Cleavage indole

Direct oxidative hydroxylation of pyrrole and indole derivatives is rare. The susceptibility of the heterocyclic rings to oxidation facilitates ring cleavage. Indole, 3-methylindole and tetra-hydrocarbazole have been hydroxylated using H2O2 in SbFs-HF. A mixture of 4-, 5-, and 6-... 

Beckmann rearrangement, 4, 292 pyrolysis, 4, 202 synthesis, 4, 223 Wittig reaction, 4, 294 Wolff-Kishner reduction, 4, 291 Indole, 1-acyl-2,3-disubstituted photoisomerization, 4, 204 photo-Fries rearrangement, 4, 204 photoisomerization, 4, 42 synthesis, 4, 82 Indole, 2-acyl acidity, 4, 297 synthesis, 4, 337, 360 Indole, 3-acyl-acidity, 4, 297 cleavage, 4, 289 reduction, 4, 289 synthesis, 4, 360 Indole, 7-acyl-synthesis, 4, 246... 

DEM protection of an indole is also effective (46-82% yield), and cleavage occurs efficiently with 2 A HCl (EtOH, rt, 0.5 h, 86-93% yield). ... 

Hi) Dehydrogenation. j3-Carboline derivatives may be obtained from tetrahydro-)3-carbohnes by zinc dust distillation or high temperatmre dehydrogenation with selenium or palladium black. Many of the complex indole alkaloids may be degraded, with bond cleavage, to yield simple )3-carbolines under these conditions and this approach has become a standard method in structural elucidations. Examples are numerous but outside the scope of this review. 

Cleavage of the hetero ring in a number of extended tetrahydro-j8-carboline systems was observed in the course of structural elucidation of tetrahydro-jS-carboline alkaloids. A few examples only will be given. The indole derivative 287 was isolated as one of the products of the selenium dehydrogenation of yohimbine (358 R = and... 

In synthesis of the alkaloid tjipanazole E (19b), the required symmetric dichloro-indolo[2,3-fl]carbazole 20a was obtained in a two-step procedure starting fi-om 4-chlorophenylhydrazine hydrochloride and 1,2-cyclohexanedione employing a Fischer indolization. Subsequent attachment of an acetyl-protected glucopyranosyl moiety to one of the nitrogens, followed by cleavage of the protective groups with ammonia in methanol, produced the desired natural product (91X7739). 

The intramolecular Heck reaction of polymer bound aryl halides such as 84 affords indole analogs 85 after cleavage of the final product from the resin with TFA <96TL4189>, Other notable uses of the Heck cyclization include a synthesis of an antimigraine agent <96TL4289>, and thia-tryptophans <96T14975>. 

Condensation of aromatic methylesters such as methyl 4-methoxybenzoate 351 a or methyl 4-hydroxybenzoate 351b with excess sodium-HMDS 486 in a mixture of THF-l,3-dimethyl-imidazolin-2-one (DMEU) at 185 °C in a closed vessel affords 59 or 93% of 4-hydroxybenzonitrile 298 as well as 26% 352 with smooth cleavage of the aromatic methyl ether in 351a (Scheme 4.47). Methyl indole-3-carboxylate gives hkewise 3-cyanoindole in 81% yield [127] (cf. also ref [92] in section 4.3). 

TABLE 7.2 Autoradiogram of the Reductive Cleavage of a 5 -32P End-Labeled 514 bp Restriction Fragment from pBR322 DNA (Ecorl/Rsal) by Cy cl open t />] indoles... 

In terms of economical synthetic approaches to indoles, the synthesis of this heterocycle from anilines and trialkylammonium chlorides was effected in an aqueous medium (H20-dioxane) at 180°C in the presence of a catalytic amount of ruthenium(III) chloride hydrate and triphenylphosphine together with tin(II)chloride <00TL1811>. Muchowski devised a novel synthetic route to indole-4-carboxaldehydes and 4-acetylindoles 86 via hydrolytic cleavage of W-alkyl-5-aminoisoquinolinium salts 85 to homophthaldehyde derivatives upon heating in a two phase alkyl acetate-water system containing an excess of a 2 1 sodium bisulfite-sodium sulfite mixture <00JHC1293>. 

A simple method was developed for the cleavage of the C-2—C-3 bond of indole alkaloids by the use of formic acid-formamide as reagent. Thus 2,3-seco derivatives of yohimbine (74), hirsutine (58), and reserpine (109) were prepared... 

Cryptopine-type indole alkaloid bumamicine (572) has been synthesized from geissoschizine methyl ether (31) (287). In the first step, geissoschizol (34) was prepared, and then cleavage of the C/D ring fusion was carried out by means of ethyl chloroformate. Finally, C-3 carbonyl and 7V-methyl groups were developed by simple oxidation, reduction, and repeated oxidation steps. 

Murase and co-workers generated the A-methoxyindolylborate 147 and effected coupling with several indoles to give 148, and, by reductive cleavage of the A-methoxyl group, arcyriacyanin A [25],... 

The Larock indole synthesis was adapted to the solid phase both for the synthesis of 1,2,3-trisubstituted indole-5-carboxamides [396] and, as illustrated, for the "traceless" synthesis of 2,3-disubstituted indoles 308 [397], As seen earlier, the trimethylsilyl group is fastened to C-2 with complete regioselectivity. The TMS group is cleaved under the resin cleavage conditions. The original Larock conditions were not particularly successful. 

The Pd-catalyzed electro-cleavage of the C—O bond of allyl aryl ether proceeds smoothly in a DMF-Bu4NBp4-(Mg)-(Stainless Steel) system, giving depro-tected products in 73 99% yield [437]. The sp-sp intermolecular coupling reaction with the Pd water-soluble catalyst prepared in situ from Pd(II) acetate and sul-fonated triphenylphosphine in an MeCN-H2O system yields diynes in 45 65% yields [438]. Similarly, the sp -sp coupling of 2-iodophenols or 2-iodoanilines and terminal alkynes followed by intramolecular cyclization gives indol and furan... 

In case of pyrrole molecular ion, HCN loss is somewhat less important than with indole, i.e., the [M-C2H2] ion at m/z 41 is more abundant than the [M-HCN] ion at m/z 40. This may in part be due to the twofold possibility to eliminate C2H2 (Fig. 6.55). The introduction of iV-substituents has similar effects as observed for the saturated heterocycles before, i.e., rearrangement fragmentations and a-cleavage of the substituent take control [230]... 

---