BINAP catalyst system

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

Mikami and Hatano70 demonstrated the efficiency of the dicationic [Pd(MeCN)4](BF4)2/BINAP catalyst system in DMSO with the highly enantioselective synthesis of a variety of quinoline derivatives, including spiro-compound 99 (Equation (63)), resulting from olefin isomerization of the Alder-ene product. 

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... 

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... 

It is quite clear from these data that by employing a tertiary amine in the Ru(BINAP) catalyst system and by modifying the reaction conditions in the production of naproxen, one can achieve excellent e.e. s even under moderate H2 pressure. 

Also, the pyridazino-fused ring system 124 containing an indole core can be readily synthesized upon using a Pd(OAc)2-BINAP catalyst system for the amination-CH activation sequence, as recently demonstrated by Matyus and coworkers [100,101] (Scheme 44). 

The first example of the intermolecular AHR was reported by Hayashi et al. and involved the asymmetric arylation of 2,3-dihydrofurans using aryl triflates [18]. Although little or no enantiomeric excess was obtained when aryl iodide/silver salt combinations were used, the use of triflates along with the familiar Pd(OAc)2/ BINAP catalyst system resulted in the formation of the 2-aryl-2,3-dihydrofuran product 54, together with minor amounts of the 2, 5-dihydrofuran isomer 55. The rationale proposed by the authors for this outcome is shown in Scheme 12 it is hypothesized that addition of the catalytic complex to either face of the sub-... 

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). ... 

This ligand class is quite useful for the synthesis of unsymmetrical alkyl diaryl amines.39 Typically, a primary aliphatic amine is first arylated using the Pd/BINAP catalyst system. The second arylation is then carried out with L6, Xantphos, or PPF-OMe (with CS2CO3 if a base sensitive aryl bromide). Ligand choice for the second arylation depends upon the electronic nature of the N-alkylaniline and Ar2Br as outlined in the table. They were unable to couple 2-bromobenzaldehyde, 4-(4 -bromophenyl)-2-butanone, or 4 -bromoacetophenone with N-alkylanilines (alkyl > Me). 

Functionalized benzo[b]furans are conveniently obtained from 2-ethinylphenols (21) by transition-metal-mediated cychzations. Use of an Au(I)/Ag(I)- or Rh/BINAP-catalyst system gives 2-substituted benzo[b]furans (22) directly [48], while application of a Pdl2/thiourea/CBr4 cocatalysis system followed by carbonylation of the Pd-intermediate (simplified as 23) in methanol yields benzo[b]furan-3-carboxylates 24 [49] ... 

Carreira has recently described Pd-catalyzed N-arylation reactions of N-Boc-2,6-diazaspiro[3.3]heptane [240]. For example, the coupling of this nucleophile with 2-bromotoluene proceeded in 97% yield using the Pd2(dba)3/BINAP catalyst system (Eq. 43). This core may serve as a useful structural analog to the piperazine ring, which is a common moiety in many biologically active molecules and pharmaceuticals. A number of studies have examined Pd-catalyzed N-arylation reactions of piperazine derivatives [217, 241, 242] and other rigid cyclic diamine... 

Manufacture of ruthenium precatalysts for asymmetric hydrogenation. The technology in-licensed from the JST for the asymmetric reduction of ketones originally employed BINAP as the diphosphine and an expensive diamine, DAIPEN." Owing to the presence of several patents surrounding ruthenium complexes of BINAP and Xylyl-BINAP, [HexaPHEMP-RuCl2-diamine] and [PhanePHOS-RuCl2-diamine] were introduced as alternative catalyst systems in which a cheaper diamine is used. Compared to the BINAP-based systems both of these can offer superior performance in terms of activity and selectivity and have been used in commercial manufacture of chiral alcohols on multi-100 Kg scales. 

Many enantioselective catalysts have been developed for reduction of functional groups, particularly ketones. BINAP complexes of Ru(II)C12 or Ru(II)Br2 give good enantioselectivity in reduction of (3-ketoesters.49 This catalyst system has been shown to be subject to acid catalysis.50 Thus in the presence of 0.1 mol % HC1, reduction proceeds smoothly at 40 psi of H2 at 40° C. 

The catalyst system employed was the cationic rhodium solvent complex [Rh(P-P)S2]+ (P-P = BINAP, CHIRAPHOS, S = solvent). The BINAP ligand enhances the activity of the complex (Table 10), although additional studies have revealed that both the solvent and the substituents on Si influence the levels of enantioselectivity (Scheme 29).131,132... 

Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared from [IrCl(cod)]2, (S)-BINAP, NBu 4 BH4, gives with high enantioselectivity the corresponding A-hydroxylamines which are important biologically active compounds and precursors of amines (480). Further reduction of hydroxylamines to secondary amines or imines can be realized upon treatment with Fe/AcOH (479), or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature (481). 

For example, the hydrogenation of 1-acetonaphthone with a catalyst system consisting of RuCl2[(X)-BINAP](DMF)n, (S.S)-1.2-diphenylethylenediamine... 

When the C=N bond is fixed in a ring system in which no (E)/(Z) isomerization can take place, the asymmetric hydrogenation of the C=N bond can be highly enantioselective. Oppolzer et al." found that cyclic sulfonimide was hydrogenated with an Ru(BINAP) catalyst to give a product with essentially quantitative optical yield (Scheme 6-45). 

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