Acylation malonate magnesium salts

Acyl imidazolides are more reactive than esters but not as reactive as acyl halides. /1-K.cto esters are formed by reaction of magnesium salts of monoalkyl esters of malonic acid with imidazolides. 

An essentially neutral process for C-acylation relies on the reaction of imidazolides (542) with the magnesium salt (543) of a malonic acid half thiol ester (Scheme 119) (79AG(E)72>. The method requires slight modification when applied to an w-hydroxycarboxylic acid since a primary hydroxyl reacts with carbonyldiimidazole. The use of malonic acid half thiol esters in this fashion patterns the scheme proposed for carbon-carbon bond formation in the biosynthesis of fatty acids. 

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. ... 

C-Acylation. C-Acylation can be realized by treatment of acylimidazoles, derived from carboxylic acids and 1, with the magnesium salts of malonic esters prepared by using Bu2Mg. Acyl imidazoles can also undergo Claisen-type condensation with the dianion of -keto esters (eq 38). ... 

The preparation of diethyl benzoylmalonate (entry 12) represents the use of an acid anhydride, a function in which it is much more reactive than an ester, as the acylating agent. The reaction must be carried out in nonnucleophilic solvents to prevent solvolysis of the anhydride from competing with the desired reaction. Other limitations on the use of highly reactive acylating agents, such as acid anhydrides and acid chlorides, in reactions with enolates derive from the fact that O-acylation may be the dominant reaction. The magnesium salt of diethyl malonate (entries 12 and... 

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