Atropisomeric transition state analogs

Transition state mimicry is one of the most powerful concepts in enzyme inhibitor design and has led to the development of catalytic antibodies. Transition state analogs are compds. with a fixed shape that resemble the geometry and charge distribution of the transition state of a given reaction. Stabilization of a transition state like conformation is most often achieved by incorporating a ring system into the analog. We show herein that atropisomerism can be used as a new principle for enforcing a transition state like conformation. Atropisomerism relates to the existence of stereoisomers of structurally constrained mols. due to a frozen rotation about a single bond, as for example in binaphthol. The 1-aminomethylnaphthalene deriv. I1 exhibits atropisomerism due to a frozen rotation about the C(1)-C(methylene) single bond, which holds the dihedral angle ?[C(2)-C(1)-C(methylene)-N] close to 90°. Compd. I mimics the transition state for hydride transfer between 1,4-dihydroquinolines and acetone. [on SciFinder(R)]