Asymmetric phosphonium salts

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. 

K. Manabe, Asymmetric Phase-Transfer Alkylation Catalyzed by a Chiral Quaternary Phosphonium Salt with a Multiple Hydrogen-Bonding Site , Tetrahedron Lett. 1998, 39, 5807-5810. 

K. Manabe, Synthesis of Nobel Chiral Quaternary Phosphonium Salts with a Multiple Hydrogen-Bonding Site, and Their Application to Asymmetric Phase-Transfer Alkylation , Tetrahedron 1998, 54, 14465-14476. 

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). 

In summary, there are now several examples of phosphonium salt-based Lewis acids as catalysts known, which have shown a good catalytic activity. However, an asymmetric catalyzed reaction with an enantiopure phosphonium salt has not been reported yet. 

Cleavage reactions are best carried out in aqueous solution. In aprotic solvents, electrogenerated bases lead to the conversion of onium salts to the ylids which are not reducible [49]. The sequence of reactions shown in Scheme 5.2 shows that the bond cleavage process for phosphonium salts proceeds with retention of configuration around the phosphorus atom [50]. Retention of configuration at arsenic is also observed [51]. This electrochemical process is a route to asymmetric trisub-stituted phosphorus and arsenic centres. 

It must be pointed out than, in the case of phosphonium salts in which the phosphorus atom is a prochiral centre, attempted alkaline hydrolyses with asymmetric induction... 

Apart from these well-known catalysts, much effort has been expended in the synthesis and applications of chiral phase-transfer catalysts that include various quaternary ammonium salts, metal-salen complexes, phosphonium salts, and chiral amines. However, few of these catalysts have shown promising levels of asymmetric induction in asymmetric reactions. 

The asymmetric benzylation of 16 was promoted by phosphonium salt 12 in moderate yield with encouraging levels of enantioselectivity when the catalyst loading was as low as 0.20 mol % (Table 7.1, entry 3). Further, a low temperature improved the enantiomeric excess to 50% ee (entry 5). A low enantiomeric excess obtained using the phosphonium salt 13 (entry 6) suggested a critical role for two mandelamide units in the catalytic efficiency of phosphonium salt 12. Unfortunately, this reaction proved to be highly substrate-sensitive, and other alkylating agents or different ester substituents in 16 afforded low enantioselectivities. 

Ferrocenyl ligands, via zinc reagents, 9, 120 Ferrocenylmethyl phosphonium salts, with gold(I), 2, 274 Ferrocenylmonophosphine, in styrene asymmetric hydrosilylation, 10, 817 Ferrocenyl oxazolines, synthesis, 6, 202 Ferrocenylphosphines with chromium carbonyls, 5, 219 in 1,3-diene asymmetric hydrosilylation, 10, 824-826 preparation, 6, 197 various complexes, 6, 201 Ferrocenylselenolates, preparation, 6, 188 Ferrocenyl-substituted anthracenes, preparation, 6, 189 Ferrocenyl terpyridyl compounds, phenyl-spaced, preparation 6, 188 Ferrocifens... 

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). 

Interest in the chemistry of phosphines and phosphonium salts continues at a high level, and, as in previous years, considerable selection has been necessary in the preparation of this Report. A noticeable feature has been the large number of papers concerned with the preparation of chiral phosphines and their use in the homogeneous catalysis of asymmetric synthesis. Of these, only those involving some new aspect of organophosphorus chemistry are included here. 

The effects of temperature and cathode material and the use of aluminium electrodes on the electrolysis of phosphonium salts have been studied. Miscellaneous. Patent specifications have appeared for the convenient resolution of tertiary phosphines by complexation with the asymmetric palladium(n) complex (20). 

The strategy eluded to in Scheme 7.3.6 is elaborated upon in Scheme 8.10.3 and involves the allyl sugar derivative shown. Conversion of the allyl group to the phosphonium salt is accomplished in eight steps. Wittig olefination with the illustrated protected aldehyde provides the cis olefin which is dihydroxylated under asymmetric conditions and selectively protected as the PMB ether. 

The final strategy, eluded to in Scheme 7.3.8, further exemplifies the range of C-disaccharides available from a single polyol when utilizing different methods of cyclizations. As shown in Scheme 8.10.7, the easily prepared aldehyde is coupled to the phosphonium salt described in Scheme 8.10.3. The resulting cis olefin was asymmetrically dihydroxylated and the resulting diol... 

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. ... 

The respective fractions of the phosphomiim salt, v hen treated in aqueous solution with potassium iodide, yield an optically inactive iodide hence the asymmetric phosphonium compound has not been resolved. 

An all organic catalyst system 38 has been reported by the Maruoka group for directing asymmetric additions of oxindole enolates derived from 36 to nitro-aUcenes 37 under phase-transfer conditions [26] (Scheme 10). The methodology was extended to the synthesis of a tetrahydropyrroloindole scaffold bearing two chiral centers. Asymmetric Michael and Mannich reactions of 3-aryloxindoles directed by chiral phosphonium salt phase-transfer catalysts have been described by the same group [27]. 

For the synthesis of carotenoids labelled in the central part of the molecule, the C15 + C10 + C15 scheme [62] is used. The preparation of the labelled C 10-central units and the Ci5-end groups as phosphonium salts has been discussed in Sections B.1-B.3. From these synthons, symmetrical carotenoids are synthesized in a one-step procedure, asymmetrical carotenoids in a three-step procedure. By this procedure any carotenoid can be synthesized with C-labels in the central part of the molecule. The procedure is illustrated by the synthesis of the symmetrical carotenoids p,P-carotene (3) and astaxanthin (403) (Scheme 25) and an asymmetrical carotenoid, spheroidene (97) (Scheme 26). 

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