Conjugate Additions to Phenylglycinol-Derived Unsaturated δ-Lactams. Enantioselective Synthesis of Uleine Alkaloids

The stereochemical outcome of the conjugate addition of a variety of stabilized nucleophiles (2-indoleacetic enolates and sulfur-stabilized anions) to the phenylglycinol-derived unsaturated lactams
trans-2, cis-2, and its 8-ethyl-substituted analogue 10 is studied. The factors governing the exo or
endo facial stereoselectivity are discussed. This methodology provides short synthetic routes to
either cis- or trans-3,4-disubstituted enantiopure piperidines as well as efficient routes for the
enantioselective construction of the tetracyclic ring system of uleine alkaloids, both in the normal
and 20-epi series. The formal total synthesis of several alkaloids of this group is reported.