Diphosphinite ligand

Scheme 2.10 Cu-catalysed 1,4-additions of ZnEt2 and AlEt3 to 2-cyclohexenone with thioether-phosphinite ligands and diphosphinite ligands bearing xylo-furanose backbone.

Furanoside diphosphinite ligands 10 and 11 (Fig. 11) were applied in the Ir-catalyzed asymmetric hydrogenation of several dehydroaminoacid derivatives [25]. The best enantioselectivities (ee s up to 78%) were obtained in the reduction of methyl W-acetamidoacrylate with ligand 10. These results using the lr/10-11 catalysts precursor show that enantiomeric excesses are strongly dependent on the absolute configuration of the C-3 stereocenter of the carbohydrate backbone. The best enantioselectivity were therefore obtained with ligand 10 with an... 

Fig. 11 Summary of the best results obtained in the Ir-catalyzed hydrogenation using furanoside diphosphinite ligands 10 and 11...

Later, furanoside diphosphinite ligands 12, but with C2-symmetry, provided enantioselectivities up to 70% in the asymmetric hydrogenation of several N-arylimines (Fig. 12) [26]. The electronic effect of the ligand on enantioselectivity is considerable. Results were best when electron-donating groups are present on the phenyl rings (ligand 12b). On the other hand, the use of additives was detrimental to both conversion and enantioselectivity. 

The furanoside phosphite-phosphinite ligand 13, related to the previously diphosphinite ligands 12, was also applied to the asymmetric hydrogenation of N-arylimines, increasing the enantioselectivities up to 76% (Fig. 13) [26]. Precursors based on cationic [Ir(cod)2]BF4 provided better yields and enantioselectivities than... 

An interesting asymmetric transformation is the asymmetric conjugate addition to a-acetamidoacryhc ester 30 giving phenylalanine derivative 31, which has been reported by Reetz (Scheme 3.10) [10]. The addition of phenylboronic acid 2m in the presence of a rhodium complex of l,T-binaphthol-based diphosphinite ligand 32 gave a quantitative yield of 31 with up to 11% enantiomeric excess. In this asymmetric reaction the stereochemical outcome is determined at the hydrolysis step of an oxa-7r-aUylrhodium intermediate, not at the insertion step (compare Scheme 3.7). 

Asymmetric Hydrogenation. Asymmetric hydrogenation with good enantio-selectivity of unfunctionalized prochiral alkenes is difficult to achieve.144 145 Chiral rhodium complexes, which are excellent catalysts in the hydrogenation of activated multiple bonds (first, in the synthesis of a-amino acids by the reduction of ol-N-acylamino-a-acrylic acids), give products only with low optical yields.144 146-149 The best results ( 60% ee) were achieved in the reduction of a-ethylstyrene by a rhodium catalyst with a diphosphinite ligand.150 Metallocene complexes of titanium,151-155 zirconium,155-157 and lanthanides158 were used in recent studies to reduce the disubstituted C—C double bond with medium enantioselectivity. 

RajanBabu and Casalnuovo [19, 20] tested diphosphinite ligand systems (5 and 6 in Figure 4) based on carbohydrate backbones. The steric and electronic properties depended on the substituents on the aryl groups on the phosphorus atoms. The use of different chlorophosphine precursors led to the electronically asymmetric ligand 6. This approach resulted in both enantiomers of naproxen nitrile from MVN in 91 % ee (S)-nitrile (ligand 5) and 95 % ee (R)-nitrile (ligand 6) at 0 °C. 

New inq)etus for asymmetric hydroformylations came primarily from Takayas phosphine-phosphinite ligand (BINAPO) 4 which constitutes an enormous breakthrough l In combination with rhodium the BINAPO ligand gave enantioselectivities up to 95% and i/n ratios > 86/14 in the hydroformylation of substituted styrene derivatives. Conversions are > 99% at substrate/catalyst ratios between 300 and 2000. Shortly afterwards, similar catalytic results were reported by Union Carbide with chiral diphosphinite ligands, e.g. 5 . After many years of stagnation these new catalysts now point the way towards fixture developments in asymmetric hydroformylation. 

Ohe and Uemura investigated the asymmetric hydrogenation of several enam-ides and itaconic acid in water in the presence of Rh(I) catalyst based on disaccharide (e.g., trehalose) diphosphinite ligands 12 [18]. When sodium dodecyl sulfate (SDS) was used as an additive the amount of the catalyst could be significantly reduced. Simultaneously the enantioselectivity in the product was enhanced. 

In further investigations, AMPP ligands derived from linear amino acids and several 3,l,2-oxazaphosphabicyclo[3.3.0]octanes (derived from proline) were used for the same cy-clodimerization reaction catalyzed by bis(l,5-cyclooctadiene)nickel(0). Optical yields were as high as 26% if (2R,3/ )-Threophos, an aminophosphane-diphosphinite ligand derived from threonine, was used58 63. 

The new mannitol-based diphosphinite ligands 233 (R = Ph, cyclopentyl, cyclohexyl) have been prepared, and used in rhodium complexes for the asymmetric hydrogenation of prochiral ketones. The cases where R = cyclohexyl gave highest enantioselectivity, up to 86% for the reduction of methyl pyruvate to give methyl R-lactate. °... 

Chiral diphosphinite ligands derived from D-glucose (c/. 3, 324, 325) can be used in the hydrogenation of a-acetamidoacrylic acids leading to a-amino-acids of >80% optical purity. Optimized conditions have been worked out for the large-scale resolution of the useful ligand diphos. ... 

The coordination of sterically constrained diphosphinite ligands containing 2-/< t7-butylphenolate groups reacted with [Rh(/i-Cl)(CO)2]2 leading to an orthometallated complex of Rh 258. ... 

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