Homologation of aldehydes and ketones

A convenient way of six-carbon homologation of aldehydes and ketones is the nucleophilic addition of the dianion generated from sorbic acid, (2 ,4 )-hexa-2,4-dienoic acid and subsequent dehydration to form the corresponding trienoic acid (equation 43)81. The 3-methyl analogue of sorbic acid has been used in a similar fashion for a short synthesis of vitamin A carboxylic acid (equation 44)82. 

Diethyl N-benzylideneaminomethylphosphonate (5) has been previously employed as an intermediate in the synthesis of B-lactam antibiotics6 and as a reagent for the homologation of aldehydes and ketones via intermediate 2-azadienesJ Other derivatives of dialkyl am1nom thylphoxphon t. s hav alio... 

Hoppe, D. Follmann, R. Homologization of aldehydes and ketones to fhiiranes or S-vinyl thiocarbamates via 2-alkylimino-l,3-oxafhio-lanes. Angew. Chem. Int. Ed. 1977, 36, 462-463. 

Homologation of aldehydes and ketones to thiiranes (3) and 1-alkenes (4). 2,2-Disubstituted thiiranes and 1-alkenes can be prepared from the hthio salt of (1) as formulated. This synthesis is not general for 2,3-disubstituted thiiranes or... 

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... 

A sequence of reactions has been described for the one-carbon homologation of aldehydes and ketones to carboxylic acids, esters, and amides through the initial formation of a-t-butoxyacrylonitriles (Scheme 42). ... 

A Wadsworth-Emmons type reaction of diethyl t-butoxy(cyano)methyl-phosphonate (1) has been used for the homologation of aldehydes and ketones to acids, esters, and amides (Scheme 2). Clearly, the method is limited to compounds which are reasonably stable to both heat and Lewis acids. In addition, ketonic precursors must have at least three a-protons. Inside these limits, good yields are obtained (57—88%). 

It is readily converted to trimethylsilylmethylmagnesium chloride (see [13170-43-9] above) in —90% yield. It reacts with n-BuLi in pentane to give trimethylsilylmethylLi [Sommer et al. J Am Chem Soc 71 2750 1949, which reacts with anhydrous cerium (III) chloride to form trimethylsilylmethyl cerium dichloride. The latter reacts with acyl hahdes to provide bis-p-silylethyl tertiary alcohols that effidently undergo a trimethylchlorosilane-promoted Peterson reaction to generate allylsilanes in high overall yields [Anderson Fuchs Synth Commun 17 621 7987]. It is useful also for Peterson olefination and homologation of aldehydes and ketones via 1,2-epoxysilanes [Lee et al. Tetrahedron 45 5877 7989]. Trimethylsilylmethyl bromide [18243-41-9] has M 167.1, b 115.5 /atm, 1.17, Up 1.444 [Beilstein 4 IV 3878], and trimethylsilylmethyl iodide [4206-67-1] has M 214.1, h 139-141 /atm, df 1.433, ng 1.491 [Beilstein 4 IV 3878], and both should be stored in the dark. 

Benzyl enol ethers may be prepared by homologation of aldehydes and ketones with the dianion of benzyloxyacetic acid [equation (3)]. ... 

Diethyl trimethylsilyloxycarbonylmethanephosphonate" and diethyl car-boxymethanephosphonate " are the preferred reagents for the two-carbon homologation of aldehydes and ketones to give a,/8-unsaturated carboxylic acids, while 2,2-difluoro-l-tosylvinyl-lithium is a novel effective reagent for the preparation of a-keto-acids from carbonyl compounds (Scheme 21). a-Methoxy-aliphatic acids have been prepared from aliphatic aldehydes and chloroform using... 

A one-carbon homologation of aldehydes and ketones to carboxylic acids has been reported to involve the Horner-Emmons modification of the Wittig reaction using diethyl-/er/-butoxy(cyano)-methylphosphonate (EtO)2 P0CH(CN)0/-Bu to produce ethyl-/pr/-butoxyacrylonitriles. The /er/-butyl ether group is cleaved by zinc chloride in refluxing acetic anhydride, and the a-acetoxyacrylonitrile is converted to the acid by solvolysis. 

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