Enantiomeric phosphine oxide

P-chiral phosphines, which are potential ligands for transition metal-catalyzed reactions, were synthesized through hpase-catalyzed optical resolution of the corresponding racemic phosphine oxide compounds (Fig. 10.29). For example, lipase from C. rugosa (CRL) was used for the enantioselective hydrolysis of acetoxynaphthyl phosphine oxide (Fig. 10.29(a)). The P-enantiomer was hydrolyzed selectively, leaving the (S)-acetoxy compound, which was further subjected to chemical hydrolysis. Both enantiomeric phosphine oxides were obtained in >95% after recrystallization. Methylation followed by reduction with triethyl amine/trichlorosilane, with inversion of configuration, yielded the desired chiral phosphine. 

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

The high diffusivity and low viscosity of sub- and supercritical fluids make them particularly attractive eluents for enantiomeric separations. Mourier et al. first exploited sub- and supercritical eluents for the separation of phosphine oxides on a brush-type chiral stationary phase [28]. They compared analysis time and resolution per unit time for separations performed by LC and SFC. Although selectivity (a) was comparable in LC and SFC for the compounds studied, resolution was consistently... 

Macaudiere et al. first reported the enantiomeric separation of racemic phosphine oxides and amides on native cyclodextrin-based CSPs under subcritical conditions [53]. The separations obtained were indicative of inclusion complexation. When the CO,-methanol eluent used in SFC was replaced with hexane-ethanol in LC, reduced selectivity was observed. The authors proposed that the smaller size of the CO, molecule made it less likely than hexane to compete with the analyte for the cyclodextrin cavity. 

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

Scheme 18. Example of synthesis of enantiomerically pure phosphine oxides...

A modification of this procedure allowed the isolation of 1,3,2-oxazaphospholidine 52a as a single diastereomer [41] and its application to asymmetric synthesis of enantiomerically and diastereomerically pure phosphinic acid derivatives 53 and 54 and tertiary phosphine oxides 55 (Scheme 20) [45], A few years later, a similar approach for the synthesis of enantiomerically pure tertiary phosphine oxides 55... 

Analytical Properties Ionically bonded to silica, this phase provides good resolution of enantiomeric quasiequatorial frans-dehydriols of unsubstituted and methyl- and bromo-substituted benz[a]anthracene derivatives covalently bonded to silica, this phase provides good resolution of enantiomeric pairs of quasidiaxial frans-dihydrodiols of unsubstituted and methyl- and bromo-substituted benz[a]anthracene derivatives by addition of a third solvent (chloroform) to the classical binary mixture (hexane-alcohol) of the mobile phase, resolution of enantiomers of tertiary phosphine oxides is possible Reference 31-33, 36, 37... 

A noteworthy synthetic application for the reaction of J with a,g-unsaturated phosphoryl compounds is represented by the addition involving hitherto unknown (-)-(Sp)-methylphenylvinylphosphine oxide J 2. The resulting tertiary phosphine oxides 13 with saturated carbon chains and known stereochemistry at phosphorus constitute attractive starting materials for the preparation of optically pure phosphines. The organophosphorus substrate 12 was obtained by decarbomenthoxylation of the enantiomeric ester... 

No organolithium a to phosphorus has been shown unequivocally to be configurationally stable. The phosphonamide 279 is configurationally unstable on a macroscopic timescale,128 the phosphine oxide 280 gives racemic products on lithiation even in the presence of an internal quench,129 and in a Hoffmann test the phosphine oxide 281 gave the same ratio of diastereoisomers with either racemic or enantiomerically pure 6.129... 

When an enantiomerically pure alkynol is used, a single enantiomer of an allenyl phosphine oxide 4 with axial chirality is obtained25. 

Wittig Reaction. The intramolecular Wittig reaction of an ylide obtained from (-P)-CAMP occurred with 77% ee to give the ( -bicyclic diketone. Although a stoichiometric amount of the optically pure phosphine was required, the phosphine oxide (-t)-CAMPO could be recycled. Enantiomeric excesses using CAMP were much higher than similar reactions which employed other chiral phosphines. 

