Chiral phosphonium salts, enantiomeric

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 phosphonium salt 21 having a multiple hydrogen-bonding site which would interact with the substrate anion was applied to the phase transfer catalyzed asymmetric benzylation of the p-keto ester 20,[18 191 giving the benzylated P-keto ester 22 in 44% yield with 50% ee, shown in Scheme 7 Although the chemical yield and enantiomeric excess remain to be improved, the method will suggest a new approach to the design of chiral non-racemic phase transfer catalysts. 

Most of the problems related to the phosphonium salts stereochemistry are discussed under synthesis (Section II), reactivity (Section III) and spectrometric characteristics (Section I.C.). Because of the tetrahedral geometry of phosphorus, chirality arises from the presence of four different substituents. Enantiomeric forms may be separated by... 

A by now classic retrosynthesis of prostaglandins PGFj and PGEj (Fig, 4) leads to the bicydic lactone [12), five-carbon phosphonium salt [13], and phosphonate [14] (19). These compounds contain all the carbon atoms of the prostaglandins and, in [12], aU but one of the chiral centers. Lactone [12] has come to be knovm genetically as the Corey lactone, and its synthesis in one enantiomeric form has been the subject of numerous complementary investigations. 

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. 

Reactions of Phosphonium Salts.— Asymmetric induction is observed on alkaline hydrolysis of the prochiral phosphonium salts (132) under phase-transfer conditions in the presence of an optically active quaternary ammonium salt, forming the chiral oxides (133) with a 0—8 % enantiomeric excess. Alkaline hydrolysis of monobenzyl quaternary salts of a,co-bis(diphenylphosphino)alkanes gives a route to diphosphine monoxides, e.g., (134). Aqueous hydrolysis of (dibromo-fluoromethyl)triphenylphosphonium bromide gives a high yield of dibromo-fluoromethane and triphenylphosphine oxide. When the reaction is carried out in the presence of radiolabelled Br, the evidence points to the involvement of the dibromofluoromethyl carbanion, and not to a carbene intermediate as was observed in the reaction of the related (bromodifluoromethyl)phos-phonium salt. ... 

A new route to optically active trialkylphosphine oxides, and hence phosphines, has been reported. The key step, the conversion of the optically active phos-phinite (4) to phosphine oxide, is extremely sensitive to the solvent mixture used, and even under the most favourable conditions involves considerable racemization. Small levels of optical activity (0—8 % enantiomeric excess) have been induced in the phosphine oxide product by hydrolysis of the phosphonium salt (5) under phase-transfer conditions using optically active quaternary ammonium salts as chiral catalysts. ... 

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