Alkylations indoles, palladium® acetate

By using an olefin embedded into the parent molecule Stoltz developed the oxidative annulation of indoles. The optimal catalyst consisted of palladium acetate and ethyl nicotinate, and molecular oxygen was used as the oxidant in the process. The reaction proceeded equally well irrespective of the attachment point of the alkyl chain bearing the pendant olefin bond on the five membered ring, and the formation of five and six membered rings were both effective (6.95.),127... 

Indolines are produced in good yield from 1-benzenesulfonylindoles by reduction with sodium cyanoborohydride in TFA at 0°C (Equation 5) (89TL6833). If acyl groups are present at C-2 or C-3 in the substrate, they are reduced to alkyl groups. Indole is also reduced to 2,3-dihydroindole by sodium cyanoborohydride and acetic acid or triethylamineborane and hydrochloric acid. An alternative method for preparing indolines involves treatment of indoles with formic acid (or a mixture of formic acid and ammonium formate) and a palladium catalyst (82S785). Reduction of the heterocyclic ring under acidic conditions probably involves initial 3-protonation followed by reaction with hydride ion. 

Pyrroles 531 are formed from the chromium complex 529 and alkynes 530 (R = H, Me or Ph = Me, Ph or NEt2). The dicobaltoctacarbonyl-catalysed reaction of cyanotrimethylsilane with a variety of acetylenes R C=CR (R R = alkyl or Ph) furnishes pyrroles 532, in which the bulkier of the two substituents of unsymmetrical internal acetylenes appears at the position marked with an asterisk . An indole synthesis from o-iodo-aniline and alkynes R C=CR (R R =alkyl or Ph) in the presence of palladium(II) acetate, triphenylphosphine, lithium chloride and potassium carbonate has been described (equation 56). In the case of unsymmetrical alkynes, the bulkier substituent tends to be in position 2 of the indole. ... 

The palladium-catalyzed C-3 alkylation of indoles via nucleophilic allylic substitution on allylic carbonates and acetates has been described [67, 68]. Two clever indole ring syntheses involving oxidative cyclization are illustrated below [69, 70]. 

Franzen and coworkers described a series of indole-phos-phine-oxazoline (IndPHOX) ligands, 231-238 (Scheme 35). The power of these ligands is demonstrated by the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphe-nyl-2-propenyl acetate with dimethyl malonate with 98%... 

Bach reported the C2 selective alkylation of protected tryptophan via a palladium(II)-norbornene system (178, 72% yield) (13JOC12263). Azidirine-substituted indole 179 was prepared by Vedejs in 40% yield by the Stille coupling of an aziridinyl stannane with the corresponding indole (13JOC5061).The direct C2 cyanation of Al-pyrimidylindole was achieved using acetonitrile as the cyanide source with catalytic amounts of copper(II) acetate (180,70%) (13JOC9494). 

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