Magnesium thioamide enolates

Thioamide enolates are also interesting substrates for the stereoselective aldol-type reactions. The aldol stereochemistry is very sensitive to the conditions of preparation of magnesium thioamide enolates and it generally gives different results depending on the procedure used. Illustrations of some aspects of the reactivity are provided in the examples presented below. 

With (Z)-amide enolates and (Z)-thioamide enolates a strong preference for sm-adducts is also observed. In general, boron or zirconium (Z)-enolates of ketones and amides display a higher simple diastereoselectivity in favor of syn-products than the corresponding lithium or magnesium enolates6,7. 

F. Reactions of Magnesium Thioesters and Thioamide Enolates with Electrophiles... 

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-... 

Thioamides of secondary amines are deprotonated with isopropyhnagnesium to give (Z)-enolates. Thioamides of primary amines react with two equivalents of /-PrMgBr to afford dianions that have been shown to have the (Z)-configuration. These magnesium species are versatile intermediates in stereoselective aldol reaction (equation 50, Table 5 ... 

TABLE 5. Stereochemistry of aldol reaction of magnesium enolates derived from thioamides with aldehydes... 

S, entries 1-9). The stereoisomer ratios observed seem to be kinetic, rather than thermodynamic, since the same yield and enantiomeric excess are observed at reaction times of 3 or 60 min (Table 25, entries 3 and 4). Stereoselectivity decreases as the size of increases (entries 1,2,3 and 6). Addition of HMPA has a deleterious effect on stereoselectivity. The magnesium enolate shows excellent diastereoselectivity. Again, stereoselectivity diminishes as the size of increases (Table 25, entries 10, 11, 14 and 16) and HMPA has a detrimental effect (entry 18). The analogous thioamide was prepared and studied, but it appears to offer no advantage over the oxoamide. ... 

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