Carbonyl compounds phosphonate anions

Olefination Reactions Involving Phosphonate Anions. An important complement to the Wittig reaction involves the reaction of phosphonate carbanions with carbonyl compounds 253 The alkylphosphonic acid esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are generated by treating alkylphosphonate esters with a base such as sodium hydride, n-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.254... 

Among the olefination reactions, those of phosphonium ylides, phosphonate anions, silylmethyl anions, and sulfone anions are discussed. This chapter also includes a section on conjugate addition of carbon nucleophiles to a, (J-unsaturated carbonyl compounds. The reactions in this chapter are among the most important and general of the carbon-carbon bond-forming reactions. 

Another example is the electrocatalytic reaction between aromatic carbonyl compounds and dialkyl phosphonates. Here, rearrangement of the product anion leads to a phosphate as the product [136]. 

Horner-Wadsworth-Emmons reactions are C—C-forming condensation reactions between the Li, Na, or K salt of a /J-keto- or an -(alkoxycarbonyl)phosphonic acid dialkyl ester and a carbonyl compound (cf. Figure 4.41). These reactions furnish a,f)-unsaturated ketones or a j8-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced fraus-selectively or in the case of olefins with trisubstituted C—C double bonds -selectively. 

The thiopyranyl phosphonate 323 has been isolated by other authors as a colorless solid, which in a few weeks turns to a brown viscous oil (80JOC2453). This behavior is due to the partial isomerization of 323 to the 2H isomer 325. Compound 323 has been lithiated by butyllithium in THF at -78°C. The 41/-lithiated species is a kinetically controlled product that equilibrates to the more staljle 2//-lithiated species even at -78°C. The 4H anion, as previously shown by Krivun and co-workers (73ZOB359), can react with carbonylic compounds, providing a convenient synthetic route to 4-alkylidene-2,6-diphenylthiopyrans (80JOC2453 81JHC627). 

The better defined participation of carbonyl radical anions is evident [56] in the electrocatalyzed reaction between aromatic carbonyl compounds (or other easily reduced carbonyl compounds) and dialkyl phosphonates (Scheme 18). In similar vein, and also in Scheme 18, radical anions generated from aromatic aldehydes may abstract a proton from an added acidic hydrocarbon such as fluorene (pXa22.6) or indene (pXa20.1), and the resulting carbanion adds to unreduced aldehyde. The chain reaction is propagated by protonation of the addition product by another molecule of hydrocarbon [57]. Reaction is by controlled potential coelectrolysis in THE, at the aldehyde reduction potential, and substantial yields are only obtained with 2,6-dichlorobenzaldehyde. 

Anions of a-silyl phosphonates of type (153) also undergo additions to carbonyl compounds. The corresponding addition products, 3-silyl alkoxides, can react with ketones to yield the product of the Peterson alkenation or the Wittig reaction. In practice only the Peterson product (154) is obtained, indicating that loss of OSiMes is faster than elimination of C PPhs (Scheme 68). 72 If the a-silyl carbanion is adjacent to a chlorine atom (155), an internal displacement reaction follows the initial formation of the -silyl alkoxide, and epoxides (156) are formed (Scheme 69). 74... 

Another variation of the Wittig reaction is the Wittig-Horner reaction, in which the anion generated ot- to phosphine oxide is used as a nucleophile to react with carbonyl compounds. The intermediate formed in this reaction, -hydroxyphosphine oxide, is isolable particularly when bases with lithium counterion are used for deprotonation. Since the j6-hydroxyphosphine oxides are diastereomers, they can be separated and subjected to elimination to form the corresponding alkenes. Since the elimination of phosphonate moiety is syn, stereospecific alkenes are obtained from the elimination step. As expected, the generation of erythro and threo isomers is dependent on the solvent and the reaction conditions. 

Wadsworth-Emmons olefination, or in brief, the Homer-Emmons reaction, a phosphonate carbanion 7, produced by deprotonating a phosphonate 8, reacts with a carbonyl compound 9 to give an olefin 10 and a dialkyl phosphate anion 11 (Scheme 2). 

