Synthesis of α-fluoro-β, γ-alkenylphosphonates and conjugated fluoroenynes from a common intermediate (α-fluoropropargyl) phosphonate

Stereoselective Synthesis of Conjugated Fluoro Enynes

“…10c On the other hand, reactions of carbonyl compounds and (α-fluoropropargyl)phosphonates, with phenyl- or alkyl-substituted alkynes, gave internal enynes in poor yields and typically with no selectivity. 10a,b Since Sonogashira coupling offers a convenient route to internal alkynes, we wanted to explore conversions of the deprotected terminal fluoro enynes, obtained from the condensations, to internal fluoro enynes (Scheme 5). Fluoro enynes 4 and 16 , when subjected to Sonogashira couplings with phenyl iodide, gave phenyl-derived fluoro enynes in good yields.…”

“…8 The few modular approaches reported involve metal-catalyzed synthesis of 1-fluoro, 9a–c 2-fluoro, 9d–h di 9a,9i–k and trifluoro 9a,9j 1,3-enynes, as well as the Horner-Wadsworth-Emmons approach to 2-fluoro-1,3-enynes (Figure 2). 10 Among natural products, synthesis of a ( E )-13-fluoro-13-hexadecen-11-ynyl acetate, a fluorinated analog of a sex pheromone, has been reported. 11 Here, the fluoro enyne analog was prepared from the corresponding enyne by dehydration of a fluorohydrin intermediate.…”

The First α-Fluoroallenylphosphonate, the Synthesis of Conjugated Fluoroenynes, and the Stereoselective Synthesis of Vinylfluorophosphonates Using a New Multifunctional Fluorine-Containing Building Block

“…For example, saturated and unsaturated aldehydes, as well as ketones, reacted with 6a , and in all cases very good to excellent yields of fluoroenynes and fluoroenediynes 7a − f were obtained. In stark contrast, 1a produced trace amounts of enediynes, and its reaction with pentanal and other saturated aldehydes gave exclusively aldol condensation products . Along the same lines, the synthesis of α-alkyl substituted fluoropropargylphosphonate 6c , an impossible task using 1a , was easily accomplished with 6a .…”

“…However, their synthesis remains elusive. In total, less than a handful of syntheses have been reported, all low yielding . As Table shows, the merit of silylfluoropropargylphosphonate 6a as a building block is obvious in the synthesis of fluorolefins under WHE conditions.…”

“…The synthesis of 1a enabled us to prepare 2 and 3 via Wadsworth−Horner−Emmons (WHE) olefination and catalytic hydrogenation, respectively (Scheme ). Two intrinsic disadvantages hinder a wider use of 1 as fluorine synthon: (1) the small pool of commercially available propargyl aldehydes (e.g., RC⋮CCHO) needed as starting material and (2) the instability of the α-carbanion of 1a .…”