Solvent-Promoted Catalyst-Free Nucleophilic Fluoroalkylation of Aldehydes

Fluoroalkyl silanes are useful building blocks for nucleophilic introduction of fluoroalkyl groups into organic molecules. In general, fluoroalkyl silanes per se are stable compounds, but they are amenable to reactions as fluoroalkyl anion equivalents in the presence of base such as fluoride ion. Usually, KF acts as a good catalyst for nucleophilic fluoroalkylation of carbonyl compounds. To avoid the use of hygroscopic fluoride salts, we have developed a convenient catalyst-free method for nucleophilic fluoroalkylation of aldehydes and ketones by the use of fluoroalkyl silanes. Trifluoromethyl(trimethyl)silane (Me3Si-CF3), and other fluoroalkyl silanes (Me3Si-R-f) underwent solvent-promoted nucleophilic addition to aldehydes smoothly to give fluoroalkylated alcohols in good yields. In the present reactions, the use of polar solvents such as DMSO, DMF or NMP is essential to the formation of 1,2-adducts.