Other Water-soluble Chiral Ligands

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]. 

In the same way, cationic complexes of amine derivatives of BDPP and CHIRA-PHOS were prepared which showed unlimited solubility in water and negligible solubility in common organic solvents. They were used in asymmetric hydrogenation of dehydroamino acids and provided modest to high enantioselectivities [20 b], The presence of the dimethylamino group in the DIOP derivative resulted in a reversal in the observed dominant product antipode, which was attributed to a change in the preferred ligand conformation. 

Ar = C6H4-CH2N+(C2H5)2CH3 BF4 (16a) Ar = 3,5-di(methyl)phenyl (16b) 

Nonionic, asymmetric polyoxy-1,2- and -1,4-diphosphines, analogs of Prophos and DIOP have been prepared [23a,b], as well as a chiral polyether phosphite ligand derived from (S)-binaphthol [23c] and PEG-BINAP [23d] through polycondensation of 5,5 -diamino-BINAP, polyethylene glycol, and terephthalic chloride. 

Reetz et al. prepared /3-cyclodextrin-modified diphosphine 18 and a series of derivatives by phosphinomethylation of the corresponding amino-substituted cyclodextrin precursors [25], The ligands were used in biphasic hydroformylation of 1-octene and competitive hydrogenation of 1-alkenes, with rather poor results. The chiral cavity in the backbone might achieve molecular recognition of certain pro-chiral substrates and thus provide enantioselectivity in the products. 

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The commercial success of rhodium-trisulfonated triphenylphosphine (TPPTS) catalysts1 has prompted considerable interest in TPPTS and other water-soluble ligands.2 The potential for new applications for the synthesis of both bulk and fine chemicals in water has led to methods for the preparation of a wide variety of sulfonated phosphines including chiral phosphines3 and... 

Ethylene chlorohydrin (38) is formed in the Wacker process as a byproduct. Chlorohydrins are obtained as main products when PdCl3 (pyridine) is used [29]. The optically active chlorohydrin 40 with high ee was obtained without forming the regioisomer 41 from allyl phenyl ether (39) and other substituted alkenes when the bimetallic Pd complex 42 coordinated by water soluble chiral BINAP-based ligand 43 (II-9) was used [30]. 

Cyclopropanation is an important synthetic method, and enantioselective catalytic reactions of olefins and diazoacetates provide access to valuable products with biological activity. In general, these reactions are conducted in anhydrous solvents and in several cases water was found to diminish the rate or selectivity (or both) of a given process. Therefore it came as a surprise, that the Cyclopropanation of styrene with (+)- or (-)-menthyl diazoacetates, catalyzed by a water-soluble Ru-complex with a chiral bis(hydroxymethyldihydrooxazolyl)pyridine (hm-pybox) ligand proceeded not only faster but with much Wgher enantioselectivity (up to 97 % e.e.) than the analogous reactions in neat THF or toluene(8-28 % e.e.) (Scheme 6.34) [72]. The fine yields and enantioselectivities may be the results of an accidental favourable match of the steric and electronic properties of hm-pybox and those of the menthyl-dizaoacetates, since the hydroxyethyl or isopropyl derivatives of the ligand proved to be inferior to the hydroxymethyl compound. Nevertheless, this is the first catalytic aqueous cyclopropanation which may open the way to other similar reactions in aqueous media. 

Chiral phosphines can be made water soluble by using similar approaches and the two most important chiral diphosphines are sulfonated 2,2 -bis-(diphenylphosphinomethyl)-l,l -binaphthyl (BINAS)-8 15 and the BISBIS 16 (Figure 9). The preparation of these types of ligands involves sulfonation with fuming sulfuric acid, similarly to the other phosphines. The position of the sulfonate groups depends on the temperature and the SO3 concentration. The oxidation of the product can be hindered by the preparation of superacidic media from orthoboric acid and anhydrous sulfuric acid. ... 

Few other asymmetrie reactions have been performed using insoluble or soluble polymer-supported ligands. The first example is a Mukaiyama-aldol condensation between silyl ketene acetal and different aldehydes using polymeric Box analog of 99 as chiral ligands and Cu(OTf)2 as metal soiu ce in water (Scheme 147) [216]. When using benzaldehyde as substrate, yields were very low (12-34%) and ee were moderate (40-62%) whatever the polymer-supported Box. The same level of enantioseleetivity was observed with other aldehydes while the yield was better with all the ligand/Cu complexes used. 

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