An operationally simple protocol has been discovered that couples a primary or secondary amine with an N-aryl substituted lactam to deliver a differentiated diamine in high yield. The pathway 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. The conditions have been optimized, including the selection of compatible solvents and optimal temperatures for each reaction step, so that the reactions could 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 in high yields. Furthermore, this methodology has been applied to N-aryl pyrrolidinone substrates with an ester at the 5-position and α-amino piperidinones were obtained in a stereospecific manner. The development of this chemistry has enabled the consideration of amides as functional group handles instead of terminal moieties.

Utilization of cyclic amides as masked aldehyde equivalents in reductive amination reactions

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.