Yet another way to obtain a 1 -monohalogenated alkylphosphonic diester is based on the application of the Wadsworth-Emmons adaptation of the Wittig reaction (Scheme 10). Here, the anion from tetraisopropyl (fluoromethyl)bisphosphonate reacts with a carbonyl compound to give the (l-fluoroalk-l-enyl)phosphonic esters 126 as an E-Z mixture (80-95 20-5) hydrogenolysis of these mixtures yields (l-fluoroalkyl)phosphonic esters. In a review of the literature the authors pointed out the widely different results experienced by other workers in their attempts to alkylate carbanions derived from fluorinated alkylphosphonic diesters and, as a result of their own work, advocated the use of alkyl triflates, which appear to react with lithiated carbanions very quickly and cleanly. 

The various steps in the overall sequence will here be considered individually, but only briefly, and no attempt will be made to indicate the scope of the WEH procedure which, as has already been indicated, has been widely reviewed. The aldol condensation which leads to the ions 154 is considered to be essentially reversible, a feature which has been observed in the reactions between diethyl (prop-2-enyl)phosphonate anion and aromatic aldehy-des Reversibility has also been demonstrated in a variety of other reactions that include crossover experiments, based on the system from benzaldehyde and 153 (Z = CN or COOMe) into which a more electrophilic aldehyde is added this results in the incorporation of the latter into products in such a way that the dissociation of the phospho-nate-benzaldehyde adduct must have occurred The addition of an aldehyde to a deuterium-labelled adduct in the presence of NaOEt-EtOH affords a mixture of labelled and unlabelled alkenes in the ratio of ca 1 1. The product (158) from the interaction of HO (Na2C03 in Et0H-H20) and a dialkyl (a-cyanoethenyl)phosphonate decomposes into the expected alkene, but also dissociates into a carbonyl compound together with a carbanion the latter can then be trapped by the addition of a different aldehyde or ketone (Scheme 30) ... 

Generation of Phosphorus Ylides and Phosphonate Anions. NaHMDS isthemostutiUzedbaseforthedeprotonation of a variety of phosphonium salts to generate the corresponding ylides, which then undergo Wittig reaction with a carbonyl compound. More recently, it was shown that such a base is compatible with a variety of other systems. For instance, it was shown that allenes and dienes could be prepared, respectively, from aromatic and alicyclic aldehydes when reacted with (Me2N)3P=CH2 in the presence of 4 equiv of NaHMDS and titanium trichloride iso-propoxide (eqs 30 and 31). ... 

The principle of the reaction is shown in Scheme 6 the phosphonate carbanion 25, produced by deprotonating the phosphonate 24, reacts with carbonyl compounds to give olefins 25 with elimination of the dialkyl phosphate anion 26. 

Demir et have reported the first, catalytic, intermolecular aldehyde-ketone (103) coupling with acyl phosphonate (102). The cyanide ion catalyzed formation of acyl anion from acyl phosphonates, which next reacted with activated carbonyl compounds to furnish products (104) in 41-95% yields after phosphorylation of the resulting oxyanion (Scheme 23). 

The possible role of the monoalkyl phosphonate anion [(R0)PH(0)0] as a proton acceptor from dialkyl H-phosphonate has also been discussed in the mechanism proposed by M. Kabachnik and E. Tsvetkov [175] for addition of dialkyl H-phosphonates to carbonyl compounds. 

Summary Carbonyl compounds readily react with phosphonate anions to give alkenes (Horner-Wadsworth-Emmons reaction)... 

In the Peterson reaction of an a-silyl carbanion bearing a phosphorus substituent on the anionic carbon atom, there are two possibilities for alkene formation, that is, the Peterson reaction to form phosphorus-substituted alkenes and the Wittig-Horner reaction and the Wadsworth-Emmons reaction to form silicon-substituted alkenes. Most of the reports on these competing reactions have been focused on the reactions of a-silyl phosphonates with carbonyl compounds. It is noteworthy that the alkenylphosphonates have been exclusively obtained in almost every case. That is, the Peterson reactions override the Wittig and Wadsworth-Emmons reactions. 

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