Chiral phosphinites, synthesis

Certain chiral phosphinite or aminophosphine ligands are also useful for amino acid synthesis. Hydrogenation with a CYCPHOS-Rh complex occurs rapidly to produce high optical yields. The efficacy of this reaction is ascribed to the flexibility of the ligand, which speeds the reaction and gives a fixed chelate ring conformation (26). 

A significant development that has received widespread attention is the synthesis of new mono-and bis-substituted chiral phosphinite, phosphonite, and phosphite ligands. The standard protocol for their syntheses is based on that illustrated in Figure 5. For example, the synthesis of the chiral diphosphinite (182)409 is shown in Equation (45), this basic procedure working extremely well for other chiral diphosphinites such as (183) and (184).410,411... 

Busacca and co-workers have prepared menthol-derived phosphinite boranes 101 and 102, by direct addition of anionic secondary phosphine borane 100 to carbodiimides, yielding the chiral phosphinite boranes under ambient temperature conditions (Scheme 25). These and other derivatives, prepared by hydrophosphination of carbodiimides, were used in the synthesis of enantiomerically enriched phosphaguanidines with potential use as ligands in asymmetric catalysis. 

Chiral bis(phosphinites) derived from (2/J,51 )-2,5-di(hydroxymethyl)tetrahydrothiophene have been prepared (Equation 73). These ligands have been used in the synthesis of rhodium complexes from Rh(COD)2X (COD = cyclooctadiene X = OTf, SbF6) and tested in the asymmetric hydrogenation of methyl a-acetamidocinna-mate. A maximum of 55% enantioselectivity was observed <19980M4976>. 

Due to the great importance of phosphines and phosphinites as chiral ligands for asymmetric catalysis, several hundred compounds of this type have been prepared. In this section, only those compounds which have been mentioned in this Houben-Weyl volume will be discussed. Because of their close relation to the specific topics, biaryl phosphines have already been mentioned in Section 6 and ferrocene derivatives in Section 7.1. All other phosphorus compounds are treated here. An excellent review on the synthesis of enantiomerically enriched compounds where phosphorus is a stereogenic center has recently been published73. 

One of the few available examples is represented by the synthesis of cilastatine by a chiral Cu complex promoted cyclopropanation reaction developed by Sumitomo Chemical Co. [78]. Another is the catalytic asymmetric hydrocyanation of vinylarenes developed at DuPont [79]. In this process (Fig. 27) sugar-derived phosphinites are used in combination with a Ni catalyst to prepare enantiomerically enriched precursors of the NSAID naproxen. 

Fogassy, G., Tangier, A., Levai, A. (2003) Enantioselective hydrogenation of exocyclic alpha,beta-unsaturated ketones. Part 111. Hydrogenation with Pd in the presence of cinchonidine, y. Mol. Catal. A. Chem. 192, 189-194. Hapiat, F., Agboussou, F., Mortreux, A. (1994) Synthesis of new chiral arene Ru(ll) aminophosphine-phosphinite complexes and use in asymmetric hydrogenation of an activated keto compounds. Tetrahedron Asymm. 5, 515-518. 

The menthyl phosphonites and menthyl phosphinites were used for the preparation of F-chiral monodentate ligands. For example, Imamoto used menthyl phosphinite borane complexes for the synthesis of DIPAMP analogues, as shown in Scheme 6 [23]. The treatment of phosphinite borane (/ p)-8 with methyllithium. 

In addition to the previously discussed diphosphanes, some phosphinite-type ligands are among those that are considered as ligands of the state-of-the-art systems. The naturally abundant mono- and disaccharides provide a chiral skeleton for the facile synthesis of diphosphinites as 2,3-Carbophos and 3,4-Carbophos (34), tris-phosphinite, and glucophinite (35). 

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