Homologation Aldehyd

Synthesis of a-Chiral and Homologated Aldehydes, Acids, and P-Chiral Alcohols. 

Synthesis of lower homolog aldehydes from o,0-unsaturated carboxamides (via Hofmann degradation)... 

In addition to hexadecanal, Cormier and Strehler (1953) discovered that homologous aldehydes, such as decanal and dodecanal, were also active in stimulating bacterial luminescence. Thus, they showed that bacterial luminescence requires a saturated long-chain aldehyde, but the specific aldehyde that is actually involved in the in vivo luminescence remained unknown for the next 20 years. 

Aldehydes.1 This Wittig-Horner reagent (available from Fluka) converts aldehydes or ketones into a,fi-unsaturated isocyanides, which can be hydrolyzed to the one-carbon homologated aldehyde. 

Formylation of an alkyl or aryl halide to the homologous aldehyde by transformation to the corresponding organometallic reagent then addition of DMF (M = Li, Mg, Na, and K). 

Similarly, 1,1-dibromoalkanes can be prepared from lithium diphenyltelluromethane, whereas homologated aldehydes are obtained via iodination (probably through the hydrolysis of an intermediate diiodide). ... 

A procedure for converting an aldehyde or ketone RR CO to the homologous aldehyde RR CHCHO consists of treating the substrate with lithium bis(ethylenedioxyboryl)methide, followed by oxidation with aqueous H2O2 602... 

Brambilla. G. Sciaba. L.. Faggin, P, Maura, A., Marinari. U.M., Ferro. M. Esterbauer. H. (1986) Cytotoxicity. DNA fragmentation and sister-chromatid exchange in Chinese hamster ovary cells exposed to the lipid peroxidation product 4-hydroxynonenal and homologous aldehydes. Mutat. Res.. 171. 169-176... 

Aldehyde synthesis.1 Hindered ketones, which do not react with methoxy-iiietliylenetriphenylphosphoranc (I, 671), do react with 1 to form an enol ether, which is readily hydrolyzed by acid to the homologous aldehyde. Representative aldehydes (and the yield) available by this method are formulated. 

Few examples of the Prins reaction of homologous aldehydes and ketones are known.73,74 Acetaldehyde was shown to react smoothly with isobutylene under mild conditions, whereas other, less substituted alkenes were found to be very unreactive.73... 

The oxidative effects of silver(II) complexes of pyridine carboxylates have been studied for a variety of substrates. With ar-amino acids, a rapid reaction occurred at 70 °C in aqueous solution with bis(pyridyl-2-carboxylato)silver(II). 4 The product was the next lower homologous aldehyde and yields were generally greater than 80%. Other substrates included primary and secondary amines, alcohols, monosaccharide derivatives, alkenes, arylalkanes and arylalkanols.90 Only minor differences were detected in efficiencies when 2-, 3- or 4-mono-, or 2,3-di-carboxylates were used as the oxidant. 

Aldehydes from alkylhoronic esters, RB(OR1)2. This reagent reacts with al-kylboronic esters (2) to provide an ate complex (a). Addition of HgCl2 induces alkyl migration from boron to carbon to give 3, which is oxidized to a homologated aldehyde 4.1... 

Further transformations of the intermediate alkenyloxydialkylboranes (46), as shown in Scheme 10, include aqueous hydrolysis to the homologated aldehydes or ketones 30 electrophilic additions to afford the corresponding a-dialkylaminomethyl aldehydes and ketones (47),31 and a-halogenated (48)32 or a-arylselenylated aldehydes or ketones (49) 33 transmetallation-alkylation to afford a-substituted aldehydes or ketones (50) 34 and aldol condensations with aldehydes (51).35 These reagents offer the equivalent of the tandem 1,4-conjugate addition-electrophile-trapping protocol. A prototypical prosta-... 

Detection and Determination of the Aldehydes.—The aldehydes present in spirits are mainly acetaldehyde, paraldehyde, formaldehyde, acetal and, in small quantities, higher homologous aldehydes (butyral-dehyde, valeraldehyde) and other aldehydes (acraldehyde, furfuraldehyde, etc.). They are detected and determined as follows ... 

Homologated aldehydes.1 The anion of the reagent converts carbonyl compounds into the I I IP cnol other of onc-carbon homologated aldehydes (equation I). 

Cometto-Muniz, J.E., Cain, W.S. and Abraham, M.H. (1998) Nasal pungency and odor of homologous aldehydes and carboxylic adds. Experimental Brain Research, 118, 180-8. 

Although reaction of organozirconocene compounds fails with most organic electrophiles, treatment with sterically unhindered isocyanides, such as rcBuNC, is possible." Organometallic species 24 attacks nBuNC 25 to give isocyanide-insertion product 26, which is finally hydrolyzed to the one-carbon homologated aldehyde 6. 

Enamines are highly valued intermediates in organic synthesis. Almost invariably they are prepared by reaction of a carbonyl compound with a secondary amine. In principle, another attractive route to enamines could be based on construction of the double bond by a Wittig- or Horner-Wittig reaction. The enamines J thus obtained could be easily converted into the corresponding homologous aldehydes, if desired fitted with an extra electrophilic substituent at the original carbonyl carbon atom. 

The ylide reacts with aldehydes in THF to form epoxides (2) or in THF/HMPA to form phenylthioenol ethers (3).1 The former products rearrange readily to o-phenyl-thio ketones, the latter to homologated aldehydes. 

Formally the reactions amount to an a-formylation of styrene. The homologous aldehyde may be prepared from propenylben-zene.10 ... 

One-carbon homologation. The products 3) obtained by reaction of 2 with alkyl halides can be converted under mild conditions lo one-carbon homologated aldehydes, carboxylic acids, or enol methyl ethers. 

Hydroformylation. Rhodium catalysts are generally preferred to cobalt catalysts by industry for hydroformylation of alkenes to give the homologous aldehydes because of the former s greater activity and higher regioselectivity. ... 

Considering the homologation of alcohols, the reaction can be directed to the selective formation of the homologous aldehyde. 

Homologated aldehydes. Unlike diethyl methoxymethylphosphonate, (C2H50)2P(0)CH20CH3, which does not undergo Wittig-Horner reactions, the anion of 1 reacts readily with both aldehydes and ketones to give 1,2-adducts (2) in... 

Aldehydes. The reagent can serve as a formyl anion equivalent, which is unmasked by thermolysis. An example of the use of 1 for conversion of an alkyl halide into the corresponding homologous aldehyde is shown in equation (1). 

Synthesis of aldehydes and ketones. This substance can function as a protected cyanohydrin of formaldehyde in an extension of Stork and Maldonado s synthesis of ketones from aldehydes, RCHO —> RCOR, by way of cyanohydrins (4, 300-301). Thus the anion of 1, generated with LDA, does not undergo self-condensation, but can be alkylated the product on hydrolysis gives the homologous aldehyde of the alkyl halide. Thus the reagent serves as the latent anion of formaldehyde, HC=0. An example is shown in equation (I). 

Since enamines are readily hydrolyzed by dilute acid, this sequence can be used for synthesis of homologous aldehydes. 

It is also worthwhile to add that the versatility of the Wittig reaction suggested entirely new opportunities for the synthetic utilization of carbonyl compounds. Thus, the employment of methoxymethylenephosphorane 83 (easily prepared from chloromethyl ether) as the ylide component represents a standard protocol for the transformation of aldehydes or ketones into homologous aldehydes 84, via the intermediate formation of enol ether 84a. 

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