Methylindole derivatives, intramolecular

V-(2 -bromobcnzyl)-2-methylindole derivatives were cyclized relatively easily to pyrrolophenantridines in the presence of tetrakis(triphenyl-phosphino)palladium (4.29.). In the absence of the 2-methyl group the intramolecular attack of the intermediate arylpalladium complex is directed at the five membered ring giving indoloisoquinoline.33... 

Magnus et al. (153,154) reported total synthesis of ( )-aspidospermidine (330) by applying the intramolecular Diels-Alder reaction to the enamide 329 prepared from the 2-methylindole derivative 328 (Scheme 118). 

The intramolecular photoelimination of HC1 from JV-chloroacetyl derivatives of suitable amines is a useful and versatile approach to the synthesis of azaheterocycles. The iV-chloroacetyl derivative 357 has been converted in this way to 7-oxodesethylcatharanthine (358) in 55% yield.300 Investigations in this area have been particularly concerned with the A-chloroacetyl derivatives of benzylamines and phenethylamines the N-chloroacetyl-benzylamine 359 on irradiation affords the two 3-oxo-l,2,3,4-tetrahydroiso-quinolines 360 and 361.301 Competing photocyclizations have been observed in the case of l-[3-(chloroacetylamino)propyl]-3-methylindole (362) which is converted into three photoproducts, 363, 364, and 365.302... 

In the absence of efficient Nps-Q (92) capture, this intermediate reacts with the indole side chain of tryptophan residues to produce the related 2-Nps derivatives 96 (Scheme 48). Although reaction of sulfenyl hahdes with indoles was exploited by Wieland et al.t for the synthesis of phaUoidin, this side reaction leads to irreversible modification of Trp-containing peptides.This side reaction does not occur via an intramolecular electrophilic substitution as postulated previously,but by a direct attack of the Nps-Cl (92) in fact, it is efficiently suppressed by the addition of a large excess of an indole derivative as a scavenger.These scavengers serve also to decrease the proton activity of the acids vide supra). Due to the unpleasant odor of 2-methylindole the less volatile 1-acetyltryptophan butyl ester has been proposed as scavenger.f ... 

Indoles and Carbazoles. - Formation. 2-Arylindoles (132) are formed by intramolecular Wittig reaction of the phosphonium salts (131). The hydroxamic acids PhN(OH)COCH2COR (R = alkyl or aryl) cyclize in boiling toluene to mixtures of indoles (133) and 3-isoxazolones (134). Irradiation of a solution of o-iodoaniline and the potassium enolate of acetone affords 2-methylindole. The enamino-ketone (135) cyclizes photochemically to 1,2-dimethylindole (136) with elimination of acetaldehyde/ The styrene derivative (137), obtained by the action of Meerwein s acetal, Me2NCH(OMe)2, on o-nitrotoluene, yields 1-hydroxyindole on treatment with zinc/ Azidobenzocyclobutanes (138 R = Me, Ph, or CH2Ph) are converted into indoles (133) by the action of concentrated sulphuric acid/ ... 

Oxidative amination of aromatic amines which are less basic than aliphatic amines proceeds smoothly without protection of amines. The intramolecular reaction of aniline derivatives offers good synthetic methods for heterocycles. 2-Methylindole is obtained by 5-exo amination of 2-allylaniline [50]. As an application, A-methyl-2-methyl-3-siloxyindole 114 was prepared from A-methyl-2-(l-siloxyallyl)aniline 113. Without silyl protection, no reaction occurred [51]. If there is another olefinic bond in the same molecule, the aminopalladation product 116 of the amide 115 undergoes olefin insertion to give the tricyclic compound 117 [50]. 2,2-Dimethyl-1,2-dihydroquinoline (119) was obtained by 6-endo cyclization of 2-(3,3-dimethylallyl)aniline (118). 

Figure 15 highlights a novel application of sp -CH activation. In this example, 7-methylindole is synthesized from an aromatic isocyanide derivative, via an intramolecular cyclization reaction. The suspected mechanism involves coordination of the ruthenium center to the C=N triple bond, followed by insertion into the benzylic C—H bond. Ru(dmpe)2(naphthyl)H (Chart 1) (dmpe = dimethylphos-phinoethane, a bidentate phosphine) is the catalytic system used (59). 

One-pot intramolecular reaction between trialkyl-( 1 -methyl-2-indolyl)borate and allylpalladium intermediate has been reported [20]. This. simultaneous 1,2-alkylmigration from boron to carbon provides a novel pathway to afford [i>]-an-nelated indole derivatives in 10-56% yields (Scheme 32.8). Trialkylindolylbo-rate 14 is generated in situ by the hydroboration of diene 13 with 9-BBN in THF followed by treatment with 2-lithio-1 -methylindole. The THF solution ofborate 14 containing 10 mol% of Pd(Ph3P)4 was heated under reflux for 1-3 h to afford [fc]-annelated indole 15 [20]. 

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