Horner-Wadsworth-Emmons olefination reaction

To start with the first option of such a chemoenzymatic process sequence, namely initial biotransformation and subsequent chemocatalytic or classical chemical reaction(s), an early example from the Gijsen and Wong [40] already in 1995 demonstrated a one-pot process for the synthesis of a cyclitol, which is based on an initial enzymatic aldol reaction of aldehyde 37 with 0-monophosphorylated dihy-droxyacetone, followed by a subsequent spontaneous cyclization via intramolecular Horner-Wadsworth-Emmons olefination reaction (Scheme 19.14). Furthermore, the resulting functionalized cyclopentene derivative 39 was deprotected in situ in the presence of an added phosphatase. By means of this one-pot three-step process, the desired trihydroxylated cyclopentene derivative 40 was formed, which was then further transformed via acetylation into the desired product 41 with an overall yield of 71%. A closely related process represents the combination of an enzymatic aldol reaction with a subsequent nitroaldol reaction (Henry reaction). Examples for such a type of process were developed independently by the Wong [41] and Lemaire [42] groups. 

Syntheses follow a kind of bio-mimetic approach [283, 284] in building up the chain during a sequence of Wittig-type reactions or Horner-Wadsworth-Emmons olefination, adding two carbons to the chain at a time with either methyl- or ethyl-branches. As the final products need to be highly pure (E)-stereoisomers, reaction steps and purification need to be carefully controlled. 

The enoates 17 were obtained in good yield and diastereoselectivity by subjecting the crude hydroformylation products 6 to Horner-Wadsworth-Emmons olefination conditions (HWE). Reaction of enoates 17 with dialkyl Gilman cuprates gave the anti 1,4-addition... 

Related reactions , Horner-Wadsworth-Emmons olefination - Still-Gennari modification, Julia-Lithgoe olefination, Peterson... 

Related reactions Horner-Wadsworth-Emmons olefination, Homer-Wadsworth-Emmons olefination - Still-Gennari modification, Julia-Lithgoe olefination, Takai-Utimoto olefination, Tebbe oiefination, Wittig reaction, Wittig reaction - Schiosser modification ... 

Related reactions Horner-Wadsworth-Emmons olefination, Horner-Wadsworth-Emmons oiefination - Stiii-Gennari modification,... 

Reaction with aldehydes or ketones (such as benzaldehyde) in the presence of base gave the olefination product 556 (in 84% yield).502 These variations have come to be called the Horner-Wadsworth-Emmons modiflcation of the Wittig reaction, or Horner-Wadsworth-Emmons olefination.503 It is sometimes called Horner-Emmons olefination. 

Burtoloso and coworkers have studied Arndt-Eistert reactions of a,p-unsaturated diazomethyl ketones, easily prepared by Horner-Wadsworth-Emmons olefination. This approach provided... 

HORNER - WADSWORTH - EMMONS Olelination Wittig type reaction of ptwsptionale stabilized carbanions with aldehydes or ketones to form olefins... 

This variation of the Wittig reaction uses ylides prepared from phosphonates.12 The Horner-Wadsworth-Emmons method has several advantages over the use of phosphoranes. These ylides are more reactive than the corresponding phosphoranes, especially when substituted with an electron withdrawing group. In addition the phosphorus product is a phosphate ester and soluble in water - unlike the Ph3PO product of the Wittig reaction - which makes it easy to separate from the olefin product. Phosphonates are also cheaper than phosphonium salts and can easily be prepared by the Arbuzov reaction from phosphanes and halides. 

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... 

At this point it should be noted, that olefination involving reaction of PO-stabilized carbanions like those from phosphonates, phosphinates, phosphine oxides, phos-phonamides or thiophosphonates (Horner reaction 47), Horner-Wadsworth-Emmons reaction48 ) with carbonyl compounds almost exclusively yields ( )-olefins. This olefination is essentially restricted to PO-activated compounds carrying stabilizing groups on the carbanionic C-atom. However, these compounds are more reactive than the corresponding resonance-stabilized ylides. Therefore, this olefination method... 

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. 

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