The C-F bond as a tool in the conformational control of amides

The conformation of 2-fluoro-N-(2-fluoroethyl)-propionamide 4 in the solid state indicates the influence of both a P-fluorine-amide gauche effect and an alpha-fluoroamide effect. The structure reveals the influence of two recently observed stereoelectronic effects associated with the C-F bond, which has resulted in the successful prediction of the solid state conformation of amide 4. A gauche relationship (-69.9degrees) was observed for atoms N(1)-C(4)-C(5)-F and a syn planar (2.0degrees) relationship was observed for N(1)-C(3)-C(2)-F. The paper demonstrates the predictive power of using the C-F bond as a tool in influencing the conformation of amides and peptides. (C) 2002 Elsevier Science B.V. All rights reserved.