Homologization of ketones with diazo compounds

Homologization of ketones with diazo compounds from oc Diketones... 

We have seen that the traditional Roskamp process and its stereoselective variants allow one to substitute a synthetically valuable unsubstituted or substituted alkoxy ethanoyl functicm in place of the formyl C-H bmid. The analogous homologation of ketone acceptors with stabilized diazo compounds promises to become a highly advantageous tool for the synthetic chemist. Unfortunately, since ketones are far less reactive than aldehydes, comparably fewer reports in this area are known that still meet the modem criteria of catalysis, high efficiency, and stereocontrol. 

Reaction of carbonyl compounds with aliphatic diazo compounds to deliver homologated ketones. 

Wolff rearrangement of /)-diazenyl-a -diazo ketone 83 in the presence of water, methanol (or even with primary and secondary amines) under varied reaction conditions comes with surprise Instead of the expected homologous acid 89, methyl ester 90 (or the respective amide), 2-phenylcinnolin-3(2E0-one (91) is the only product indicative of the anticipated in situ formation of ketene intermediate 88 (Scheme 22). Obviously, the apparent 67r-electrocyclization reaction prevails forming the isolated heterocyclic product 91, a so far unknown compound. 

Diazo compounds react with aldehydes and ketones to give homologated carbonyl compounds and epoxides. Lewis acids accelerate these processes, and in some cases direct the reactions to single products. frara-Epoxides result from aldehydes and ethyldiazoacetates in the presence of MeReOs (although this can occur via a metal carbene pathway rather than a Lewis acid mechanism) [139], whereas... 

The Wolff rearrangement of a-diazocarbonyl compounds (8.58, R = H, alkyl, aryl, OR) has great synthetic importance because in most cases the ketenes formed react smoothly with water, alcohols, and amines (Scheme 8-34). An early application that still has considerable importance is the homologization of carboxylic acids (Arndt-Eistert reaction Arndt and Eistert, 1935). As shown in Scheme 8-34, the reaction starts from the chloride of the acid RCOOH, which leads to an a-diazo ketone with diazomethane (R = H), followed by the Wolff rearrangement and the hydrolysis of the ketene intermediate to give the homologous carboxylic acid (8.59, R =H). In alcohols and amines esters (8.60) and amides (8.61, R = H), respectively. 

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