A new fluorinating reagent system: Alkyl fluorides from alcohols under mild reaction conditions
16 July 2004
Most of the previously reported reagents for converting alcohols to alkyl fluorides [e.g. SF4, pyridinium poly(HF) (Olah’s reagent), fluoroalkylamino reagents (FAR), DAST (diethylaminosulfur trifluoride) and Deoxo-Fluor (bis(2-methoxyethyl)aminosulfur trifluoride], are limited by one or more of the following: instability, poor availability, aggressive reaction conditions, difficulty in handling and workup, cost, and limited scope and/or functional group compatibility.
Process chemists at Merck have recently reported* a new reagent mixture for the high-yielding conversion of primary, secondary and tertiary alcohols to the corresponding fluorides.
The reagents are readily available, cheap, easy to handle, and the mild, near-neutral reaction conditions do not generate free HF, and allow for good functional group compatibility. Functional groups that are tolerated included esters, ethers, alkyl tosylates, ketones and aldehydes.
The triethylamine-based reagent system is effective for most substrates, although notably not for primary or benzylic alcohols, where the Hunig’s base system was superior.
* J. Yin et al.,Organic Letters, 2004, 6(9), 1465.