Phosphorus compounds, optically active

Concerning phosphorus chemistry, the synthesis of condensed compounds, optically active, with pentaco-ordinated phosphorus adopting helicoidal or macrocyclic structures, represents, in our opinion, significant progress. Thus, hydroxyphosphoranes lb, 2b are tautomers of hydroxyphosphoric esters, similar to phosphoric esters of natural polyhydroxylated compounds. 

Organophosphorus compounds. Phosphorus-carbon bond fonnation takes place by the reaction of various phosphorus compounds containing a P—H bond with halides or tritlates. Alkylaryl- or alkenylalkylphosphinates are prepared from alkylphosphinate[638]. The optically active isopropyl alkenyl-methylphosphinate 778 is prepared from isopropyl methylphosphinate with retention[639]. The monoaryl and symmetrical and asymmetric diarylphosphi-nates 780, 781, and 782 are prepared by the reaction of the unstable methyl phosphinate 779 with different amounts of aryl iodides. Tnmethyl orthoformate is added to stabilize the methyl phosphinate[640]. 

Phosphorus is m the same group of the periodic table as nitrogen and tricoordi nate phosphorus compounds (phosphines) like amines are trigonal pyramidal Phos phmes however undergo pyramidal inversion much more slowly than amines and a number of optically active phosphines have been prepared... 

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. 

In molecules in which the nitrogen atom is at a bridgehead, pyramidal inversion is of course prevented. Such molecules, if chiral, can be resolved even without the presence of the two structural features noted above. For example, optically active 12 (Trdger s base) has been prepared. Phosphorus inverts more slowly and arsenic still more slowly." Nonbridgehead phosphorus," arsenic, and antimony compounds have also been resolved... 

In the skeleton of many chelating diphosphines, the phosphorus atoms bear two aryl substituents, not least because the traditional route to this class of compounds involves the nucleophilic substitution with alkali metal diarylphosphides of enantiopure ditosylates derived from optically active natural precursors, approach which is inapplicable to the preparation of P-alkylated analogs. The correct orientation of these aryl substituents in the coordination sphere has been identified as a stereo chemically important feature contributing to the recognition ability of the metal complex [11,18-20]. 

Hydroformylation has been extensively studied since it produces optically active aldehydes which could be important precursors for pharmaceutical and fine chemical compounds. Thus, asymmetric hydroformylation of styrene (Scheme 27) is a model reaction for the synthesis of ibuprofen or naproxen. Phosphorus ligands were used for this reaction with excellent results, espe-... 

Aaron, H.S., Uyeda, R.T., Frack, H.F., and Miller, J.I., The stereochemistry of asymmetric phosphorus compounds. IV. The synthesis and stereochemistry of displacement reactions of optically active isopropyl methylphosphonochlo-ridate, /. Am. Chem. Soc., 84, 617, 1962. 

The stereochemistry of optically active phosphorus thio-acids has been reviewed2 and published lectures have covered such topics as phosphate and phosphonate compounds based on adamantane3 and AW-dihalogeno-amides of phosphoric acids.4... 

The optically active thiones (4), readily obtainable from (—)-ephedrine, undergo P—N bond fission, with inversion of configuration at phosphorus, when treated with ethanolic HC1 this provides a highly recommendable method for the preparation of valuable amounts of optically active acyclic compounds (5), isolable as the 5-methyl esters (6).9... 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaUy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphorus [7723-14-0]y produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-lithiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has litde commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Finally, heterophosphonium salts are reduced with cleavage of the phosphorus-heteroatom bond optically active aminophosphonium compounds are usefully reduced to phosphines with retention of configuration747. Methyltrineopentoxyphosphonium trifluoromethanesulphonate gave the quantitative formation of dineopentylmethyl phos-phonite, which is indicative of P—O bond cleavage748 (reaction 223)... 

