Conformational preference in difluoroacetamide oligomers: probing the potential for foldamers with C–H⋯O hydrogen bonds

The C–H bond of a difluoroacetamide group, acidified by two adjacent fluorine atoms, could in principle provide conformational organisation for foldamers based on C–H⋯O hydrogen bonds. We find that in model oligomeric systems, this weak hydrogen bond leads only to partial organisation of the secondary structure, with the conformational preference of the difluoroacetamide groups being predominantly governed by dipole stabilisation. Hydrogen-bonded foldamers,1,2 and more recently polarity-coherent but conformationally flexible oligoureas based on ethylenediamine linkers 1 (Fig. 1A),3 have found widespread use in structural chemistry4 and catalysis,5,6 and as switchable devices,7 and have demonstrated potential biological applications.8 Hydrogen-bonded foldamer structures incorporate a range of structural motifs, but the most common are oligoamides and oligoureas or thioureas.9 These functional groups provide conformational control through strong N–H⋯O[double bond, length as m-dash]C hydrogen bonds, similar to those governing secondary structures in peptides.