Highly Efficient and Stereoselective Julia–Kocienski Protocol for the Synthesis of α‐Fluoro‐α,β‐unsaturated Esters and Weinreb Amides Employing 3,5‐Bis(trifluoromethyl)phenyl (BTFP) Sulfones

Abstract

Abstract α‐Fluoroacetates 3 and Weinreb amide 4 , bearing a α‐[3,5‐bis(trifluoromethyl)phenyl]sulfonyl (BTFP‐sulfonyl) group at the α‐position, are employed in the highly stereoselective synthesis of α‐fluoro‐α,β‐unsaturated alkenoates and Weinreb amides, respectively. Aromatic and aliphatic aldehydes are condensed under extremely mild and simple reaction conditions using potassium carbonate in dimethylformamide at room temperature under solid‐liquid phase‐transfer catalysis conditions in good yields and high Z ‐diastereoselectivities, specially in the case of the fluorinated Weinreb amides. A detailed computational mechanistic study suggests a final non‐concerted elimination of sulfur dioxide and 3,5‐bis(trifluoromethyl)phenoxide and explains the observed high stereoselectivities for the reaction on the basis of thermodynamic and kinetic considerations.