One-pot Fluorination and Organocatalytic Robinson Annulation for Asymmetric Synthesis of Mono- and Difluorinated Cyclohexenones

Xin Huang; Weizhao Zhao; Xiaofeng Zhang; Miao Liu; Stanley N S Vasconcelos; Wei Zhang

doi:10.3390/molecules23092251

One-pot Fluorination and Organocatalytic Robinson Annulation for Asymmetric Synthesis of Mono- and Difluorinated Cyclohexenones

Molecules. 2018 Sep 4;23(9):2251. doi: 10.3390/molecules23092251.

Authors

Xin Huang¹, Weizhao Zhao², Xiaofeng Zhang³, Miao Liu⁴, Stanley N S Vasconcelos⁵, Wei Zhang⁶

Affiliations

¹ College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, China. xin.huang@zjnu.cn.
² College of Chemistry and Life Sciences, Zhejiang Normal University, Jinhua 321004, China. zhao792129582@163.com.
³ Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA. Xiaofeng.Zhang002@umb.edu.
⁴ Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA. liumiaomarcus@gmail.com.
⁵ Departamento de Farmácia, Universidade de São Paulo, Av. Prof. Lineu Prestes, 580 São Paulo, SP 05508-000, Brazil. stanleynsv@gmail.com.
⁶ Department of Chemistry, University of Massachusetts Boston, 100 Morrissey Boulevard, Boston, MA 02125, USA. wei2.zhang@umb.edu.

Abstract

A one-pot fluorination and organocatalytic Robinson annulation sequence has been developed for asymmetric synthesis of 6-fluoroyclohex-2-en-1-ones and 4,6-difluorocyclohex-2-en-1-ones. The reactions promoted by cinchona alkaloid amine afforded products bearing two or three stereocenters in good to excellent yields with up to 99% ee and 20:1 dr.

Keywords: Michael addition; Robinson annulation; cyclohexenone; fluorination; organocatalysis; α-fluoro-β-keto ester.

MeSH terms

Catalysis
Chemistry, Organic / methods*
Cyclohexanones / chemical synthesis*
Cyclohexanones / chemistry*
Halogenation*
Proton Magnetic Resonance Spectroscopy

Substances

Cyclohexanones