Chan-Lam Coupling: Synthesis of N-alkylated Derivatives of ε-Caprolactams from Bicyclic Amidine DBU

The reactivity of bicyclic amidine 1,8-diazabicyclo[5.4.0]undec-8-ene (DBU) with phenyl boronic acid forming N-alkylated derivatives represents an advanced example to the existing classical Chan-Lam Cross Coupling of amines. The conversion of DBU to important heterocyclic scaffolds, in which DBU is acting as a nucleophile forming N-alkylated derivatives of epsilon-caprolactam is described. This copper-catalyzed reaction of DBU with phenylboronic acids represents a new paradigm of Chan-Lam amination. This type of transformation has opened up a new direction for the synthesis of 1-(3(phenyl amino) propyl)azepan-2-ones directly from the diimide, DBU in a single synthetic operation. The reaction was compatible with bicyclic amidines, 1,5-diazabicyclo-[4.3.0]non-5-ene (DBN) and 1,5,7 triazabicyclo[4.4.0]dec-5-ene (TBD), providing a robust system to access valuable bioactive epsilon-caprolactams.