SYNPHOS ligand

The sense of diastereoselectivity in the dynamic kinetic resolution of 2-substi-tuted / -keto esters depends on the structure of the keto ester. The ruthenium catalyst with atropisomeric diphosphine ligands (binap, MeO-biphep, synphos, etc.) induced syn-products in high diastereomeric and enantiomeric selectivity in the dynamic kinetic resolution of / -keto esters with an a-amido or carbamate moiety (Table 21.21) [119-121, 123, 125-127]. In contrast to the above examples of a-amido-/ -keto esters, the TsOH or HC1 salt of /l-keto esters with an a-amino unit were hydrogenated with excellent cwti-selectivity using ruthenium-atropiso-... 

Based on hydrogenations of model substrates, several new ligands promise to have a similar potential as those described above. For example, Ru-Solphos (Solvias) catalysts have been shown to hydrogenate various yS-keto esters and / -diketones with ee-values up to >99% and TONs of up to 100000 (for ethyl-3-oxobutanoate) [75], while Ru-Synphos (Synkem) [107] catalysts achieved 99.4% ee at an SCR of 7000 for the hydrogenation of ethyl acetoacetate (for ligand structures, see Fig. 37.28). 

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 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). 

After the initial reports by Banerjee et al. on the intramolecular reductive Heck reaction in the synthesis of abeo-abietane-type diterpenoids, " Node et al. adopted the intramolecular asymmetric Heck reaction for the synthesis of (—)-dichroanal B, (—)-dichroanone, and taiwaniaquinone H. Palladium cyclization of triflate 18 using (/ )-Synphos as ligand and successive hydrogenation afforded the key intermediate (5)-19 in 86% yield and 94% ee. Significantly, both E/Z triflates of 18 gave the desired Heck product 19 indicating an equilibrium between the two isomers (Scheme 13.7). 

The synthesis of the C6-C13 subunit was started with asymmetric hydrogenation of (3-keto ester 44 promoted by Ru(II)-(5)-SYNPHOS catalyst. Reaction was accomplished in EtOH at 80°C and 11 bar H2-pressure affording (S)-45 in 82% yield and 97% ee. After protection and chain elongation, (5)-46 was hydrogenated in methanol at room temperature under 80 bar hydrogen pressure in the presence of Ikariya-Mashima s catalyst 47 that bear (5)-SYNPHOS as a chiral ligand. Under these conditions, (35,55)-48 was obtained in 93% yield with 98% de. 

The C(l)-C(5) fragment was thus synthesized in seven steps from (R)-methyl 3-hydroxy-2-methylpropanoate in 33% overall yield with excellent diastereoselectivity in the construction of the C(2) and C(3) stereocenters. Diastereo-selective hydrogenation of (R)-49 was accomplished with Ru(II)-catalyst prepared in situ from [Ru(COD)(r -2-methylallyl)2] and (5)-SYNPHOS as a chiral ligand. The product of hydrogenation (3/ ,4R)-50 was obtained in 94% yield and > 95% de. To achieve the Cl-Cl 3 fragment, both subunits C1-C5 and C6-C13 were coupled with the Horner-Wadsworth-Emmons reaction procedure to create the C5-C6 bond. 

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