The transition metal catalyzed amide
bond forming reaction of esters
with amines has been developed as an advanced approach for overcoming
the shortcomings of traditional methods. The broad scope of substrates
in transition metal catalyzed amidations remains a challenge. Here,
a manganese(I)-catalyzed method for the direct synthesis of amides
from a various number of esters and amines is reported with unprecedented
substrate scope using a low catalyst loading. A wide range of aromatic,
aliphatic, and heterocyclic esters, even in fatty acid esters, reacted
with a diverse range of primary aryl amines, primary alkyl amines,
and secondary alkyl amines to form amides. It is noteworthy that this
approach provides the first example of the transition metal catalyzed
amide bond forming reaction from fatty acid esters and amines. The
acid–base mechanism for the manganese(I)-catalyzed direct amidation
of esters with amines was elucidated by DFT calculations.
An operationally simple method to employ non-activated carboxylic acids as alkylating agents in N-alkylation of heterocycles is reported through an electrochemically driven anodic decarboxylative process. A wide substrate scope across a range of heterocycles is demonstrated along with a series of applications that significantly reduce the step-count required to access such medicinally relevant structures.
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