Chiral ethylene-bridged flavinium salts: the stereoselectivity of flavin-10a-hydroperoxide formation and the effect of substitution on the photochemical properties

A series of chiral non-racemic N¹,N¹⁰-ethylene bridged flavinium salts 4 was prepared using enantiomerically pure 2-substituted 2-aminoethanols (R?=?isopropyl, phenyl, benzyl, 4-methoxybenzyl, 4-benzyloxybenzyl) derived from amino acids as the sole source of chirality. The flavinium salts were shown to form 10a-hydroperoxy- and 10a-methoxy-adducts with moderate to high diastereoselectivity depending on the ethylene bridge substituent originating from the starting amino acid. High diastereoselectivities (dr values from 80:20 to >95:5) were observed for flavinium salts bearing benzyl substituents attached to the ethylene bridge. The benzyl group preferred the face-to-face (syn) orientation relative to the flavinium unit; thereby effectively preventing nucleophilic attack from one side. This conformation was found to be the most stable according to the DFT calculations. Consequently, the presence of benzyl groups causes intermolecular fluorescence quenching resulting in a significant decrease in the fluorescence quantum yield from 11% for 4a bearing an isopropyl substituent to 0.3% for 4c containing a benzyl group and to a value lower than 0.1% for the benzyloxybenzyl derivative 4e.