Switchable Regioselectivity in the Opening of Aziridine by Fluoride: DFT Calculation and Synthesis of Fluorinated Piperidines. Issue 43 (26th November 2019)

• Record Type: Journal Article
• Authors: Zou, Liangjing; Ruan, Yao; Jiang, Wei; Yan, Nan; Liu, De‐Yong; Yu, Chu‐Yi; Hu, Xiang‐Guo
• Is Part Of: ChemistrySelect. Volume 4:Issue 43(2019)
• Page Start: 12683
• Page End: 12688
• Publication Date: 2019-11-26
• Subjects: Aziridine -- Conformation -- Regioselectivity -- β-Fluoroamine -- 1, 3-allylic strain; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201903403
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: We have investigated the ring‐opening reaction of two pairs of aziridine‐containing piperidines by fluoride (TBAF). We find that the regioselectivities could be predicted according to the Fürst‐Platter rule and were switchable by the introducing or removing of the pseudo‐1, 3‐allylic strain through protecting or deprotecting the nitrogen group of the piperidine. The DFT calculation validated the switchable regioselectivity based on pseudo‐1, 3‐allylic strain argument. The synthetic utility of this work was demonstrated through the synthesis of four regio‐isomers of fluorinated piperidines and a fluorinated amino acid bearing a β‐fluoroamine group, valuable building blocks in medicinal chemistry. In a broader perspective, this work can serve as a clear example for the comparison of the chemical properties between an aziridine and an epoxide. Abstract : This work describes the investigation of the ring‐opening reaction of two pairs of aziridine‐containing piperidines by fluoride. The regioselectivity could be predicted, and is switchable by introducing or removing the pseudo‐1, 3‐allylic strain. DFT calculations and the synthetic utility of this reaction are presented.