Acetals, acid catalyzed from amides

The rhodium acetate complex catalyzed the intramolecular C-H insertion of (/ )-diazo-fR)-(phenylsulfonyl)acet-amides 359 derived from (f )-amino acids to afford in high yield the 6-benzenesulfonyl-3,3-dimethyl-7-phenyl-tetrahydro-pyrrolo[l,2-c]oxazol-5-one 360 (Equation 63) <2002JOC6582, 2005TL143>. 

The total synthesis of ( + )-Erysotramidine (2) has been described by Ito et al. (137) starting from the amide (174) (Scheme 39). After O-mesylation to 177, base-catalyzed reaction gave the cyclopropane derivative (178) which with zinc in acetic acid was reduced to 179, which was identical to the product (135) of O-methylation of 172. Conversion of 178 to the thioketal (180) was followed by reaction with phenylselenyl chloride. A mixture of two compounds, 181 and 182, was produced the former could be transformed quantitatively to the latter. Finally, treatment of 182 with silver nitrate in methanol gave 183, which was then desulfurized to yield erysotramidine (2). 

A drawback of all of these methods is that they produce racemic amino acids. If the product is to be used in place of a natural amino acid, it must first be resolved. This can be accomplished by the traditional method of preparing and separating diastereomeric salts. Alternatively, nature s help can be enlisted through the use of enzymes. In one method the racemic amino acid is converted to its amide by reaction with acetic anhydride. The racemic amide is then treated with a deacylase enzyme. This enzyme catalyzes the hydrolysis of the amide back to the amino acid. However, the enzyme reacts only with the amide of the naturally occurring L-amino acid. The L-amino acid is easily separated from the unhydrolyzed D-amide. The following equation illustrates the use of this process to resolve methionine ... 

A similar approach was described by Kim et al. <01MI1403> to build the Furstner synthon from the vinylogous amide 9, previously described, and the commercially available dimethyl aminomalonate hydrochloride as building block for pyrrole systems. The cyclocondensation reaction between the vinylogous amide 9 and dimethyl aminomalonate hydrochloride was performed in acetic acid at room temperature to yield the presumed Intermediate 12 via an acid-catalyzed nucleophilic substitution reaction. The mixture was then diluted with additional acetic acid and heated under reflux to facilitate the intramolecular ring closure and the loss of the methoxycarbonyl moiety to produce the desired pyrrole. Formation of lamellarin O dimethyl ether was achieved as in the Furstner approach <95JOC6637>. 

Table 19.2 gives examples of two reactions of acetic anhydride. In the first, the anhydride carbonyl is converted to the more stabilized carbonyl group of an ester in the second, a more stabilized amide carbonyl results. Hydrolysis under neutral or acid-catalyzed conditions yields two moles of a carboxylic acid per mole of anhydride, but, like hydrolysis of acyl chlorides is of little preparative value and is not included in the table. Likewise, hydrolysis in aqueous base according to the following equation is omitted from the table. 

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