A Novel Intramolecular Horner-Wadsworth-Emmons Reaction: A Simple and General Route to .alpha.-Fluoro-.alpha.,.beta.-unsaturated Diesters

Abstract

Diethyl (fluorocarbethoxymethyl)phosphonate (1), prepared from triethyl phosphite and ethyl bromofluoroacetate, reacts with n-butyllithium in THF to give the phosphonate carbanion 2.Addition of the pregenerated carbanion 2 to a THF solution of methyl or ethyl oxalyl chloride at -78 °C forms the acylated phosphonate (Et0)2P(0)CF(C0C02R)CC>2Et (3). In situ reaction of 3 with Grignard reagents affords a-fluoro-a,/3-unsaturated diesters R'(C02R)C=CFC02Et in moderate to good yields with high E-stereoselectivity. The reaction is applicable to primary, secondary, and tertiary alkyl, alkenyl, alkynyl, aryl, cyclohexyl, and perfluorinated Grignard reagents. The assignment of E and Z configuration is based on NOE experiment. The E/Z ratio of unsaturated diesters formed in the reaction varies with the metal ion and cosolvent. However, solvents and bases have little influence on the stereoselectivity.1:1 mixture of ethylenic triethyl esters (Et02CCFH)(C02-Et)C=CHC02Et and the isomerization product (Et02-CCH2)(C02Et)C=CFC02Et.8 Alkylation of (ethylphenyl)t Chung Cheng Institute of Technology.

Inhibition of monoterpene cyclases by inert analogues of geranyl diphosphate and linalyl diphosphate

“…2-FGPP (7) [18] and (±)-2-FLPP (8) [19] were prepared as outlined in Schemes 1 and 2. Olefination of 6-methyl-5-hepten-2-one (12) with the sodio form of triethyl fluorophosphonoacetate (13) [20] in benzene afforded a 1:1 mixture of cis and trans fluoro esters, and reduction of the mixture with LiAlH 4 in THF followed by chromatographic separation gave 2-fluoronerol (14, 50%) and 2-fluorogeraniol (15, 43%) (Scheme 1) [18]. The configuration of the 2,3-double bond in the isomers was confirmed by correlation of the 1 H and 19 F NMR spectral data with literature values for the fluoro alcohols [18] and with data for the corresponding 2-fluorofarnesol isomers [21].…”

A General and Efficient Route for the Preparation of Phenyl-Substituted Vinyl Fluorides

“…Dehydroiodination of 1-fluoro-2-iodo-1-phenylpropane also leads to the preparation of cis-and trans-(1-fluoroprop-1-enyl)benzenes [12]. Recent research from our laboratory has focused on the use of fluoroethoxycarbonyl-substituted phosphorus or phosphonate ylides as synthons for the preparation of a-fluorocarbonyl compounds such as a-fluoro-a,b-unsaturated esters [13], a-fluoro-b-keto esters [14], a-fluoro-a-alkyl esters [15], and a-fluoro-a,b-unsaturated diesters [16]. Herein, we describe a general, one-pot synthesis of Phsubstituted vinyl fluorides RR'CCFPh, which permits variation of the group in the bposition from the reaction of diethyl a-fluorobenzylphosphonate carbanion [(EtO) 2 …”

“…However, in the preparation of 6h, the (Z)-isomer was obtained preferentially. This result may possibly be explained by the repulsive interactions between 3,4-(MeO) 2 C 6 H 3 and Ph groups [16]. The stereoselectivity of 6a and 6i is dependent on the solvent, base, cosolvent, or metal ion present in the reaction mixture.…”

“…However, the presence of excess LiCl had no influence on the The formation of Ph-substituted fluoro alkenes is analogous to the Wittig reaction [21] and is illustrated in Scheme 5. The formation of the intermediate 9 from 3 and carbonyl compounds is reversible [22], and that intermediate can exist in two diastereoisomeric forms, 9a and 9b [13] [16]. Complexation of soluble Li salts [23] with the intermediate 9 retards the reversibility between the isomers 9a and 9b.…”

“…The relative rates of formation and decomposition of the intermediate should determine the (E)/(Z)-ratio. Slow decomposition of alkoxy anions should lead to increased reversibility of the initial step to form the (Z)-isomer as the major product [16]. The decisive influence of dissolved Li salts on the isomer ratio in Wittig and related reactions is well-documented [24].…”