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 oxoammonium cation (TEMPO+) was used, followed enzymatic resolution corresponding alkoxyamino-2-piperidones with Candida antarctica lipase (CAL-B), yield title compounds in high enantiomeric excess (ee). The absolute configuration determined using chemical correlation and circular dichroism (CD) spectroscopy. former method highlights oxidative ring contraction trans-alkoxyamine-2-piperidone into its 2-pyrrolidinone.