posted on 2023-12-02, 15:04authored byHannah
B. Minshull, Guy C. Lloyd-Jones
As reported by Zhao,
the TBAT ([Ph3SiF2]−[Bu4N]+)-initiated reaction of
ethyl salicylate with TMSCF3 in THF generates α,α-difluoro-3-coumaranones
via the corresponding O-silylated ethoxy ketals.
The mechanism has been investigated by in situ 19F and 29Si NMR spectroscopy, CF2-trapping, competition,
titration, and comparison of the kinetics with the 3-, 4-, 5-, and
6-fluoro ethyl salicylate analogues and their O-silylated
derivatives. The process evolves in five distinct stages, each arising
from a discrete array of anion speciations that modulate a sequence
of silyl-transfer chain reactions. The deconvolution of coupled equilibria
between salicylate, [CF3]−, and siliconate
[Me3Si(CF3)2]− anions
allowed the development of a kinetic model that accounts for the first
three stages. The model provides valuable practical insights. For
example, it explains how the initial concentrations of the TMSCF3 and salicylate and the location of electron-withdrawing salicylate
ring substituents profoundly impact the overall viability of the process,
how stoichiometric CF3H generation can be bypassed by using
the O-silylated salicylate, and how the very slow
liberation of the α,α-difluoro-3-coumaranone can be rapidly
accelerated by evaporative or aqueous workup.