2- -indole, oxidative cyclizations

As foretold in the introduction, ring formation via attack on a double bond in the endo-trig mode is not well exemplified. The palladium(II) catalyzed oxidative cyclization of o-aminostyrenes to indoles has been described (78JA5800). The treatment of o-methyl-selenocinnamates with bromine in pyridine gives excellent yields of benzoselenophene-2-carboxylates (Scheme 10a) (77BSF157). The base promoted conversion of dienoic thioamides to 2-aminothiophenes is another synthetically useful example of this type (Scheme 10b) (73RTC1331). 

The photocyclization of enamides has been widely employed in the construction of heterocyclic systems the N-acryloyl-2-aminopyridines 37, for example, are converted on irradiation to the lactams 38.36 Numerous benzylisoquinoline alkaloids have been prepared using this approach, and in particular, the syntheses of benzo[c]phenanthridine alkaloids have been reviewed.37 Thus, irradiation of the [Z]-l-ethylidene-2-benzoyltetra-hydroisoquinoline 39 affords the corresponding 8-oxoberberine 4038 competing photoisomerization to the E-isomer is observed but cyclization occurs only via the Z-isomer. Examples of syntheses of Amaryllidaceae and indole alkaloids have also been reported. In this way, the precursor 41 of ( )-lycoran has been obtained by oxidative cyclization of the enamide 42.39... 

Oxidative cyclization of N- [2-indol-3-yl)ethyl] piperidine (146) with 3 molar equivalents of mercuric acetate and EDTA disodium resulted in ( )-l in 85% yield (106). 

An improved procedure for the synthesis of octahydroindoloquinolizine (1) from 3-(2-piperidino-ethyl)indole by oxidative cyclization process has been reported (392). 

Oxidative addition consumes one equivalent of expensive Pd(OAc)2 in most cases. However, progress has been made towards the catalytic oxidative addition pathway. Knolker s group described one of the first oxidative cyclizations using catalytic Pd(OAc)2 in the synthesis of indoles [19]. They reoxidized Pd(0) to Pd(II) with cupric acetate similar to the Wacker reaction, making the reaction catalytic with respect to palladium [20]. 

Pyrrole rings frequently serve as precursors to indole rings [37] and PdCl2 induces the oxidative cyclization of pyrrole 37 to a mixture of 38 and 39 [38]. Since the oxidation of tetrahydroindoles to indoles, such as 38 to 39, is usually straightforward, this transformation can be viewed as a novel and efficient indole ring synthesis. 

Most of the early applications of palladium to indole chemistry involved oxidative coupling or cyclization using stoichiometric Pd(II). Akermark first reported the efficient oxidative coupling of diphenyl amines to carbazoles 37 with Pd(OAc)2 in refluxing acetic acid [45]. The reaction is applicable to several ring-substituted carbazoles (Br, Cl, OMe, Me, NO2), and 20 years later Akermark and colleagues made this reaction catalytic in the conversion of arylaminoquinones 38 to carbazole-l,4-quinones 39 [46]. This oxidative cyclization is particularly useful for the synthesis of benzocarbazole-6,11-quinones (e.g., 40). 

The double iron-mediated arylamine cyclization provides a highly convergent route to indolo[2,3-fc]carbazole (Scheme 16). Double electrophilic substitution of m-phenylenediamine 34 by reaction with the complex salt 6a affords the diiron complex 35, which on oxidative cyclization using iodine in pyridine leads to indolo[2,3-b]carbazole 36 [98].Thus,ithasbeen demonstrated that the bidirectional annulation of two indole rings can be applied to the synthesis of indolocarbazoles. 

Stoichiometric Pd(II)-mediated oxidative cyclization of alkenyl anilines to indoles. Cf. Wacker oxidation. 

Another important example of oxidative cyclization leading to bridgehead heterocyclic compound is the conversion of indole derivative 211... 

Mahboobi et al. described a novel synthesis of staurosporinone (293) (791). The intermolecular Michael addition of l-(indol-3-yl)-2-nitroethene (1472) to methyl indol-3-ylacetate (1313) provided with high diastereoselectivity methyl 2,3-bis(indol-3-yl)-4-nitrobutanoate (1473). Catalytic hydrogenation and lactamization afforded 2,3-bis(indol-3-yl)-y-butyrolactam (1474) in 87% yield. Oxidative cyclization of the ds-lactam 1474 with DDQ in the presence of catalytic amounts of p-TsOH led to staurosporinone (293) (791) (Scheme 5.249). 

Oxidative cyclizations of 3-(/ -azidoethyl)indoles with BTIB afford pyr-roloiminoquinones 15, compounds that appear as sub-structures in biologically active marine alkaloids such as the makaluvamines and discorhabdins (Scheme 22) [67- 69]. In fact, BTIB-mediated sulfide and azide cyclizations, and a-azido-nation of the cyclic sulfide with PhIO/TMSN3, were incorporated into the first total synthesis of ( )-makaluvamine F [68,69]. 

A related oxidative cyclization of a complex indolic intermediate constituted a key step in the total synthesis of sporidesmin-A [58],... 

Tab. 13. Carbazole synthesis by PIFA-mediated oxidative cyclization of bis(indole)maleimides.

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>. 

An oxidative spiroannulation reaction was carried out for simple phenols and as a result good yields of spiro-compounds containing tetrahydrofuran rings were obtained <02TL3597>. In the stereospecific and enantiospecific total synthesis of the sarpagine indole alkaloid dehydro-16-epinormacusine B, an oxidative cyclization of the alcohol shown below was the key and final step <02OL4681>. 

A Mannich-type reaction is used in the PictetSpengler synthesis of tetrahydroisoquinolines 181 (Scheme 108) . Indoles similarly give -carbolines (Section 3.3.1.5.7.4). A variation of the PictetSpengler reaction involves the oxidative cyclization of 182 using ceric ammonium nitrate (CAN) (Scheme 109) <1998JOC860>. 

By reaction of secondary V-arylketoenamines in the aminocyclopentenone series and quinones, the cyclopent[Z ]indole skeleton and dibenzo[6,d]cyclopent[/]azepines are accessible. The reaction involves an oxidative cyclization of the Michael adduct by attack of either the nucleophilic nitrogen atom or of the aromatic o-position of the aniline moiety on the quinone317 (equation 235). 

An oxidation-cyclization was observed to take place on an indole enamine by simple swirling the solution in air in the presence of K2C0334 (Scheme 19). For X = O, air-oxidation mediated by dimethyl sulphoxide and potassium terf-butoxide resulted in dehydrogenation with formation of the 2-pyridone derivative. 

Benzoyl-substituted anilino 1,1-enediamines 233 underwent oxidative cyclization with lead tetraacetate (LTA) to give iminoisoxazolines 235 in moderate yields183. In some cases, substituted indoles 236 were also formed. The formation of 235 and 236 has been assumed to arise through the initially formed JV-plumbylated adducts 234 (Scheme 14). 

Addition of the propargyl Grignard reagent to 3,4-dihydro-p-carboline followed by silver(I)-mediated oxidative cyclization to the dihydroindolizino[8,7-fo]indole and chemoselective hydrogenation provide racemic harmicine (three steps, 46 % overall yield). 

Scheme 15.6 lron(0)-mediated oxidative cyclization of alkylamines to indoles. 

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