Direct
catalytic alcoholysis of unactivated amides is one of the
most difficult challenges in organic chemistry, and an applicable
method for cleaving amides used as directing groups in regioselective
functionalization reactions has not been reported. Herein, we report
direct catalytic alcoholysis of 8-aminoquinoline amides, which are
highly effective directing groups in regioselective functionalization
reactions. The reactions proceeded with a simple combination of substrates,
air-stable catalysts, and alcohols, affording the corresponding esters
in good yields with broad functional group tolerance. Highly chemoselective
cleavage of the 8-aminoquinoline amides in the presence of related
carbonyl functionalities and preliminary mechanistic studies are also
described.
2-Acylimidazoles are widely used as post-transformable carboxylic acid equivalents in chemoselective and enantioselective reactions. Their transformations, however, require pretreatment with highly reactive, toxic methylating reagents to facilitate C−C bond cleavage. Here, we demonstrate that such pretreatment can be avoided and the C−C bond cleaved under neutral conditions without the use of additional reagents or catalysts. The scope of the reaction, including the use of products reported in the literature as substrates, and some mechanistic insights are described.
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