DIFLUORPHOS ligand

More recently, Liao et al. showed a comparison between Pd-complexes of different biaryl-linked bisphosphines possessing varied dihedral angles. Scheme 15, in an enantioselective arylation of methylindanone (82). The result not only demonstrates the effect of the dihedral angle on enantioselectivities but also illustrates the influence of the electronic properties on the achieved enantioselectivity. The DIFLUORPHOS ligand (81) having a narrower dihedral angle and poor... 

Scheme 6.17 a-Arylation of cyclic ketones with aryl triflates in the presence of an in situ generated nickel catalyst derived from the Difluorphos ligand. 

SYNPHOS AND DIFLUORPHOS AS LIGANDS FOR RUTHENIUM-CATALYZED HYDROGENATION OF ALKENES AND KETONES... 

Ruthenium(II) complexes bearing atropisomeric diphosphine ligands have proved to be efficient systems for the hydrogenation of a wide range of prochiral substrates. A new catalytic system has been developed based on ruthenium complexes having SYNPHOS and DIFLUORPHOS as chiral diphosphanes (Figure 3.6). 

The group of Yamamoto reported the catalytic enantioselective hetero-Diels-Alder reactions of azo compound 209 and dienes 208 (Scheme 2.54).87 In a ligand screening the use of BINAP (87) gave higher conversion and enantioselectivity than both Segphos (211) and Difluorphos (212). Interestingly, the optimal silver... 

The Rh-complexes of SYNPHOS (13b) and DIFLUORPHOS (81) (see Figure 14) have provided improved activities and enantioselectivities in asymmetric PKR, as compared to BINAP-type ligands (Scheme 11). The improved yields are attributed to the low dihedral angles of this ligand family (07ASC1999). 

Table 5.7 Comparison of difluorphos and other ligands in the Ru-catalyzed hydrogenation of perfluoroalkyldiketones 64...

Asymmetric a-atylation or heteroarylation of ketones can be carried out using a combination of Ni(COD)2 and a chiral phosphine ligand (f )-BINAP (for a-arylation) or (f )-DIFLUORPHOS (for a-heteroarylation) as catalyst. For example, reaction of indanones and tetralones with various electron-poor and electron-rich atyl chlorides catalysed by Ni(COD)2/(R)-BINAP gave the corresponding coupling products in 41-89% yields and 90-99% ee (Scheme 14.57). Compared with aryl chloride electrophiles, atyl bromides result in lower yield and enantioselectivity. This is ascribed to formation of a... 

Very recently, an enantioselective version of this transformation and its application towards the synthesis of alkaloids esermethole (217) and physostigmine (218) has been described by Zhn and coworkers [115]. In the new protocol, KCN is replaced by the less toxic K4[Fe(CN)6], Pd(OAc)2 is nsed as catalyst and (S)-DIFLUORPHOS (221) as ligand, leading to oxindole 220 in np to 78% yield and 77% ee (Scheme 8.55). Lautens and coworkers [116] also made use of this general concept by combining a Mizoroki-Heck/C—H activation/cyanation step for the preparation of polycyclic benzonitriles under microwave irradiation. 

The first example of an enantioselective intramolecular cascade Mizoroki-Heck-cyanation sequence was recently reported which included the reaction of amide 104 (Scheme 12.24) [33], The cyanide source employed was potassium ferro(II)cyanide, which has been utilized for the palladium-catalysed cyanation of aryl halides. The proposed reaction pathway for the Mizoroki-Heck-cyanation involves capture of a a-alkylpalladium intermediate. Previous examples of enantioselective Mizoroki-Heck cyclization-anion capture most often involve trapping of the 7r-allylpalladium complexes in group-selective reactions. Reaction conditions were surveyed for the Mizoroki-Heck cyanation sequence. It was found that Pd(dba)2 afforded better enantioselectivities than Pd(OAc)2 with Ag3P04 as the additive. Using PMP under neutral conditions led to racemic product. To improve the enantioselectivity, several bidentate ligands were screened, and the ligand DIFLUORPHOS 54a was found to give the best enantioselectivity. 

Further studies were undertaken to develop a second generation of Ugands with a broader scope. After extensive experimentation, it was found that mixed-ligand complexes of the type [Ru(dmpe)(H)(P )]BPh4, containing a dmpe and one chiral diphosphine, gave the best results. The structures of the best two phosphines, MeO-BiPHEP and DIFLUORPHOS are shown in Figure 6.4. 

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