Wittig reaction aldehydes stabilized

Water has been illustrated as an efficient medium for the Wittig reaction employing stabilized ylides and aldehydes.63 It has been demonstrated that the solubility of the reagents and substrates is relatively unimportant, even though pronounced hydrophobic entities are present. 

Oxidative chain extension Reaction conditions for oxidation of alcohols to aldehydes and the Wittig reaction with. stabilized phosphonium ylides are compatible. Accordingly, three-carbon homologation of alcohols is feasible in one operation. Remarkably, the transformation is successful with unaetivated aleohols such as nonanol. 

This is a modified Wittig reaction of stabilized phosphonate carbaiuons with aldehydes or ketones [110,111]. Various examples for the preparation of such copolymers have been detailed [109]. 

The Horner-Wadsworth-Emmons reaction (or HWE reaction) is the reaction of stabilized phosphonate carbanions with aldehydes (or ketones) to produce predominantly -alkenes. In 1958, Horner published a modified Wittig reaction using phosphonate-stabilized carbanions [32]. Wadsworth and Emmons further defined the reaction [33]. Compared to phosphonium ylides used in the Wittig reaction, phosphonate-stabilized carbanions are more nucleophilic and more basic. Likewise, phosphonate-stabilized carbanions can be alkylated, unlike phosphonium ylides. The dialkylphosphate salt by-product is easily removed by aqueous extradion. A reliable and versatile synthesis of a stilbene derivative, 2,2-aryl-substituted cinnamic acid esters, using the Wittig reaction was reported [34—36] (Figure 1.3). 

Dambacher, J., Zhao, W., El-Batta, A., Anness, R., Jiang, C. and Bergdahl, M., Water is an efficient medium for Wittig reactions employing stabilized ylides and aldehydes. Tetrahedron Lett., 2005, 46, 4473-4477. 

Bergdahl and coworkers have reported the successful use of on water conditions for Wittig reactions of stabilized ylides. Although the protic stabUity of stabilized ylides is well known, these types of Wittig reactions are generally carried out in aprotic solvents. The authors describe a number of examples where rate acceleration is apparent in reactions carried out in water. For instance, the olefination of aldehyde 55 was reported to be unsuccessful in organic solvents (Fig. 11.18) on the other hand, the reaction in water afforded a 67% yield of a,-unsaturated ester 56. 

Sinou et al. have developed a Wittig reaction of stabilized perfluorinated phos-phonium ylides with aldehydes performed in a perfluorosolvent. This protocol allows an easy separation of the alkene product from the perfluorinated phosphine oxide byproduct by simple liquid-liquid extraction [149]. 

An important complement to the Wittig reaction is the reaction of phosphonate carbanions with carbonyl compounds.151 The alkylphosphonate esters are made by the reaction of an alkyl halide, preferably primary, with a phosphite ester. Phosphonate carbanions are more nucleophilic than an analogous ylide, and even when R is a carbanion-stabilizing substituent, they react readily with aldehydes and ketones to give alkenes. Phosphonate carbanions are generated by treating alkylphosphonate esters with bases such as sodium hydride, w-butyllithium, or sodium ethoxide. Alumina coated with KF or KOH has also found use as the base.152... 

With the fully functionalized heterocyclic core completed, synthetic attention next focused on introduction of the 3,5-dihydroxyheptanoic acid side-chain. This required initial conversion of the ethyl ester of 35 to the corresponding aldehyde through a two-step reduction/oxidation sequence. In that event, a low-temperature DIBAL reduction of 35 provided primary alcohol 36, which was then oxidized to aldehyde 37 with TRAP. Subsequent installation of the carbon backbone of the side-chain was accomplished using a Wittig olefination reaction with stabilized phosphonium ylide 38 resulting in exclusive formation of the desired -olefin 39. The synthesis of phosphonium ylide 38 will be examined in Scheme 12.5 (Konoike and Araki, 1994). 

