Triplet Reactivity and Regio-/Stereoselectivity in the
Macrocyclization of Diastereomeric Ketoprofen−Quencher
Conjugates via Remote Hydrogen Abstractions
posted on 2007-06-13, 00:00authored bySergio Abad, Francisco Boscá, Luis R. Domingo, Salvador Gil, Uwe Pischel, Miguel A. Miranda
Intramolecular excited triplet state interactions in diastereomeric compounds composed of a
benzophenone chromophore (ketoprofen) and various hydrogen donor moieties (tetrahydrofuran, isopropylbenzene) have been investigated by laser flash photolysis. The rate constants for hydrogen abstraction
by excited triplet benzophenone are in the order of 104−105 s-1, with the highest reactivity for the
tetrahydrofuran residue. A remarkable diastereodifferentiation, expressed in the triplet lifetimes of the
carbonyl chromophore (e.g., 1.6 versus 2.7 μs), has been found for these compounds. With an alkylaromatic
moiety as donor, related effects have been observed, albeit strongly dependent on the length of the spacer.
The reactivity trend for the initial hydrogen transfer step is paralleled by the quantum yields of the overall
photoreaction. The biradicals, formed via remote hydrogen abstraction, undergo intramolecular recombination
to macrocyclic ring systems. The new photoproducts have been isolated and characterized by NMR
spectroscopy. The stereochemistry of the macrocycles, which contain up to four asymmetric carbons, has
been unambiguously assigned on the basis of single-crystal structures and/or NOE effects. Interestingly,
a highly regio- and stereoselective macrocyclization has been found for the ketoprofen−tetrahydrofuran
conjugates, where hydrogen abstraction from the less substituted carbon is exclusive; cisoid ring junction
is always preferred over the transoid junction. The photoreaction is less regioselective for compounds with
an isopropylbenzene residue. The reactivity and selectivity trends have been rationalized by DFT (B3LYP/6-31G*) calculations.