Due to the n_N-to-π*_C═O conjugation, the direct functionalization of unactivated amides via C−N activation is a longstanding challenge in functional group interconversion involving ubiquitous amide linkages. Herein, we report highly chemoselective esterification of unactivated tertiary amides with various equivalent oxygen nucleophiles, including both aliphatic alcohols and weakly nucleophilic phenols, for the first time. In this reaction, amide C−N bonds are electrophilically activated through cooperative acid/iodide catalysis via the selective formation of a highly reactive acyl iodide species. This powerful strategy enables the use of a stoichiometric quantity of O−H nucleophiles and provides the first general method for converting unactivated N,N-dialkyl amides into the corresponding esters with exquisite chemoselectivity. An exceptionally wide substrate scope of both amides and oxygen nucleophiles is demonstrated with high functional group tolerance, including the late-stage modification of some drugs’ amide derivatives and bioactive O−H nucleophiles (>100 examples). We anticipate that this powerful esterification of amides will find wide application in synthetic organic chemistry.

中文翻译：

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酸/碘化物协同催化通过亲电 N-C（O） 活化对未活化的叔酰胺进行高化学选择性酯化反应


由于 n_N 对 π*_C═O 偶联，通过 C-N 活化将未活化的酰胺直接官能化是涉及普遍酰胺键的官能团相互转化中长期存在的挑战。在此，我们首次报道了未活化的叔酰胺与各种等效亲氧试剂（包括脂肪醇和弱亲核酚）的高化学选择性酯化反应。在该反应中，酰胺 C-N 键通过选择性形成高反应性酰基碘化物物质，通过酸/碘化物协同催化进行亲电活化。这种强大的策略能够使用化学计量量的 O-H 亲核试剂，并提供了将未活化的 N，N-二烷基酰胺转化为具有出色化学选择性的相应酯的第一种通用方法。酰胺和氧亲核试剂的底物范围非常广泛，具有高官能团耐受性，包括一些药物的酰胺衍生物和生物活性 O-H 亲核试剂的后期修饰（>100 例子）。我们预计这种强大的酰胺酯化作用将在合成有机化学中得到广泛应用。