Tritiodefluorination of alkyl C-F groups

Abstract

A straightforward methodology of fluorine substitution by tritium/deuterium is reported. The described method is selective towards the F─C (sp³ ) group and leaves both the aromatic F─C (sp² ) and F₂ ─C (sp³ ) moieties unaffected. Alkylfluorides, readily synthesized from appropriate alcohols by treatment with diethylaminosulfur trifluoride (DAST) reagent in an overall yield up to 76%, undergoes activation with the boron-based Lewis acid B(C₆ F₅ )₃ , and stoichiometric in situ reduction with a tritide/deuteride reagent-the [TMP²⁽³⁾ H][²⁽³⁾ HB(C₆ F₅ )₃ ] system of frustrated Lewis pair. This methodology provides an isolated yield of up to 93% of regio-specifically labeled small organic compounds with superior ² H-enrichment of over 95%. The specific activity of prepared 1-(2-[³ H]-ethyl)naphthalene was determined at 29.0 Ci/mmol. The site selectivity of the Lewis acid/ [TMP²⁽³⁾ H][²⁽³⁾ HB(C₆ F₅ )₃ ] approach is orthogonal to currently used methods and allows for isotopic labeling of complementary positions in molecules. Reported labeling methodology proceeds well at ultra-mild reaction conditions (220 mbar of T₂ ), allowing very low consumption of the radioactive source (4.2 Ci/156 GBq), and producing limited amount of radioactive waste.

Keywords: C─F activation; deuterium labeled alkane; deuterodefluorination; frustrated Lewis pairs; hydrogen activation; non-metallic reagent; tritiodefluorination; tritium labeled alkane; ultra-mild reaction conditions; very low tritium pressure.