Wittig reactions with pyrrole-2-aldehyde led to the esters (79) which were cyclisized to 3a-azaazulen-4-ones (80).104,105 4-Methylene-3a-aza-azulenes (81) have been obtained from 80 with stabilized phos-phoranes.36 Reaction of dimethyl acetylenedicarboxylate with 81 could not be achieved. A similar cycloaddition was successful in the synthesis of cycl[3,3,3]azines (2) (Section V). 

The hemiacetal exists as an equilibrium mixture of cyclic compound 20 and its open counterpart (21), but an aldehyde addition reaction can occur only with the acyclic form A Wittig reaction of the stabilized ylide leads to an a. (3-unsaluraied ester that has the configuration with respect to the double bond. This reaction occurs under neutral conditions, so 1,4-addition of the alcohol to the a.p-unsaturated ester is avoided.6 A subsequent DIBAH reduction leads to ally lie alcohol 6 in a reaction that ordinarily shows complete 1,2-selectivit. ... 

Bringing together the reaction mixture, resulting from the oxidation of an alcohol with TPAP, with a solution containing a non-stabilized phosphorous ylide allows to perform a Wittig reaction with no need to isolate an intermediate aldehyde. 

It is possible to carry out an in situ Wittig reaction with a stabilized phosphorous ylide and an aldehyde obtained by a BaMnC>4 oxidation of a primary benzylic or allylic alcohol.77... 

Selective reactions. Wittig reactions of 1 with an aldehyde are possible in the presence of keto, ester, and amino groups.2 Wittig reagents react under normal conditions with acid chlorides. The stabilized ylid I reacts preferentially with the acid chloride group of 4-lormylhcnzoyl chloride (2) lo give 3 as the major product. ... 

The Wittig Reaction allows the preparation of an alkene by the reaction of an aldehyde or ketone with the ylide generated from a phosphonium salt. The geometry of the resulting alkene depends on the reactivity of the ylide. If R is Ph, then ihe ylide is stabilized and is not as reactive as when R=alkyl. Stabilized ylides give ( )-alkenes whereas non-stabilized ylides lead to (Z)-alkenes. 

The primary alcohol is first oxidized to an aldehyde, which is then the substrate in a Wittig olefination reaction. Here a stabilized ylide is employed and therefore the E double bond is formed exclusively. (For a detailed description of the Wittig reaction see Chapter 13 the selectivity issues are explained in Chapter 9.)... 

With non-stabilized ylides ( R = H or Me) and numerous saturated or unsaturated aldehydes and ketones the Wittig reaction ( i ix) gives the corresponding dithianes 7 in good yields (70-93 %) The autoxidation of these ylides gives the expected products 8 and 9. The semi-stabilized ylides (R1= 0) react only with a reactive aldehyde. 

All P ylides for Wittig reactions are obtained by deprotonation of phosphonium salts. Depending on whether one wants to prepare a nonstabilized, a semistabilized, or a stabilized ylide, certain bases are especially suitable (see Table 11.1 an unusual, i.e., base-free, generation of ylides is described in Side Note 11.1). In stereogenic Wittig reactions with aldehydes, P ylides exhibit characteristic stereoselectivities. These depend mainly on whether the ylide involved is nonstabilized, semistabilized, or stabilized. This can also be seen in Table 11.1. 

The possibility of synthesizing pure (Z)-olefins by means of reactive salt-free ylides predestinates the (Z)-double bond at C-5 in e.g. 106 and 107 to be introduced into the corresponding aldehyde via the Wittig reaction. The ( )-configurated double bond at C-13 (105,106 and 107) with its vicinal hydroxy group was frequently formed by the phosphonate method (cf. Chapter 2). In some cases, however, it could also be obtained by ( )-selective Wittig olefination using resonance-stabilized phosphoranes. 

Among the fragrance and aroma substances a great variety of mono- and polyole-finic aliphatic alcohols, aldehydes, ketones, carboxylic acids, and their esters, as well as lactones are found 158). Of these aroma substances, (J5)-2-alkenals, ( )-2-alkenoic acids, ( )-2-alkenoic esters as well as (JS)-2-alken-l-ols are predestinated for the synthesis via the Wittig reaction because of the ( )-stereoselectivity of the olefination using resonance-stabilized ylides. 

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