Phosphine oxides prochiral

Other Oxidations. Glycol formation by oxidation of styrene [75], as well as oxidation of prochiral phosphines to the optically active phosphine oxides [76] by chiral PTC, gave only low asymmetric inductions. 

The first enzymatic desymmetrizations of prochiral phosphine oxides was recently reported by Kielbasinski et al.88 Thus, the prochiral bis(methoxycarbonylmethyl)-phenylphosphine oxide 93 was subjected to the PLE-mediated hydrolysis in buffer affording the chiral monoacetate (RJ-94 in 72% ee and 92% chemical yield. In turn, the prochiral bis(hydroxymethyl)phenylphosphine oxide 95 was desymmetrized using either lipase-catalyzed acetylation of 95 with vinyl acetate as acyl donor in organic solvent or hydrolysis of 97 in phosphate buffer and solvent affording the chiral monoacetate 96 with up to 79% ee and 76% chemical yield. 

Figure 47 Lipase-catalyzed desymmetrizations of prochiral phosphine oxides.

Kielbasinski, P. Zurawinski, R. Albrycht, M. Mikolajczyk, M. The first enzymatic desymmetrizations of prochiral phosphine oxides. Tetrahedron Asymmetry 2003, 14, 3379-3384. 

The biocatalytic desymmetrization of various C2-symmetric tertiary phosphine oxides was used for the preparation of P-chiral phosphines. Mikolajczyk et al. [183-185] studied the desymmetrization of bis-functional phosphinates and phosphine oxides. The hydrolysis of prochiral bis(methoxycarbonylmethyl) phenylphosphine oxide 274 was carried out in phosphate buffer in the presence of... 

Two metal-catalysed reactions not based on phosphido complexes are also discussed in this chapter Rh-catalysed desymmetiisation of prochiral dialkynyl-phosphine oxides and Ru- or Mo-catalysed metathesis. 

In this reaction, both triple bonds in 1,6-diynes 100 and one of the prochiral alkynes in the phosphine oxides 101 react enantioselectively in a Rh-catalysed [2- -2-h2] cycloaddition, generating an aromatic ring attached to the newly... 

Scheme 6.48 Ru-catalysed desymmetrisation of prochiral (114) and achiral (116) phosphine oxides via CM.

These desymmetrisations by CM are challenging because selectivity has to be controlled at several levels. There are many alkenes in the reaction mixture that can undergo undesired self-metathesis reactions. In addition, double metathesis yielding achiral products has to be minimised. Finally, there is the issue of EjZ selectivity. Despite these hurdles, several examples of F-stereogenic (but racemic) phosphine oxides 115 were obtained from prochiral phenyl divinylpho-sphine oxide (114) in 47 6% yield. A three-fold excess of 114 was used to minimise double metathesis. In all but one case none of the E isomer of 115 is formed. The vinyl group in 115 was further functionalised by CM with styrene. 

Finally, there is a report on Mo-catalysed asymmetric ring closing metathesis (ARCM) for the enantioselective desymmetrisation of prochiral phosphinates and phosphine oxides (Scheme 6.53). This constitutes the first example where ARCM is used to prepare chiral compounds with a heteroatom as stereogenic centre. 

In 2003 Kielbasinski, Mikolajczyk and co-workers reported the first enzymatic desymmetrisations of prochiral phosphine oxides. They desymmetrised prochiral phosphine oxide 157 by PLE-catalysed hydrolysis (Scheme 6.61). 

The monoacetate phosphine oxide 158 was isolated in 92% yield and 72% ee. The absolute configuration was shown to be R by chemical correlation after preparing the known phosphine oxide 159. As in the previously described kinetic resolutions of phosphoryl derivatives, the sense of the chiral induction can be explained by the Jones model of the PLE active site. In the same report the enzyme-catalysed preparation of P-stereogenic phosphine oxide 156 from prochiral precursors was described (Scheme 6.62). 

Catalytic asymmetric hydrosilylation of prochiral olefins has become an interesting area in synthetic organic chemistry since the first successful conversion of alkyl-substituted terminal olefins to optically active secondary alcohols (>94% ee) by palladium-catalyzed asymmetric hydrosilylation in the presence of chiral monodentate phosphine ligand (MOP, 20). The introduced silyl group can be converted to alcohol via oxidative cleavage of the carbon-silicon bond (Scheme 8-8).27... 

Simpkins and coworker have reported desymmetrization of a meso-phos-pholane oxide involving discrimination of prochiral protons by a chiral lithium amide (Table 7) [78]. The addition of LiCl was effective to enhance the selectivity, probably due to lesser aggregation of the hthium salt [79]. In certain cases the enantiomeric excesses of the products could be increased up to 97% ee by recrystallization. The obtained phospholane oxides can be readily reduced to optically active phosphines, which are known to be useful as chiral ligands. 

The methods described in this chapter are based on the enantioselective deprotonation of alkyl groups in - usually achiral - phosphine derivatives, which provide highly enantioenriched a-carbanions that are versatile precursors of a variety of mono- and diphosphines. This method was developed by combining two known facts firstly, that the methyl group in methylphosphines and their oxides, boranes and sulfides can be deprotonated with strong bases and secondly common organolithium reagents ( -, s- or r-BuLi) can exert enantioselective deprotonations in prochiral substrates in the presence of certain chiral auxiliaries. ... 

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