An
operationally simple protocol has been discovered that couples
primary or secondary amines with N-aryl-substituted
lactams to deliver differentiated diamines in moderate to high yields.
The process allows for the partial reduction of a lactam in the presence
of Cp2ZrHCl (Schwartz’s reagent), followed by a
reductive amination between the resulting hemiaminal and primary or
secondary amine. These reactions can be telescoped in a one-pot fashion
to significantly simplify the operation. The scope of amines and substituted
lactams of various ring sizes was demonstrated through the formation
of a range of differentiated diamine products. Furthermore, this methodology
was expanded to include N-aryl pyrrolidinone substrates
with an enantiopure ester group at the 5-position, and α-amino
piperidinones were prepared with complete retention of stereochemical
information. The development of this chemistry has enabled the consideration
of lactams as useful synthons.
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