Carbonyl-stabilized phosphonium ylides

Carbonyl-stabilized phosphorus ylides are less nucleophilic and hence do not react with (phosphine)gold(I) halides, but their gold(I) complexes can be generated from precursors such as [Au(acac)(PPh3)] or [AuCl(SC4Hg)] by reaction with phosphonium salts and ylides, respectively, and again both mono- and bis(yhde) complexes have been obtained (equation 48 and Scheme 8)206 207. The ylide carbon atoms in these complexes are centres of chirality, but no stereospecificity was observed in the coordination process and racemic mixtures are formed throughout. 

Related dinuclear complexes with carbonyl-stabilized phosphorus ylide ligands (6) are accessible from the reaction of the phosphonium chlorides [Ph2P(CH2C02R)2]Cl (R = Me, Et) with Ag2C03 (equation 6)18. The precipitation of AgCl is regarded as the driving force of these reactions. 

Phosphonium ylides form complexes with almost every metal of the periodic table [8-13]. The first ylide complexes involved carbonyl-stabilized ylides at Pd (II) and Pt(II) metal centers. One early example was reported by Amup and Baird in 1969 [61]. The scope of the ylide coordination chemistry was then extensively investigated by Schmidbaur [8]. 

Application of the Wittig reaction in the carbohydrate field is accompanied by certain difficulties. A correct choice of the initial sugar components is the main problem, owing to the basicity of phosphoranes and, especially, to the drastically basic conditions employed with phosphonium ylides (2a). It is not surprising, therefore, that protected (acetalated and aeetylated) aldehydo sugars and resonance-stabilized phosphoranes were used at first,3-5 although partially protected, and even unprotected, aldoses were shown to be amenable to the reaction with various resonance-stabilized phosphoranes, thanks to the presence of the carbonyl form in the mobile equilibrium. The latter reactions, however, are extremely complicated (see Section IV, p. 284). 

Sulfonium salts react in several ways. They may behave as a leaving group, undergoing substitution by a nucleophile or fragmenting with the formation of an alkene. However, the most important reaction of sulfonium salts involves the formation of an ylide in the presence of a base. The carbanion of this sulfur ylide is stabilized by the adjacent positively charged sulfonium ion. The reaction of the carbanion with a carbonyl group parallels that of a phosphonium ylide in the Wittig reaction. However, the decomposition of the intermediate dipolar species is different and leads to the formation of an epoxide (oxirane) rather than an alkene. 

Many Wittig reagents do not possess electron-withdrawing substituents on the carbanion carbon. Such alkyl-substituted phosphonium ylides are referred to as non-stabilized and react readily with carbonyl and other polar groups. Addition of the ylide to the carbonyl group takes place rapidly with aldehydes or ketones, both of which usually react equally well with these reagents. The number and nature of the alkyl substituents on the carbanion carbon normally has little influence on the extent of nucleophilic character of the phosphonium ylide. 

Intramolecular Wittig reactions can be used for the preparation of cyclic alkenes. The formation of the phosphonium ylide must be compatible with other functionality in the molecule and thus stabilized ylides are used most commonly. Wittig reactions with carbonyl groups other than aldehydes or ketones, such as carboxylic esters, are known. For example, a route to the indole or penem ring systems uses a carboxylic amide or a thioester respectively as the intramolecular electrophile (2.77). 

Formation of the C=C bond enables the couple carbonyl compound-ylide as a nucleophile. An electron pair of carbanions in phosphonium ylide forms one of two C=C bonds with the carbonyl C atom the second one is formed by an electron pair hidden in the P-C bond. Here a general scheme is presented for the reaction of carbonyl compounds with stabilized carbanions and ylides in the preparation of alkenes (Scheme 2.12). 

The new reagent (PhO)3PMe CF3S02 overcomes the problems associated with side-reactions in the Arbuzov reaction ROH displaces one PhO group and reacts with added nucleophiles to give products including ROR, RCN, RNCS, and RI. The phosphonium salt (84), derived by O-alkylation of a carbonyl-stabilized ylide, functions in a new synthesis of cyclohexenones, via (85), by condensation with a ketone. 

A very useful modification of the Wittig reaction involves the reaction of phosphonate-stabilized carbanions with aldehydes or ketones, which is known as the Homer-Wadsworth-Emmons (HWE) reaction [7, 151,152], This reaction was originally described by Homer et al. [153, 154] and further defined by Wadsworth and Emmons [155]. Phosphonate-stabilized carbanions are more nucleophilic and more basic than phosphonium ylides. They are prepared by the addition of suitable bases to the corresponding alkylphosphonates, which are readily accessible through the Michaelis-Arbuzov reaction of trialkyl phosphites with alkyl halides (usually a-halo carbonyl compounds) [143]. In contrast to the Wittig reaction, the HWE reaction yields phosphate salt byproducts that are water-soluble and hence are readily separated from the desired alkene products by simple extraction. 

Miscellaneous. The phosphonium salt (92) has been shown to be an excellent reagent for the carboalkenylation of carbonyl compounds. For example, the sodium enolate (93) and (92) give a cyclic product (94) which is thought to arise from a stabilized ylide by cyclization via an intramolecular Wittig reaction. 

Stabilized species in the phosphorus ylide category are normally generated in a two-step sequence beginning with the formation of the quaternary phosphonium salt. This is usually accomplished with ease by the reaction of triphenylphosphine with the appropriate haloalkane. Salt formation is followed by deprotonation at the carbon adjacent to phosphorus using an appropriate base to generate a zwitterionic species stabilized by the adjacent functionality (illustrated in equation 20). The resultant phosphorus species reacts with an introduced carbonyl compound to generate an intermediate oxaphosphatane that undergoes decomposition to produce alkene and phosphine oxide at relatively low temperatures (equation 21). 

The deprotonation of the phosphonium salt can be accomplished with NaOH because the electron pair of the conjugate base (carbanion of the ylide) is stabilized by resonance with the carbonyl group. 

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