TMSCF₃-Mediated Conversion of Salicylates into α,α-Difluoro-3-coumaranones: Chain Kinetics, Anion-Speciation, and Mechanism

Abstract

As reported by Zhao, the TBAT ([Ph 3 SiF 2 ] − [Bu 4 N] + )-initiated reaction of ethyl salicylate with TMSCF 3 in THF generates α,α-difluoro-3-coumaranones via the corresponding O -silylated ethoxy ketals. The mechanism has been investigated by in situ 19 F and 29 Si NMR spectroscopy, CF 2 -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, [CF 3 ] − , and siliconate [Me 3 Si(CF 3 ) 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 TMSCF 3 and salicylate and the location of electron-withdrawing salicylate ring substituents profoundly impact the overall viability of the process, how stoichiometric CF 3 H 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.

Synthesis of Alkynylsilanes: A Review of the State of the Art

“…[153] This compound has found very broad applications not only in organosilicon chemistry [154][155][156] but primarily in organic chemistry as a fluoromethylating agent. [157][158][159][160] However, in this review, our focus will be directed towards the utilization of this compound as a silylating reagent in processes leading to 1-alkynylsilanes.…”

Speciation and kinetics of fluoride transfer from tetra-n-butylammonium difluorotriphenylsilicate (‘TBAT’)

“…The latter is generated in situ by very rapid transfer of fluoride from TBAT to TMSCF 3 , concomitantly producing fluorotriphenylsilane (FTPS), Scheme 1e . 14 Herein we report on a detailed investigation into the kinetics and mechanism of fluoride transfer from TBAT. We have studied this under three sets of conditions, two involving degenerate fluoride exchange (with FTPS and with 2-naphthalenyl fluorosulfate, ARSF) and one involving fluoride transfer to benzyl bromide (BzBr).…”