Chiral water-soluble

Bidentate chiral water-soluble ligands such as (S,S)-2,4-bis(diphenyl-sulfonatophosphino)butane BDPPTS (Fig. 2) or (R,R) 1,2-bis(diphenylsul-fonatophosphinomethyl)cyclobutane have been prepared [25]. Their palladium complexes catalyze the synthesis of chiral acids from various viny-larenes and an ee of 43% has been reached for p-methoxystyrene with the BDPPTS ligand. Furthermore, recycling of the aqueous phase has shown that the regio- and enantioselectivity are maintained and that no palladium leaches. 

Dehydropeptides were reduced (Scheme 3.9) on a preparative scale in two-phase systems with catalysts prepared in situ from [ RhCl(COD) 2] and chiral water-soluble ligands 35, 36, and 37 (Ch.2). The highest (87%) diastereoselectivity was obtained with [ RhCl(COD) 2] + tetrasuhbnated 2,4-bis(diphenylphosphino)pentane, BDPPTS, 36 [121]. 

Reaction of the anion 21 with Cp or Cp metal fragments provides further metallocene-type complexes with a pendant phosphaferrocene side-chain. For example, the reaction of the thallium derivative T1 21 with [Cp RhCl2]2 yields the cationic pentamethylrhodocenium 24 as its chloride (Scheme 1.5.10). This is an interesting species because it is a chiral water-soluble P ligand. The chloride anion can be exchanged by PF,s to make the compound more soluble in organic solvents. 

Transfer hydrogenation of ketones using metal complexes with a chiral water-soluble [97,98] and a dendritic ligand [99] was investigated for use in recycling catalysts. The reaction with immobilized catalysts has also been reported [100]. 

When chiral water soluble ligands are used the technique can be applied to asymmetric hydrogenations [26]. Some examples are shown in Fig. 7.9. 

Recycling of the catalyst has been investigated by using Ru complexes with a chiral water-soluble ligand [286, 287], a dendritic ligand [288], or a TsDPEN immobilized on a polystyrene resin [289, 290],... 

C.S. Wilcox and his research team designed and synthesized chiral water-soluble cyclophanes based on carbohydrate precursors. These compounds are also dubbed as glycophanes and they are potentially valuable enzyme models. The key macrocyclization step utilized the Glaser coupling and the reaction was carried out in a thermal flow reactor at 80 °C in 67% yield. 

Bukownik, R. R., Wilcox, C. S. Synthetic receptors. 3,6-anhydro-7-benzenesulfonamido-1,7-dideoxy-4,5-0-isopropylidene-D-altro-hept-1-ynitol a useful component for the preparation of chiral water-soluble cyclophanes based on carbohydrate precursors. J. Org. Chem. 1988, 53, 463 67. 

Figure 78 A chiral, water-soluble cyclophane for enantioselective binding [104]...

The aqueous conditions allowed the use of chiral water-soluble catalysts such as Zn + complexes of a-amino acids [180] or )3-cyclodextrin [181] with, however, low selectivities. Similarly, the water-soluble unprotected sugars can be extended by one carbon atom by reaction with formaldehyde (Scheme 36) [182]. 

Although enantiopure sulfonated diphosphines have been successfully used in the hydrogenation of some prochiral substrates, very low enantioselectivities were obtained in other reactions. Thus elaboration of new chiral water-soluble catalysts is of utmost importance for the future. The use of micelles should also be extended to reactions other than asymmetric hydrogenation. 

Interesting chiral water-soluble aminosulfonamide ligands containing a phenyl-sulfonic acid substituent have been synthesized and engaged directly with a ruthenium precursor to reduce enantioselectively aromatic ketones to the corresponding alcohols [84]. As concluded by the authors, these ligands should be evaluated in bi-phasic catalysis. 

Di)phosphines containing chiral backbones equipped with diphenylphosphino-substituents are the most successful and best-investigated chiral ligands in asymmetric homogeneous catalysis. Thus, a variety of chiral water-soluble ligands were prepared by direct sulfonation of these phosphorus ligands under conditions similar to those for the synthesis of achiral sulfonated phosphines. 

Stelzer and co-workers reported a number of chiral water-soluble secondary phosphines [14], prepared by nucleophilic phosphination of primary phosphines with fluorinated aryl sulfonates in the superbasic medium DMSO/KOH. Further reaction with alkyl halides gives bidentate tertiary phosphines with P-chirality, but only racemic versions have been reported so far. Hanson et al. introduced so-called surface-active phosphines into asymmetric aqueous-phase catalysis. One of the main problems inherent to two-phase catalysis is the often very low miscibility of the substrates in the aqueous phase. Insertion of long alkyl chains between phosphorus atoms and phenyl groups in sulfonated phosphine ligands has been proven to increase reaction rates in the Rh-catalyzed hydroformylation of 1-octene [15], This concept was extended to a number of chiral ligands, i.e., the monoden-... 

Among the other accesses to chiral water-soluble ligands, the introduction of a quaternary ammonium group is one of the most studied. Nagel et al. reported on the preparation of diphosphine 13 by quaternization of (3i ,4R)-3,4-bis(diphenyl-phosphino-l-methylpyrrolidine) with Me3OBF4 after protecting the phosphorus through complexation to rhodium [19]. 

Figure 7 Chiral water-soluble quaternized diphosphine.

The enantioselective hydrogenation of some a-amino add precursors 1 [Eq. (1)) in water or in an aqueous/organic two-phase system has been thoroughly investigated using rhodium or mthenium complexes assodated with chiral water-soluble ligands 3-13. Some of the most interesting results are summarized in Table 1. 

Figure 6.6 Chiral water-soluble, polyhydroxyphosphine ligands.

---