Stereochemical evidence for the mechanism of nucleophilic substitution at a tetracovalent phosphorus atom has been mainly forthcoming from the experiments of Michalski et a/.48-50 with esters containing thiophosphoryl centers. Until recently, the inaccessibility of suitable optically active phosphorus compounds precluded stereochemical investigations on the mechanisms of their hydrolysis. 

H. B. Kagan, Chiral Ligands for Asymmetric Catalysis, in J. D. Morrison, ed., Asymmetric Synthesis, Vol. 5, Chap. 1, Academic Press, New York, 1985 H. B. Kagan and M. Sasaki, Optically Active Phosphines Preparation, Uses and Chiroptical Properties, in F. R. Hartley, ed., The Chemistry of Organo-phosphorus Compounds, Vol. 1, Chap. 3, John Wiley Sons, New York, 1990. 

Optical activity was first observed with organic compounds having one or more chiral carbon atoms (or centres) (i.e. a carbon substituted with four different groups). In the structures (1) to (17) the chiral carbons are specified with an asterisk. Subsequently compounds having chiral centres at suitably substituted heteroatoms (e.g. silicon, germanium, nitrogen, phosphorus, arsenic, sulphur, etc.) were also synthesised. Molecular dissymmetry, and hence chirality, also... 

Among the preparative methods used for obtaining P-chiral phosphorus compounds, there are procedures involving the use of optically pure auxiliaries like (—)-menthol [40], (—)-ephedrin [41,42], or more recently, the kinetic resolution of 1-hydroxymethylalkylphenylphosphine oxides using Pseudomonas or Candida antarctica lipases [43], It has been found that some [(alkyl-substituted)arene] phosphinates and phosphine oxides can also be resolved efficiently by inclusion complexation with optically active 2,2 -dihydroxy-1, 1 -binaphthyl (17) [44],... 

Analysis of nmr spectra allowed us to determine the absolute configuration of the phosphorus atom of pentaco-ordinated compounds la, 2a and lb, 2b. Protons P-O-CH-CH-O-P and exocyclic substituents P-H and P-0 X (X = H...DMF, HNEtlj) are in a cis position. The more likely structure of oligomers lji and lb is a sequence of TBP drawn up as helix (fig. 1), while dimers 2a and 2b should present an emetic structure with a pentaco-ordinated phosphorus atom (fig. 2). All these compounds manifest strong optical activity. 

The earliest method of preparation of an optically active phosphorus compound was by resolution of a phosphine oxide Meisenheimer resolved ethyl-... 

On account of the theories of valency alluded to before (p. 52),a compounds of the types [PRJX and [OPR3] are of the same stereochemical type, and contain an atom of phosphorus co-ordinated to four atoms or groups which are symmetrically disposed in space. When the groups denoted by R are different, the resulting compounds PR1R2R3R4X and PORjRgRj should be capable of existing in optically active forms. 

The first preparation of the type PRjRjRaRjX could not be resolved,3 nor could an anilino-p-toluidinophosphoric acid1 be resolved into optically active isomers by fractional crystallisation with active bases. The first compound which was proved to contain an asymmetric phosphorus atom was phenyl-p-tolylphosphoric acid, the dZ-hydrindamine of which—... 

Also the 18-trimethoxybenzoate (XLV) can undergo the same series of reactions as given for the acetate XLII. Ring closure with phosphorus oxychloride to an analogous quaternary compound (XLVII) can also be carried out with the racemic or optically active lactone XLVI (192). 

Dialkylzinc initiates homo- and copolymerization of aldehydes such as acetaldehyde 151, 234, 310, 487, 533), formaldehyde 310, 495), butyraldehyde 468), glutardehyde 386), cyanopropionaldehyde 479), chloroacetaldehyde 233, 234, 324, 325, 412, 495, 533), and dichloro-acetaldehyde 325). Aluminum triisopropoxide 485) and phosphorus compounds 339) were proposed as additives for the polymerizations. Polymerization of optically active aldehydes was also reported ). 

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