Indole derivatives 3- vinyl

Vinyl- and acetylenic tricarbonyl compounds are reactive dienophilic components in Diels-Alder reactions. Cycloadditions of these compounds with substituted butadienes were recently used to develop a new synthetic approach to indole derivatives [14] (Scheme 2.9) by a three-step procedure including (i) condensation with primary amines, (ii) dehydration and (iii) DDQ oxidation. 

Blechert and co-workers successfully employed the [4 -I- 2] cycloaddition for the transformation of indole derivatives [79-81], For instance, using 2-vinyl-indole derivatives as heterodienes, (3-acceptor-substituted cyclic and acyclic ena-mines (dienophile), and triarylpyrylium tetrafluoroborate as the photosensitizer, the corresponding Diels-Alder adducts were formed in moderate to good yields with complete regiochemical and stereochemical control [79], Alternatively, good results could be obtained in the reaction of indoles and exocyclic 1,3-dienes, thus providing an easy excess to multifunctionalized carbazoles [80], Quantum... 

Some synthetically useful reactions not covered in the above sections should be mentioned. An unusual heterocyclization to form indole derivatives is found in the aminomercuration of allylenaminones (equation 130).261 Palladium(II)-catalyzed cyclizations of o-allyl- and -vinyl-anilines and amino-quinones are discussed elsewhere.30 Other electrophiles used to form dihydroindole derivatives include phenylselenenyl chloride216 and methyl(bismethylthio)sulfonium salts.231... 

The reaction of vinylindoles containing the vinyl function incorporated in a carbocyclic ring provide access to novel polycyclic indole derivatives. The reaction of 46 with DMAD under forced conditions gave a mixture of Diels-Alder (47), Michael (48), and ene (49) adducts (91LA357). 

As an extension of this work, photoinduced [2+2]-cycloadditions of 1-acetylisatin (13) with cyclic enolethers (furan, benzofuran, 2-phenylfuran, 8-methoxypsoralen), and acyclic enolethers (//-butyl vinyl ether and vinyl acetate) were investigated which afforded the spiro-oxetanes in high yields (82-96%) and with high regio- and diastereoselectivity (Sch. 4) [19]. Treatment of the furan-derived oxetane 15 with acid resulted in oxetane ring opening and yielded the 3-(furan-3-yl)indole derivative 16. 

To check the different reactivity for the carbolithiation reaction of a lithiated double bond by vinyl- or aryllithiums, tertiary amine 341 was synthesized and treated with 6 equivalents of f-BuLi and TMEDA. Subsequent deuteriolysis led to a 6 1 mixture of the dihydropyrrole derivative 342 and the indole derivative 343 in very good overall yield, showing that intramolecular carbolithiation reaction of a lithiated double bond by a vinyllithium is faster than the corresponding carbolithiation reaction by an aryllithium (Scheme 88)141. 

Solid sodium sulphonate species 41 (Figure 43) impregnated with [dbim][SbF6] (25% wt) is itself capable to catalyse the 1,4-addition of several indole derivatives to methyl vinyl ketone (MVK) and other Michael acceptors in water (Figure 46)7 ... 

Russell s studies of vinylation reactions using vinylstannanes also examined similar reactions of vinyl sulfides, sulfoxides and sulfones [43a]. For example, isopropyl radical, generated from isopropyl mercuric chloride, adds to the non-sulfur-substituted alkene carbon of compounds 96, 97 and 98 to form the vinylated product 99 (Scheme 19). Recently, Caddick applied an intramolecular version of this process using alkyl halides and sulfides or sulfoxides in the presence of tributyltin hydride to the synthesis of indole derivatives [57]. 

In some instances the vinyl azide does not undergo the conversion to the 2/f-azirine and instead yields a nitrene, which adds to alkenes and dienes. This is seen with the azide 653 which, on irradiation through Pyrex, affords the corresponding nitrene that adds to alkenes stereospecifically to yield aziridines. Stereo specific addition to dienes is exemplified by the irradiation of the quinone azide 654 in the presence of trans,trans-hQX3,-2,4-diene. Aziridines do not result from this process and instead the stereoisomeric indole derivatives 655 and 656 are obtained. This process has been developed as a route to... 

