Palladium BINAP catalyst

Similar to A-allvlanilincs. their ease of formation makes N-acryloylanilines also an attractive starting material for the preparation of indole derivatives. Acrylates having an cr-substituent give rise to chiral oxindole derivatives, both a common building block of natural products and a frequently employed synthon en route to them.18 By using a chiral palladium-BINAP catalyst Overmann was able to achieve high enantioselectivity in the transformation shown in 3.14.19... 

One of the rare examples, where the palladium catalyzed closure of a six membered ring leads to an aromatic heterocycle is presented in 4.18. Intramolecular transformation of the 2-bromoindole derivative in the presence of a palladium-BINAP catalyst led to the formation of the a-carboline (pyrido[2,3- ]indole) skeleton. The ring closure was accompanied by the oxidation of the intermediate dihydrocarboline derivative.21... 

The enantioselective introduction of aromatic substituents into the 3-position of the heterocycles is also possible, starting from 2,5-dihydroaromatics. In a representative example A-protcctcd 2,5-dihydropyrrole was coupled with er-naphthyl tiflate in the presence of the chiral palladium-BINAP catalyst to give the 3-naphthyl-2,3-dihydropyrole derivative in moderate yield and enantioselectivity (6.55.),85... 

Certain 3-halothiophenes were successfully coupled with a series of amines in the presence of a palladium-BINAP catalyst system. The proper choice of the substituents on the thiophene ring as well as the choice of the halide were crucial for the success of the process (6.76.), 3-Bromo-2-thiophenecarboxylic acid derivatives, for example, coupled readily, while the conversion of 4-bromo-2-cyanothiophene failed completely.107... 

Chloropyridine, for example, was found to react readily with cyclohexylamine already at 70 °C in the presence of a palladium-BINAP catalyst and sodium /ert-butoxide (7.69.), Under similar conditions 2,6-dibromopyridine also reacted smoothly with the less nucleophilic aniline and the 2,6-disubstituted pyridine derivative was isolated in good yield (7.70.)90... 

The coupling of halopyridines was also extended to chiral amines. 2-Bromo-4-picoline was coupled with a series of enantiopure amines in the presence of Buchwald s palladium-BINAP catalyst system (7.71.).91... 

The 1,4-disilylation of a,p-unsaturated ketones usinga disilane with a palladium BINAP catalyst has also been achieved with good enantiomeric excess. For example, with a,p-unsaturated ketone (2.157), the initially formed product (2.158) can be converted into the P-silyl ketone (2.159) by addition of methyllithium followed by hydrolysis. However, quenching the intermediate lithium enolate (formed on addition of MeLi) with an alkylating agent leads to an a-substituted product... 

For the activation of a substrate such as 19a via coordination of the two carbonyl oxygen atoms to the metal, one should expect that a hard Lewis acid would be more suitable, since the carbonyl oxygens are hard Lewis bases. Nevertheless, Fu-rukawa et al. succeeded in applying the relative soft metal palladium as catalyst for the 1,3-dipolar cycloaddition reaction between 1 and 19a (Scheme 6.36) [79, 80]. They applied the dicationic Pd-BINAP 54 as the catalyst, and whereas this type of catalytic reactions is often carried out at rt or at 0°C, the reactions catalyzed by 54 required heating at 40 °C in order to proceed. In most cases mixtures of endo-21 and exo-21 were obtained, however, high enantioselectivity of up to 93% were obtained for reactions of some derivatives of 1. 

Based on these reactions, Imada et al. reported the first enantioselective alkylation of 2,3-alkadienyl phosphates 96 by employing malonate derivatives 97 in the presence of palladium complex catalysts bearing MeOBIPHEP or BINAP as ligand (Scheme 14.21) [49]. The highest enantioselectivity (90% ee) was obtained by the catalyst combination Pd2(dba)3-CHC13 and (R)-MeOBIPHEP. 

Both pyrimidine and quinazoline derivatives have been investigated as ligands for palladium-mediated reactions. Examples of ligands prepared include the phosphine-free bipyrimidine 1181, which gave the isolable palladium dichloride catalyst 1182 <2001JOM(634)39>, and the chiral oxazolinyl-quinazoline BINAP analogs 1183 and 1184 <20060L5109>. 

