Olefination reactions Wadsworth-emmons reaction

Scheme 2.19 provides some examples of the Peterson olefination. The Peterson olefination has not been used as widely in synthesis as the Wittig and Wadsworth-Emmons reactions, but it has been used advantageously in the preparation of relatively... 

We have already seen the bishydroxylation using 0s04 and NMO this time lead tetraacetate is used to cleave the diol and yield the aldehyde. The phosphorane (Me0)2P(0)CHN2 is named the Gilbert-Seyferth reagent. 8 It basically behaves like the phosphoranes in the Horner-Wadsworth-Emmons reaction described above, except that the olefin subsequently loses nitrogen, creating the desired triple bond (also see Chapter 10). 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

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 stereostructure of the alkoxide intermediate of a Horner-Wadsworth-Emmons reaction which finally leads to the trans-o cim was recorded in Figure 9.14 (as formula A). The Still-Gennari variant of this reaction (Figure 9.15) must proceed via an alkoxide with the inverse stereostructure because an olefin with the opposite configuration is produced. According to Figure 9.16, this alkoxide is a 50 50 mixture of the enantiomers C and ent-C. Each of these enantiomers contributes equally to the formation of the finally obtained cw-configured acrylic ester D. 

All the carbons of the target were introduced by a Horner-Wadsworth-Emmons reaction of ent-427 with a-ethylacrolein, which gave a mixture of ( ) and (Z) olefins 437. The synthesis of the E) isomer of 437 constitutes a formal synthesis of coronafacic acid because its conversion to the natural product has been reported by Nara, Toshima, and Ichihara [90]. They reported that 437-E could be cyclized with base to hydrindenones 438 and 439 in 71 % yield. After purification, the major diastereomer 438 could be hydrolyzed to coronafacic acid in 95 % yield. 

The section begins with reports of two mechanistic studies relevant first to phosphate ester hydrolysis and secondly to an olefin-forming reaction akin to the Homer-Wadsworth-Emmons reaction but involving a spirooxyphosphoranyl... 

An added and valuable advantage found in this attractive and mild approach to dialkyl cyanoalkylphosphonates is the possibility of trapping the phosphonate carbanions in situ by reaction with an aldehyde or ketone when the desired product is the olefin resulting from the Homer-Wadsworth-Emmons reaction (Scheme 6.6). 

The unstable silyl ether in 232 was replaced by a more stable acetoxy ketone 233 which was not isolated. A Horner-Wadsworth-Emmons reaction was used for the Wittig-style olefination (chapter 15). A nitrile 234 replaced the carbonyl group in 230 as it was found easier to reduce nitriles in conjugative fashion. 

The Wadsworth-Emmons reaction of the aldehyde (190) with the complex phosphonate (191) has been used to construct the Cio-Cn double bond in a convergent synthesis of lacrimin A (192) (Scheme 27). Phosphonate-based olefination has been extensively used in the synthesis of cytohalasans (e.g. 193), a group of biologically active fungal metabolites. 12 The phosphonate (194) has been used to construct a triene function which ultimately forms the tricyclic structure through an intramolecular Diel s Alder reaction. 14,15-Dehydroforskolin (196) has been prepared by the base-induced reaction of the aldehyde (195) with dimethyl diazomethylphosphonate.l 13 Under certain conditions the phosphonate (197) can be isolated and this provides evidence for the involvement of the Wadsworth-Emmons intermediate (198) in the reaction. The phosphonate... 

A one-pot synthesis of 4-hydroxycyclopent-2-en-l-ones (150), involving (Z)-stereoselective olefination of a-diketones to give (149) followed by intramolecular aldol condensation, has been reported. Wadsworth-Emmons reactions of bis(2,2,2-trifluoroethyl)phosphono sulfoxides (151) with aromatic aldehydes give predominantly (Z)-a,p-unsaturated sulfoxides while similar reactions with the corresponding sulfides (152) give ( )- or lower (Z)-selectivity. In olefinations using (5)-dimethyl phosphorylmethyl p-tolyl sulfoxide (153) substantial racemisation at sulfur occurs when -butyllithium is used as base. ... 

A Wadsworth-Emmons reaction of the phosphonate (250) with the aldehyde (251) has been used as a key step in a total synthesis of analogues (252) and (253) of topostin B-1, an inhibitor of mammalian DNA topoisomerase The enzyme-catalysed aldol condensation between the phosphonate aldehyde (254) and dihydroxyacetone phosphate is followed by spontaneous intramolecular olefination of the product to give the cyclitol (256) in spite of the reaction being below pH 7 at all times.Attempts at a similar reaction of the homologue (255) were unsuccessful probably because (255) is a poor substrate for the aldolase. 

The Homer-Wadsworth-Emmons reaction is also a useful option for producing olefins in the solid phase. Supported stabilized phosphonoactates, as they are more acidic than phosphonium salts, can readily give the corresponding ylides with weak bases such as DBU, DIPEA, EtaN. One still has to make sure that these reaction conditions are chemoselective. Both types of reactions, Wittig and Homer-Wadsworth-Emmons, have been successfully used in cyclative and/or functionalizing cleavage. 

A new electron donor tetrathiafulvalene vinylogue (240) has been synthesized using both phosphonium ylide- and phosphonate-based olefinations (Scheme 20). 25 Both Wittig reactions and Wadsworth-Emmons reactions have also been applied to the synthesis of new vinylogous tetrathiafulvalenes, e.g. (243). from (241) and (242). 26... 

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