Phosphonium salts, optically active

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 reduction of optically active phosphonium salts by lithium aluminum hydride, which probably does involve 70 as an intermediate, affords racemic phosphines, presumably by pseudorotation in 70 before it decomposes 63). 

Reactions.—Alkaline Hydrolysis. The first total resolution of a heterocyclic phosphonium salt containing an asymmetric phosphorus atom (128) has been reported, providing ready access to optically active phospholan derivatives of value for studies of the stereochemistry of nucleophilic displacement at phosphorus.124 Alkaline hydrolysis of (128) proceeds with retention of configuration at phosphorus to form the oxide (129). Stereochemical studies in the phospholan series have also been facilitated by the X-ray investigation125 of an isomer of l-iodomethyl-l-phenyl-3-methylphospholanium iodide, which is shown to have the structure (130). 

Cathodic deprotection of tosylates of chiral alcohols was achieved without racemization by cleavage of the O—SO2 bond [351]. Optically active quaternary arsonium [352, 353] and phosphonium salts [354] are cathodically cleaved to tertiary arsines and phosphines respectively, with retention of the configuration. The first enantiomer enriched chiral phosphines have been prepared this way. 

Sodium-naphthalene reduction of organotrineopentoxyphosphonium salts led to the instantaneous loss of phosphonium ion phosphonates and phosphites were obtained748 (reaction 224). Alkali metal amalgams are efficient reagents for the reductive cleavage of both achiral and optically active phosphonium salts configuration is retained750 (Table 23). 

By applying alternative alkylation and cathodic cleavage Horner etal S07 synthesized optically active phosphines and phosphonium salts. In reversal of their usual application as reageqts in nucleophilic substitution halides, if converted to... 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

According to the list of natural carotenoids by O. Straub 38), more than half of the over 400 natural carotenoids described are chiral. The asymmetric optically active terpene phosphonium salts which have recently become known, and which can be employed for the synthesis of chiral carotenoids, are contained in a review article by H. Mayer 47). 

Metals such as Na or alkali metal amalgams can also be used in the cleavage of the C—P" bond. In the latter case, reductive cleavage of achiral and optically active quaternary phosphonium salts succeeds in high yields with retention of configuration. ... 

Optically active quaternary arsonium [396,397] and phosphonium [398] salts are electro-reductively decomposed to tertiary arsines and phosphines, respectively, with retention of configuration. Since the tertiary products can be converted again into different quaternary salts with alkylating regents, this decomposition reaction may be useful for transformation between a variety of optically active quaternary salts [397]. 

The reductive cleavage of achiral and optically active quaternary phosphonium and arsonium salts with alkali metal amalgams to form tertiary phosphines and arsines succeeds in high yield with retention of configuration [124]. The reduction with the amalgams was found to give better yields than the conventional cathodic cleavage. 

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. 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

The key step of the synthesis is the rearrangement of the a-acetylenic alcohol 97 into the unsaturated carbonyl compound 124. This rearrangement was carried out with tris(triphenylsilyl)vanadate, triphenylsilanol and benzoic acid to give a mixture of the isomers 124 and 125. The latter was converted by iodine catalysis into the desired isomer 124. This key intermediate was afterwards transformed into the Cis-phosphonium salt 123 by standard procedures. The Wittig olefination of the Cio-dial 45 first with the fucoxanthin end group 123 and then with the peridinin end group 122 gave, in five steps, the C4o-carotenoid 126. Finally the epoxidation of this compound resulted in optically active fucoxanthin (121) and its (5S,6R)-isomer (Scheme 28). 

Sardnaxanthin (230), a Cso-carotenoid containing two cyclic y end groups with an additional Cs-unit was first prepared as a racemate [100], For the synthesis of the optically active compound the C20 + C10 + C20 = C50 strategy was chosen. For the synthesis of the C2o-phosphonium salt 231, the key building block of the synthesis, camphoric acid (144) was selected as starting material [101] (Scheme 51). 

The quaternization of (iS)-( - )-benzylmethylphenylphosphine with aryl bromides, by the complex salt method using nickel bromide, proceeds with predominant retention of configuration at phosphorus. Optically active phosphonium salts are also obtained by quaternization of optically active triarylphosphines with benzynes. ... 

Following a comparison of the behaviours of trialkyl phosphites, mixed alkyl phenyl phosphites and triphenyl phosphite towards iodomethane and, in the last case, the breakdown of the phosphonium salt when treated with an alcohol, Landauer and Rydon considered that all the reactions involve a stage identical with that of the normal Michaelis-Arbuzov reaction. The absence of any rearrangement during the decomposition of complexes from neopentyl phosphites, and the configurational inversion which occurs when optically active 2-halooctanes are produced from optically active phosphite triesters (themselves obtained from optically active octan-2-ol), suggest that the mode of breakdown of the intermediate complexes is of S 2 character. 

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