Nitrogen nucleophiles, in a similar manner to oxygen- and sulfur-based functionality, undergo transition metal-catalyzed cross-coupling with halopyridines. The use of palladium(O) catalysts is most effective in combination with chelating bis-(phosphine) ligands such as BINAP that prevent the formation of pyridine-palladium complexes that... 

The synthesis of fluoroquinoline antibacterials almost invariably involves substitution of the chlorofluoroquinolone with an amine as the final step (Scheme 1). Thus, the above model studies indicate excellent potential for the palladium-catalyzed amination reaction to succeed. However, initial attempts to couple the chlorofluoroquinolone derivative 2 with piperazine using the Pd2dba3/binap catalyst system and NaOtBu in toluene solvent resulted only in the recovery of unreacted starting material. Changing to more polar solvents (DMSO, DMF) or the addition of iodide salts (in an attempt to generate the iodo derivative) had no effect. It was believed that the insolubility of the carboxylic acid 2 played a role in its failure to react and that the ethyl ester would be a more productive substrate. Conveniently, the ethyl ester of 2 is an intermediate in the standard synthesis of Norfloxacin, thus, the synthesis of 13 was readily accomplished (eq 2). ... 

The palladium-catalyzed amination of aryl halides has recently emerged as a powerful alternative to other methods for the synthesis of aryl amines.5 This method allows for the cross-coupling of aryl halides and triflates with amines in the presence of a stoichiometric amount of a base and catalytic amounts of palladium complexes bearing tertiary phosphine ligands. As shown in Tables I and II, the Pd/BINAP catalyst is highly effective for reactions of aryl bromides and triflates with primary and cyclic... 

Takasago Perfumery Ltd. manufactures optically pure (Jl)-muscone from the racemic compound by way of its silyl enol ether which is dehydrosUylated with palladium acetate to the pure (Z)-enone. [202] The enantioselective hydrogenation with ruthenium-BINAP catalysts finally gives the enantiomericaUy pure product. [203]... 

In another example, in the presence of a high concentration of bromide aniones, the typical Wacker oxidation can again be suppressed in favor of a palladium(ll)-catalyzed 1,2-dibromination reaction. The development of such a reaction had been widely neglected, probably due to the fact that 1,2-dibromides are usually obtained via direct bromination of alkenes. However, the use of palladium(II) catalysts 157 and 158 with a chiral 2,2 -Bis(diphenylphosphino)-l,l -binaphthyl (BINAP) ligand offers an attractive approach to prepare compounds 159 in enantiomerically enriched form from 154 (Scheme 16.43) [109]. 

AUylation of the /3-ketoester 136 was achieved with good enantioselectivity using the Trost ligand 20. AUylation of the ketone 138 could also be achieved, and although trimethyltin chloride was usually added, it was not an essential feature for obtaining reaction, once the ketone had been deprotonated with lithium diisopropylamide. Alkylation of cinnamyl acetate 140 using the /3-ketophosphonate 141 has been carried out using a palladium/BINAP 17 catalyst (Scheme 30). ... 

Helmchen and coworkers employed a,co-amino-1,3-dienes as substrates [51]. By using palladium complexes with chiral phosphino-oxazolines L as catalysts, an enantiomeric excess of up to 80 % was achieved. In a typical experiment, a suspension of Pd(OAc)2, the chiral ligand L, the aminodiene 6/1-90 and an aryltriflate in dimethylformamide (DMF) was heated at 100 °C for 10 days. Via the chiral palladium complex 6/1-91, the resulting cyclic amine derivative 6/1-92 was obtained in 47% yield and 80% ee (Scheme 6/1.23). Using aryliodides the reaction time is shorter, and the yield higher (61 %), but the enantiomeric excess is lower (67% ee). With BINAP as a chiral ligand for the Pd°-catalyzed transformation of 6/1-90 and aryliodide, an ee-value of only 12% was obtained. 

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