Wittig methylenation formation

Combined uses of epoxide opening and the above-mentioned sequence involving ketone formation, Wittig methylenation and reduction was exploited by Lukacs to produce all possible stereoisomers of methyl 2,4-dideoxy-2,4-dimethyl hexopyranosides (key compounds of macrolide antibiotics syntheses). The sequence, illustrated in Scheme 11.25, utilized the altro derivative 7, which was transformed into a 3 1 mixture of 104 and 105 via olefin 103. 

The cycloadduct 113 was then transformed into y,3-unsaturated cyclohexenone 114, which was subjected to intramolecular [4 + 2] cycloaddition. Upon exposure to pyrrolidine in MeOH at 60°C, enone 114 afforded intramolecular Diels-Alder adduct 116 in 78% yield after chromatography. This seemed to be the result of initial reversible iminium formation via dehydrative condensation of pyrrolidine and enone 114. Under the reaction condition, isomerization of the transient iminium species to several distinct dienamine constitutional and stereoisomeric forms would occur. Among all possible isomers in dynamic equilibration, only dienamine 115 is conducive to a favorable intramolecular Diels-Alder transition state, resulting in ketone 116 after enamine hydrolysis. The final steps of the synthesis involved Wittig methylenation followed by... 

PhSSPh with retention/ or photochemically/ Methyl phenyl N-methyl-sulphoximide gives adducts with ketones after conversion into its carban-ion, from which either tertiary alcohols are obtained by Al-Hg reduction under neutral conditions, or alkenes by reduction in aqueous acid, thus providing an alternative to the Wittig methylenation reaction/ Oxosul-phonium ylides formed by N-dimethylation followed by carbanion formation with NaH are useful as alkylidene-transfer reagents/ Uses of sulphoximides in heterocyclic synthesis have been reported methyl phenyl sulphoximide reacts through N with ethoxymethylene malonate esters. ... 

Fluonnated ylides have also been prepared in such a way that fluonne is incorporated at the carhon P to the carbamonic carbon Vanous fluoroalkyl iodides were heated with tnphenylphosphine in the absence of solvent to form the necessary phosphonium salts Direct deprotonation with butyUithium or hthium dusopropy-lamide did not lead to yhde formation, rather, deprotonation was accomparued by loss of fluonde ion Flowever deprotonation with hydrated potassium carbonate in thoxane was successful and resulted in fluoroolefin yields of45-S0% [59] (equation 54) P-Fluorinated ylides may also be prepared by the reaction of an isopropyli-denetnphenylphosphine yhde with a perfluoroalkanoyl anhydnde The intermediate acyl phosphonium salt can undergo further reaction with methylene tnphenylphosphorane and phenyUithium to form a new yhde, which can then be used in a Wittig olefination procedure [60] (equation 55) or can react with a nucleophile [6/j such as an acetyhde to form a fluonnated enyne [62] (equation 56)... 

The Wittig reaction consists in the replacement of carbonyl oxygen of aldehydes and ketones by a methylene group with the aid of phosphine-methylenes resulting in the formation of cis or trans olefines. The reaction proceeds through the nucleophilic addition of Wittig reagent (phosphine methylene) across the > C = O bond and formation of an intermediate cyclic. 

The Wittig olefination of the tricyclic y-oxo ester 231f affords the 6-methylene tricycle 244. Treatment of the latter with diluted hydrochloric acid results in the formation of the 6-methyl-2-oxobicyclo[3.2.1]oct-6-ene derivative 240f in 94% yield (Scheme 70) [106,108]. This transformation maybe realized also in a one-pot procedure giving compound 240n in 70% yield (Scheme 70) [104b]. The overall yield in the step-by-step preparation of this compound, as shown in Schemes 65 and 68, was only 55% starting from the chloro ester 1-Me. 

Dormond ef rrZ. have exploited compounds 30 and particularly 32 as synthetically useful reagents. The uranium-mediated methylenation of carbonyl compounds (cf.. the Wittig, Peterson or Tebbe reactions) is illustrated in Equation (5.1). The instantaneous formation under ambient conditions of the insertion product 33 was essentially quantitative (e.g./ =... 

Vinylpyrroles and vinylindoles are extremely sensitive to acid-catalyzed dimerization and polymerization and it is significant that much of the early research was conducted on systems which were produced in situ. Even by this approach, the dimerization of, for example, 2-(3-indolyl)propene and l-(3-indolyl)-l-phenylethylene was difficult to prevent (see the formation of 110 and 120, Section 3.05.1.2.8). Similarly, although it is possible to isolate ethyl 2-(2- and 3-indolyl)propenoates, they appear to be extremely unstable at room temperature even in the absence of acid (81UP30500) to give [ 4 + 2] cycloadducts of the type (348) (cf. 77JCS(P1)1204>. For many years simple vinylpyrroles also eluded isolation, on account of their facile acid-catalyzed polymerization. Application of the Wittig reaction, however, permits the synthesis of vinyl-pyrroles and -indoles under relatively mild and neutral conditions (see Section 3.05.2.5). In contrast, heteroarylvinyl ketones, esters, nitriles and nitro compounds, obtained by condensation of the appropriate activated methylene compound with the heteroaryl aldehydes (see Section 3.05.2.5), are thermally stable and... 

Methylene trimethylarsorane (the term trimethylarsonium methylide is equally correct) had already been formulated in 1953 by Wittig and Torssell (104) who studied the reaction of tetramethylarsonium salts with organolithium compounds. Although this method cannot be used for the preparation of the salt-free material due to the strong complexation by the lithium cations, it is clear from reactions of the product mixture that the ylide is present in solution. The formation of arsonium salts upon addition of alkyl halides is a typical example ... 

In a paper edited in 1953, concerned with the preparation of the stereoisomeric forms of pentaphenylphosphorus, Wittig and GeiBler described the reaction of methylene-triphenylphosphorane 1 and benzophenone 2, forming 1,1-diphenylethylene 3 and triphenylphosphine oxide 4 (Scheme 1). Soon afterwards, it could be demonstrated that alkylidenephosphoranes (phosphine alkylenes, phosphorus ylides) generally react with carbonyl compounds such as aldehydes and ketones to give alkenes with the formation of phosphine oxide 1,2). 

The Wittig olefination of 1,5-oxazocine 416 with [(methoxy)methylene]triphenylphosphorane led to the formation of the enol ether 431a (88% yield) as an inseparable mixture of E and Z isomers (2.5 1 ratio). Instead, when the reaction was carried out using methyltriphenylphosphorane as Wittig reagent, the as 3,5-disubstituted diastereoisomer 431b was exclusively formed in 85% yield (Scheme 84) <1998JOC3492>. 

The reaction of diazomethane with zinc halides has been studied previously by several workers 70, 326, 475), and the formation of a zinc halide—methylene complex was suggested. Wittig and Schwarzen-bach 542) demonstrated the formation of iodomethylzinc iodide (I) and bis(iodomethyl)zinc (VIII) by the reaction of zinc iodide with diazomethane. The reaction of diazomethane with zinc chloride gives bis(chloro-methyl)zinc (IX) 544). 

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