Facile Two-Step Synthesis of Methyl Bis(2,2,2-trifluoroethyl)phosphonoacetate by Exploiting Garegg–Samuelsson Reaction Conditions

Abstract

A facile two-step synthesis of methyl bis(2,2,2-trifluoroethyl)phosphonoacetate (Still–Gennari reagent) has been developed by exploiting Garegg–Samuelsson reaction conditions. Starting from trimethyl phosphonoacetate, Still–Gennari reagent was prepared in 94% yield via methyl 2-{bis[(trimethylsilyl)oxy]phosphoryl}acetate intermediate. This synthetic procedure was also used to prepare some kinds of Horner–Wadsworth–Emmons reagents and related compounds.

Pyrethroid insecticides Chapter IVb. Selected transformations of chrysanthemic acid and its lower esters to Pyrethroid. Use of the Wittig and related reactions

“…with methyl dimethylphosphonoacetate and the resulting trimethylsilylphosphonate transesterified using the Garegg-Samuelsson reagent system (triphenyl phosphine, iodine and imidazole) and 2,2,2-trifluoroethanol to deliver the methyl bis(2,2,2trifluoroethyl)phosphonoacetate in up to 94% yield (Scheme 97). 208 This method has been successfully extended to other alcohols and phenols. 208 Scheme 97.…”

“…208 This method has been successfully extended to other alcohols and phenols. 208 Scheme 97. Synthesis of bis(trifluoroethyl)phosphonoacetate from dimethyl phosphonoacetate implying the Garegg-Samuelsson reagent.…”

“…Synthesis of bis(trifluoroethyl)phosphonoacetate from dimethyl phosphonoacetate implying the Garegg-Samuelsson reagent. 208 The synthesis of phenoxy phosphonates that also allow the stereoselective synthesis of α,β-unsaturated esters is disclosed below in Scheme 119 entries g-i. [248][249][250][251]…”

“…As already pointed out, the phosphorus-containing moiety acidifies the α-hydrogen by a combination of field/inductive and polarizability effects. 199 Thus phenyllithium or butyllithium in ethers, 208 sodium hydride in DMF, 208 sodium amide in liquid ammonia, 208 dimsyl sodium, 209 sodium ethylate in DMF 208 or potassium tbutoxide in THF, 208 among others have been successfully used to metalate alkyltriphenylphosphonium salts.…”

“…Specific examples involving hexyl triphenylphonium bromide are disclosed in Scheme 100. 208 Nevertheless the reader should be aware of competing processes that usually take place when butyllithium is used as a base. They produce small quantities of co-products often difficult to locate in the desired product as exemplified in Scheme 98.…”