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

Abstract

A one-pot synthesis of fluorinated chiral alcohols from α-bromoarylketones and fluoroalcohols is described. The fluorinated ketone intermediates were formed from α-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, K 3 PO 4 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.