Ketones Wittig reaction modification

Step 1 (3-keto phosphonates often are used for olefmation of ketones (Horner-Wadsworth-Emmons modification of the Wittig reaction). Steps 2 + 3 The cuprate-mediated 1,4-addition and subsequent Lemieux-Johnson oxidation of a vinyl group are excellent procedures for the introduction of the p-formyl group. 

Horner-Wadsworth-Emmons Reactions of Phosphonate Anions. - As with the Horner modification of the Wittig reaction, the principal focus of papers that mention the Horner-Wadsworth-Emmons reaction relate to synthetic applications. The use of pressure to induce the synthesis of P-amino esters, p-thioesters and P-thionitriles via tandem Horner-Wadsworth-Emmons and Michael reactions has been reported. The reagent (l-tritylimidazol-4-yl)methylphosphonate (99) has been prepared and, when treated with aldehydes and ketones, affords (E)-vinylimidazoles in high yields. ... 

In direct analogy to the Peterson methylenation, the triaryl- and trialkyl-stannylmethyllithiurn reagent (91) can be added to aldehydes and ketones (90), followed by elimination of the hydroxystannane (92) to obtain the methylene derivative (93 Scheme 20). This reaction, like the titanium and cerium modifications of the Peterson methylenation of Kaufmann and Johnson, may prove advantageous, in comparison to the Wittig reaction, for enolizible substrates. 

Because the Wittig reaction is so useful for the preparation of alkenes, chemists have explored several variations of it. One of the most useful of these, known as the Homer-Emmons-Wadsworth modification, uses a phosphonate ester derived from an a-haloester or a ketone to generate the Wittig carbanion. 

NaH stirred ca. 45 min. at 65-70° under Ng in excess dimethyl sulfoxide until Hg-evolution is complete, allowed to react with 1 equivalent of ethyl triphenyl-phosphonium bromide, then with 0.85 equivalent of benzophenone 1,1-di-phenyl-l-propene. Y 97.5%.—The reactivity of the methylsulfinyl carbanion (formed by reaction of NaH with dimethyl sulfoxide), which is even more basic than the trityl anion, is sufficient to convert phosphonium salts into ylides thereby permitting a simple and convenient modification of the Wittig reaction. E. J. Gorey and M. Ghaykowsky, Am. Soc. 8A, 866 (1962) / -diketones from carboxylic acid esters and ketones (s. Synth. Meth. 6, 737), sym. ) -diketones, s. J. J. Bloomfield, J. Org. Chem. 27, 2742 (1962). 

The synthetic utility of lithium salts of (l-methylthio)alkylphosphonate esters for the preparation of ketones is reported in an extension of the Wadsworth-Emmons-Horner modification of the Wittig reaction. ... 

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. 

A one-carbon homologation of aldehydes and ketones to carboxylic acids has been reported to involve the Horner-Emmons modification of the Wittig reaction using diethyl-/er/-butoxy(cyano)-methylphosphonate (EtO)2 P0CH(CN)0/-Bu to produce ethyl-/pr/-butoxyacrylonitriles. The /er/-butyl ether group is cleaved by zinc chloride in refluxing acetic anhydride, and the a-acetoxyacrylonitrile is converted to the acid by solvolysis. 

Wittig reactions, and various modifications thereof, convert aldehydes or ketones to alkenes, by one-pot double-bond formation. Chemo- and stereoselective versions of the reaction are available. 

Reactions of Thiophen Aldehydes and Ketones.— Thiophen aldehydes have been extensively used as components in the Wittig reaction. - - It was found that o-halogeno-substituted thiophen aldehydes with o-halogeno-substituted thenyltriphenylphosphonium salts gave especially high proportions of substituted cis-1,2-dithienylethenes, and also in the phospho-nate modification unusually much cis-isomer was found. Some oligomeric aa-unsymmetrically disubstituted dithienylenevinylenes (171) were pre-... 

Allyltin compounds can be prepared by simple modifications of the usual reaction involving allyl Grignard reagents (139), by the 1,4-addition of trialkyltin hydrides to 1,3-dienes 140,141), or by the reaction of an aldehyde or ketone with the appropriate, tin-carrying, Wittig reagents (142). 

Arylthallium bis(trifluoroacetate)s are converted by successive treatment with KF and BF3 into aryl fluorides.Thallium(iii) nitrate (TTN) readily oxidizes dialkyl sulphides and selenides to the corresponding sulphoxides or selenoxides, and 2-(alkylthio)-l-arylethanones (37) into compounds (38) in methanolic solution.In a modification of the TTN oxidative conversion of aryl alkyl ketones into arylacetic acids, enol ethers derived from the ketones are used instead of the ketones themselves. This reduces the formation of side products. Cyclic aralkyl ketones (39) may be ring-expanded and alkylated to give compounds (40) via treatment of their Wittig-derived alkenes with TTN/ an extrapolation of the basic reaction discovered previously. 

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