Synthesis of Allenyl Esters by Horner–Wadsworth–Emmons Reactions of Ketenes Mediated by Isopropylmagnesium Bromide

Abstract

The synthesis of conjugated allenyl esters (tri-substituted allenes) was achieved by magnesium(II)-mediated Horner-Wadsworth-Emmons reaction of methyl bis(2,2,2-trifluoroethyl)phosphonoacetate with disubstituted ketenes. In addition, a novel access to α-fluorinated allenyl carboxamides (tetrasubstituted allenes) is presented.

Synthesis of Methyl 2-[Bis(benzylthio)phosphoryl]acetate as a Novel Horner–Wadsworth–Emmons-Type Reagent and Its Application to the Diastereodivergent Synthesis of (E)- and (Z)-α,β-Unsaturated Esters

“…We recently reported an efficient two-step synthesis of methyl 2-[bis(2,2,2-trifluoroethoxy)phosphoryl]acetate (Still–Gennari reagent; 1 ) based on Garegg–Samuelsson reaction conditions (triphenylphosphine, iodine, and imidazole) from methyl 2-(dimethoxyphosphoryl)acetate ( 2 ) via methyl 2-{bis[(trimethylsilyl)oxy]phosphoryl}acetate ( 3 ) as an intermediate (Scheme 1 ). 3 4 This procedure has been found to be applicable not only to the synthesis of Still–Gennari reagent ( 1 ), but also to the synthesis of other HWE-type reagents that have phosphorus–sulfur or phosphorus–nitrogen single bonds instead of phosphorus–oxygen single bonds. Herein, we report an efficient synthesis of methyl 2-[bis(benzylthio)phosphoryl]acetate ( 4a ) as a novel HWE-type reagent, and its application in the diastereoselective synthesis of ( E )- and ( Z )-α,β-unsaturated esters by an HWE-type reaction of 4a with various aldehydes.…”

Horner–Wadsworth–Emmons reaction as an excellent tool in the synthesis of fluoro-containing biologically important compounds

“…92 Sano et al described an easy, one-pot synthesis of fluorinated allenyl ester 149 by the HWE reaction using i-PrMgBr as a base (Scheme 26). 93 The preparation of allenyl esters is important in the context of their use for the synthesis of new cysteine protease inhibitors. 94…”

Synthesis of Mono‐fluoroallenes through Copper‐Catalyzed Defluorinative Silylation of α,α‐Difluoroalkylalkynes

“…[ 2 ] Nevertheless, the fluorinated allenes were underexplored in spite of their great potential for the synthesis of fluorinated compounds, which are extremely valuable in pharmaceutical, agrochemical and material sciences. [ 3 ] Early endeavors for the preparation of fluorinated allene include difluorovinylidenation of aldehydes and ketones, [ 4 ] indium‐mediated S E 2’ or magnesium organocuprate S N 2’ substitution of gem ‐difluoropropargyl bromide, [ 5‐7 ] aldol reaction of alkynylenolate, [ 8 ] Shapiro reaction of trifluoromethylketones, [ 9 ] Horner–Wadsworth–Emmons reaction of ketenes, [ 10 ] and others. [ 11 ] However, the heavy reliance on elaborated starting materials and/or strong nucleophiles of these methods results in the poor functional group tolerance and largely limits their broad application.…”