Phosphine-Catalyzed Intermolecular Acylfluorination of Alkynes via a P(V) Intermediate

Abstract

We report on the phosphine-catalyzed intermolecular carbofluorination of alkynes using acyl fluorides as fluorinating reagents. This reaction promises to be a useful method for the synthesis of highly substituted monofluoroalkene derivatives, since acyl fluorides can be easily prepared from the corresponding carboxylic acid derivatives and the reaction proceeds under ambient conditions without the need for a transition-metal catalyst. Experimental and computational studies indicate that a five-coordinated fluorophosphorane is involved as the key intermediate in the fluorination step.

Three-Component Coupling of Acyl Fluorides, Silyl Enol Ethers, and Alkynes by P(III)/P(V) Catalysis

“…The catalytic reaction starts with the addition of PR3 to an alkynoate to generate the carbanion IM0, which subsequently undergoes nucleophilic acyl substitution with an acyl fluoride to form the fluorophosphorane 1. 12 Ligand metathesis between 1 and the silyl enol ether driven by the formation of a stable Si-F bond proceeds to afford alkoxyphosphorane 2, in preference to the ligand coupling of 1, to form a C-F bond. The [3,3]-sigmatropic rearrangement of 2 forges a new carbon-carbon bond between the α-carbon of the silyl enol ether and α-carbon of an electron-deficient alkyne to afford the phosphonium ylide IM3.…”

“…The ylide moiety in IM3 abstracts the α-hydrogen derived from the silyl enol ether to generate the enolate IM4. This [1,3]-proton transfer could be mediated by a trace amount of endogenous water in the system, 25,26 which also explains the decrease in the deuterium Density functional theory (DFT) calculations were carried out using PMe3 as a model catalyst in order to examine the feasibility of the proposed mechanism after the formation of 1 12 (Fig. 4c).…”

“…1,7,8 However, examples reported thus far are limited to relatively simple, prototypical transformations, including hydrogenation, 9 reduction of allyl bromides, 10 and acylfluorination of alkynes. 12 Herein, we report on extending P(III)/P(V) catalyst system to a phosphine-catalyzed formal hydrovinylation reaction by the three-component coupling of acyl fluorides, silyl enol ethers, and alkynoates.…”

“…2a). 12 In this reaction, a pentacoordinate fluorophosphorane 1 is involved as the key intermediate, and a C-F bond is formed via ligand coupling (LC) on 1, an alternative to reductive elimination on transition metal complexes.…”

“…4a-(i)). Monofluoroalkene 10ba, which can also be formed by phosphine-catalyzed carbofluorination 12 between acyl fluoride 4b and alkynoate 6a, is a potential intermediate in this three-component coupling. However, the desired product 7bba was not formed from 10ba under these reaction conditions, ruling out the involvement of 10ba (Fig.…”