Work

Stereocontrolled synthesis of 3-hydroxy-2-piperidinone carboxamides by catalytic ring-opening aminolysis of bridged δ -lactam-γ-lactones

Year: 2025

Type: article

Abstract: The α-hydroxy-δ-valerolactam, 3-hydroxypiperidine, and piperidine-3-carboxamide topologies are resident in several natural products and pharmaceuticals, including anticonvulsant and antithrombotic agents. A modular and stereocontrolled strategy that merges these privileged scaffolds into one motif could facilitate the discovery of more small molecules with medicinal value. Here, we demonstrate that bridged valerolactam-butyrolactones can be skeletally remodelled to highly decorated 3-hydroxy-2-piperidinone carboxamides by catalytic and site-selective deconstructive aminolysis with primary and secondary amines. The products are obtained in a sterocontrolled manner following oxidative addition and concomitant trapping with the amine. The scaffold hopping proceeds with exclusive acyl C-O bond cleavage under palladium catalysis and represents the first catalytic method for activating the acyl C-O bonds of γ-lactones.

Source: RSC Advances

DOI: 10.1039/d5ra02161h

Authors: Timothy K. Beng, Katharyn Curry, Alan Gitonga, Keegan Yu, Samuel Edwards

Institution: Central Washington University

Language: English

Topic: Asymmetric Synthesis and Catalysis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $1,042

Funders: Central Washington University, School of Graduate Studies and Research, Central Washington University, Office of the Provost, Office of Undergraduate Research, College of Arts and Sciences, Washington University in St. Louis