Imides from acyl halides

Evans and Oppolzer s auxiliaries are of comparable efficacy with regard to chemical yields and the stereoselectivities they induce in the a-alkylation process. In some cases Oppolzer s imide enolates are superior because they give slightly higher stereoselectivities, the resultant a-branched iV-acylsultams are often more easily purified by simple crystallization, and the auxiliary is easier and cleaner to remove. For both auxiliaries, the iV-acylated derivatives required for alkylation are readily accessible by treatment of the deprotonated auxiliaries with the respective acyl halides or mixed anhy-drides , generated in situ from the free acid (or the sodium salt) and pivaloyl chloride in... 

Chiral oxazolidinone auxiliaries derived from D-xylose were applied by Koell et al. [156]. The oxazolidinones were acylated with various acid halides furnishing imides, which are substrates for a-alkylation reactions. For example, the butyric acid derivative 213 was deprotonated with LDA to give the (Z)-configured enolate 214, which was reacted with methyl iodide (Scheme 10.71). The methylated product 215 was formed in a moderate yield of 45% and a diastereomeric ratio of 7 1. The approach of the electrophile occurred from the less hindered /-face of the enolate... 

In 1982, Evans reported that the alkylation of oxazolidinone imides appeared to be superior to either oxazolines or prolinol amides from a practical standpoint, since they are significantly easier to cleave [83]. As shown in Scheme 3.17, enolate formation is at least 99% stereoselective for the Z(0)-enolate, which is chelated to the oxazolidinone carbonyl oxygen as shown. From this intermediate, approach of the electrophile is favored from the Si face to give the monoalkylated acyl oxazolidinone as shown. Table 3.6 lists several examples of this process. As can be seen from the last entry in the table, alkylation with unactivated alkyl halides is less efficient, and this low nucleophilicity is the primary weakness of this method. Following alkylation, the chiral auxiliary may be removed by lithium hydroxide or hydroperoxide hydrolysis [84], lithium benzyloxide transesterification, or LAH reduction [85]. Evans has used this methology in several total syntheses. One of the earliest was the Prelog-Djerassi lactone [86] and one of the more recent is ionomycin [87] (Figure 3.8). 

Imides are alkylated with alkyl halides at N only (112). The formation of N-alkylimides (113) by treatment of the lithium salts with alkyl chloroformates actually involves 0-acylation, which is followed by decarboxylative alkyl transfer from O to N. 

The chemical transformations of the carboxyl group include formation of halo[ C]acetyl halides, amides, imides, alcohols, aldehydes and amines. Methods for the preparation of halo[ " C]acetyl halides from [ " C]acetic acid have already been mentioned. In addition, chloro[ " C]acetyl chloride has become available through treatment of chloro[ C]acetic acid with thionyl chloride or phthaloyl chloride, whereas for bromo[ " C]acetyl chloride, thionyl chloride or phosphorus pentachloride is recommended. Numerous applications of halol Clacetyl halides have been published, out of which the following C-, N- and 0-acylations may illustrate their versatility. 

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