C-acylation of active methylene compounds

C-Acylation. C-Acylation of active methylene compounds is usually conducted under basic conditions. Masamune et al. have developed a new method for conducting this reaction under neutral conditions that is patterned on the enzymic synthesis of fatty acids. The acylating reagent is the imidazolide of a carboxylic acid (1) prepared in situ. The substrate is the neutral magnesium salt of a mono ester or thioester of a malonic acid (2), prepared with magnesium ethoxide. The reaction of 2 with 1 is conducted in THF at 25-35° for 18-24 hours the yield of products (3) is generally >85%. ... 

C-Acylation of Active Methylene Compounds. Treatment of an acylimidazole, derived from a carboxylic acid and (1), with the magnesium salt of a malonic or methyhnalonic half thiol ester results in C-acylation under neutral conditions (eq 7)7 The presence of secondary hydroxyl functionality in the carboxylic acid is tolerated, but primary alcohols require protection. Magnesium salts of malonic esters may be used equally effectively. Intramolecular C-acylation of ketones has also been reported. ... 

DEPC in combination with NEtj has proved to be a new efficient reagent for the direct C-formylation of active methylene compounds with carboxylic acids and also for the iV-acylation (peptide bond formation), 5-acylation (thioester formation) and O-acylation (esterification).4,5 Reaction of DEPC with carboxylic acids 11 in the presence of triethylamine produces transient acyl cyanides, which in the presence of alcohols or thiols results in the formation of the corresponding esters (12) or thioesters (13). 

The enolate ions of acetoacetic ester and other active methylene compounds react with 0-propiolactone to give the ethoxycarbonyl derivative, but the yields are generally not high. Application of this reaction to 2-ethoxycarbonyldodecanone (equation 53) has been recently patented, with the product reported to be a useful perfume intermediate (77JAP(K)77133952). The reaction is used quite widely with diketene, which gives C-acylation rather than alkylation of the enolate ion, followed by cyclization (72CPB1574). 

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