Synthesis of Bulky <i>N</i>‐Acyl Heterocycles by DMAPO/Boc<sub>2</sub>O‐Mediated One‐Pot Direct <i>N</i>‐Acylation of Less Nucleophilic <i>N</i>‐Heterocycles with α‐Fully Substituted Carboxylic Acids
Atsushi Umehara, Soma Shimizu, Makoto Sasaki
Abstract
Abstract This report describes a general method for the one‐pot direct N ‐acylation of N ‐heterocycles using our previously developed 4‐( N , N ‐dimethylamino)pyridine N ‐oxide (DMAPO)/di‐ tert ‐butyl dicarbonate (Boc 2 O) system. This system enables one‐pot N ‐acylation reactions to provide bulky N ‐acyl heterocycles starting from a wide variety of less nucleophilic N ‐heterocycles and sterically hindered α‐fully substituted carboxylic acids in high yields. Moreover, this one‐pot method does not involve pre‐activation of substrates. The protocol has been successfully extended to one‐pot N ‐acylation of 7‐azaindoles.
Topics & Concepts
ChemistryAcylationNucleophileSteric effectsPyridineMedicinal chemistryOrganic chemistryCombinatorial chemistryCatalysisChemical Synthesis and AnalysisCatalytic C–H Functionalization MethodsSynthesis and Catalytic Reactions