DIRECT LITHIATION OF FUNCTIONALLY SUBSTITUTED ACRYLIC ACID DERIVATIVES; LITHIATION OF β-(2-FURANYL)- AND β-(2-THIENYL)-ACRYLIC ACIDS

Article abstract of DOI:10.1016/S0040-4020(01)91922-2

Direct C-lithiation of β-functionally-substituted acrylates yields versatile building units for syntheses of butenolides, tetronates, cyclopentenones and derivatives, which are portions of many natural products.A wide variety of α- and β-substituents are compatible with this lithiation: alkyl-, aryl- and electron donating substituents in α-position or for instance an electron withdrawing ester group in β-position.Lithiation of aminomethylene malonitrile derivative 17 led to a new azafulvene 18. β-(2-Furanyl)- and β-(2-thienyl)-acrylates (23-30) were directly C-lithiated in α-, β-, or 5-position and α- or 5-position, respectively.Reactions with different electrophiles were carried out.The presence of the unprotected electrophilic carboxylic group allows for interesting ring closure reactions, for instance with carbonyl compounds to butenolides 42 and 43.The three vinylic positions (α, β and C-5) are accessible to a highly site-selective successive lithiation and reaction with electrophiles, as demonstrated for the transformation of 25 to 45 via 42 and 44.