Enantioselective Discrimination in the Intramolecular Quenching of an Excited Aromatic Ketone by a Ground-State Phenol

Abstract

Chiral recognition is a subject of increasing interest in photochemistry.1 In principle, this can be achieved with optically active photosensitizers if an enantiodifferentiating interaction occurs in the relevant excited state. Photosensitized electron transfer processes appear specially suitable for such purposes, as the donor and the acceptor must form a highly coupled system for some time.2 The use of chiral compounds as both excited sensitizers and quenchers could enable examination of pure chiral discrimination through comparison of the quenching rates, since enantiomers have otherwise the same electronic nature and the same size. Leigh et al.3 have suggested that hydrogen abstraction from phenols by carbonyl π,π* triplets involves electron transfer within a hydrogen-bonded triplet exciplex, followed by proton transfer. In this context, we have prepared bichromophoric compounds containing enantiomerically pure aryl ketones and phenols, to check the stereochemical aspects of intramolecular electron transfer by means of laser flash photolysis studies. Benzoylthiophene is a heterocyclic diaryl ketone with a lowest lying π,π* triplet.4 This excited state involves predominantly the thenoyl chromophore; it has an energy4 of ca. 63 kcal mol-1 and is able to react with phenols, such as p-cresol and tyrosine methyl ester.5 Both substructures are present in the four enantiomerically pure bichromophoric compounds prepared in this work: TPATyr [(R,S)-1, (S,S)-1] and SUP-Tyr [(R,S)-2, (S,S)-2] (Scheme 1). We have studied the intramolecular electron-transfer process by laser flash photolysis through phenol quenching of the ketone triplet state and found a high degree of stereoselectivity, which agrees with a geometry where interaction between the π-systems of the phenol and the aromatic ketone is maximized. Compounds 1 and 2 differ in the relative aromatic ketone versus phenol orientation. They were obtained by condensation of the corresponding racemic acid, tiaprofenic acid (TPA) or suprofen (SUP), with the methyl ester of the natural occurring amino acid (S)-tyrosine, in the presence of a carbodiimide {(1-ethyl-3-[3dimethylamino]propylcarbodiimide), EDC}. In both cases, after purification of the resulting amides, one of the diastereoisomers crystallized. The other stereoisomers were further purified by HPLC chromatography [potassium dihydrogen phosphate (0.06 M):acetonitrile:triethylamine (317:183:0.1 by volume)]. All the bichromophoric compounds were fully characterized by 1H NMR, 13C NMR, and elemental analysis.