Synthetic Strategy for Unsymmetrical α-Fluoro-α'-aryl Ketones

Shubham Dutta; Avijit Maity; Shengwen Yang; Rajendra K Mallick; Manash P Gogoi; Vincent Gandon; Akhila K Sahoo

doi:10.1021/acs.orglett.4c04486

Synthetic Strategy for Unsymmetrical α-Fluoro-α'-aryl Ketones

Org Lett. 2025 Jan 13. doi: 10.1021/acs.orglett.4c04486. Online ahead of print.

Authors

Shubham Dutta¹, Avijit Maity¹, Shengwen Yang², Rajendra K Mallick¹, Manash P Gogoi¹, Vincent Gandon³, Akhila K Sahoo⁴

Affiliations

¹ School of Chemistry, University of Hyderabad, Hyderabad 500046, India.
² Institut de Chimie Moléculaire et des Matériaux d'Orsay, Université Paris-Saclay, 91400 Orsay, France.
³ Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), CNRS UMR 8182, Université Paris-Saclay, 17 avenue des Sciences, 91400 Orsay, France.
⁴ School of Chemistry, University of Hyderabad, Gachibowli, Telangana 500046, India.

PMID: 39804713
DOI: 10.1021/acs.orglett.4c04486

Abstract

α-Fluoro-α'-aryl ketones are crucial in pharmaceuticals and agrochemicals. However, synthesizing unsymmetrical α-fluoro-α'-aryl ketones poses regioselective challenges. This study presents a one-pot aryl-oxy-fluorination method for synthesizing such unsymmetrical fluoro-aryl ketones. Using ynamide, aryl boronic acid, and F-source under Pd-catalysis, this method efficiently produces a wide range of valuable α-fluoro-α'-aryl ketones with potential applications. Through a combination of control experiments and DFT studies, we proposed a reaction mechanism involving in situ acetic acid formation.