Highly Diastereoselective Intramolecular [1,2]-Stevens Rearrangements—Asymmetric Syntheses of Functionalized Isopavines as Morphinomimetics

The power of visual imagery can reach Daliesque proportions in the mind's eye of the synthetic chemist. The topologically interesting isopavine nucleus, with an orthogonal orientation of two aryl groups, can be obtained as two diastereomeric structures, depending on the course of a [1,2]-Stevens rearrangement. When viewed as a constrained piperidine, a close spatial relationship with morphine (1) becomes apparent. Indeed, tetracyclic isopavine 2 exhibits morphine-like activity toward the human μ-opioid receptor.