Dynamic Helical Chirality of an Intramolecularly Hydrogen-Bonded Bisoxazoline

The synthesis and conformational properties of 2,6-bis-[2-((4S)-4-methyl-4,5-dihydro-1,3-oxazol-2-yl)phenyl]carbam oylpyridines, 2, have been described. Bisoxazoline 2a was prepared in five steps from 2-nitrobenzoyl chloride in an overall yield of 71%. In contrast to related structures such as 1, bisoxazoline 2a exhibits a highly biased P-type helical conformation in solution and in the solid state. In the crystal lattice, 2a further assembles into a left-handed helical superstructure aligned along the crystallographic c axis. The barrier to helical interconversion, as measured by line-shape analysis of the temperature-dependent (1)H NMR spectra of thiobenzyl derivative 2b, was determined to be quite low ((Delta)G(++) = 12.3 kcal/mol), indicating the presence of a highly dynamic helical chirality.