Regio- and stereoselective synthesis of fluoroalkenes by directed Au(I) catalysis

Abstract

Au-catalyzed hydrofluorination reactions of a range of functionalized alkynes are reported. In the presence of an appropriate directing group, localized with particular spacing from the pendant alkyne, regioselective and predictable conversion of the alkyne to the Z-vinyl fluoride may be achieved. In selected cases, yields and selectivities are excellent. Additional experiments with two directing groups installed have established some initial principles with respect to a hierarchy of directing groups and their capacity for influencing hydrofluorination regioselectivity.

Scheme 1

Au-Catalyzed Hydrofluorination of Alkynes

Scheme 2

Ester-Directed Hydrofluorination of Alkynes ^{a a} Yields reported as the average combined yield of all isomers for two reactions, unless otherwise noted. Isomeric ratios determined by ¹⁹F NMR. ^b Yield determined using an internal ¹⁹F NMR standard. ^c Isolated yield of the major product.

Scheme 3

Hydrofluorination of Dicarbonyl Substrates ^{a a} Yield determined using an internal ¹⁹F NMR standard and reported as the average combined yield of all isomers for two reactions.

Figure 1

Possible intermediates representing interruptions of the catalytic cycle for the hydrofluorination of 29.

Figure 2

A mechanistic hypothesis for the directed hydrofluorination of alkynes.