Wittig ylides

Several steps are involved in these reactions. First, the enolate of the (1-kelocstcr opens the cyclopropane ring. The polarity of this process corresponds to that in the formal synthon B because the cyclopropyl carbons are electrophilic. The product of the ringopening step is a stabilized Wittig ylide, which can react with the ketone carbonyl to form the carbocyclic ring. 

Tetrakis(trifluoromethyl)-l,3-dithietanes react with nucleophiles to give products expected from monomeric bis(trifluoromethyl)thione. In fact, fluoride ion in DMF produces monomer (76BCJ2491), anilines give imines, and phenylhydrazine gives hydrazone (73BCJ3260). Triphenylphosphine gives a Wittig ylide that reacts with aldehydes to produce... 

The reaction with the Wittig ylide takes place under neutral conditions without the need for additional base. 

Benzylic, allylic, and propargylic alcohols can be oxidized by o-iodosylbenzoic acid (IBX) 7 in the presence of stabilized Wittig ylides to generate a>/3-unsaturated esters 30 in a one-pot procedure, Scheme 11. This is useful when the intermediate aldehydes are unstable and difficult to isolate [70]. 

It was shown <1999BML3255> that a crystalline ozonide obtained by ozonolysis of the A-allylamidc of Cbz-L-phenylalanine inhibits papain, a cysteine protease. Reduction of that ozonide in excess dimethyl sulfoxide (DMSO) generates in situ a peptide aldehyde, as proved by coupling with a stabilized Wittig ylide forming thereby an unsaturated ester. 

These last results combine the Wittig ylide chemistry with Brownes hydroboration reaction. We hope that a preparatively interesting ylide-borane chemistry will arise from this new "alloy". 

For C-extension in the (5/ )-hydroxyhexanal case it was found (58), that the pyranoid lactol form 41 is so stable that reaction with Wittig ylides cannot be effected under standard conditions. Thus, the acylic form had to be elaborated, which was effected by thioketalization, acetylation (41 - 43) and desulfurization, the resulting 5-O-blocked hexanal 44 then smoothly affording the olefin 45. Liberation of the hydroxyl function and ensuing lactonization... 

Wittig reactions of phosphonium fluorides in dipolar non-HBD solvents can be carried out without an additional base e.g. 4-nitrobenzaldehyde reacts slowly with (4-nitrobenzyl)triphenylphosphonium fluoride in refluxing acetonitrile to give 4,4 -nitro-stilbene in good yield (84 cmol/mol) [642], In this reaction, the fluoride ion attacks its own cation to give the corresponding Wittig ylide as intermediate. 

The HWE reaction can be carried out on a ketone, but often the stereoselectivity is not as good as the reaction of a substituted phosphonate carbanion with the corresponding aldehyde. Because of the greater reactivity of the phosphonate reagent relative to the phosphonium carbanion, the HWE reaction has proven to be effective with hindered ketones that were unreactive toward classical Wittig ylides. 

Diazomethylenephosphorane 21 can also be used as a synthetic equivalent of "naked carbon". Indeed, when a toluene solution of 21 was heated (70°C) in the presence of excess elemental sulfur, the chlorophosphine was obtained along with CS2 (88 % yield). Carbon disulfide formally results from the trapping of naked carbon by sulfur. However, it is quite clear that the first step of the reaction is the nucleophilic attack of the ylidic carbon at sulfur, as observed in the reaction of elemental sulfur with Wittig ylides. The transient adduct 22 could then eliminate the chlorophosphine, giving the thioxodiazomethane 23 which finally reacts with sulfur with loss of dinitrogen (Scheme 9). 

The reagent is prepared by treating the half-ester of maleic acid with triethyl phosphite and converting the product into the phosphonate carbanion by stirring with a slurry of 50% sodium hydride in 1,2-dimethoxyethane. The carbanion reacts with carbonyl compounds like a Wittig ylide but is more reactive. 

The general approach can be enlarged and conditions for condensation made milder by the use of further-activated esters, thus condensation with methyl nitroacetate produces 3-nitro-coumarins, condensations with Wittig ylides " allow orffto-hydroxyaryl ketones to be used ° and the use of diethyl malonate (or malonic acid ) (a 3-ester can be removed by hydrolysis and decarboxylation ), malononitrile, ethyl trifluo-roacetoacetate, or substituted acetonitriles in a Knoevenagel condensation, produces coumarins with a 3-ester, 3-trifluoroacetyl, " 3-cyano, or 3-alkyl or -aryl substituent. Condensation with IV-acetylglycine generates 3-acetylamino-coumarins. ... 

Fig. (3). Various Wittig ylide applied for the ulosonic acids synthesis.

Scheme 11 indicates the usefulness of salts derived from Wittig ylide reagents and anhydrides of perfluorocarboxylic acids in the synthesis of fluorinated alkenylphosphonic diesters (127), often together with (epoxyalkyl)phosphonic diesters (128)(Rf = CF3 or... 

Total synthesis is applied for carotenoids on a lO t scale per year. One usually starts with the cheapest carbonyl components (formaldehyde, acetone) and carbanions (acetylide, acetoacetate, cyanide, Wittig ylides) available. A typical industrial synthesis of retinol acetate (vitamin A) is outlined in Scheme 5.3,1. 

The second synthesis reported by the National Chemical Laboratories group, a two-step process with 89% overall yield, utilizes Wittig ylide generated in-situ from citraconimide with the corresponding aldehydes [80]. This is probably the simplest and most efficient synthesis reported to-date and requires simply refluxing the imide and triphenylphosphine in glacial acetic acid followed by hydrolysis of the resulting imide (Scheme... 

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