Asymmetric Synthesis of trans-3-Alkoxyamino-4-Oxygenated-2-Piperidones Mediated by Transition-Metal-Free Dual C-H Oxidation and Its CAL-B-Assisted Enzymatic Resolution

A general chemo-enzymatic approach to synthesize both enantioenriched trans-3-alkoxyamino-4-oxy-2-piperidones, which are important scaffold for various naturally occurring alkaloids, is reported. To this end, a selective transition-metal-free dual C−H oxidation of piperidines mediated by the TEMPO o...

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Bibliographic Details
Published in:Catalysts
Main Authors: Julio Romero-Ibañez, Marina A. Ortega-Rojas, Jonathan R. Valdéz-Camacho, Luis G. Hernández-Vázquez, Fernando Sartillo-Piscil, Jaime Escalante
Format: Text
Language:English
Published: Multidisciplinary Digital Publishing Institute 2023
Subjects:
trans -3-Alkoxyamino-4-oxygenated-2-piperidones
selective C−H oxidation
transition-metal-free
enzymatic resolution
CAL-B
deconstructive lactamization
alkaloids
Antarc*
Antarctica
Online Access:https://doi.org/10.3390/catal13040703
Description
Summary:A general chemo-enzymatic approach to synthesize both enantioenriched trans-3-alkoxyamino-4-oxy-2-piperidones, which are important scaffold for various naturally occurring alkaloids, is reported. To this end, a selective transition-metal-free dual C−H oxidation of piperidines mediated by the TEMPO oxoammonium cation (TEMPO+) was used, followed by enzymatic resolution of the corresponding alkoxyamino-2-piperidones with Candida antarctica lipase (CAL-B), to yield the title compounds in high enantiomeric excess (ee). The absolute configuration of both enantioenriched compounds was determined using chemical correlation and circular dichroism (CD) spectroscopy. The former method highlights the oxidative ring contraction of the trans-alkoxyamine-2-piperidone ring into its corresponding 2-pyrrolidinone.

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