The chemistry of secondary phosphine oxides, R2P(H)0 and their phosphi-nous acid tautomers, R2POH, has continued to attract attention. The study of the phosphinous acid tautomers has been aided by the development of stereoselective procedures for direct conversion of secondary phosphine oxides to the phosphinous acid-boranes (83). Treatment of the secondary phosphine oxide with either a base-borane complex or boron trifluoride and sodium borohyd-ride provides the phosphinous acid-borane with predominant inversion of configuration at phosphorus. The phosphinous acid tautomers are usually trapped as ligands in metal complexes and further examples of this behaviour have been noted. Discrimination of enantiomeric forms of chiral phosphinous acids, Ph(R)OH, coordinated to a chiral rhodium complex, has been studied by NMR. °° Palladium complexes of di(t-butyl)phosphinous acid have found application as homogeneous catalysts.A lithium salt of the tellurophos-phinite Ph2PTeH has been prepared and structurally characterised. ... 

Normal phases composed of hexane modified with 2-propanol have been successfully used with the 3,5-dimethylphenyl carbamate and para-toluoyl ester forms of the CD CSP. The P-CD CSP has been used in subcritical fluid chromatography with a mobile phase composed of carbon dioxide modified with methanol, ethanol, or 2-propanol (69). Under these conditions, racemic amides and phosphine oxides were enantiomerically resolved. 

More recently, Shibasaki et al. have extended this methodology to the enan-tioselective cyanosilylation of ketones by designing a novel bifunctional catalyst 56 containing titanium and phosphine oxide (Table 9). Thus, enantiomeric excesses up to 95% in numerous cases have been obtained [62]. 

One feasible method for the exploration of chiral open-framework compounds is the use of chiral chemical units as primary building blocks by coordinating with metal or other assembly methods to form 2-D layer or 3-D open-framework structures with optical activity. A notable example is the enantiomerically pure zinc phosphonate based on a mixed phosphonic acid-phosphine oxide chiral building block reported by Bujoli and coworkers in 2001.[91] The reaction procedures are shown as follows. 

F. Fredoueil, M. Evain, D. Massiot, M. Bujoli-Doeuff, and B. Bujoli, Enantiomerically Pure Zinc Phosphonates Based on Mixed Phosphonic Acid-phosphine Oxide Chiral Building Blocks. J. Mater. Chem., 2001, 11, 1106-1110. 

To assess the stereospecificity of the Grignard and organolithium reactions with menthyl phosphinates, the diastereomeric purity of starting menthyl esters was estimated by pmr spectroscopy (see Sect. 2.2) and, in most cases, highest reported rotations were used to estimate the. enantiomeric purity of the derived optically active phosphine oxides The method of preference for determining the enantiomeric purity of a phosphine oxide, even in those cases in which a value for the rotation of optically pure material is reported, involves stereospecific reduction of the phosphine oxide with hexa-chlorodisilane (see Sect. 2.4) to the corresponding phosphine, followed by quatemization with 2-phenyl-2-methoxy-ethyl bromide and pmr analysis of the diastereomeric phosphonium bromides (Eq. (1)) > This method for determining optical purity, shown ) to be applicable... 

Tertiary phosphines, in the absence of special effects 2 ), have relatively high barriers 8) ca. 30-35 kcal/mol) to pyramidal inversion, and may therefore be prepared in otically stable form. Methods for synthesis of optically active phosphines include cathodic reduction or base-catalyzed hydrolysis 3° 31) of optically active phosphonium salts, reduction of optically active phosphine oxides with silane hydrides 32), and kinetic 3 0 or direct 33) resolution. The ready availability of optically pure phosphine oxides of known absolute configuration by the Grignard method (see Sect. 2.1) led to a study 3 ) of a convenient, general, and stereospecific method for their reduction, thus providing a combined methodology for preparation of phosphines of known chirality and of high enantiomeric purity. 

Recently the first use of the paracyclophane backbone for the placement of two diphenylphosphano groups to give a planar chiral C2-symmetric bisphos-phane was reported [102]. The compound 159 abbreviated as [2.2]PHANEPHOS was used as a ligand in Rh-catalyzed hydrogenations. The catalytic system is exceptionally active and works highly enantioselective [ 103]. The preparation of [2.2]PHANEPHOS starts with rac-4,12-dibromo[2.2]paracyclophane (rac-157), which was metalated, transmetalated and reacted with diphenylphosphoryl chloride to give racemic bisphosphane oxide (rac-158). Resolution with diben-zoyltartaric acid and subsequent reduction of the phosphine oxides led to the enantiomerically pure ligand 159. 

---