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26.4.1.1.1.5 Variation 5: Nucleophilic Acylation of Carboxylic Acid Derivatives by Acyllithium ­Reagents

DOI: 10.1055/sos-SD-026-00532

Landais, Y.; Vincent, J. M.Science of Synthesis, (200526660.

The insertion reaction of carbon monoxide into a CLi bond generates an acyllithium intermediate that can then react with electrophiles to give the corresponding carbonyl derivatives.[‌43‌] This strategy has been used to prepare various symmetrical and unsymmetrical alkyl- and/or aryl-substituted 1,2-diketones in an efficient manner.[‌44‌,‌45‌] As described in Section 26.4.1.1.1, this method is of general use and leads to functionalized unsymmetrical 1,2-diketones in good yield, which can be extended to reactions on a large preparative scale. For the method to be of synthetic value, the acyllithium intermediate must be generated at very low temperatures (135 to 110°C). At such low temperatures, the reaction of organolithiums with carbon monoxide is generally much faster than the direct alkylation of the electrophile. Moreover, the reaction of the acyllithium is also faster than any other processes that might consume the acyllithium intermediate. Therefore, these reactions are generally carried out by mixing the organolithium and carbon monoxide in the presence of electrophilic substrates in the same vessel at very low temperatures. In the first protocol used for this reaction, carbon monoxide is bubbled through a solution of 2 equivalents of the ester (electrophile) in tetrahydrofuran/diethyl ether/pentane (4:4:1) and then 1 equivalent of organolithium reagent is added very slowly at 110°C. However in some cases byproducts resulting from the direct addition of the organolithium or the acyllithium to the electrophile appear in various amounts. Thus, a second protocol has been introduced that involves using a stoichiometric amount of the organolithium and the ester at 110°C in tetrahydrofuran/diethyl ether/pentane (4:4:1) (Scheme 17).[‌44‌] Still better yields of the 1,2-diketone 62 are obtained at 135°C by using the same organolithium/ester ratio but in dimethyl ether/tetrahydrofuran (3:1), which maintains the fluidity of the medium. The reactions have been carried out on a 10 millimole scale but have also been performed on a preparative scale thus providing 1,2-diketones 62 in good yield.

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References


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