Phosphines phosphonium ylide synthesis

Review.1 This review covers use of phosphonium ylides, phosphoryl carbani-ons, and phosphine oxide carbanions in synthesis with particular emphasis on (Z)-and (E)-selectivities (558 references). 

The cyclohexanone (S3), an intermediate for the synthesis of thromboxane antagonists, has been prepared by a combination of phosphine oxide- and phosphonium ylide-based olefinations.30 Reaction of the lactone (50) with methoxymethyldiphenylphosphine oxide anion gave a poorly characterized adduct (presumably (51)) which on reduction with sodium borohydride, followed by treatment with sodium hydride gave the vinyl ether (52) in 80% overall yield from (SO) (Scheme 8). Further modification gave the required cyclohexanone (53). 

In addition to the synthetic routes described, tertiary phosphines react with miscellaneous compounds (epoxides, nitrilimines, sulfuranes, amidines) leading to phosphonium ylides. These reactions, however, seem not to represent generally applicable methods for the synthesis of phosphonium ylides. 

The Synthesis and Characterisation of Phosphonium Ylides. - Bertrand and co-workers have reported the instantaneous quantitative formation of phosphorus ylides (15) when stable phosphanylcarbenes are treated with phosphines (Scheme 1). Ylides (15) are very readily oxidised by atmospheric... 

The reaction is most often used for epoxide synthesis via methylene transfer. An important point concerns the difference in reactivity of sulfonium versus phosphonium ylides. The former gives three-membered rings the latter gives alkenes via the Wittig reaction. Thermodynamics is believed to account for a good deal of this difference the P+-0 bond in a phosphine oxide (BDE 544 kJ/mol) is much stronger than the S+-0 bond in DMSO (BDE for DMSO DMS + O 389 kJ/mol), which would form if the sulfonium ylide reaction resulted in an alkene. 

The employment of phosphorus-stabilized carbon nucleophiles for alkene synthesis was initiated by the discovery of the Wittig reaction [10], which provides a convenient method for the preparation of a wide variety of polysubstituted alkenes with complete positional selectivity and generally high levels of geometrical control. Moreover, the phosphonium ylides used in the Wittig reaction are readily formed by the addition of suitable bases to the corresponding phosphonium salts, which are commonly prepared by treating alkyl halides with phosphines. 

Allylic phosphonium ylides can also be generated in situ by the nucleophilic attack of phosphines on aziridines (or epoxides) followed by a set of proton transfers. On the basis of these reaction pathways, Hou et al. have realized a slightly E selective synthesis of conjugated dienes from aldehydes (or ketones) and aziridines (or epoxides) in the presence of tributylphosphine (Scheme 27) [122]. 

Compounds containing phosphorus can be both valuable synthetic intermediates and target compounds of solid-phase synthesis. Important synthetic intermediates include phosphonium salts and phosphorus ylides, which are key intermediates in carbonyl olefinations. Their preparation is discussed in Section 5.2.2.1. The preparation of oligonucleotides, these being the most important phosphorus-containing target molecules in solid-phase synthesis, is considered in Section 16.2. In this chapter, the preparation of phosphines, phosphonic acid derivatives, and phosphinic acid derivatives is discussed. 

Ethylene oxide or 1,2-epoxybutane may also be used for the synthesis of ylides. The resulting ylide is in equilibrium with its conjugated salt (equation 15). The use of ethylene oxide offers some advantages over more conventional bases used in Wittig reactions. The application is simple since ylides and most often also phosphonium salts (from phosphine and alkyl halide) need not to be prepared separately. The reaction medium is neutral, so that base-induced side reactions fail to appear. The method is however less applicable to weakly acid phosphonium salts, since deprotonation requires high temperatures (150 C). 

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