Methylenation, Wittig condensation

Wilkinson s catalyst 117,345,777 Wittig condensation 73 Wittig homologation 503 Wittig methylenation 649 Wittig reaction 17, 68 f., 86 f.,... 

The basic nature of methylenetriphenylphosphorane caused D-homoannulation of 17a-acetyloestr-4-en-17/3-ol (294) before effecting a Wittig condensation the mixed 17-methylene-D-homoandrostanes (295) were formed. When the 17/3-OH group was protected by acetylation, an intramolecular Claisen condensation occurred in polar solvents under Wittig conditions, giving the spiro-lactone (296) and a... 

Two six-membered necic acid lactones 46 (integerrinedc acid lactone) and 47 (senedc acid lactone) having an exo-a-methylene moiety were synthesized by Wiemer et al. [45] in the stereocontrolled Horner-Wittig condensation of the a-phosphonolactone 48 with acetaldehyde (Scheme 20). When KHMDS in acetonitrile was used as a base in this reaction, a 9 1 mixture of E and Z products was obtained from which the -isomer of integerrinecic acid lactone 46 was isolated in 77% yield. When K2C03/18-crown-6/toluene was employed in a parallel... 

Dehydro-PGEi (LXXXIV) has been synthesised by cyclisation with alkali of the diketone (LXXXV), prepared by condensation of 3-oxo-undecan-l,ll-dioic acid with styryl glyoxal, to give the cyclopentenone (LXXXVI), followed by Pappo-Allen oxidation to the aldehyde (LXXXVII), zinc-acetic acid reduction and Wittig condensation with n-hexanoyl-methylene triphenylphosphorane [154], The product was mixed with its 11-epimer which was separated chromatographically. 

Condensation of ester (44e) with the anion of malononitrile gave the alkene (44g) <91JPR35>. Oxadiazole (43e) and triethyl phosphite gave a methane phosphate which underwent a Wittig reation with aldehydes ArCHO to form alkenes (43f). When the alkyl side chain contained an active methylene group, as in (43g), reaction with arenediazonium salts ArN2X yielded arylhydrazones (43h) <88LA909>. 

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... 

Rotane was first synthesized by Rippol and Conia29. The key steps included the synthesis of dispirononanone 13 (equation 11). Condensation of 13 with formaldehyde provided the tetrahydroxymethyl derivative 32, which was converted into the tetraspiro compound 33 by tosylation-bromination followed by reductive cyclization. Subsequent Wittig methylenation and cyclopropanation of the ketone 33 completed the synthesis (equation 30). 

Quinazoline-4(3// )-thione condenses with ethyl bromocyanoacetate " and ethyl 2-chloro-3-oxobutanoate in the presence of sodium ethoxide in ethanol with sulfur extrusion to form ethyl 2-cyano-2-(quinazolin-4-ylidene)acetate (5, R = CN) and ethyl 2-(quinazolin-4-ylidene)-acetate (5, R = H), respectively. It has been suggested that the initial adduct of quinazoline-4(3//)-thione and a methylene compound is deprotonated to give the corresponding ylide which undergoes electrocyclic closure to a thiirane derivative and then desulfurization. A C - C double bond is formed between the methylene carbon atom and the electrophilic carbon C4, providing an alternative to the Wittig reaction. 

The reactivity of pyridazine-3- and 4-carbaldehydes towards active methylene reagents under the conditions of Knoevenagel, Wittig, and Hantzsch-type reactions has been examined. The 4-aldehyde reacts readily with malononitrile and methyl cyanoacetate, and less readily with triethyl phos-phonoacetate, indane-l,3-dione and alkyl acetoacetates/ammonia (e.g.. Scheme 52). Condensation with nitroethane is successful, but nitromethane gives an unstable intermediate which decomposes. The 3-aldehyde has similar reactivity to the 4-aldehyde, but some reactions are unsuccessful due to reduced reactivity, or instability of the products <90JHC1313>. 

Peterson Alkenation. Trimethylsilylmethyllithium (1) provides an alternative to a Wittig approach for the preparation of methylene compounds from carbonyl precursors. In some cases the use of (1) is superior to the Wittig approach. Condensation of (1) with a carbonyl compound results in the formation of a 8-hydroxysilane. Elimination to the alkene can be acconqtlished by use of acidic or basic conditions (eq 1). acetyl chloride or thionyl chloride can also be used to accomplish this elimination. A wide variety of aldehydes and ketones have been used as substrates in this reaction. The use of cerium(III) chloride has been advocated with reagent (1) to favor nucleophilic addition with enolizable carbonyl corrqtounds. The use of the lithium agent (1) gives superior yields compared to the use of trimethylsilylmethyl-magnesium chloride with cerium, ... 

The introduction of ring A was effected by crotonic condensation of the aldehyde (92) with 4-hydroxycyclohexanone, which led to a mixture of equal amounts of (96) and (97), these being separated by chromatography on alumina. The epimer (97) corresponding to the natural series was converted by the Wittig reaction into the corresponding methylene derivative (98), the isomerization of which on irradiation with UV light led to vitamin D3 (99) ... 

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... 

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