Thioamides enolates

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... 

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. 

If thioamide enolates are prepared by conjugate addition of Grignard reagents to a,/3-unsaturated thioamides of secondary amines, the reaction of these enolates with aldehydes affords anti aldols. These results are rationalized by the formation of a boat-like, chelate transition state" Representative examples are provided in equation 112 and Table 16. 

A nice example of the foregoing stratagem is seen in equation (17) enone (6) undergoes copper(I)-catalyzed reaction with vinylmagnesium bromide from its less-hindered face to give an enolate that reacts with formaldehyde from the opposite face to provide decalone (7), an intermediate in the synthesis of insect antifeedants. Yoshida and coworkers have used this method for the stereospecific generation of tetrasubstituted thioamide enolates, which undergo remarkably stereoselective aldol reactions (equation 18). ° The stereochemistry of this process is discussed in Section 1.6.3.6. 

Thioamide enolates may be prepared by conjugate addition of organometallics to a, -unsaturated thioamides. Reaction of these enolates with aldehydes affords anti aldols, often in excellent dia-stereomeric excess (equation 103 Table 15). It is believed that the conjugate addition reactions provide (Z)-enolates, via a cyclic, six-centered transition state. The anti stereochemistry observed in the aldol reactions of these (Z)-enolates would result from a boat-like, chelated transition state. The transition state has boat-like character to avoid a serious gauche interaction between R and the bulky secondary alkyl group in the thioamide enolate. Several of the intermediate enolates in this study e.g. Table 15,... 

Direct catalytic, intramolecular conjugate addition of a thioamide group to a,p-unsaturated ester moiety has been developed, (275) (276). The reaction is catalysed by a complex generated from (MeCN)CuPFg and (277) and is believed to proceed via the in situ catalytic deprotonation that generates the corresponding copper thioamide enolate, followed by conjugate addition/protonation to afford (276) in >20 1 dr and <93%... 

On the other hand, the cyclic form of a thioamide (enolic form) could be a possible candidate but was found to be extremely unstable in water, reacting like a Schiff base to give the open ring system. 

Oare, D.A., Henderson, M.A., Sanner, M.A., and Heathcock, C.H. (1990) Stereochemistry of the Michael addition of A(A-disubstituted amide and thioamide enolates to a, -unsaturated ketones. Journal of Organic Chemistry, 55,132-157. 

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