Preparation of Intermediates for Fluorinated Lignans by Conjugated and Tandem Additions on 3-Fluorofuran-2(5H)-one

Abstract

Two syntheses of 3-fluorofuran-2(5H)-one (1) based on Wittig-Horner reaction of ethyl (diethoxyphosphoryl)fluoroacetate (15) with 2-oxoethyl acetate (16) or on transformation of D-erythronolactone (10) are given. 3-Fluorofuran-2(5H)-one (1) and ethyl 2-fluorobut- 2-enoate (2) undergo conjugate addition with soft nucleophiles based on arene- carboxaldehyde dithioacetals 7 to form 2-fluorolactones 3 and 2-fluoroalkanoates 4. Intermediate enolates can be trapped in the sense of tandem addition with arenecarboxaldehydes 8 or (arylmethyl)bromides 9 to form intermediates 5 and 6 for fluorolignans. Although the conjugate addition proceeds with low stereoselectivity yielding mixture of both diastereoisomers, the electrophile in tandem addition attacks the intermediary fluoroenolate exclusively anti to its bulky β-substituent in good accord with non-fluorinated furan- 2(5H)-ones.

Fluorinated Analogues to the Pentuloses of the Pentose Phosphate Pathway

“…Keeping the reaction temperature below 0 °C showed to be crucial to avoid di‐ O ‐tosylation. [35] The resulting mono‐tosylate 36 then underwent a two‐step nucleophilic substitution process in the presence of potassium carbonate [36] to give the desired 2,3‐anhydro‐ d ‐ erythro ‐1,4‐lactone ( 37 ) [37] with a net retention of configuration at C‐2 (Scheme 5 ).…”

New modification of the Perkow reaction: halocarboxylate anions as leaving groups in 3-acyloxyquinoline-2,4(1H,3H)-dione compounds

“…An analogous Horner-Wadsworth-Emmons synthesis using ethyl (diethoxyphosphoryl)-fluoroacetate prepared from ethyl fluoroiodoacetate has been reported for the preparation of the α-fluoro-α,β-unsaturated acyclic esters and lactones. [ 14 ] However, when 1-benzyl-3-butyl-3-(fluoroiodoacetoxy)quinoline-2,4(1 H ,3 H )-dione ( 4 ) was reacted with triethyl phosphite an unexpected product 9 (Scheme 3 ) was obtained instead of the desired Horner-Wadsworth-Emmons intermediate 1-benzyl-3-butyl-3-(diethoxyphosphoryl)fluoroacetyloxy-quinoline-2,4(1 H ,3 H )-dione. We assume the newly observed reaction to be due to the increased electron-withdrawing character of the acyl moiety.…”

“…In the reaction of the fluoroiodoacetyl derivative 4 , triethyl phosphite does not attack the C-I bond to form the corresponding product of Michaelis-Arbuzov reaction as is usual for the alkyl fluoroiodoacetates. [ 14 ] Instead, the phosphorus atom of triethyl phosphite attacks either the carbonyl group of the R 3 -CO acyl function, or the carbonyl located at C-4 on the heterocyclic ring (Scheme 4 ). Fluorinated acyloxy derivatives 5 and 6 reacted in a similar fashion at the carbonyl carbon atom of the acyl group or at C-4 of the heterocyclic ring (Table 1 ).…”