Palladium BINAP

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 imines 12 (X = 4-CH3-QH4-SO2 (Ts), Ar, C02R, COR, etc.) preformed or generated in situ from N,0- or N,N-acetals or hemiacetals are another important class of Mannich reagents frequently used for diastereo- and/or enantioselective aminoalkylation reactions catalyzed by chiral Lewis acids (usually copper or palladium BINAP complexes such as 13). Among other things excellent results were obtained in the aminoalkylation of silyl enol ethers or ketene acetals [24], A typical example is the synthesis of Mannich bases 14 depicted in Scheme 5 [24b], Because of their comparatively high electrophilicity imines 12 could even be used successfully for the asymmetric aminoalkylation of unactivated alkenes 15 (ene reactions, see Scheme 5) [24h, 25], and the diastereo- and/or enantioselective aminoalkyla-... 

Binap 3.43 is also a good ligand for palladium complexes. Although 71-allyl palladium-binap complexes have met limited applications in asymmetric allylation of malonate like derivatives [872], binap-PdCl2 complexes induce enantioselective Heck reactions [902] and 1,4-disilylations of a-enones [903],... 

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... 

The asymmetric fluorination of 3-ketoesters has been achieved in 62-90% ee using F-TEDA (Selectfluor) as fluorine source in the presence of 0.5 mol% of the chiral nonracemic titanium-based Lewis acid (5.108). ° A greater range of p-ketoesters are fluorinated with higher ee using catalytic quantities of the palladium-BINAP complex (5.109) and N-fluorobenzenesulfonamide (NFSI). ° In both cases the reaction proceeds through the intermediacy of a chiral enolate. 

Enantiomerically enriched rose oxide is obtained according to a procedure of Takasago, by a palladium-BINAP-catalysed cyclisation of dehydrodtronellol. By using (S)- and (f )-citronellol and (R)- and (S)-BINAP, all four diastereomers, which are distinguishable by their smeU, may be obtained in enriched form. [29] The (4R)-cis isomer has the lowest scent threshold (5 ppb) and a sharp, pure, metallic rose scent. [30]... 

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). ... 

Faller JW, Wilt JC (2005) Palladium/BINAP(S)-catalyzed asymmetric allylic amination. Org Lett 7 633-636... 

Cationic BINAP-palladium and platinum complexes 30a,b can catalyze highly enantioselective cycloaddition reactions of arylglyoxals with acyclic and cyclic... 

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. 

A novel chiral dissymmetric chelating Hgand, the non-stabiUzed phosphonium ylide of (R)-BINAP 44, allowed in presence of [Rh(cod)Cl]2 the synthesis of a new type of eight-membered metallacycle, the stable rhodium(I) complex 45, interesting for its potential catalytic properties (Scheme 19) [81]. In contrast to the reactions of stabihzed ylides with cyclooctadienyl palladium or platinum complexes (see Scheme 20), the cyclooctadiene is not attacked by the carbanionic center. Notice that the reactions of ester-stabilized phosphonium ylides of BINAP with rhodium(I) (and also with palladium(II)) complexes lead to the formation of the corresponding chelated compounds but this time with an equilibrium be-... 

Concerning enantioselective processes, Fujihara and Tamura have proved that palladium NPs containing (S)-BINAP (2,2 -bis(diphenylphosphino)-l,l -binaphthyl) as chiral stabiliser, catalyse the hydrosilylation of styrene with trichlorosilane, obtaining (S)-l-phenylethanol as the major isomer (ee = 75%) [42]. In contrast, the palladium complex [Pd(BINAP)(C3H5)]Cl is inactive for the same reaction [43]. 

Some of the details of the mechanism may differ for various catalytic systems. There have been kinetic studies on two of the amination systems discussed here. The results of a study of the kinetics of amination of bromobenzene using Pd2(dba)3, BINAP, and sodium r-amyloxide in toluene were consistent with the oxidative addition occurring after addition of the amine at Pd. The reductive elimination is associated with deprotonation of the animated palladium complex.166... 

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. 

With the exception of intramolecular amination reactions, all of the early aryl halide aminations were catalyzed by palladium complexes containing the sterically hindered P(o-tol)3. In papers published back-to-back in 1996, amination chemistry catalyzed by palladium complexes of DPPF and BINAP was reported.36,37 These catalysts allowed for the coupling of aryl bromides and iodides with primary alkyl amines, cyclic secondary amines, and anilines. 

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