Palladium-catalysed substitution

Potassium hydride (1 eq.) was washed with hexanes and suspended in anhydrous ether at 0°C. 7-Bromoindole was added as a solution in ether. After 15 min, the solution was cooled to — 78°C and t-butyllithium (2 eq.) which had been precooled to — 78°C was added by cannula. A white precipitate formed. After 10 min DMF (2 eq.) was added as a solution in ether. The reaction mixture was allowed to warm slowly to room temperature and when reaction was complete (TLC) the suspension was poured into cold 1 M H3PO4. The product was extracted with EtOAc and the extract washed with sat. NaHCOj and dried (MgS04). The product was obtained by evaporation of the solvent and purified by chromatography on silica gel (61% yield). 

Kunimoto and L Yamada, Chem. Pharm. Bull. 33, 3696 (1985). 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

Heck type vinylation of 4-bromo-l-(4-methylphenylsulfonyl)-indole proceeds in good yield with such alkenes as methyl acrylate, styrene and N-vinylphthalimide using Pd(OAc)2 (5 mol%) and tri-o-tolylphosphine as the 

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The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

An efficient aqueous phase Suzuki-Miyaura reaction of activated aryl chlorides with aryl boronic acids has been reported. The method uses a new D-glucosamine-based dicyclohexylarylphosphine ligand for the palladium catalyst and works well with nitro-and cyano-activated chlorides.32 The aryl fluoride bond has been considered inert to palladium-catalysed substitution reactions. However, a computational study, backed up by experiment, shows that the presence of a carboxylate group ortho to fluorine will allow reaction both with phenylboronic acids in a Suzuki-type reaction and with organotin reagents in a Stille-type reaction the presence of the adjacent oxyanion stabilizes the transition state.33... 

The first reaction is between epoxycyclopentadiene and adenine, one of the heterocyclic building blocks of nucleic acids, and follows the course we have just described to give a cis-1,4-disubstituted cyclopentene. The alcohol is then activated by conversion into the carbonate, which reacts with phenylsulfonylnitromethane, which could later be converted into an alcohol. Once again, retention of stereochemistry during the palladium-catalysed substitution gives the cis product. 

Most commonly, palladium-catalysed substitutions on pnrines are carried ont on the halo-purine, bnt some metallated pnrines are useful. 2-Stannyl-6-chloropurines can be prepared via direct (C-H) lithiation, without protection of C-8 (27.7.1). 6-Pnrinyl zinc componnds can be prepared by reaction of the iodide with activated zinc metal." ... 

Formal carboboration of a terminal alkyne could be achieved by bromoboration and subsequent palladium-catalysed substitution of alkyl for bromine with alkylzinc chloride. 

Monfort s synthesis of methyl (3S,7S)-jasmonate starts from an enantiomerical-ly pure acetoxycyclopentenol, one which also plays an important role in prostaglandin syntheses (see section 5.6). [97] In the first step, which involves a double inversion, the acetoxy group undergoes a palladium-catalysed substitution by malonate. Following mono-demethoxycarbonylation, the alcohol is treated with... 

The palladium catalysed substitution of an allylic acetate provides an example. OAc ... 

Petrakis, K.S. Nagabhushan, T.L. (1987) Palladium catalysed substitutions of triflates derived from tyrosine-containing peptides and simpler hydroxyarenes forming 4-(diethoxy-phosphinyl)phenylalanines and diethyl arylphosphonates, J. Am. Chem. Soc., 109,2831-1... 

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