“On-water” defluorophosphorylation of trifluoromethylated enones with phosphine oxides

Abstract

The distinctive fluorine effects on “on-water” chemistry remained less explored. In this work, an “on-water” reaction of β-trifluoromethylated enones with phosphine oxides was developed for the preparation of highly functionalized...

“On-water” defluorinative cyclization of trifluoromethyl enones with phosphine oxides: synthesis of polysubstituted furans

“…This result also supported the specific properties of the "on-water" reaction. 22 Based on these findings and previous reports, 12,[15][16][17][18][19][20][21][22]24 we propose a reaction mechanism (Scheme 3). Under basic conditions, the reaction of phosphoryl anion A with electrophilic trifluoromethyl enone 1 initially affords intermediate B, which undergoes rapid anionic F-elimination to form phosphorylated gem-difluoroalkene C. 19a During this process, the electrondeficient nature of the CF 3 group favors the selective occurrence of the S N 2′-type nucleophilic attack on the C-C double bond adjacent to the carbonyl group.…”

“…Subsequent investigations of different solvents revealed the specific ability of water to control reaction selectivity 21,22 as compared to MeOH, MeCN, and DMSO, where competitive byproducts 3aa-I-3aa-IV were formed (entries 9-11). 16 With the optimal conditions established, the generality of this defluorinative cascade was tested by employing a wide array of commercially available phosphine oxides, as described in Table 2. In principle, diarylphosphine oxides 2 with electron-varied substituents on the aryl moiety did not affect the reaction efficiency.…”

“…Furthermore, the presence of the carbonyl group attached to CF 3 -alkenes provides promising potential for adjusting reactivity and chemoselectivity. 16 Our aim was to explore the feasibility of assembling heterocycles and introducing functional groups specifically at the γ-position through the intermolecular defluorocyclization of CF 3 -alkenes containing a pre-installed auxiliary unit (Fig. 2A, below).…”

Combining Hydrodefluorination and Defluorophosphorylation for Chemo- and Stereoselective Synthesis of gem-Fluorophosphine Alkenes

“…Very recently, the dual C–F bond functionalization of trifluoromethyl alkenes for accessing a monofluorocyclohexene framework was enabled through a stepwise photoredox radical/polar crossover procedure . Inspired by these elegant works and in continuation of our interest in defluorinative reactions, we herein presented a formal hydrophosphorylation reaction of β-CF 3 -substituted enones by combining hydrodefluorination and defluorophosphorylation in one pot. This three-component tactic has high versatility for the chemo-, regio-, and stereoselective synthesis of skeletally important ( Z )- gem -fluorophosphine alkenes.…”

“…On the basis of these control experiments and previous reports, we proposed a plausible reaction mechanism (Scheme ). − Initially, the carbonyl-containing trifluoromethyl alkenes react with reductive PhSiH 3 to realize hydrodefluorination through an S N 2′-type nucleophilic process and a simultaneous carbonyl reduction, leading to gem -difluorinated alkene B (pathway a). Subsequently, phosphoryl anion D selectively adds to the highly electrophilic α-position in gem -difluoroalkenes, followed by β-fluorine elimination to deliver the desired product 3 .…”