Wittig with aldehydes, reactiv

Intermediates 18 and 19 are comparable in complexity and complementary in reactivity. Treatment of a solution of phosphonium iodide 19 in DMSO at 25 °C with several equivalents of sodium hydride produces a deep red phosphorous ylide which couples smoothly with aldehyde 18 to give cis alkene 17 accompanied by 20 % of the undesired trans olefin (see Scheme 6a). This reaction is an example of the familiar Wittig reaction,17 a most powerful carbon-carbon bond forming process in organic synthesis. 

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. 

This revised strategy demonstrates that a simple change in hydroxyl protecting groups can markedly influence reactivity and selectivity. While formation of the Wittig salt 51 could now be achieved at atmospheric pressure, its coupling with aldehyde 45 only proceeded in moderate yield and selectivity. 

The nature of the phosphorane used in Wittig reactions with aldehydes and ketones can have an influence on both the ease of the reaction and also its stereochemical outcome. For example, Bu3P=CHC02Me is generally more reactive than Ph3P=CHC02Me and a greater (E) selectivity is often observed with stabilized phosphoranes in which the a-carbon is alkylated. The stereocontrol of these... 

Wittig-Horner olefination. This reaction can be effected with LiCl (I equiv.) and either diisopropylethylamine or DBU (1 equiv.) in CH,CN at room temperature. This variation is particularly useful in reactions with aldehydes or phosphonates that can undergo epimerization or aldol-type reactions under standard conditions (NaH or K,CO,). Yields are usually >80%. The reaction also shows a high (E)-selectivity. Presumably a chelated lithium enolate of the phosphonate is the reactive species. 

N-vinylic phosphazenes react with isocyanates to yield N-vinylic carbodiim-ides. The reaction of isothiocyanates and an N = P moiety has been used to prepare oxazole derivatives The reactivity of the — N = P moiety in synthetic procedures has also been demonstrated by the aza-Wittig reaction with aldehydes " ... 

The methyl groups in 1,2,4-triazines are sufficiently CH acidic to react with aldehydes to give, after dehydration, the vinyl-1,2,4-triazines 8 in this reaction the 5-methyl group is the most reactive group.296-344 Vinyl-1,2,4-triazines arc also obtained by reaction of trichloromethyl-1,2,4-triazines with triphenylphosphane and subsequent Wittig reaction with aldehydes.291 298... 

A.iu. Phosphine Oxides and Phosphonate Esters. Many extensions of the Wittig reaction have been introduced that improve or modify the reactivity and/or stereoselectivity of the ylid. Horner et al. showed that a-lithiophosphine oxides such as that derived from 552 react with aldehydes or ketones to give a p-hydroxy phosphine oxide (553) as an isolable species. Subsequent treatment with base liberates the alkene, (554). Wadsworth and Emmons modified the Horner reaction to use phosphonate ester derivatives such as... 

This conclusion is in agreement with a remark of Lewis who stated that slower reacting systems tend to show a greater effect under microwave radiation than faster reacting ones [82]. In this way, during solvent-free Wittig olefination with phosphoranes, it was shown that the benefit of MW irradiation increases with less reactive systems. The best stabilized phosphoranes do not react at all in the solid state with aldehydes or ketones under conventional heating but necessitate MW irradiation [83]. 

The mixed phosphonium-iodonium ylides (Section 2.1.10.1), such as the tosylate 796, represent a useful class of reagents that combine in one molecule the synthetic advantages of a phosphonium ylide and an iodonium salt [1091-1100]. Specifically, phosphorane-derived phenyliodonium tosylate 796 reacts with soft nucleophiles, such as iodide, bromide, benzenesulfinate and thiophenolate anions, to form selectively the respective a-functionalized phosphonium ylides 797 (Scheme 3.315), which can be further converted into alkenes (e.g., 798) by the Wittig reaction with aldehydes [1092]. The analogous arsonium-iodonium ylides have a similar reactivity toward nucleophiles [1091, 1094, 1101]. 

In Wittig-type reactions with aldehydes and ketones, arsonium ylides have been shown to give either epoxides or alkenes or mixtures thereof (Scheme 3.88) [140]. However, the semi-stabihzed yHde 457 can be directed onto either pathway by tuning the basicity of the solvent [141]. In pure TH F, the epoxide 459 was formed, whereas in THF/HMPA mixtures the conjugated diene 461 was obtained. This complete switch was observed for a variety of aldehydes and ketones. Rationalization lies in the assumption of zwitterionic intermediates 458 and 460, which react via different conformations. Thus, the anti-conformer 458 is reactive in unipolar solvents, presumably via aggregate formation to give the epoxide, whereas in the presence of HMPA the monomeric species 460 is formed, which undergoes syn-elimination. 

The selective intermolecular addition of two different ketones or aldehydes can sometimes be achieved without protection of the enol, because different carbonyl compounds behave differently. For example, attempts to condense acetaldehyde with benzophenone fail. Only self-condensation of acetaldehyde is observed, because the carbonyl group of benzophenone is not sufficiently electrophilic. With acetone instead of benzophenone only fi-hydroxyketones are formed in good yield, if the aldehyde is slowly added to the basic ketone solution. Aldols are not produced. This result can be generalized in the following way aldehydes have more reactive carbonyl groups than ketones, but enolates from ketones have a more nucleophilic carbon atom than enolates from aldehydes (G. Wittig, 1968). 

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