Metal‐Free Access to (E/Z)‐α‐Fluorovinyl Phosphorus Compounds from gem‐Difluorostyrenes

Abstract

A facile and efficient method for the synthesis of (E/Z)‐α‐fluorovinyl phosphorus compounds from gem‐difluorostyrenes with diphenylphosphine oxide/dialkyl phosphate and DBU at room temperature was developed. A series of 1‐fluorovinyl phosphine oxides/phosphonates were obtained with moderate to excellent yields in these reactions. Additionally, most isomers (E/Z type) of the target compounds could be easily separated and purified by column chromatography.

Rhodium‐Catalyzed Defluorinative Vinylation of gem‐Difluoroalkenes for the Synthesis of 2‐Fluoro‐1,3‐dienes

“…Among the established protocols, C—H activation coupled C—F bond functionalization is of particular interest because of the outstanding efficiency and broad substrate scope. Our group recently reported that merging C—H and C—F bonds activation gave rise to defluorinative arylation products under mild conditions . This reaction paradigm of coupling gem ‐difluoroalkenes with Ar—H species was subsequently followed by a series of C(sp 2 )—H/C(sp 3 )—H activation engaged defluorinative arylation/alkylation reported by the groups of Li, Ackermann, Fu, Wang and others (Scheme b) .…”

gem‐Heteroatom‐Substituted Fluoroalkenes as Mimics of Amide Derivatives or Phosphates: A Comprehensive Review

“…In 2019, Hao, Yang and coworkers developed a new reaction in mild conditions using DBU in DMF at room temperature to prepare α-fluorovinyl phosphine oxides, from gem-difluoroalkenes and diphenylphosphine oxide (18 examples), dialkylphosphine oxide (1 example) or dimethylphosphite (2 examples) (Scheme 47). [73] They obtained moderate to high yields albeit with low E/Z selectivity. Nevertheless, most of the E and Z compounds could be separated by column chromatography.…”

Highly E-Selective Synthesis of α-Fluoro-β-arylalkenyl Sulfones from gem-Difluoroalkenes with Sodium Sulfinates

“…Gas chromatographic analyses were performed on a Shimadzu GC 2030 gas chromatography instrument with a FID detector, and adamantane was added as an internal standard. 1 H, 13 C{ 1 H}, and 19 F NMR data were recorded with Bruker AVANCE NEO (600 MHz) and Agilent DD2 600 (600 MHz) spectrometers with tetramethylsilane as an internal standard. All chemical shifts (δ) are reported in parts per million and coupling constants (J) in hertz.…”

“…In particular, selective cleavage and transformation of one C–F bond gem -difluoroalkene provides an attractive alternative to functionalized monofluoroalkenes that can be used as peptide bond isosteres in drug discovery . The difluoromethylene carbon of gem -difluoroalkenes is susceptible to nucleophilic attack, such as various carbon-, oxygen-, nitrogen-, boron-, silicon-, sulfur-, and phosphine-centered nucleophilic intermediates. Very recently, we disclosed the visible-light-promoted E -selective synthesis of α-fluoro-β-arylalkenyl sulfides with gem -difluoroalkenes and sodium sulfinates via a deoxygenation/isomerization process .…”