Thioamides aldol reaction, stereoselectivity

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 ... 

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. 

Iwata et al. also established the direct catalytic asymmetric aldol reaction of thioamides (Scheme 8.39)." Treatment of an aldehyde and thioamide 259 in the presence of the catalyst containing [Cu(MeCN)4]BF4, (7 ,/ )-Ph-BPE, and lithium phenoxide 260 gave (3-hydroxythioamide 261 in good yield with high stereoselectivity. Thioamide features the direct transformation into aldehyde by using a Schwarz reagent (Scheme 8.40)." They converted aldol adduct 261 into (3-siloxyal-dehyde 262, which was further submitted to the direct stereoselective aldol reaction. Both diastereomers 263 and 264 were obtained in good yield. This protocol is effective to synthesize sequential 1,3-polyols. 

The aldol condensation of benzaldehyde with the thioacetamide carbanion (RCHCSNRV), derived from the desilylation of the silyl-thioether with tetra-/i-buty-lammonium fluoride, is stereoselective at—80°C producing the erythro isomer of the p-hydroxy thioamide preferentially (Scheme 6.18, R = Me, erythro threo 95 5) via a conformationally mobile intermediate. However, when R is bulky, a greater amount of the threo isomer is formed. Predictably, as the reaction temperature is raised, so the stereoselectively decreases. This procedure contrasts with the corresponding condensation catalysed by titanium salts, where the complexed intermediate produces the threo isomer [47, 48],... 

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. 

---