One-Pot Construction of Fluorinated Chiral Alcohols via Sequential Substitution/Asymmetric Transfer Hydrogenation of α-Bromoarylketones and Fluoroalcohols

作者：Zhao, Rongrong; Wei, Qiao; Huang, Yuxin; Qu, Qin; Liu, Qixing^*; Zhou, Haifeng^*

来源：Advanced Synthesis and Catalysis, 2023, 365(14): 2410-2415.

DOI：10.1002/adsc.202201219

• fluorinated chiral alcohols
• one-pot
• substitution
• asymmetric transfer hydrogenation

A one-pot synthesis of fluorinated chiral alcohols from alpha-bromoarylketones and fluoroalcohols is described. The fluorinated ketone intermediates were formed from alpha-bromoarylketones with fluoroalcohols as nucleophiles and solvents, which were reduced subsequentially by adding a chiral Ru catalyst and a mixture of formic acid and triethyl amines (FA: TEA=1.1:1) as hydrogen donor to give 27 examples of fluorinated chiral alcohols in 60-93% yields and 85-98% ee values. Notably, K3PO4 acts as a base in nucleophilic substitution and an additive in reductive step to enhance the reactivity and enantioselectivity, which is crucial for constructing compatible conditions for one-pot process. This one-pot process is also applicable to gram-scale synthesis.