Fig. 4: Preliminary mechanistic experiments to probe the involvement of a C–F RE.
From: Pd-catalysed direct β-C(sp3)–H fluorination of aliphatic carboxylic acids
a, Possible pathways for the generation of fluorinated acids 2 from intermediate 2. Path A denotes the direct fluorination via a C–F reductive elimination from Int-3 as shown in more detail in Fig. 1. Path B consists of a C–O RE forming a β-lactone 3, followed by a nucleophilic substitution with fluoride to give fluorinated acid 2. b, A control experiment shows that an independently synthesized β-lactone 3a is not converted to the respective fluorinated acid 2c under the reaction conditions. A second control experiment shows that, when substrate 1a is present alongside 3a, it is converted to 2a in 55% yield as expected from the scope studies. β-Lactone 3a is recovered in both control experiments, thereby excluding product formation via β-lactones as intermediates as potential mechanistic scenario and corroborating to a mechanism involving a direct C-F RE. Yields were determined by 1H NMR spectroscopic analysis of the crude reaction mixture using 1,3,5-trimethoxybenzene as an internal standard.
