Synthesis and Conformational Studies of Urobilin Difluoroboron Complexes. Unprecedented Solvent-Dependent Chiroptical Properties of the BF2 Chelate of an Urobilinoid Analogue1

Abstract

Optically active difluoroboron complexes of both a conventional urobilin derivative (3) and a nonracemizable urobilin analogue (4) have been synthesized for the first time, and their structures have been determined, in solution, by means of 1H{1H}NOE difference experiments. Whereas the BF2 chelate 5 occurs in a “stretched” 9Z,4(5)-ac, 5(6)-sc,10(11)sp,14(15)-sc,15(16)-ac conformation in both dimethylformamide and methylene chloride solutions, the preferred conformation (6 or 7) of the difluoroboron complex of 4 is dependent on the solvent, thus giving rise to opposite CD curves in the aforementioned solvents. As revealed by X-ray diffraction analysis, however, only conformer 6 is present in the solid state, in which extended intermolecular hydrogen bonding involving the lactam groups takes place, independently of the solvent used for crystallization. Conformer 7, on the contrary, is stabilized, in solution, by intramolecular NH···F bonds, as evidenced by measurements of “through-space” 1H−19F spin−spin coupling.