Cleavage phosphonium salts

Preparation.—The hydroxyalkylphosphines (106) (obtained by the cleavage of THF or tetrahydropyran with lithium diorganophosphides) are converted in good yield into the cyclic phosphonium salts (107), (108) on treatment with hydrogen bromide followed by a weak base.108... 

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. 

The first three retrosynthetic cleavages are formation of the C7-C8 aldol by intramolecular chromium-Reformatsky reaction of linear precursor 51, esterification between northern and southern half building blocks and Wit-tig reaction of phosphonium salt 52 known from Mulzer s work [85] and northern half precursor 53. The final disconnections were placed at the C2-C3 aldol in 51 (again to be formed by chromium-Reformatsky reaction, here between bromoacetimide 56 and aldehyde 57) and the C14-C15 bond by alkylation of acetoacetate 54 with neryl bromide 55. 

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. 

The action of water on cyanines 8d for longer periods of time (with or without careful exclusion of oxygen) leads to 1,3-diefhyl-benzimidazolium-tetrafluoroborate 19. This corresponds to the hydrolytic cleavage of quaternary phosphonium salts. 

This result has been corroborated by numerous other examples43,593,597,601,608-614 and fits well with the classical mechanism described in Scheme 2. Only a few examples of second-order reactions are known they concern in particular the alkaline hydrolysis of phosphonium salts 29s 86,615 and 30616. In both cases, the second-order kinetics are very likely the result of a direct substitution induced by the very high stability of the carbanion resulting from the P—C bond cleavage. 

TABLE 18. Stereochemistry of alkaline hydrolysis of phosphonium salts with overcrowded residual group, depending on the facility of cleavage for the leaving group. 

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). 

The phosphonium salts undergo reductive cleavage by reaction 2142 ... 

Phosphonium salts can be dealkylated by treatment with alkoxides to yield alkanes. Although the hydrolytic cleavage of phosphonium salts in solution has been well investigated, the solid-phase variant of this reaction has not yet found broad application. One example, in which traceless linking was based on the alkoxide-induced dealkylation of a resin-bound phosphonium salt, is given in Table 3.48 (Entry 1). 

This reaction is only of limited synthetic utility, and has mainly been used to verify that metallations had indeed taken place [1-3], or for the regioselective introduction of deuterium or tritium into a molecule. The solvolysis of silanes, organogermanium compounds, and phosphonium salts to yield alkanes with simultaneous cleavage from the support is discussed in Section 3.16. 

Phenyl-substituted diphosphines, R2P(CH2) PR2, can also be cleaved by Na or Li in liquid ammonia or THF to yield MPhP(CH2) PPhM,M which are very useful starting materials for the production of unsymmetrical bidentate ligands PhRP(CH2) PRPh. However, care should be taken in these reactions as Ph—P cleavage is sometimes accompanied by P—CH2 fission. For the production of unsymmetrical bidentate phosphines, such as R2P(CH2) PPh2, stepwise formation of mono- and di-phosphonium salts provides a facile route (see Section 14.2.4). 

From the activation energy of 67 kJ/mol the author assumes that the dissociation of phosphonium salt-epoxide or phosphonium salt-anhydride complexes is the ratedetermining step of initiation because cleavage of a hydrogen bond and transfer of a proton to the epoxy or anhydride oxygen are assumed. 

Convenient alternatives to direct deprotonation of ethers are tin-lithium exchange [199, 258-261], halogen-magnesium exchange [262], or reductive cleavage of 0,Se-acetals [263, 264], Another synthetic equivalent of a-metalated ethers are (alkoxymethyl)phosphonium salts [265]. 

For the thioacetal cleavage in the second step (ia) a classical cerium(IV)-catalysed hydrolysis gives good yields ( > 85 %) with any phosphonium salts we have tested. Subsequent elimination of triphenylphosphine by reaction of the salts 5 with triethylami-ne was always nearly quantitative. 

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... 

The synthesis of chiral phosphines from resolved phosphonium salts or phosphine oxides is an intrinsically limited approach. The groups attached to phosphorus must be present prior to resolution and, furthermore, the preparation of phosphine oxides and phosphines from phosphonium salts by chemical or electrochemical cleavage reactions requires that one of the groups bonded to phosphorus be substantially easier to cleave than the other three. 

Annelation. Cleavage of l-(trimethylsilyloxy)-2-alkoxycarbonylcyclo-propanes (1) with KF-18-crown-6 generates y-oxo-a-ester enolate anions, which can be trapped by electrophiles. Trapping with a vinyl phosphonium salt results in [3 + 2] annelation to provide annelated cyclopentanones (2).1... 

By this method (Z)-monounsaturated fatty acids and esters could be obtained with an ( )-isomer content of less than 10% this stereoselectivity being however inferior to that of the commonly used acetylenic approach 55,56). However, the salt-free techniques used today in Wittig reactions allow (Z)-alkenoic acids to be synthesized with less than 2% of the ( )-isomers. Thus, Bestmann et al. prepared methyl and ethyl esters of (Z)-4,5,6,7,8,9,ll- and 13-alkenoic acids of different chain lengths 35,57 62), which served as intermediates in the synthesis of insect pheromones, both by reaction of co-alkoxycarbonyl-substituted alkyl-triphenyl-phosphonium salts with simple alkanals and of co-formylalkanoic esters with alkylidenephosphoranes. As the starting material for the synthesis of -substituted alkyl-phosphonium salts co-chloro- and -bromocarboxylic esters were used. The corresponding -substituted aldehydes can usually be obtained by ozone cleavage of suitable olefin derivatives or by oxidation of alkohols 57,58). 

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