The regiochemical and stereochemical courses of the photocycloaddition of A-acylindoles with monosubstituted olefins such as methyl acrylate and vinyl acetate, as well as the possible mechanistic pathways for these reactions, have been the subject of several reports. In one of the earliest examples, the photocycloaddition of 1 -benzoylindole (8) and methyl acrylate (9) produced the compound 10, which was then converted via a short synthetic sequence to a variety of 2a,7b-dihydrocyclobut[h]indole derivatives 11 (Scheme 2). These compounds were in turn converted to the corresponding l//-l-benzazepines 12, through silver ion-catalyzed thermolysis reactions at 100-160°C [14, 15]. 

An alternative method for the synthesis of pyrrolo[l,2-a]indoloquinones was explored [39]. It was found that thermal isomerization of 2-(l-pyrrolidinyl)-2-vinyl-l,4-benzoquinones such as 127 gave the desired compounds (e.g., 128) as mixtures of isomers in good yields. Interestingly, thermal isomerization of the 0-methylated hydroquinone analog 129 gave the corresponding pyrrolo [l,2-a]indole derivative 130 as the cis isomer only in 86% yield. 

This reaction involves the elelctrophilic attack of an aryldiazonium cation on the enol carbon atom of an active methinyl compound to give an azo intermediate, which then hydrolyzes to form an arylhydrazone. Tautomerization of aryl hydrazone yields the vinyl hydrazine, which undergoes [3,3] sigmatropic rearrangement and subsequently cyclizes to give an indoline derivative which, upon evolution of ammonium ion, yields the indole derivative, as shown below. 

Reaction of the cyclometallated derivative of phenyl-2-pyridylketone 73 leads to indenol-chelated, palladium-containing derivatives 74. Here, incorporating an electrophilic (CO) function in the starting palladacycle signifies that, following alkyne insertion in the Pd-C bond, an intramolecular attack of the vinyl palladated unit on the metal-bound, activated CO function occurs. This is in sharp contrast to the reaction described in Scheme 9 whereby incorporating a nucleophilic, masked, secondary amine function leads to indole derivatives 40 and to the azepinium synthesis from the metallated benzylpyridine complex 34. Therefore, these reactions are rather sensitive to the nature of other potentially reactive functions within the metallacyclic framework. 

A combination of enzymatic resolution and orthoester rearrangement has been used by Brenna in a short synthesis of (R)-(-)-baclofen 503 (Scheme 6.79) [123a]. R) or (S)-3-Methyl-2-phenylbutylamine 506 were recently obtained using the same strategy (Scheme 6.79) [123bj. A Claisen-Johnson rearrangement of a benzyl vinyl ether studied by Raucher provided substituted arenes 510. Better results were observed with electron donating substituted arenes. This reaction has been extended to indole derivatives 511 (Scheme 6.79) [124]. 

Instead of allyl bromide derivative, vinyl diazoacetate in the presence of rhodium acetate also allowed the formation of substituted indolines in excellent yields (Scheme 9.34). N-deprotonated allyl thionium was postulated as intermediate [157], no reaction being observed with an N-methyl indole analogue. 

Palladium catalysis can also provide an avenue to derivatize the products of cyclization, often in concert with the cyclization itself. Lautens, Bisseret and Alper have all effectively demonstrated the power of this approach in the construction of indole derivatives with a high degree of modularity [51]. These tandem palladium-catalyzed methods have typically employed 1,1-dibromoalkenes in indole cyclization, wherein one vinyl bromide bond is available for palladium-catalyzed indole formation, and the second for subsequent functionalization. As shown in Scheme 6.39,... 

Iwasawa has reported the gold(III)-catalyzed reaction of N-(o-ethynylphenyl)imi-nes with electron-rich alkenes to form polycyclic indole derivatives [26]. As an example, reaction of N-[l-(l-pentynyl)phenyl]imine 28 and tert-butyl vinyl ether with a catalytic amount of AuBrs in toluene at room temperature led to isolation of the polycyclic indole 29 in 80% yield as a mixture of diastereomers (Scheme 11.3). Conversion of 28 to 29 presumably occurs via initial intramolecular hydroamination to form the gold carbene containing azomethine ylide 30 that undergoes intermo-lecular [3 + 2] cydoaddition with tert-butyl vinyl ether to form the carbene complex 31. 1,2-Migration of the 7t-propyl group to the metal-bound carbon atom coupled with deauration then forms 29. This transformation is also catalyzed efficiently by PtCl2 [26]. 

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