Aldehydes methylene homologation

The acid portion of 1 was assembled by enantio-and diastereocontrolled addition of Z-crotyl borane to the aldehyde 8, following the Brown protocol. Hydroboration and oxidation led to 9, which was condensed with the allenyl silane 10 to give 11 with high diastereocontrol. Conversion of the alcohol to the iodide followed by three-carbon homologation by the Myers procedure then led to 1, which was cyclized with > 10 1 regio- and diasterocontrol to give 12. Ozonolysis and methylenation of the less hindered ketone then delivered 3. 

An apparently similar reaction to the Arndt-Eistert process is the homologization of aldehydes and ketones by diazomethane. In the lUPAC nomenclature of transformations (1989 c), both are methylene insertions, but the homologization of aldehydes and ketones does not involve a carbene or ketene intermediate. We discussed it therefore in Section 7.7 in the context of dediazoniations via diazonium ions and carbocations. It is worthwhile to draw attention to the early work of Wolff, as mentioned at the beginning of this section. He discussed in one of his early papers the striking fact that, in boiling water, diazoacetophenone yields the expected (at least at that time) product of a hydroxy-de-diazoniation, but, in the presence of silver... 

The slope of the regression of Int vs N at 20 C is steeper for aldehydes (1.0417) than for the acetates (1.0072). In principal all homologous series should have the same slope because all are incrementally increased by a methylene group, but this principal is only approximately true. Deviations of similar magnitude in slopes for different functional group series are also known in gas chromatography (20). 

Carbonylation of alcohols leads to the formation of aldehydes or alcohols containing one more methylene group compared to the starting alcohol, and therefore this reaction is called homologation reaction ... 

D. B. Ramachary, M. Kishor, K. Ramakumar, Tetrahedmn Lett. 2006, 47, 651-656. A novel and green protocol for two-carbon homologation a direct amino acid/KjCO -catalyzed four-component reaction of aldehydes, active methylenes, Hantzsch esters and alkyl halides. 

Saturated alcohols can also be hydroformylated, giving aldehydes or alcohols larger by one methylene group [306, 307]. The reaction has also been called Homologation [308]. The reaction rate of the alcohols decreases in the order tertiary, secondary, primary. Benzyl alcohol is very reactive. 

Flash vacuum pyrolysis of 4-methylene-5-oxo-4,5-dihydro-l,2-oxazoles (93) at 700—800 C gives terminal acetylenes in good yield, provided that (93) is volatile and stable at this temperature. Thus a range of heteroaromatic aldehydes can be converted into the corresponding homologous acetylenes by this route. 

By reacting 1,4-butane diol with paraformaldehyde in the presence of sulfuric acid at 150-180" , the seven-membered 1,3-dioxepane is prepared. With other aldehydes, homologous 2-alkyl-substituted 1,3-dioxepanes have also been prepared using a cationic ion exchange resin instead of sulfuric acid. This latter technique was introduced by Astle [42]. The dioxepanes have been converted to polymers in methylene dichloride or in 1,2-dichloro-ethylene. The initiator used was boron trifluoride etherate the reaction temperatures ranged from -10° to +10°. The reactions were carried out under anhydrous conditions by techniques suitable for reaction kinetics studies. The work indicated that, at least for this class of compounds, the polymerization propagation step involves linear alkoxycarbenium ions [47]. 

A new -arylethylamine synthesis by aryl aldehyde homologation has also been developed. A procedure has been found for the specific ortho alkylation of aromatic amines.A review of the use of quaternary ammonium compounds in organic synthesis has recently appeared. Mannich bases may be prepared regiospeclfically using the reaction of enol borates with dimethyl (methylene)-ammonium iodide. A very complete review of... 

Homologation of the aldehyde 13 and subsequent oxidation were straightforward, but subsequent methylenation of the hindered carbonyl was not. At last, it was found that Peterson olefination worked well. Metathesis then delivered the cyclopentene 2. The last carbons of the skeleton were added by intramolecular aldol cyclization of the thioester 16. 

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