Magnesium dicarbonyl enolates

D. Reactions of Magnesium Dicarbonyl Enolates with Eiectrophiles... 

Although the antithyroid activity of compounds incorporating an enolizable thioamide function was discussed earlier, this activity was in fact first found in the pyrimidine series. The simplest compound to show this activity, methylthiouracil (80) (shown in both enol and keto forms), is prepared quite simply by condensation of ethyl acetoacetate with thiourea.Further work in this series shows that better activity was obtained by incorporation of a lipophilic side chain. Preparation of the required dicarbonyl compound starts with acylation of the magnesium enolate of the unsyrametrically esterified malonate, 81, with butyryl chlo-... 

Magnesium enolates derived from /S-dicarbonyl compounds can be easily obtained by metallation with l-PrMgBr. A stable cyclic chelate is obtained. As example, the magnesium enolate of mixed malonate is shown in equation 48. 

Base-catalyzed transformations can be carried out elsewhere on a complex molecule in the presence of such protected -dicarbonyl magnesium chelate. For example, the chelated magnesium enolate of a /3-ketoester such as 71 prevents the carbonyl keto group becoming an acceptor in aldol condensations. However, in the presence of excess of magnesium methanolate, exchange of the acetyl methyl protons can occur via a carbanion 72 stabilized by delocalization into the adjacent chelate system (equation 99). 

Synthesis of 1,3-dicarbonyl compounds by this approach requires the acylation of malonates or other simple 1,3-dicarbonyl compounds as a first step. Sodium or potassium enolates (58) acylate on oxygen but in the corresponding magnesium enolates (59) the oxygen atoms are chelated by the metal, leaving the carbon free to react. 

New syntheses of enamino-ketones by the ring-opening of isoxazoles with samarium di-iodide and with pentacarbonyliron, by the reaction of 2-alkyl-thiomethyl-3-alkylthioacrylophenones with amines, and by the intramolecular photoarylation of A -[2-(haloaryl)ethyl]-(3-enaminones, of enamino-diketones by the reaction of (3-chlorosulphonic acid chlorides with amines and by amino-methylenation of cyclic (3-dicarbonyl compounds, and of enamino-esters by aminomethylenation of esters and lactones and by the reaction of nitriles with magnesium enolates have been reported. 

Probably the oxophilic aluminum compound attacks the carbonyl groups to form 5, which is then reduced to enolate 7. As long as this enolate is not quenched by protonation, one could continue with other transformations in a molecule of this type without touching the 1,3-dicarbonyl moiety. As predicted, this type of enolate formation can also be exercised with magnesium as the countercation, and as an example one notices the dimerization of cyanoacetate to form the P-dicarbonyl system 10 [7]. 

Mechanistic studies indicate that the reaction proceeds via initial coordination of the 1,3-dicarbonyl compound to the magnesium center, acidifying the 2-proton. Deprotonation by the amine base results in a chiral magnesium enolate which ad diastereoselectively to the nitroalkene to set the new chiral center. 

---