 which may be trapped with an electrophile to afford 3-substituted indolines 80. Aside from ease of preparation, an additional benefit of the intramolecular carbolithiation of <7-lithio-W,Al-diallyl-anilines is the production of Al-allyl-protected indolines, which are easily deprotected using... 

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