Menthyl phosphinates

Two contrasting conclusions have been reported in the reactions of lithium aluminium hydride in THF with phosphine oxides and phosphine sulphides respectively. The secondary oxide, phenyl-a-phenylethylphos-phine oxide (42), has been found to be racemized very rapidly by lithium aluminium hydride, and this observation casts some doubt on earlier reports of the preparation of optically active secondary oxides by reduction of menthyl phosphinates with this reagent. A similar study of the treatment of (/ )-(+ )-methyl-n-propylphenylphosphine sulphide (43) with lithium aluminium hydride has revealed no racemization. These results have been rationalized on the basis of the preferred site of attack of hydride on the complexed intermediate (44), which, in the case of phosphine oxides (X = O), is at phosphorus, and in the case of the sulphides (X = S), is at sulphur. Such behaviour is comparable to that observed during the reduction of phosphine oxides and sulphides with hexachlorodisilane. ... 

All of the bisphosphines in Table I were prepared by the reaction of the appropriate Grignard reagent on a resolved menthyl phosphinate ester as described in our previous work (3). R was either phenyl (II) or o-anisyl (3). Rx corresponds to Ri group in Table I. 

FIG. 10. Synthesis of chiral oxides by reaction of Grignard reagents with diastereo-merically pure menthyl phosphinates. Deoxygenation of chiral phosphine oxides gives chiral phosphines. 

So far we have discussed the synthesis of useful P-chiral phosphorus intermediates that can be converted into a variety of phosphines by reaction with a nucleophile (and deprotection). However, Imamoto and co-workers found that one-electron reducing agents react with resolved menthyl phosphine oxides and boranes to give metal phosphides that retain their configuration at phosphorus (Scheme 26).49... 

When chlorodiorganophosphines react with magnesium butadiene163, 3,4-bis(diorganophos-phino)-l-butenes 2 are obtained. For example, reaction of chlorobis(menthyl)phosphine gives 3,4-bis[bis(menthyl)phosphino]-l-butene in 52% total yield, but with only 16% de16. 

However, dichloroorganophosphines bearing bulky substituents afford, on treatment with magnesium butadiene, vinyl-substituted phosphiranes 3 in 36-58% yield consisting predominately of the eis-isomers. When dichloro(menthyl)phosphine was used, the phosphiranes were obtained with a diastereomeric ratio of 4 82 8 6, the major isomer being the trans-compound the diastereomers were not separated17. 

A second route to phosphine oxides consists of a reaction between a diastereomerically enriched menthyl phosphinate 38. This reaction proceeds with inversion of configuration at phosphorus, even though in... 

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... 

Configurational Correlation of Menthyl Phosphinates by Nuclear Magnetic Resonance... 

Menthyl phosphinates, in addition to being useful precursors for the synthesis of optically active tertiary phosphine oxides 5), phosphinamides ),and phosphonothioates were found to exhibit pmr spectra which are a rich lode of structural information. For menthyl n-alkylphenylphosphinates (8) the upfield portion of the pmr spectra features the three methyl doublets of the menthyl moiety. Chemical shifts of these signals for diastereomers... 

A synthetically useful development in the stereochemistry of menthyl phosphinates has been achieved by the finding that menthyl phenylphosphinate may be stereospecifically alkylated with retention of configuration Thus, a single precursor suffices for the synthesis of a wide variety of alkyldiaryl-and aryldialkylphosphine oxides of known absolute configuration. Chart V... 

Such species bear comparison with those proposed for the transformation of menthyl phosphinate and phosphinothioate esters (113 Z = O or S R = Me or Et ML = PFg, BF4 or SbCl6) by other alkylating species (Scheme 21. The formation of an intermediate qua-... 

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. 

Table 1 Preparation of 5a-i from menthyl //-phosphinates 2 (Scheme 4)...

Scheme 8 (iS,25,5S)-Menthyl phosphinate 19 as starting chiral reactant... 

Assmimetric homogeneous catalytic hydrogenation of geranic acid (163) using (for example) the menthyl-phosphine (164) as chiral ligand leads to (R)-(+)-citronellic acid (96) with 44 — 79% e.e. Related work using other chiral phosphines has... 

Figure 3 Phosphorus-containing chiral derivatizing agents. [4] 2-chloro-3,4- dimethyl- 5-phenyl -1,3,2-oxazophospholidine-2-sulfide [5] 2-chloro-4,5-dimethyl-1,3,2-dioxaphospholane-2-oxide [6] 2-dimethyl amino-1,3-dimethyloctahydro-1 H-1,3,2-benzodiazaphosphole [7] 5,5-dimethyl-2-hydroxy-4-phenyl-1,3, 2-dioxaphosphonan-2-oxide [8] L-menthyl(phenyl)phosphoryl-chloride [9] 2-chloro-1,3-dimenthyl-4,5-diphenyl-1,3,2-diaza-phosphole [10] dichloro(menthyl)phosphine.

Optically active (-)-menthyl phosphinate (J p)-(727) have been described as good substrates in the C-I activated phosphorylation of the arene (728), giving stereospecifically the (5p)-phosphoryl substituted phenolic products (729) with retention of configuration at the phosphorus center (Scheme 202). ... 

Scheme 1-42. Optically active phosphines from menthyl phosphinates (54) or menthyl phosphinite-borane complexes (55) by stereocontrolled R O/R displacement.

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