Methylenation Reactions

Oxazole, 2,5-dihydro-4-methoxy-synthesis, 6, 228 Oxazole, dihydro-2-methylene-reactions, 6, 215... 

Heterocyclic enamines A -pyrroline and A -piperideine are the precursors of compounds containing the pyrrolidine or piperidine rings in the molecule. Such compounds and their N-methylated analogs are believed to originate from arginine and lysine (291) by metabolic conversion. Under cellular conditions the proper reaction with an active methylene compound proceeds via an aldehyde ammonia, which is in equilibrium with other possible tautomeric forms. It is necessary to admit the involvement of the corresponding a-ketoacid (12,292) instead of an enamine. The a-ketoacid constitutes an intermediate state in the degradation of an amino acid to an aldehyde. a-Ketoacids or suitably substituted aromatic compounds may function as components in active methylene reactions (Scheme 17). 

Several phosphonodicarboxylates (59 R=Et X=H or Me) and the corresponding acids have been prepared by typical active methylene reactions during a study of the oxidation of... 

Methylenation reaction (typical procedure) A mixture of iodomethyl triphenylphosphonium iodide (0.530 g, 1.0 mmol), dibutyl telluride (0.242 g, 1.0 mmol) and p-bromoben-zaldehyde (0.096 g, 0.5 mmol) in THF (5 mL) is heated under reflux for 30 h, then cooled and filtered. The residue is purified by TLC, giving p-bromostyrene (0.080 g (87%)). 

These compounds come from methylenation reactions of the corresponding carbonyl derivative by means of an ylide. Several experimental conditions have been described. In most cases, CF2Br2 and HMPT (hexamethyl phosphorotriamide) are employed. The reaction occurs with aldehydes as well as with ketones in the furanose and pyranose series. The reaction can also be performed with lactones the fluoromethyl group is then introduced in the anomeric position. With these substrates, the Julia olefmation, which uses difluoromethyl sulfone, has also been reported to be an efficient method. Some examples of these reactions are shown in Figure 6.24. 

The methylenation reaction of ester gives vinyl ether. As shown in Scheme 12, the addition of TMEDA is necessary for the desired methylenation38. 

Treatment of 2,3-epoxyalkanol with bis(iodozincio)methane (3) gave homoallylic alcohol derivatives (equation 49). The formation can be explained via a pinacolone rearrangement followed by methylenation reaction (equation 50)74. The rearrangement is induced by the presence of bis(iodozincio)methane (3). 

The chief evidence for reaction (38) was that upon addition of 02 to a few millimeters pressure to the reaction mixture ethane formation was almost entirely eliminated whereas methane and ethylene formation were much less drastically reduced, the assumption being that 02 would suppress methyl reactions but not methylene reactions (see Sec. IV-C). 

With olefins two reactions occur (a) insertion in one of the carbon-hydrogen bonds, and (6) reaction at the double bond to give an episulfide. The insertion reaction is suppressed by addition of carbon dioxide as would be expected. In the case of singlet methylenes, reactions with the double bond are stereospecific while those of the triplet methylenes are not. Here Gunning and his coworkers found the sulfur atoms to behave differently and both singlet and triplet atoms reacted stereo-specifically with double bonds in olefins. 

VIS (methylene Reaction of sulfide, ferric chloride, blue method) and dimethyl-p-phenylenediamine to produce methylene blue, which has X at 660 nm. 

Table 8 shows the examples that have been prepared thus far. Ester formation, mediated by DCC and 4-DMAP proved to be routine. A large excess of the methylenating reagent was required for the methylenation reactions to be driven to completion. In all the cases, 35 to 40 mo % of the RCM catalyst 7 was needed to achieve complete reaction. It is noteworthy that the three-step protocol works quite well even when both groups to be cyclized are on the same side of the pyranose ring as in entry 3. No evidence of other cyclized products by TLC or NMR were noted in the crude reaction mixtures. 

Suitably constructed bridged carbenes exhibit a tendency for structural rearrange ment and undergo the so-called foiled methylene reaction 141 142) with formation of bicyclo[3.3.0]octane derivatives. The behavior of P6143) and 97144) exemplifies such conversions. Carbonium ion analogies to such reactions are known. ... 

For a review on the methylenation reaction with Tebbe s reagent, see H. U. Reissig, Org. Synth. Highlights, 1991, 192. 

Deacylative condensation a-methylenation Reaction of the carbanion of a-alkylated 8-keto esters with paraformaldehyde in THF at -78° initially and finally at reflux leads to -methylenated esters (equation I). 

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