Optically Active Phosphine Oxides

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. 

Brown and co-workers synthesized optically active phosphine oxides from phosphorus trichloride by sequential addition of nucleophiles to chiral oxazaphospholidine [Eq. (24)]. The key step in this synthesis is control of the stereochemistry of the oxazaphospholidine, since the stereochemistry from the other steps is well characterized. The overall result is a greater than 94% e.e. 

Stereospecific Conversion of Menthyl Phosphinates to Optically Active Phosphine Oxides Using Organometallic Reagents, ... 

Requisite diastereomerically enriched menthyl phosphinates may be conveniently obtained by unexceptional methods and examples which constitute the partial realization of this scheme for configurational intercorrelations are shown in Chart II. The absolute configurations of menthyl esters 1 and 2 follow from their correlation with 3, whose chirality at phosphorus is known from X-ray analysis ). The stereochemical direction (inversion) of these highly stereospecific Grignard reactions, and thus the absolute configurations of the derived optically active phosphine oxides, was established by chemical correlations with a second reference compound (4) of known absolute configuration . 

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. 

Homer and Balzer had earlier reported 32) that reduction of optically active phosphine oxides with either trichlorosilane (HSiCls), HSiClj/pyridine, or HSiCls/N, N-diethylaniline affords phosphines with overall retention of configuration, whereas reduction with HSiCls/triethylamine affords phosphine with inversion of configuration at phosphorus. In summary, it was suggested 32) that this difference in overall stereochemistry of reduction reflected a difference in the mode of hydride transfer from silicon to phosphorus intra- and intermolecular hydride transfer led to retention and inversion, respectively. The essential features of these mechanistic rationalizations are represented by Eq. (3). The intramolecular hydride transfer mechanism ), which may include pseudorotation (see Sect. 3) if intermediate phospho-HSiClj + O=PR3 - 0 PRj PRj + [ClsSiOH]... 

Phosphine oxide-based olefination reactions continue to be widely used in synthesis, for example, in those leading to vitamin D3 and its derivatives. An alternative method for the conversion of diastereomerically pure menthyl phosphinates to optically active phosphine oxides has been reported. Structural studies on a variety of phosphine oxide binary and ternary co-crystallization compounds have been carried out and the first complex involving the binary PO ligand has been prepared. 

Triarylphosphine oxides are prepared by coupling aryl halides or triflates with diphenylphosphine oxide (36), and they are reduced to triarylphosphine with HSiCls. Selective monophosphination of 2, 2 -bis-triflate of binaphthol (35) with diphenylphosphine oxide occurred to give the optically active phosphine oxide (37) using DPPB or DPPP. No bis-substitution was observed [6,7], The phosphine oxide 37 can be converted to the phosphine by treatment with HSiCls and an amine. Various optically active monodentate phosphines such as MeO-MOP (VI-12) are prepared from 37 via 38. On the other hand, bis-substitution of 35 takes place to afford the bis-phosphine when NiCl2(dppe) is utilized as a catalyst, and the reaction is used for the preparation of BINAP (XV-1) [8]. 

Korpiun O, Lewis RA, Chickos J, Mislow K (1968) Synthesis and absolute configuration of optically active phosphine oxides and phosphinates. J Am Chem Soc 90 4842-4846... 

Reduction of an optically active phosphine oxide. The choice of reducing agent determines whether inversion or retention of confignration occurs. The use of Si2Cl( , for example, produces an inversion of configuration, whereas PhSiH3 usually results in retention. 

The phospha-Mannich condensation of 2- or 4-pyridinecarboxyaldehydes, primary amines and secondary phosphine oxides was carried out in different variations, applying achiral reactants, optically active phosphine oxides and/or (+ )-a-phenyl-ethylamine (Scheme 29). ... 

Korpiun O, Mislow K (1967) New route to the preparation and configurational correlation of optically active phosphine oxides. J Am Chem Soc 89 4784-4786... 

Pietrusiewicz, K.M. Zablocka, M. (1988) Optically active phosphine oxides. Conjugate addition to vinyl phosphine oxides in aqueous media. Tetrahedron Lett., 29,937-40. 

The electrochemical reduction of mono- and bis(acyl)phosphine oxides was observed to lead to the corresponding radical anions/ In the field of optically active phosphine oxides, the resolution of l-butyl-3-methyl-3-phospholene oxide with TADDOL derivatives was described/ The preparation of the enantiomers of BINAP and its derivatives was summarized in a review/ The deracemization of tert-butyl-phenylphosphine oxide using dibenzoyltartaric acid afforded one enantiomer in a configurationally stable form, in contrast to suggestions in the literature and to general opinion. The enantiomer of the secondary phosphine oxide was utilized in the preparation of a-hydroxyphosphine oxides (Scheme 64). The adducts were obtained in >95% ee and in >95% de. °... 

In another variation, optically active phosphine oxides were converted to phosphonium salts with a non-nucleophilic counterion hy all lation of the P=0 bond with methyl triflate or trialkoxonium tetrafluoroborate (Meerwein s salt). Hence, the Arbuzov fission could be avoided and the salt was reduced to the corresponding phosphine borane with inversion of configuration (Scheme 69). ... 

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